U.S. patent application number 17/287668 was filed with the patent office on 2021-12-23 for apparatus and method for measuring physiological parameters of mammal subject and applications of same.
The applicant listed for this patent is NORTHWESTERN UNIVERSITY. Invention is credited to Ha Uk CHUNG, Bong Hoon KIM, Jong Yoon LEE, Jungyup LEE, John A. ROGERS, Shuai XU.
Application Number | 20210393155 17/287668 |
Document ID | / |
Family ID | 1000005835348 |
Filed Date | 2021-12-23 |
United States Patent
Application |
20210393155 |
Kind Code |
A1 |
ROGERS; John A. ; et
al. |
December 23, 2021 |
APPARATUS AND METHOD FOR MEASURING PHYSIOLOGICAL PARAMETERS OF
MAMMAL SUBJECT AND APPLICATIONS OF SAME
Abstract
An apparatus for measuring physiological parameters of a mammal
subject includes a first sensor system and a second sensor system
that are time-synchronized to each other and spatially separated.
Each sensor system has a plurality of electronic components and a
plurality of flexible and stretchable interconnects that are
electrically connecting to different electronic components, and an
elastomeric encapsulation layer at least partially surrounding the
plurality of electronic components and the plurality of flexible
and stretchable interconnects to form a tissue-facing surface and
an environment-facing surface. The plurality of electronic
components includes a sensor member for measuring at least one
physiological parameter of the mammal subject, a system on a chip
(SoC) having a microprocessor coupled to the sensor member for
receiving data from the sensor member and processing the received
data, and a transceiver coupled to the SoC for wireless data
transmission and wireless power harvesting.
Inventors: |
ROGERS; John A.; (Wilmette,
IL) ; XU; Shuai; (Bala Cynwyd, PA) ; CHUNG; Ha
Uk; (Evanston, IL) ; LEE; Jong Yoon;
(Evanston, IL) ; KIM; Bong Hoon; (Evanston,
IL) ; LEE; Jungyup; (Evanston, IL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
NORTHWESTERN UNIVERSITY |
Evanston |
IL |
US |
|
|
Family ID: |
1000005835348 |
Appl. No.: |
17/287668 |
Filed: |
October 31, 2019 |
PCT Filed: |
October 31, 2019 |
PCT NO: |
PCT/US2019/059131 |
371 Date: |
April 22, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62753303 |
Oct 31, 2018 |
|
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|
62753453 |
Oct 31, 2018 |
|
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62753625 |
Oct 31, 2018 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/0022 20130101;
A61B 5/7285 20130101; A61B 5/0006 20130101; A61B 5/746 20130101;
A61B 2560/0214 20130101; A61B 2562/0271 20130101; A61B 5/11
20130101; A61B 5/742 20130101; A61B 5/02028 20130101; A61B 2562/164
20130101; A61B 5/28 20210101; A61B 5/02427 20130101; A61B 2503/40
20130101; A61B 2503/045 20130101; A61B 5/7405 20130101; A61B 5/01
20130101; A61B 5/022 20130101; A61B 5/7225 20130101; A61B 5/6828
20130101; A61B 5/6825 20130101; A61B 5/6833 20130101; A61B 5/0816
20130101; A61B 5/6823 20130101; A61B 2562/0219 20130101; A61B
5/14542 20130101; A61B 5/0024 20130101 |
International
Class: |
A61B 5/024 20060101
A61B005/024; A61B 5/00 20060101 A61B005/00; A61B 5/28 20060101
A61B005/28; A61B 5/02 20060101 A61B005/02; A61B 5/01 20060101
A61B005/01; A61B 5/11 20060101 A61B005/11; A61B 5/08 20060101
A61B005/08; A61B 5/022 20060101 A61B005/022; A61B 5/145 20060101
A61B005/145 |
Claims
1. An apparatus for measuring physiological parameters of a mammal
subject, comprising: a first sensor system and a second sensor
system that are time-synchronized to each other, each of the first
sensor system and the second sensor system comprising: a plurality
of electronic components, and a plurality of flexible and
stretchable interconnects electrically connecting to different
electronic components, wherein the plurality of electronic
components comprises a sensor member for measuring at least one
physiological parameter of the mammal subject, a system on a chip
(SoC) having a microprocessor coupled to the sensor member for
receiving data from the sensor member and processing the received
data, and a transceiver coupled to the SoC for wireless data
transmission and wireless power harvesting; and an elastomeric
encapsulation layer at least partially surrounding the plurality of
electronic components and the plurality of flexible and stretchable
interconnects to form a tissue-facing surface and an
environment-facing surface, wherein each of the first sensor system
and the second sensor system is attached to a respective position
on the mammal subject so that the first sensor system and the
second sensor system are spatially separated by a distance.
2. The apparatus of claim 1, wherein the distance between the first
sensor system and the second sensor system is adjustable between a
minimal distance and a maximal distance.
3. The apparatus of claim 1, wherein the plurality of flexible and
stretchable interconnects comprise at least one of serpentine
interconnects and zigzag interconnects.
4. The apparatus of claim 1, wherein the SoC comprises at least one
of a near-field communication (NFC) interface and a Bluetooth
interface.
5. The apparatus of claim 1, wherein said transceiver comprises a
magnetic loop antenna tuned to compliance with the NFC protocol and
configured to allow simultaneous wireless data transmission and
wireless power harvesting through a single link.
6. The apparatus of claim 1, wherein the plurality of electronic
components of each of the first sensor system and the second sensor
systems further comprises a battery for provide power to said
sensor system, and the elastomeric encapsulation layer is
configured to electrically isolate the battery from the mammal
subject during use.
7. The apparatus of claim 6, wherein the battery is a rechargeable
battery operably rechargeable with wireless recharging.
8. The apparatus of claim 6, wherein the plurality of electronic
components of each of the first sensor system and the second sensor
system further comprises a failure prevention element that is a
short-circuit protection component or a battery circuit to avoid
battery malfunction.
9. The apparatus of claim 4, wherein the plurality of electronic
components of each of the first sensor system and the second sensor
system further comprise a power management unit electrically
coupled between the SoC and the transceiver.
10. The apparatus of claim 1, wherein each of the first sensor
system and the second sensor system further comprises a
microfluidic chamber positioned between the tissue-facing surface
and the plurality of electronic components configured to
mechanically isolate the plurality of electronic components from a
skin surface during use.
11. The apparatus of claim 10, wherein the microfluidic chamber is
at least partially filled with at least one of an ionic liquid and
a gel.
12. The apparatus of claim 10, wherein the encapsulation layer
comprises channels or conduits configured to facilitate sweat
evaporation during use.
13. The apparatus of claim 1, wherein the encapsulation layer is
optically transparent so as to be compatible with visual inspection
of underlying tissue.
14. The apparatus of claim 1, wherein the encapsulation layer is
configured to electrically isolate each of the first sensor system
and the second sensor system from an electroshock applied to the
mammal subject.
15. The apparatus of claim 1, wherein the encapsulation layer
comprises a flame retardant material.
16. The apparatus of claim 1, wherein each of the first sensor
system and the second sensor system is radiotranslucent and
thermally stable so that each of the first sensor system and the
second sensor system is compatible with medical imaging.
17. The apparatus of claim 1, wherein each of the first sensor
system and the second sensor system is formed to be stretchable and
bendable.
18. The apparatus of claim 1, wherein each of the first sensor
system and the second sensor system is formed in a multi-layer
structure to mechanically isolate mechanically stiff components in
a mechanical island configuration to accommodate bending, twisting
or stretching without fracture or substantial degradation of an
operating parameter.
19. The apparatus of claim 1, wherein each of the first sensor
system and the second sensor system is configured to conformally
attach to a skin surface in a conformal contact without an
adhesive, wherein a contact force is generated by Van der Waals
interaction between the tissue facing surface of each of the first
sensor system and the second sensor system and a skin surface
during use.
20. The apparatus of claim 19, wherein the adhesive-free conformal
contact comprises a wrapped geometry, the sensor member of at least
one of the first sensor system and the second sensor system further
comprises a fastener connected to an external surface of the
encapsulation layer to fasten the sensor member in the wrapped
geometry to a mammal subject.
21. The apparatus of claim 1, wherein each of the first sensor
system and the second sensor system further comprises an adhesive
layer operably attached to the tissue-facing surface of the
encapsulation layer, wherein the adhesive layer has a pattern of
perforations through open regions.
22. The apparatus of claim 1, further comprising a reader system
that comprises an antenna in communication with said transceiver of
each of the first sensor system and the second sensor system for
simultaneous wireless data transmission and wireless power
delivery.
23. The apparatus of claim 22, wherein the reader system further
comprises an NFC reader module for receiving wirelessly transmitted
data from each of the first sensor system and the second sensor
system, and a Bluetooth low energy (BLE) module for transmitting
the received data to an external computing device for at least one
of real-time display of the monitored physiological parameters,
recording of the monitored physiological parameters, and alarm.
24. The apparatus of claim 1, further comprising an alarm device
for providing at least one of an optical alert and an audio alert
when a physiological parameter is out of a pre-defined range.
25. The apparatus of claim 24, wherein the alarm device is at least
one of an on-board device and an off-board device.
26. The apparatus of claim 1, wherein the first sensor system is a
conformable torso sensor system configured to attach and conform to
a torso region of the mammal subject, and the second sensor system
is a conformable extremity sensor system configured to attach and
conform to a limb or appendage region of the mammal subject.
27. The apparatus of claim 26, wherein the torso sensor system
comprises: a first electrode and a second electrode as the sensor
member; a Bluetooth low energy (BLE) SoC as the SoC; an ECG analog
front-end (AFE)/inertial measurement unit (IMU); and a power
management integrated circuit (PMIC) and a memory.
28. The apparatus of claim 26, wherein the sensor member of the
torso sensor system comprises at least two electrodes spatially
separated from each other by an electrode distance, D, for
electrocardiogram (ECG) generation.
29. The apparatus of claim 28, wherein the electrode distance D is
adjustable between a minimal electrode distance, D.sub.min, and a
maximal electrode distance, D.sub.max, wherein the minimal
electrode distance D.sub.min is a distance of said two electrodes
when the torso sensor system is in a non-stretched state, and the
maximal electrode distance D.sub.max is a distance of said two
electrodes when the torso sensor system is in a maximally stretched
state along the distance.
30. The apparatus of claim 29, wherein the at least two electrodes
comprise at least one of mesh electrodes and solid electrodes.
31. The apparatus of claim 28, wherein the sensor member of the
torso sensor system further comprises one or more of: an
accelerometer for measuring at least one of a position and a
movement; an inertial measurement unit (IMU) for measuring at least
one of seismocardiography (SCG) and a respiratory rate; and a
temperature sensor for measuring temperature.
32. The apparatus of claim 26, wherein the extremity sensor system
comprises: a Bluetooth low energy (BLE) SoC as the SoC; a PPG
analog front-end (AFE); a photodiode/light emitted diode (LED) and
an optical detector as the sensor member; and a power management
integrated circuit (PMIC) and a memory.
33. The apparatus of claim 26, wherein the extremity sensor system
is configured such that a main circuit component including at least
the SoC and the transceiver is aligned and operably wrapped around
a limb or appendage in a wrap direction; and the sensor member is
spatially separated from and electronically connected to the main
circuit component, and operably extends in a direction different
from the wrap direction to attach to a sensor region that is
spatially distinct from the wrapped portion during use.
34. The apparatus of claim 33, wherein the sensor member of the
extremity sensor system is conformable to a skin surface and
configured as a soft wrap for circumferential attaching to the limb
or appendage region.
35. The apparatus of claim 33, wherein the sensor member of the
extremity sensor system comprises a photoplethysmogram (PPG) sensor
comprising an optical source and an optical detector located within
a sensor footprint.
36. The apparatus of claim 35, wherein the optical light source
comprises light emitting diodes (LEDs).
37. The apparatus of claim 35, wherein the sensor member of the
extremity sensor system further comprises one or more of: an
accelerometer for measuring at least one of a position and a
movement; an inertial measurement unit (IMU) for a motion artifact
reduction algorithm; and a temperature sensor for measuring
temperature.
38. The apparatus of claim 1, wherein at least one of the first
sensor system and the second sensor system further comprises a
dynamic baseline control module configured to automatically
compensate for mammal subject-to-mammal subject variability and
generate an effective driving current to ensure sufficient
signal-to-noise and avoid saturation.
39. The apparatus of claim 36, wherein the driving current is
supplied to an LED to generate an optimized light intensity
provided to an underlying mammal subject region.
40. The apparatus of claim 1, wherein each of the first sensor
system and the second sensor system is encapsulated with a thin
film of silicone elastomer so that said sensor system is
waterproof.
41. The apparatus of claim 1, wherein each of the first sensor
system and the second sensor system has a thickness less than or
equal 3 mm.
42. The apparatus of claim 1, wherein each of the first sensor
system and the second sensor system has a Young's modulus less than
or equal to 1 GPa.
43. The apparatus of claim 1, wherein the physiological parameters
comprise one or more of a stroke volume and ejection fraction;
oxygenation level; temperature; skin temperature differentials;
body movement; body position; breathing parameters; blood pressure;
crying time; crying frequency; swallow count; swallow frequency;
chest wall displacement; heart sounds; core body position;
asynchronous limb motion; speaking; and biomechanical
perturbation.
44. An apparatus for measuring physiological parameters of a mammal
subject, comprising: one or more sensor systems, each of the one or
more sensor systems comprising: a plurality of electronic
components and plurality of flexible and stretchable interconnects
that are electrically connecting to different electronic
components, wherein the plurality of electronic components
comprises a sensor member for measuring at least one physiological
parameter of the mammal subject, a system on a chip (SoC) having a
microprocessor coupled to the sensor member for receiving data from
the sensor member and processing the received data, and a
transceiver coupled to the SoC for wireless data transmission and
wireless power harvesting; and an elastomeric encapsulation layer
at least partially surrounding the plurality of electronic
components and the plurality of flexible and stretchable
interconnects to form a tissue-facing surface and an
environment-facing surface, wherein each of the one or more sensor
systems is configured to attach and conform to a pre-determined
region of the mammal subject, and to be ready time-synchronized
with one another.
45. The apparatus of claim 44, further comprising a reader system
that comprises an antenna in communication with said transceiver of
each of the first sensor system and the second sensor system for
simultaneous wireless data transmission and wireless power
delivery.
46. The apparatus of claim 45, wherein the reader system further
comprises an NFC reader module for receiving wirelessly transmitted
data from each of the first sensor system and the second sensor
system, and a Bluetooth low energy (BLE) module for transmitting
the received data to an external computing device for at least one
of real-time display of the monitored physiological parameters,
recording of the monitored physiological parameters, and alarm.
47. The apparatus of claim 44, wherein the one or more sensor
systems comprises a first sensor system and a second sensor system
that are time-synchronized to each other, wherein the first sensor
system is a conformable torso sensor system configured to attach
and conform to a torso region of the mammal subject, and the second
sensor system is a conformable extremity sensor system configured
to attach and conform to a limb or appendage region of the mammal
subject.
48. The apparatus of claim 47, wherein the sensor member of the
torso sensor system comprises at least two electrodes spatially
apart from each other for electrocardiogram (ECG) generation.
49. The apparatus of claim 47, wherein the sensor member of the
extremity sensor system comprises a photoplethysmogram (PPG) sensor
comprising an optical source and an optical detector located within
a sensor footprint.
50. The apparatus of claim 48, wherein the sensor member further
comprises one or more of: an accelerometer for measuring at least
one of a position and a movement; an inertial measurement unit
(IMU) for measuring at least one of a movement, a force, an angular
rate, and an orientation; and a temperature sensor for measuring
temperature.
51. The apparatus of claim 47, wherein the extremity sensor system
is configured such that a main circuit component including at least
the SoC and the transceiver is aligned and operably wrapped around
a limb or appendage in a wrap direction; and the sensor member is
spatially separated from and electronically connected to the main
circuit component, and operably extends in a direction different
from the wrap direction to attach to a sensor region that is
spatially distinct from the wrapped portion during use.
52. The apparatus of claim 44, wherein the one or more sensor
systems comprises three or more sensor systems time-synchronized to
each other, wherein at least one of the three or more sensor
systems is a conformable torso sensor system configured to attach
and conform to a torso region of the mammal subject.
53. The apparatus of claim 52, wherein at least one of the three or
more sensor systems is a conformable extremity sensor system
configured to attach and conform to a limb or appendage region of
the mammal subject.
54. The apparatus of claim 1, wherein the mammal subject is a human
subject or a non-human subject.
55. A method for making a sensor system including a plurality of
electronic components and a plurality of interconnects electrically
connecting to the plurality of electronic components, comprising:
forming an elastomeric layer of an elastomeric material on a
substrate; forming a first electrically conductive film on the
elastomeric layer; lithographically patterning the interconnects in
the first electrically conductive film; assembling the plurality of
electronic components onto the patterned interconnects; and
encapsulating an entire area of the assembled electronic components
onto the patterned interconnects with the elastomeric material,
followed by detaching from the substrate, to fabricate the sensor
system.
56. The method of claim 55, wherein the elastomeric material
comprises PDMS.
57. The method of claim 55, wherein the electrically conductive
film is formed of an electrically conductive material including a
metal material comprises Au, Ag, or Cu.
58. The method of claim 55, wherein said forming the electrically
conductive film comprises laminating a double layered film of the
electrically conductive material on the elastomeric layer; and
removing a top layer of the double layered film.
59. The method of claim 55, wherein said assembling the plurality
of electronic components onto the patterned interconnects comprises
connecting a second electrically conductive film for a bridge and a
light source to the patterned interconnects.
60. The method of claim 55, further comprising forming a
microfluidic chamber below the plurality of electronic
components.
61. The method of claim 60, wherein said forming the microfluidic
chamber comprises attaching a layer of the elastomeric material
having the microfluidic chamber defined therein to the bottom
surface of the elastomeric layer.
62. The method of claim 60, further comprising injecting a blended
solution of at least one of ionic liquid and silica gel into the
microfluidic chamber.
63. The method of claim 55, further comprising forming a silicone
layer on the bottom of the sensor system.
64. A method of non-invasively measuring physiological parameters
of a mammal subject, comprising: conformally contacting a first
sensor system at a torso region of the mammal subject and a second
sensor system at a limb or appendage region of the mammal subject,
respectively, wherein the first sensor system and the second sensor
system are spatially separated by a distance, and configured to
measuring a torso physiological parameter and an extremity
physiological parameter, respectively; and continuously wirelessly
transmitting the time synchronized measured torso physiological
parameter and extremity physiological parameter to an external
reader, thereby non-invasively measuring the physiological
parameters of the mammal subject.
65. The method of claim 64, wherein the distance between the first
sensor system and the second sensor system is adjustable between a
minimum distance and a maximum distance.
66. The method of claim 64, further comprising applying a hydrogel
between the first sensor system and the second sensor system and
underlying tissue of the mammal subject.
67. The method of claim 64, wherein the physiological parameter is
obtained from: electrical sensing by electrodes; and oxygen sensing
by a plethysmograph.
68. The method of claim 67, further comprising measuring at least
one additional physiological parameter related to temperature;
movement; spatial position; sound; and blood pressure.
69. The method of claim 68, further comprising: determining a
mammal subject and region-specific optimized driving voltage
provided to an optical light source; and powering an LED optical
light source with the optimized driving voltage, thereby ensuring
the LED optical light source intensity provides sufficient signal
to an optical detector without saturating the optical detector.
70. A non-transitory tangible computer-readable medium storing
instructions which, when executed by one or more processors, cause
the method of claim 64 to be performed.
Description
CROSS-REFERENCE TO RELATED PATENT APPLICATIONS
[0001] This PCT application claims priority to and the benefit of
U.S. Provisional Patent Application Serial Nos. 62/753,303,
62/753,453 and 62/753,625, each of which was filed Oct. 31, 2018,
and is incorporated herein by reference in its entirety,
respectively.
[0002] This PCT application is related to a co-pending PCT patent
application, entitled "SENSOR NETWORK FOR MEASURING PHYSIOLOGICAL
PARAMETERS OF MAMMAL SUBJECT AND APPLICATIONS OF SAME", by John A.
Rogers et al., with Attorney Docket No. 0116936.214W02, and a
co-pending US patent application entitled "APPARATUS AND METHOD FOR
NON-INVASIVELY MEASURING BLOOD PRESSURE OF MAMMAL SUBJECT", by John
A. Rogers et al., with Attorney Docket No. 0116936.215US2, each of
which is filed on the same day that this PCT application is filed,
and with the same assignee as that of this application, and is
incorporated herein by reference in its entirety, respectively.
[0003] Some references, which may include patents, patent
applications and various publications, are cited and discussed in
the description of this invention. The citation and/or discussion
of such references is provided merely to clarify the description of
the present invention and is not an admission that any such
reference is "prior art" to the invention described herein. All
references cited and discussed in this specification are
incorporated herein by reference in their entireties and to the
same extent as if each reference was individually incorporated by
reference.
FIELD OF THE INVENTION
[0004] The invention relates generally to healthcare, and more
particularly, to apparatus and method for measuring physiological
parameters of a mammal subject and applications of the same.
BACKGROUND OF THE INVENTION
[0005] The background description provided herein is for the
purpose of generally presenting the context of the invention. The
subject matter discussed in the background of the invention section
should not be assumed to be prior art merely as a result of its
mention in the background of the invention section. Similarly, a
problem mentioned in the background of the invention section or
associated with the subject matter of the background of the
invention section should not be assumed to have been previously
recognized in the prior art. The subject matter in the background
of the invention section merely represents different approaches,
which in and of themselves may also be inventions. Work of the
presently named inventors, to the extent it is described in the
background of the invention section, as well as aspects of the
description that may not otherwise qualify as prior art at the time
of filing, are neither expressly nor impliedly admitted as prior
art against the invention.
[0006] Every year, 300,000 neonates are admitted to the neonatal
care unit (NICU) in the U.S. The Global Fetal and Neonatal Care
Equipment market is expected to grow from $7.32 billion in 2016 to
reach $11.86 billion by 2022. Vital sign monitoring systems,
however, have largely remained locked in time since the 1970s.
Large base units with extensive wires are still attached to
numerous electrodes.
[0007] Continuous monitoring of vital signs in the NICU is
essential to the survival of critically-ill neonates. Conventional
medical platforms in the NICU fail, however, to offer a safe,
patient-centric mode of operation, largely due to the use of
hard-wired, rigid interfaces to the neonate's fragile,
under-developed skin. Some groups have developed neonatal vests
with embedded sensors and wireless communication capabilities.
Others have instrumented neonatal beds. Those systems are
impractical because they are bulky and cover a significant surface
area of the neonate--which further complicates medical care instead
of simplifying it. Up to 90% of NICU babies have scars by age 7,
with the number one cause from devices, including sensor leads.
Furthermore, the web of wires prevents effective therapeutic
skin-to-skin contact and hinders the ability to turn or position
the baby. The existing sensor systems also suffer limited
capabilities beyond basic vital monitoring parameters and are
fundamentally incapable of being realistically adapted for home or
remote monitoring.
[0008] In addition, none of those systems have been rigorously
tested, including in operating NICUs. Other technology is still in
the research phase, requiring multiple wires and lacks the intimate
skin connection that enables high fidelity sensing, particularly in
the context of a neonate that is moving.
[0009] Therefore, a heretofore unaddressed need exists in the art
to address the aforementioned deficiencies and inadequacies.
SUMMARY OF THE INVENTION
[0010] One aspect of the invention is to provide a highly
differentiated product with advanced monitoring capabilities, and
greater safety features applicable to various market segments,
including: low-resource settings where wireless vital sign
monitoring systems have not penetrated into neonatal care; and
high-resource settings where the invented systems represent the
cutting edge, next generation systems for neonatal monitoring.
According to the invention, the systems are reliable and safe
sensor systems that are fully wireless and compatible with
conformal contact with neonatal skin surfaces, and that are
compatible with common procedures in the NICU, including under
imaging and/or operating conditions, where conventional systems
require time and effort with respect to ensuring multiple wires and
leads are appropriately connected and in patient contact to ensure
appropriate monitoring.
[0011] In one aspect, the invention relates to an apparatus for
measuring physiological parameters of a mammal subject. The
physiological parameters include, but are not limited to, one or
more of heart activities including a stroke volume and ejection
fraction, oxygenation level, temperature, skin temperature
differentials, body movement, body position, breathing parameters,
blood pressure, crying time, crying frequency, swallow count,
swallow frequency, chest wall displacement, heart sounds, core body
position, asynchronous limb motion, speaking, and biomechanical
perturbation. The mammal subject can be a living human subject or a
living non-human subject. In certain embodiments, physiological
parameters of neonates or infants are monitored and measured. It
should be appreciated to one skilled in the art that physiological
parameters of children or adults can also be monitored and measured
in practice the invention.
[0012] In one embodiment, the apparatus includes a first sensor
system and a second sensor system that are time-synchronized to
each other. Each of the first sensor system and the second sensor
system has a plurality of electronic components and plurality of
flexible and stretchable interconnects that are electrically
connecting to different electronic components, and an elastomeric
encapsulation layer at least partially surrounding the plurality of
electronic components and the plurality of flexible and stretchable
interconnects to form a tissue-facing surface and an
environment-facing surface. In one embodiment, each of the first
sensor system and the second sensor system is attached to a
respective position on the mammal subject so that the first sensor
system and the second sensor system are spatially separated by a
distance. In certain embodiments, the distance between the first
sensor system and the second sensor system is adjustable between a
minimal distance and a maximal distance.
[0013] In one embodiment, the plurality of flexible and stretchable
interconnects comprise at least one of serpentine interconnects and
zigzag interconnects.
[0014] In one embodiment, the plurality of electronic components
comprises a sensor member for measuring at least one physiological
parameter of the mammal subject, a system on a chip (SoC) having a
microprocessor coupled to the sensor member for receiving data from
the sensor member and processing the received data, and a
transceiver coupled to the SoC for wireless data transmission and
wireless power harvesting.
[0015] In one embodiment, the SoC comprises at least one of a
near-field communication (NFC) interface and a Bluetooth interface.
In one embodiment, said transceiver comprises a magnetic loop
antenna tuned to compliance with the NFC protocol and configured to
allow simultaneous wireless data transmission and wireless power
harvesting through a single link.
[0016] In another embodiment, the plurality of electronic
components of each of the first sensor system and the second sensor
systems further comprises a battery for provide power to said
sensor system, and the elastomeric encapsulation layer is
configured to electrically isolate the battery from the mammal
subject during use. In one embodiment, the battery is a
rechargeable battery operably recharged with wireless recharging.
In one embodiment, the plurality of electronic components of each
of the first sensor system and the second sensor system further
comprises a failure prevention element that is a short-circuit
protection component or a battery circuit to avoid battery
malfunction.
[0017] In yet another embodiment, the plurality of electronic
components of each of the first sensor system and the second sensor
system further comprises a power management unit electrically
coupled between the SoC and the transceiver.
[0018] In one embodiment, each of the first sensor system and the
second sensor system further comprises a microfluidic chamber
positioned between the tissue-facing surface and the plurality of
electronic components configured to mechanically isolate the
plurality of electronic components from a skin surface during use.
In one embodiment, the microfluidic chamber is at least partially
filled with at least one of an ionic liquid and a gel.
[0019] In one embodiment, the encapsulation layer comprises
channels or conduits configured to facilitate sweat evaporation
during use. In another embodiment, the encapsulation layer is
optically transparent so as to be compatible with visual inspection
of underlying tissue. In certain embodiments, the encapsulation
layer is configured to electrically isolate each of the first
sensor system and the second sensor system from an electroshock
applied to the mammal subject. In one embodiment, the encapsulation
layer comprises a flame retardant material.
[0020] In one embodiment, each of the first sensor system and the
second sensor system is radio translucent and thermally stable so
as to be compatible with medical imaging.
[0021] In one embodiment, each of the first sensor system and the
second sensor system is formed to be stretchable and bendable.
[0022] In one embodiment, each of the first sensor system and the
second sensor system is formed in a multi-layer structure to
mechanically isolate mechanically stiff components in a mechanical
island configuration to accommodate bending, twisting or stretching
without fracture or substantial degradation of an operating
parameter.
[0023] In one embodiment, each of the first sensor system and the
second sensor system is configured to conformally attach to a skin
surface in a conformal contact without an adhesive, wherein a
contact force is generated by Van der Waals interaction between the
tissue facing surface of each of the first sensor system and the
second sensor system and a skin surface during use.
[0024] In one embodiment, the adhesive-free conformal contact
comprises a wrapped geometry, the sensor member of at least one of
the first sensor system and the second sensor system further
comprises a fastener connected to an external surface of the
encapsulation layer to fasten the sensor member in the wrapped
geometry to a mammal subject.
[0025] In one embodiment, each of the first sensor system and the
second sensor system further comprises an adhesive layer operably
attached to the tissue-facing surface of the encapsulation layer,
wherein the adhesive layer has a pattern of perforations through
open regions.
[0026] In one embodiment, the first sensor system is a conformable
torso sensor system configured to attach and conform to a torso
region of the mammal subject, and the second sensor system is a
conformable extremity sensor system configured to attach and
conform to a limb or appendage region of the mammal subject.
[0027] In one embodiment, the torso sensor system comprises a first
electrode and a second electrode as the sensor member; a Bluetooth
low energy (BLE) SoC as the SoC; an ECG analog front-end
(AFE)/inertial measurement unit (IMU); and a power management
integrated circuit (PMIC) and a memory.
[0028] In one embodiment, the sensor member of the torso sensor
system comprises at least two electrodes spatially separated from
each other by an electrode distance, D, for electrocardiogram (ECG)
generation. In one embodiment, the at least two electrodes comprise
at least one of mesh electrodes and solid electrodes. In one
embodiment, the electrode distance D is adjustable between a
minimal electrode distance, D.sub.min, and a maximal electrode
distance, D.sub.max, wherein the minimal electrode distance
D.sub.min is a distance of said two electrodes when the torso
sensor system is in a non-stretched state, and the maximal
electrode distance D.sub.max is a distance of said two electrodes
when the torso sensor system is in a maximally stretched state
along the distance.
[0029] In another embodiment, the sensor member of the torso sensor
system further comprises one or more of an accelerometer for
measuring at least one of a position and a movement; an inertial
measurement unit (IMU) for measuring at least one of
seismocardiography (SCG) and a respiratory rate; and a temperature
sensor for measuring temperature.
[0030] In one embodiment, the extremity sensor system comprises a
Bluetooth low energy (BLE) SoC as the SoC; a PPG analog front-end
(AFE); a photodiode/light emitted diode (LED) and an optical
detector as the sensor member; and a power management integrated
circuit (PMIC) and a memory.
[0031] In one embodiment, the extremity sensor system is configured
such that a main circuit component including at least the SoC and
the transceiver is aligned and operably wrapped around a limb or
appendage in a wrap direction; and the sensor member is spatially
separated from and electronically connected to the main circuit
component, and operably extends in a direction different from the
wrap direction to attach to a sensor region that is spatially
distinct from the wrapped portion during use.
[0032] In one embodiment, the sensor member of the extremity sensor
system is conformable to a skin surface and configured as a soft
wrap for circumferential attaching to the limb or appendage
region.
[0033] In one embodiment, the sensor member of the extremity sensor
system comprises a photoplethysmogram (PPG) sensor comprising an
optical source and an optical detector located within a sensor
footprint. In one embodiment, the optical light source comprises
light emitting diodes (LEDs).
[0034] In another embodiment, the sensor member of the extremity
sensor system further comprises one or more of an accelerometer for
measuring at least one of a position and a movement; an inertial
measurement unit (IMU) for a motion artifact reduction algorithm;
and a temperature sensor for measuring temperature.
[0035] In one embodiment, at least one of the first sensor system
and the second sensor system further comprises a dynamic baseline
control module configured to automatically compensate for mammal
subject-to-mammal subject variability and generate an effective
driving current to ensure sufficient signal-to-noise and avoid
saturation. In one embodiment, the driving current is supplied to
an LED to generate an optimized light intensity provided to an
underlying mammal subject region.
[0036] In one embodiment, each of the first sensor system and the
second sensor system is encapsulated with a thin film of silicone
elastomer so that said sensor system is waterproof.
[0037] In one embodiment, each of the first sensor system and the
second sensor system has a thickness less than or equal 3 mm.
[0038] In one embodiment, each of the first sensor system and the
second sensor system has a Young's modulus less than or equal to 1
GPa.
[0039] In one embodiment, the apparatus further comprises a reader
system that comprises an antenna in communication with said
transceiver of each of the first sensor system and the second
sensor system for simultaneous wireless data transmission and
wireless power delivery. In one embodiment, the reader system
further comprises an NFC reader module for receiving wirelessly
transmitted data from each of the first sensor system and the
second sensor system, and a Bluetooth low energy (BLE) module for
transmitting the received data to an external computing device for
at least one of real-time display of the monitored physiological
parameters, recording of the monitored physiological parameters,
and alarm.
[0040] In another embodiment, the apparatus further comprises an
alarm device for providing at least one of an optical alert and an
audio alert when a physiological parameter is out of a pre-defined
range. In one embodiment, the alarm device is at least one of an
on-board device and an off-board device.
[0041] In another aspect, the invention relates to an apparatus for
measuring physiological parameters of a mammal subject. In one
embodiment, the apparatus includes one or more sensor systems, each
of the one or more sensor systems comprises a plurality of
electronic components and plurality of flexible and stretchable
interconnects that are electrically connecting to different
electronic components, wherein the plurality of electronic
components comprises a sensor member for measuring at least one
physiological parameter of the mammal subject, an SoC having a
microprocessor coupled to the sensor member for receiving data from
the sensor member and processing the received data, and a
transceiver coupled to the SoC for wireless data transmission and
wireless power harvesting; and an elastomeric encapsulation layer
at least partially surrounding the plurality of electronic
components and the plurality of flexible and stretchable
interconnects to form a tissue-facing surface and an
environment-facing surface, wherein each of the one or more sensor
systems is configured to attach and conform to a pre-determined
region of the mammal subject, and to be ready time-synchronized
with one another.
[0042] In one embodiment, the apparatus further includes a reader
system that comprises an antenna in communication with said
transceiver of each of the first sensor system and the second
sensor system for simultaneous wireless data transmission and
wireless power delivery. In one embodiment, the reader system
further comprises an NFC reader module for receiving wirelessly
transmitted data from each of the first sensor system and the
second sensor system, and a Bluetooth low energy (BLE) module for
transmitting the received data to an external computing device for
at least one of real-time display of the monitored physiological
parameters, recording of the monitored physiological parameters,
and alarm.
[0043] In one embodiment, the one or more sensor systems comprises
a first sensor system and a second sensor system that are
time-synchronized to each other, wherein the first sensor system is
a conformable torso sensor system configured to attach and conform
to a torso region of the mammal subject, and the second sensor
system is a conformable extremity sensor system configured to
attach and conform to a limb or appendage region of the mammal
subject.
[0044] In one embodiment, the sensor member of the torso sensor
system comprises at least two electrodes spatially apart from each
other for electrocardiogram (ECG) generation.
[0045] In one embodiment, the sensor member of the extremity sensor
system comprises a photoplethysmogram (PPG) sensor comprising an
optical source and an optical detector located within a sensor
footprint.
[0046] In one embodiment, the sensor member of each of the torso
sensor system and the extremity sensor system further comprises one
or more of an accelerometer for measuring at least one of a
position and a movement; an inertial measurement unit (IMU) for
measuring at least one of a movement, a force, an angular rate, and
an orientation; and a temperature sensor for measuring
temperature.
[0047] In one embodiment, the extremity sensor system is configured
such that a main circuit component including at least the SoC and
the transceiver is aligned and operably wrapped around a limb or
appendage in a wrap direction; and the sensor member is spatially
separated from and electronically connected to the main circuit
component, and operably extends in a direction different from the
wrap direction to attach to a sensor region that is spatially
distinct from the wrapped portion during use.
[0048] In one embodiment, the one or more sensor systems comprises
three or more sensor systems time-synchronized to each other,
wherein at least one of the three or more sensor systems is a
conformable torso sensor system configured to attach and conform to
a torso region of the mammal subject. In one embodiment, at least
one of the three or more sensor systems is a conformable extremity
sensor system configured to attach and conform to a limb or
appendage region of the mammal subject.
[0049] In yet another aspect, the invention relates to a method for
making a sensor system including a plurality of electronic
components and a plurality of interconnects electrically connecting
to the plurality of electronic components. In one embodiment, the
method includes forming an elastomeric layer of an elastomeric
material on a substrate; forming a first electrically conductive
film on the elastomeric layer; lithographically patterning the
interconnects in the first electrically conductive film; assembling
the plurality of electronic components onto the patterned
interconnects; and encapsulating an entire area of the assembled
electronic components onto the patterned interconnects with the
elastomeric material, followed by detaching from the substrate, to
fabricate the sensor system.
[0050] In one embodiment, the elastomeric material comprises
PDMS.
[0051] In one embodiment, the electrically conductive film is
formed of an electrically conductive material including a metal
material comprises Au, Ag, or Cu.
[0052] In one embodiment, said forming the electrically conductive
film comprises laminating a double layered film of the electrically
conductive material on the elastomeric layer; and removing a top
layer of the double layered film.
[0053] In one embodiment, said assembling the plurality of
electronic components onto the patterned interconnects comprises
connecting a second electrically conductive film for a bridge and a
light source to the patterned interconnects.
[0054] In one embodiment, the method further includes forming a
microfluidic chamber below the plurality of electronic
components.
[0055] In one embodiment, said forming the microfluidic chamber
comprises attaching a layer of the elastomeric material having the
microfluidic chamber defined therein to the bottom surface of the
elastomeric layer.
[0056] In another embodiment, the method further includes injecting
a blended solution of at least one of ionic liquid and silica gel
into the microfluidic chamber.
[0057] In yet another embodiment, the method further includes
forming a silicone layer on the bottom of the sensor system.
[0058] In a further aspect, the invention relates to a method of
non-invasively measuring physiological parameters of a mammal
subject. In one embodiment, the method includes conformally
contacting a first sensor system at a torso region of the mammal
subject and a second sensor system at a limb or appendage region of
the mammal subject, respectively, wherein the first sensor system
and the second sensor system are spatially separated by a distance,
and configured to measuring a torso physiological parameter and an
extremity physiological parameter, respectively; and continuously
wirelessly transmitting the time synchronized measured torso
physiological parameter and extremity physiological parameter to an
external reader, thereby non-invasively measuring the physiological
parameters of the mammal subject.
[0059] In one embodiment, the distance between the first sensor
system and the second sensor system is adjustable between a minimum
distance and a maximum distance.
[0060] In one embodiment, the physiological parameter is obtained
from electrical sensing by electrodes; and oxygen sensing by a
plethysmograph.
[0061] In one embodiment, the method further includes applying a
hydrogel between the first sensor system and the second sensor
system and underlying tissue of the mammal subject.
[0062] In another embodiment, the method further includes measuring
at least one additional physiological parameter related to
temperature; movement; spatial position; sound; and blood
pressure.
[0063] In yet another embodiment, the method further includes
determining a mammal subject and region-specific optimized driving
voltage provided to an optical light source; and powering an LED
optical light source with the optimized driving voltage, thereby
ensuring the LED optical light source intensity provides sufficient
signal to an optical detector without saturating the optical
detector.
[0064] In one aspect, the invention relates to a non-transitory
tangible computer-readable medium storing instructions which, when
executed by one or more processors, cause the above-disclosed
method.
[0065] These and other aspects of the invention will become
apparent from the following description of the preferred embodiment
taken in conjunction with the following drawings, although
variations and modifications therein may be affected without
departing from the spirit and scope of the novel concepts of the
invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0066] The following drawings form part of the present
specification and are included to further demonstrate certain
aspects of the invention. The invention may be better understood by
reference to one or more of these drawings in combination with the
detailed description of specific embodiments presented herein. The
drawings described below are for illustration purposes only. The
drawings are not intended to limit the scope of the present
teachings in any way.
[0067] FIGS. 1A-1I show schematic illustrations and photographic
images of an apparatus including ultra-thin, skin-like wireless
sensors for full vital signs monitoring in the neonatal intensive
care unit (NICU) with comparisons to clinical standard
instrumentation, according to embodiments of the invention. FIG. 1A
schematically shows a functional block diagram of an apparatus
according to certain embodiments of the present invention. FIG. 1B
is a schematic illustration of wireless, battery-free modules for
recording electrocardiogram (ECG) and photoplethysmogram (PPG) data
and skin temperature. The ionic liquid in microfluidic channel
contains blue dye for visualization purposes. FIG. 1C shows images
of devices draped over the fingers of a life-sized, transparent
mannequin hand to illustrate the sizes and physical form factors of
these devices. FIG. 1D shows an image of an ECG epidermal
electronic system (EES) stretched uniaxially in the horizontal
direction by about 16%. FIG. 1E shows a device for capturing PPG
data during operation in a lighted and a dark room. FIG. 1F shows
NICU setting with a life-sized neonate doll configured with
conventional measurement hardware and FIG. 1G shows NICU setting
with a bi-nodal (chest and foot) deployment of skin-like wireless
devices designed to provide the same functionality and measurement
fidelity. FIG. 1H is a functional block diagram showing analog
front end and electronic components of each EES, components of the
near-field communication (NFC) system on a chip (SoC) including
microcontroller, general-purpose input/output (GPIO), and radio
interface, with a host reader platform that includes an NFC reader
module and a Bluetooth low energy (BLE) interface with circular
buffer. FIG. 1I shows a functional block diagram of the two sensor
systems according to another embodiment of the invention. The power
management unit involves dual power operation mode from primary
wireless power transfer and the secondary battery for portability.
The ECG EES includes optional electrode for fECG measurement and 6
axial inertial measurement unit (IMU) for seismocardiography (SCG)
and respiratory rate measurement on top of ECG analog front end.
The PPG EES includes the pulse oximetry analog front end and 6
axial IMU for motion artifact reduction algorithm. Each individual
unit is controlled by BLE SoC.
[0068] FIGS. 2A-2I show fundamental aspects of mechanical stresses
and soft adhesion at the interface with the skin, according to one
embodiment of the invention. FIG. 2A shows simulation results for
the deformed geometry and distribution of strain in the copper
layer of an ECG EES during uniaxial stretch (about 16%) and for
FIG. 2B, the distribution of shear (upper frames) and normal (lower
frames) stresses at the interface between an ECG EES and underlying
skin interface during deformation for devices without (left) and
with (right) the microfluidic channel. Stresses in the latter case
are less than about 20 kPa, the threshold of skin sensation. FIG.
2C shows simulation results for the distribution of von Mises
stress on the skin due to peeling of a conventional NICU adhesive
(left) and the ECG EES adhesive (right). FIG. 2D shows simulation
result for the time dependence of the peel force during removal of
a conventional NICU adhesive and the ECG EES adhesive from the
skin. FIG. 2E shows images that highlight experimental studies of
peeling of a conventional NICU adhesive (left) and the ECG EES
adhesive (right) from the skin of a healthy adult. FIG. 2F shows
experimental measurement of the time dependence of the peel force
during removal of a conventional NICU adhesive and the ECG EES
adhesive from the skin. FIG. 2G shows simulation results that
highlight the role of the microfluidic channel in the peel force
associated with removal of an ECG EES from the skin, with emphasis
on the initial, non-steady state regime during peel initiation. The
circles denote the instants of initial delamination, when the
interfacial cohesive strength is reached. The inset shows the
normal stress distribution, .sigma.yy, along the interface at the
instant of initial delamination, where its peak is the cohesive
strength. FIG. 2H shows the computed peel force as a function of
time for an EES adhesive with the triangular pattern of small holes
(diameter D=200 .mu.m) on the skin. The hole area fraction is
.alpha.= 3.pi.D.sup.2/(6L.sup.2). FIG. 2I shows the computed peel
force as a function of time for triangular and square patterns of
large holes (diameter D=1 mm) with the hole area fraction
.alpha.=35%, where .alpha.=.pi.D.sup.2/(4L.sup.2) and .alpha.=
3.pi.D.sup.2/(6L.sup.2) for square and triangular patterns,
respectively.
[0069] FIGS. 3A-3N show theoretical and experimental aspects of
radiolucency, according to one embodiment of the invention. FIG. 3A
shows computational results for the distributions of the in-plane
gradient of the magnetic field density associated a mesh electrode
(FIG. 1B, top panel), a solid electrode (no mesh; middle) and a
commercial NICU electrode (right) for conditions associated with an
MRI scan at 128 MHz. FIG. 3B shows Calculated in-plane gradients of
the magnetic field density associated with a complete ECG EES at
128 MHz. FIG. 3C shows distributions of the in-plane gradient of
the magnetic field density associated a mesh electrode (FIG. 1B,
bottom panel), a solid electrode (no mesh; middle) and a commercial
NICU electrode (right) for conditions associated with an MRI scan
at 128 MHz. FIG. 3D shows the out-of-plane gradients of magnetic
field density induced on the ECG EES at 128 MHz. FIG. 3E shows the
in-plane gradient of the magnetic field density evaluated along the
horizontal dashed lines in panel FIG. 3A. FIG. 3F shows the
out-of-plane gradient of the magnetic field density along the
horizontal dashed lines in panel FIG. 3C. FIG. 3G shows S11
parameter of the ECG EEG as a function of frequency. The vertical
dashed lines indicate operating frequencies of 1.5 T, 3 T, 7 T and
9.4 T MRI scanners at 64 MHz, 128 MHz, 298 MHz and 400 MHz,
respectively. FIG. 3H shows computational results for the maximum
change in temperature of an ECG EES on skin during an MRI scan.
[0070] FIG. 31 shows temperature changes collected using two
fiber-optic thermometers located at the interface between an ECG
EES (at the loop antenna) and a piece of phantom skin (blue) and on
the surface of the phantom skin (red) during MRI scanning (3 T
MRI). FIG. 3J shows temperature changes collected by two
fiber-optic thermometers at the interface between an ECG EES (at
one of the mesh electrodes) and a piece of phantom skin (blue) and
on the surface of the phantom skin (red) during MRI scanning (3 T
MRI). FIG. 3K shows a coronal MRI image collected from the
mid-dorsum of a rat cadaver with an ECG EES mounted on the skin.
FIG. 3L shows a coronal MRI image collected from the mid-dorsum rat
cadaver with conventional ECG leads mounted on the skin. FIG. 3M
shows an X-ray image collected from the right flank of a rat
cadaver with an ECG EES mounted on the skin. FIG. 3N shows an X-ray
image collected from the right flank of a rat cadaver with
conventional ECG leads mounted on the skin.
[0071] FIGS. 4A-4J show operational characteristics of the ECG EES,
according to one embodiment of the invention. FIG. 4A shows a block
diagram of in-sensor analytics for peak detection from ECG
waveforms. FIG. 4B shows ECG signals acquired simultaneously from
an ECG EES (blue) and a gold standard (red), with detected peaks
(green). FIG. 4C shows comparison of heart rate determined using
data from the ECG EES and a gold standard. FIG. 4D shows a
respiration rate extracted from oscillations of the amplitudes of
peaks extracted from the ECG waveforms. FIG. 4E shows comparison of
respiration rate determined using data from the ECG EES and manual
count by a physician. FIG. 4F shows comparison of skin temperature
determined by the ECG EES and a gold standard thermometer. FIG. 4G
shows a thermal image of the chest collected using an IR camera.
FIG. 4H shows Temperature wirelessly measured using an ECG EES.
FIG. 4I shows a Bland Altman plot for heart rate collected from
three healthy adults using an ECG EES and a clinical standard
system. FIG. 4J shows a Bland Altman plot for respiratory rate
collected from three healthy adults using an ECG EES and a clinical
standard system.
[0072] FIGS. 5A-5L show operational characteristics of the PPG EES,
according to one embodiment of the invention. FIG. 5A shows a block
diagram of in-sensor analytics for detection of peaks and valleys
from PPG waveforms and for dynamic baseline control. FIG. 5B shows
A circuit diagram with GPIO enabled baseline control scheme. FIG.
5C shows a demonstration of dynamic baseline level control with a
sinusoidal input (blue) and corresponding output changes (red).
FIG. 5D shows a demonstration of operation of a PPG EES with (blue
and red) and without (black dot) dynamic baseline control.
Analytics on baseline level serves as an input to a control system
that combines a GPIO port on the NFC SoC with an offset to ensure
that the signal input to the ADC lies within its dynamic range
(orange). FIG. 5E shows convention for calculating direct and
alternating components of PPG waveforms collected in the red and
IR, for purposes of calculating SpO.sub.2. FIG. 5F shows empirical
formula for SpO.sub.2 calculation using R.sub.oa based on
comparison to a commercial pulse oximeter. FIG. 5G shows SpO.sub.2
determined using in-sensor analytics during a period of rest
followed by a breath hold and then another period of rest. FIG. 5H
shows convention for measuring pulse arrival time (PAT) from
R-peaks in the ECG waveforms and valley of the PPG waveforms. FIG.
5I shows values of 1/PAT acquired using an ECG EES and a PPG EES
and systolic BP data acquired using a cuff monitor. FIG. 5J shows
correlation curve between PAT and systolic BP with linear fit. FIG.
5K shows Bland Altman for SpO.sub.2 collected from three adults
using a PPG EES and a clinical standard system. FIG. 5L shows a
temperature plot showing the capability for measuring differential
skin temperatures between the torso and the foot using an ECG EES
and PPG EES.
[0073] FIGS. 6A-6G show data collection from neonates in clinical
and home settings, according to one embodiment of the invention.
FIG. 6A shows an image of a healthy term neonate with an ECG EES
and a PPG EES on the chest and the bottom of the foot,
respectively. FIG. 6B shows an image of a mother holding a healthy
term neonate showing skin-to-skin interaction with an ECG EES
mounted on the chest. FIG. 6C shows an ECS EES mounted on the back.
FIG. 6D shows another image of a mother holding her neonate in the
NICU with a magnified view of the ECG EES in the inset. FIG. 6E
shows an image of a neonate in the NICU with a PPG EES mounted on
an alternative location on the hand. FIG. 6F shows representative
ECG and PPG waveforms acquired in this manner from a healthy term
neonate. FIG. 6G shows comparison of vital signs calculated from
the ECG EES and a gold standard. Temperature and PAT data are
displayed without reference data as these measurements are only
periodically acquired with conventional hardware.
[0074] FIGS. 7A-7G show data collection from neonates in operating
neonatal intensive care units, according to one embodiment of the
invention. FIG. 7A shows a Bland Altman plot for HR using data from
an ECG EES and a clinical standard. FIG. 7B shows a Bland Altman
plot for RR using data from an ECG EES and a clinical standard.
FIG. 7C shows a Bland Altman plot for SpO.sub.2 using data from a
PPG EES and a clinical standard. FIG. 7D shows representative
results for PAT determined using combined data from an ECG EES and
a PPG EES. FIG. 7E shows differential temperature data collected
from an ECG EES and a PPG EES for three recruited neonates with GA
of 28 weeks, (FIG. 7F) 29 weeks, and (FIG. 7G) 40 weeks. The other
data presented here were collected from this same set of
neonates.
[0075] FIGS. 8A-8B show PPG EES operating while immersed in soapy
water (FIG. 8A) with and (FIG. 8B) without external lighting,
according to one embodiment of the invention.
[0076] FIGS. 9A-9B show electromagnetic characteristics including
inductance, Q factors, and S11 of (FIG. 9A) ECG EES and (FIG. 9B)
PPG EES, according to one embodiment of the invention.
[0077] FIGS. 10A-10I show a schematic illustration of the process
for fabricating the ECG EES and PPG EES, according to one
embodiment of the invention. FIG. 10A shows PDMS-coated glass slide
substrate (FIG. 10B) laminated with a double layered copper foil,
18/5 .mu.m thick, with the 5 .mu.m thick side facing down. FIG. 10C
shows after removal of the 18 .mu.m thick Cu side, photoresist was
spin-cast to (FIG. 10D) lithographically pattern the NFC coil and
interconnects in the Cu layer. FIG. 10E shows electrical circuit
components were assembled onto the Cu circuit. FIG. 10F shows a
second metal layer for the bridge and red/IR LEDs were connected to
the first metal interconnects with the back side insulated by a
thin PDMS coating. FIG. 10G shows the entire area of the ECG EES
and PPG EES was encapsulated by PDMS layer, detached from the glass
slide and then (FIG. 10H) attached to the bottom PDMS substrate
with a spin-coated anti-adhesive layer inside the microfluidic
channel. FIG. 10I shows the bottom side was covered with a Silbione
layer. A syringe with a micro-needle injected a blended solution of
ionic liquid and silica gel into the microfluidic space.
[0078] FIG. 11A shows photographic images of ECG EES and PPG EES
bent around a plastic tube, according to one embodiment of the
invention. FIG. 11B shows finite element analysis results of the
strain in the copper layer of the ECG EES and PPG EES on microfluid
channel bending to a radius of about 6.4 mm and about 5 mm,
respectively.
[0079] FIGS. 12A-12C show changes of (FIG. 12A) inductance, (FIG.
12B) Q factor, and (FIG. 12C) S11 of the ECG EES when bent,
according to one embodiment of the invention.
[0080] FIGS. 13A-13C show changes of (FIG. 13A) inductance, (FIG.
13B) Q factor, and (FIG. 13C) S11 of the PPG EES when bent,
according to one embodiment of the invention.
[0081] FIGS. 14A-14B show a schematic illustration of (FIG. 14A)
the cross-section of the ECG EES and PPG EES and (FIG. 14B) the
undeformed and uniaxially-stretched ECG EES and PPG EES with an
underlying microfluid channel, according to one embodiment of the
invention.
[0082] FIG. 15A shows photographic images of an undeformed and a
uniaxially-stretched (about 16% defined as in FIGS. 14A-14B) ECG
EES on microfluid channel, according to one embodiment of the
invention. FIG. 15B shows the strain in the copper layer for an ECG
EES without microfluid channel during 8% stretching deformation,
and the corresponding shear/normal stresses on the skin (FIG. 15C),
according to one embodiment of the invention. FIG. 15D shows the
strain in the copper layer for an ECG EES with microfluid channel
during 16% stretching deformation, and the corresponding
shear/normal stresses on the skin (FIG. 15E), according to one
embodiment of the invention. For about 16% stretching of ECG EES on
a microfluid channel, both the shear and normal stresses on the
skin are less than about 20 kPa, the threshold of skin
sensation.
[0083] FIG. 16A shows photographic images of an undeformed and a
uniaxially-stretched (about 13% as shown in FIG. 14B) PPG EES on
microfluid channel, according to one embodiment of the invention.
FIG. 16B shows the strain in the copper layer for an PPG EES
without microfluid channel during 7% stretching deformation, and
the corresponding shear/normal stresses on the skin (FIG. 16C),
according to one embodiment of the invention. FIG. 16D shows the
strain in the copper layer for an PPG EES with microfluid channel
during 13% stretching deformation, and the corresponding
shear/normal stresses on the skin (FIG. 16E), according to one
embodiment of the invention. For about 13% stretching of PPG EES on
a microfluid channel, both the shear and normal stresses on the
skin are less than about 20 kPa, the threshold of skin
sensation.
[0084] FIGS. 17A-17C show changes of (FIG. 17A) inductance, (FIG.
17B) Q factor, and (FIG. 17C) S11 of the ECG EES when stretched,
according to one embodiment of the invention.
[0085] FIGS. 18A-18C show changes of (FIG. 18A) inductance, (FIG.
18B) Q factor, and (FIG. 18C) S11 of the PPG EES when stretched,
according to one embodiment of the invention.
[0086] FIG. 19 shows a circuit diagram for the ECG EES, according
to one embodiment of the invention, showing an RFI filter, an
instrumentation amplifier, a band pass filter, and amplifier. The
reference voltage (Vref) is the half of supply voltage (VDD) for
voltage offset. The raw ECG signal passes through a radio frequency
interference (RFI) filter (f.sub.c=200 Hz) to suppress
electromagnetic interference from the primary RF source. Subsequent
amplification occurs via the instrumentation amplifier with a
common mode-rejection ratio of 100 dB and input impedance of 100
G.OMEGA. (gain=10 V/V). A passive RC high-pass filter (f.sub.c,
=0.5 Hz) eliminates the DC offset. An inverting amplifier with a
low-pass filter further amplifies the signal (gain=50 V/V) and
prevents aliasing (f.sub.c=100 Hz). Using an external
analog-to-digital converter may increase the data throughput.
[0087] FIG. 20 shows a circuit diagram for a PPG EES, according to
one embodiment of the invention, showing LED drivers,
transimpedance amplifier, voltage rectifier with a buck converter,
and amplifier including high and low pass filter. Each LED operates
in a pulsed mode with 50% duty cycle, out of phase with one
another, via current supplied through a single LED driver with an
electrical output power of 10 mW. The power supply originates from
a separate full-wave rectifier and a buck converter, coupled to a
single RF harvesting antenna to bypass limitations associated with
the internal rectifier on the NFC. The photodiode captures
backscattered light associated with operation of each LED. The
output passes through a transimpedance amplifier (transimpedance
gain=1 V/.mu.A) followed by a passive high-pass filter (f.sub.c=0.5
Hz) to eliminate DC offset and an inverting amplifier (gain=40 V/V)
with a low-pass filter configuration (f.sub.c=5 Hz) to avoid
aliasing. The baseline is controlled by general purpose
input/output automatically based on the output signal. Using an
external analog-to-digital converter may increase the data
throughput.
[0088] FIG. 21 shows data communication in ISO15693 standards
between transponder and reader with a circular buffer designed to
properly index samples, according to one embodiment of the
invention.
[0089] FIG. 22A shows a measurement setup in a NICU setting with an
NFC antenna placed unobstructively underneath the mattress,
according to one embodiment of the invention. FIG. 22B shows a
picture of the NFC/BLE reader system, which includes an NFC
receiver antenna, NFC reader module, and BLE module, according to
one embodiment of the invention.
[0090] FIG. 23 shows cohesive-zone modeling of the EES
adhesive/skin interface, where the cohesive strength .sigma.0
represents the initial delamination, .delta.f represents the
complete delamination, and G=.sigma.0 .delta.f/2 is the adhesion
energy, according to one embodiment of the invention.
[0091] FIG. 24 shows a comparison of peel force from a conventional
NICU adhesive and ECG EES adhesive, according to one embodiment of
the invention.
[0092] FIGS. 25A-25C show a cross-sectional view of the
conventional NICU adhesive (FIG. 25A), and the EES adhesive with
(FIG. 25B) and without (FIG. 25C) the ionic liquid layer, i.e. the
microfluidic channel, according to one embodiment of the invention.
Their in-plane sizes are all 4 cm.times.2 cm.
[0093] FIG. 26A shows FEA results, and associated mesh, for the
deformation of the skin and the EES adhesive with and without the
ionic liquid layer (microfluidic channel) at the instant of initial
delamination, according to one embodiment of the invention. The
contour plots show the distribution of normal stress (.sigma.yy).
FIG. 26B shows the corresponding separation of the interface
between the skin and EES adhesive, according to one embodiment of
the invention.
[0094] FIG. 27A shows the EES adhesive without holes, according to
one embodiment of the invention. FIGS. 27B-27D show the EES
adhesive with holes of diameter D: (FIG. 27B) regular triangular
pattern; (FIG. 27C) square pattern; and (FIG. 27D) square pattern
with 45.degree. rotation, according to one embodiment of the
invention.
[0095] FIG. 28A show the EES adhesive with regular triangular holes
of small diameter D=200 nm, according to one embodiment of the
invention. FIG. 28B shows the peel force versus time for different
hole area fractions .alpha., according to one embodiment of the
invention. FIG. 28C shows the normalized peel force F/(1-.alpha.)
versus time, according to one embodiment of the invention.
[0096] FIG. 29A shows the EES adhesive with square holes of small
diameter D=200 .mu.m, according to one embodiment of the invention.
FIG. 29B shows the peel force versus time for different hole area
fractions .alpha., according to one embodiment of the invention.
FIG. 29C shows the normalized peel force F/(1-.alpha.) versus time,
according to one embodiment of the invention.
[0097] FIG. 30A shows the EES adhesive with 45.degree.-rotated
square holes of small diameter D=200 .mu.m, according to one
embodiment of the invention. FIG. 30B shows the peel force versus
time for different hole area fractions .alpha., according to one
embodiment of the invention. FIG. 30C shows the normalized peel
force F/(1-.alpha.) versus time, according to one embodiment of the
invention.
[0098] FIG. 31A shows the EES adhesive with holes in a regular
triangular pattern, with diameter D, according to one embodiment of
the invention. The hole area fraction is .alpha.=35%. FIG. 31B
shows the peel force versus time for the holes with different
diameters D=200 .mu.m, 600 .mu.m, and 1000 .mu.m, according to one
embodiment of the invention.
[0099] FIG. 32A shows the EES adhesive with holes in a square
pattern, with diameter D, according to one embodiment of the
invention. The hole area fraction is .alpha.=35%. FIG. 32B shows
the peel force versus time for the holes with different diameters
D=200 .mu.m, 600 .mu.m, and 1000 .mu.m, according to one embodiment
of the invention.
[0100] FIG. 33A shows the EES adhesive with holes in a square
pattern with 45.degree. rotation, with diameter D, according to one
embodiment of the invention. The hole area fraction is .alpha.=35%.
FIG. 33B shows the peel force versus time for the holes with
different diameters D=200 .mu.m, 600 .mu.m, and 1000 .mu.m,
according to one embodiment of the invention.
[0101] FIG. 34 shows effective modulus versus hole area fraction
.alpha. for holes with different patterns, according to one
embodiment of the invention.
[0102] FIG. 35 shows a minimum work of adhesion strength of the ECG
EES (black) and the PPG EES when stretched up to 20%, according to
one embodiment of the invention.
[0103] FIG. 36A shows a schematic illustration of the
electromagnetic simulation model composed of an electrode on the
skin and a Helmholtz coil, according to one embodiment of the
invention. FIG. 36B shows electrodes with different structures
including mesh (geometry for the ECG EES electrodes), solid (i.e.
no mesh) and commercial NICU electrodes, according to one
embodiment of the invention.
[0104] FIG. 37 shows a schematic illustration of the
electromagnetic simulation model composed of the ECG EES on the
skin and a Helmholtz coil, according to one embodiment of the
invention.
[0105] FIG. 38 shows the distributions of the in-plane (top) and
out-of-plane (bottom) gradients of the magnetic field density
induced by a complete ECG EES at its resonant frequency (150 MHz),
according to one embodiment of the invention.
[0106] FIG. 39A shows the in-plane gradients of the magnetic field
density induced by a complete PPG EES at 128 MHz, according to one
embodiment of the invention. FIG. 39B shows the out-of-plane
gradients of the magnetic field density induced by a complete PPG
EES at 128 MHz, according to one embodiment of the invention.
[0107] FIG. 40A shows a schematic illustration of the cross-section
of the ECG EES, according to one embodiment of the invention. FIG.
40B shows the distribution of the temperature change on the skin at
0.24 s, which corresponds to the time of the maximum temperature
change on the skin for an MRI scan, according to one embodiment of
the invention.
[0108] FIG. 41A shows the maximum temperature change of the PPG EES
and skin versus time for an MRI scan, according to one embodiment
of the invention. FIG. 41B shows the distribution of the
temperature change on the skin at 0.25 s, which corresponds to the
time of the maximum temperature change on the skin for an MRI scan,
according to one embodiment of the invention.
[0109] FIGS. 42A-42C show ECG signal with three limb leads
configuration, according to one embodiment of the invention. (FIG.
42A) Lead I, (FIG. 42B) Lead II, (FIG. 42C) Lead III.
[0110] FIGS. 43A-43D show a demonstration of compatibility with
autoclave sterilization, according to one embodiment of the
invention. FIG. 43A shows ECG signal collected with an ECG EES
before autoclave sterilization. FIG. 43B shows ECG signal collected
with the same device after autoclave sterilization. FIG. 43C shows
PPG signal collected with a PPG EES before autoclave sterilization.
FIG. 43D shows PPG signal collected with the same device after
autoclave sterilization.
[0111] FIGS. 44A-44F show modified Pan-Tompkins algorithm for peak
detection from ECG signals, according to one embodiment of the
invention. FIG. 44A shows a raw signal. FIG. 44B shows a band-pass
filtered signal. FIG. 44C shows differentiation of the signal. FIG.
44D shows squaring the signal. FIG. 44E shows moving average
applied to the signal. FIG. 44F shows a detected peak with
automatically adjusted threshold level.
[0112] FIG. 45 shows experimental setup for calibrating the
internal temperature sensor of the ECG EES against a thermometer,
according to one embodiment of the invention. The process involves
operation under water.
[0113] FIG. 46 shows an exemplary plot showing V+ levels based on
GPIO combinations for dynamic baseline control with four channels,
according to one embodiment of the invention. Four channel GPIOs
implement 16 different levels with equal step size.
[0114] FIG. 47A shows a block diagram of the NFC interface
involving synchronization based on the high-frequency clock of
reader module, signal processing module explained previously, and
storage module in both local and cloud storage, according to one
embodiment of the invention.
[0115] FIG. 47B shows a cubic spline interpolation applied to
sampled ECG and PPG data, according to one embodiment of the
invention.
[0116] FIG. 48 shows transparency of the ECG EES demonstrated with
a plot of transmittance vs wavelength, according to one embodiment
of the invention.
[0117] FIGS. 49A-49C show Bland Altman plots for data collected
using devices similar to the ECG EES and PPG EES platforms
described in the main text, but with on-board power supply, for 18
neonates admitted to the NICU, according to one embodiment of the
invention. The mean absolute differences for (FIG. 49A) heart rate,
(FIG. 49B) blood oxygenation, and (FIG. 49C) respiratory rate are
0.5 beats/min (SD: 3.3 beats/min), 0.06% (SD: 1.8%), and 2.5
respirations/minute (SD: 4.5 breaths/minute), respectively. No
adverse events were noted for any of the subjects.
[0118] FIGS. 50A-50H show operational characteristics of the ECG
EES, according to one embodiment of the invention. FIG. 50A shows a
block diagram of in-sensor analytics for peak detection from ECG
waveforms. FIG. 50B shows ECG signals acquired simultaneously from
an ECG EES (blue) and a gold standard (red), with detected peaks
(green). FIG. 50C shows comparison of heart rate determined using
data from the ECG EES and a gold standard. FIG. 50D shows
respiration rate extracted from oscillations of the amplitudes of
peaks are derived from the ECG waveforms. FIG. 50E shows comparison
of respiration rate determined using data from the ECG EES and
manual count by a physician. FIG. 50F shows comparison of skin
temperature determined by the ECG EES and a gold standard
thermometer. FIG. 50G shows a thermal image of the chest collected
using an IR camera. FIG. 50H shows temperature wirelessly measured
using an ECG EES.
[0119] FIGS. 51A-51J show Operational characteristics of the PPG
EES, according to one embodiment of the invention. FIG. 51A shows a
block diagram of in-sensor analytics for detection of peaks and
valleys from PPG waveforms and for dynamic baseline control. FIG.
51B shows a circuit diagram with GPIO enabled baseline control
scheme. FIG. 51C is a demonstration of dynamic baseline level
control with a sinusoidal input (blue) and corresponding output
changes (red). FIG. 51D is a demonstration of operation of a PPG
EES with (blue and red) and without (black dot) dynamic baseline
control. Analytics on baseline level serves as an input to a
control system that combines a GPIO port on the NFC SoC with an
offset to ensure that the signal input to the ADC lies within its
dynamic range (orange). FIG. 51E shows convention for calculating
direct and alternating components of PPG waveforms collected in the
red and IR, for purposes of calculating SpO2. FIG. 51F shows
empirical formula for SpO2 calculation using Roa based on
comparison to a commercial pulse oximeter. FIG. 51G shows SpO2
determined using in-sensor analytics during a period of rest
followed by a breath hold and then another period of rest. FIG. 51H
shows convention for measuring pulse arrival time (PAT) from
R-peaks in the ECG waveforms and valley of the PPG waveforms. FIG.
51I shows values of 1/PAT acquired using an ECG EES and a PPG EES
and systolic BP data acquired using a cuff monitor. FIG. 51J shows
correlation curve between PAT and systolic BP with linear fit.
[0120] FIGS. 52A-52E show features of EES with the safety on skin
interface and medical imaging and inspection, according to one
embodiment of the invention. FIG. 52A shows images of peel force
measurement including the setup (left), with a conventional
adhesive (middle), and with an ECG EES (right). FIG. 52B shows a
measured peel force of a conventional adhesive and an ECG EES. FIG.
52C shows an MRI image of an ECG EES on a chicken thigh in sagittal
plane. FIG. 52D shows operation fully immersed in water--which
shows operability in high humidity conditions >80% typical of
incubators. FIG. 52E summarizes the finite element model validates
the experimental results indicating the significant decrease in
interface skin stress.
[0121] FIG. 53 shows the underlying software enables
interoperability with third party platforms, according to one
embodiment of the invention. Further capabilities include cloud
storage in a HIPAA complaint manner. The receiver may be a tablet,
smartphone, or existing vital signs monitor.
[0122] FIG. 54 shows an example of one embodiment of a user
interface, according to one embodiment of the invention. Wireless
wearable sensors that are discoverable are shown on the left panel.
Beyond the sensors themselves, our user interface and base displays
can also be used to deliver therapeutic benefit. For instance,
musical therapy has been shown to be beneficial to neonatal brain
development and neonatal stress relief. Existing displays and
monitoring systems are only capable of alarms. Also available on
the user interface is an avatar that can depict the patient
position, such as on the back, side or front.
DETAILED DESCRIPTION OF THE INVENTION
[0123] The present invention will now be described more fully
hereinafter with reference to the accompanying drawings, in which
exemplary embodiments of the present invention are shown. The
present invention may, however, be embodied in many different forms
and should not be construed as limited to the embodiments set forth
herein. Rather, these embodiments are provided so that this
disclosure will be thorough and complete, and will fully convey the
scope of the invention to those skilled in the art. Like reference
numerals refer to like elements throughout.
[0124] The terms used in this specification generally have their
ordinary meanings in the art, within the context of the invention,
and in the specific context where each term is used. Certain terms
that are used to describe the invention are discussed below, or
elsewhere in the specification, to provide additional guidance to
the practitioner regarding the description of the invention. For
convenience, certain terms may be highlighted, for example using
italics and/or quotation marks. The use of highlighting and/or
capital letters has no influence on the scope and meaning of a
term; the scope and meaning of a term are the same, in the same
context, whether or not it is highlighted and/or in capital
letters. It will be appreciated that the same thing can be said in
more than one way. Consequently, alternative language and synonyms
may be used for any one or more of the terms discussed herein, nor
is any special significance to be placed upon whether or not a term
is elaborated or discussed herein. Synonyms for certain terms are
provided. A recital of one or more synonyms does not exclude the
use of other synonyms. The use of examples anywhere in this
specification, including examples of any terms discussed herein, is
illustrative only and in no way limits the scope and meaning of the
invention or of any exemplified term. Likewise, the invention is
not limited to various embodiments given in this specification.
[0125] It will be understood that, although the terms first,
second, third, etc. may be used herein to describe various
elements, components, regions, layers and/or sections, these
elements, components, regions, layers and/or sections should not be
limited by these terms. These terms are only used to distinguish
one element, component, region, layer or section from another
element, component, region, layer or section. Thus, a first
element, component, region, layer or section discussed below can be
termed a second element, component, region, layer or section
without departing from the teachings of the present invention.
[0126] It will be understood that, as used in the description
herein and throughout the claims that follow, the meaning of "a",
"an", and "the" includes plural reference unless the context
clearly dictates otherwise. Also, it will be understood that when
an element is referred to as being "on," "attached" to, "connected"
to, "coupled" with, "contacting," etc., another element, it can be
directly on, attached to, connected to, coupled with or contacting
the other element or intervening elements may also be present. In
contrast, when an element is referred to as being, for example,
"directly on," "directly attached" to, "directly connected" to,
"directly coupled" with or "directly contacting" another element,
there are no intervening elements present. It will also be
appreciated by those of skill in the art that references to a
structure or feature that is disposed "adjacent" to another feature
may have portions that overlap or underlie the adjacent
feature.
[0127] It will be further understood that the terms "comprises"
and/or "comprising," or "includes" and/or "including" or "has"
and/or "having" when used in this specification specify the
presence of stated features, regions, integers, steps, operations,
elements, and/or components, but do not preclude the presence or
addition of one or more other features, regions, integers, steps,
operations, elements, components, and/or groups thereof.
[0128] Furthermore, relative terms, such as "lower" or "bottom" and
"upper" or "top," may be used herein to describe one element's
relationship to another element as illustrated in the figures. It
will be understood that relative terms are intended to encompass
different orientations of the device in addition to the orientation
shown in the figures. For example, if the device in one of the
figures is turned over, elements described as being on the "lower"
side of other elements would then be oriented on the "upper" sides
of the other elements. The exemplary term "lower" can, therefore,
encompass both an orientation of lower and upper, depending on the
particular orientation of the figure. Similarly, if the device in
one of the figures is turned over, elements described as "below" or
"beneath" other elements would then be oriented "above" the other
elements. The exemplary terms "below" or "beneath" can, therefore,
encompass both an orientation of above and below.
[0129] Unless otherwise defined, all terms (including technical and
scientific terms) used herein have the same meaning as commonly
understood by one of ordinary skill in the art to which the present
invention belongs. It will be further understood that terms, such
as those defined in commonly used dictionaries, should be
interpreted as having a meaning that is consistent with their
meaning in the context of the relevant art and the present
disclosure, and will not be interpreted in an idealized or overly
formal sense unless expressly so defined herein.
[0130] As used in this disclosure, "around", "about",
"approximately" or "substantially" shall generally mean within 20
percent, preferably within 10 percent, and more preferably within 5
percent of a given value or range. Numerical quantities given
herein are approximate, meaning that the term "around", "about",
"approximately" or "substantially" can be inferred if not expressly
stated.
[0131] As used in this disclosure, the phrase "at least one of A,
B, and C" should be construed to mean a logical (A or B or C),
using a non-exclusive logical OR. As used herein, the term "and/or"
includes any and all combinations of one or more of the associated
listed items.
[0132] As used in this disclosure, the term "spatially separated"
refers to two different locations on skin, wherein the two sensor
systems disposed on those locations are not in physical contact.
For example, one sensor system may be on the torso, and another
sensor system on the foot.
[0133] As used in this disclosure, the term "mammal subject" refers
to a living human subject or a living non-human subject. For the
purpose of illustration of the invention, the apparatus and method
are applied to monitor and/or measure physiological parameters of
neonates or infants. It should be appreciated to one skilled in the
art that the apparatus can also be applied to monitor and/or
measure physiological parameters of children or adults in practice
the invention.
[0134] The description below is merely illustrative in nature and
is in no way intended to limit the invention, its application, or
uses. The broad teachings of the invention can be implemented in a
variety of forms. Therefore, while this invention includes
particular examples, the true scope of the invention should not be
so limited since other modifications will become apparent upon a
study of the drawings, the specification, and the following claims.
For purposes of clarity, the same reference numbers will be used in
the drawings to identify similar elements. It should be understood
that one or more steps within a method may be executed in different
order (or concurrently) without altering the principles of the
invention.
[0135] To address the aforementioned deficiencies and inadequacies,
the invention in one aspect discloses a pair of ultrathin,
battery-free, skin-conformable electronic sensor systems capable of
coordinated, wireless collection of vital signs information at
clinical-grade levels of precision and accuracy, without any of the
limitations of standard, FDA-cleared systems. The foundational
advances in engineering science involve strategies for (1) high
bandwidth, high fidelity and wireless modes of battery-free
operation based on a single, magnetically coupled inductive link,
(2) real-time data processing, analytics and adaptive gain
modulation performed using computational resources on the sensor
platforms themselves, (3) time-synchronized, continuous streaming
of data from a complementary pair of devices mounted on different
regions of the body and (4) transparent and radiolucent device
designs compatible with visual inspection of underlying tissue and
by medical imaging techniques based on magnetic resonance, X-rays
and others. Successful demonstrations on neonates with gestational
ages ranging from 28 weeks to full term, validated in operating
NICUs against clinical `gold` standards indicates the devices have
a strong positive clinical impact.
[0136] The skin-conformable electronic sensor systems according
certain embodiments of the invention have advanced capabilities in
data transfer, in-sensor analytics and bi-nodal function enable
wireless, high fidelity measurement of full vital signs
information, including from fragile neonates. The sensors are
optionally battery-free, but can be used with batteries and
particularly batteries that can be wirelessly charged. The sensor
systems also have broad software interoperability, and so are
compatible with a range of hardware readers, including handhelds,
computers and conventional monitor systems and displays.
[0137] The sensors systems are lightweight and in a convenient
patch-like form, that are detachably attachable/mountable to skin,
for example, with a weight less than 2 g, and dimensions on the
order of 6 cm.times.3.5 cm.times.0.2 cm, or less, including less
than 3 cm.times.3 cm.times.0.2 cm.
[0138] Physiological parameters that can be measured include, but
are not limited to, one or more of heart activities including a
stroke volume and ejection fraction, oxygenation level,
temperature, skin temperature differentials, body movement, body
position, breathing parameters, ballistocardiography, respiratory
effort, blood pressure, crying time, crying frequency, swallow
count, swallow frequency, chest wall displacement, heart sounds,
core body position, asynchronous limb motion, speaking, and
biomechanical perturbation.
[0139] One aspect of the invention discloses an apparatus for
measuring physiological parameters of a mammal subject. FIG. 1A
schematically shows a functional block diagram of the apparatus
according to certain embodiments of the present invention. In the
exemplary embodiments, the apparatus 100 includes a first sensor
system 110 and a second sensor system 150 that are
time-synchronized to each other, and a microcontroller unit (MCU)
(alternatively, a reader system)190 adapted in wireless
communication with the first sensor system 110 and the second
sensor system 150. In certain embodiments, each of the first sensor
system 110 and the second sensor system 150 is in wireless
communication with the MCU 190 via a wireless transmission
protocol, such as a near field communication (NFC) protocol, or
Bluetooth protocol. Specifically, the term "time-synchronized" (or
"time-synced") refers to measurement of a parameter by different
sensors, at different locations, that are synchronized in time to
allow for measurement of novel physiological parameters. In certain
embodiments, each of the first sensor system 110 and the second
sensor system 150 is an epidermal electronic system (EES). In
certain embodiments, the first sensor system 110 is a conformable
torso sensor system configured to attach and conform to a torso
region 410 of the mammal subject for recording electrocardiogram
(ECG) data and skin temperature; and the second sensor system 150
is a conformable extremity sensor system configured to attach and
conform to a limb or appendage region 420 of the mammal subject for
recording photoplethysmogram (PPG) data and skin temperature.
[0140] FIGS. 1B-1I shows schematic illustrations and photographic
images of the apparatus including the torso sensor system 110 and
the extremity sensor system 150 for monitoring full vital signs in
the neonatal intensive care unit (NICU) with a comparison to
clinical standard instrumentation are shown according to
embodiments of the invention. As shown in FIGS. 1A and 1G, the
torso sensor system 110 (ECG EES 110) and the extremity sensor
system 150 (PPG EES 150) are operably attached to a torso region
410 such as the chest and a limb region 420 such as a foot,
respectively, of the neonate so that the ECG EES 110 and the PPG
EES 150 are spatially separated by a distance L. The distance L
between the ECG EES 110 and the PPG EES 150 is adjustable between a
minimal distance and a maximal distance.
[0141] In one exemplary embodiment shown in FIGS. 1B, 1D and 1H,
the torso sensor system 110 is a wireless, battery-free sensor
system for recording ECG data and skin temperature and includes a
plurality of electronic components 120 and a plurality of flexible
and stretchable interconnects 130 electrically connecting to
different electronic components, and an elastomeric encapsulation
member (including layers 141, 142 and 143 shown in the top panel of
FIG. 1B) at least partially surrounding the plurality of electronic
components 120 and the plurality of flexible and stretchable
interconnects 130 to form a tissue-facing surface 148 and an
environment-facing surface 149. The elastomeric encapsulation
member is formed of a silicone elastomer, or the like.
[0142] The plurality of flexible and stretchable interconnects 130
are serpentine interconnects as shown in FIG. 1B. Other forms of
flexible and stretchable interconnects such as zigzag interconnects
can also be utilized to practice the invention. The plurality of
flexible and stretchable interconnects 130 is formed of any
conductive material including a metal material such as Au, Ag, Cu,
etc.
[0143] The plurality of electronic components 120 includes a sensor
member for measuring the physiological parameters such as ECG data.
The sensor member includes, but is not limited to, two electrodes
121 and 122 spatially separated from each other by an electrode
distance, D, for ECG generation. The electrodes 121 and 122 can be
either mesh electrodes (FIGS. 1B and 1D) or solid electrodes. The
electrode distance D is adjustable between a minimal electrode
distance, D.sub.min, and a maximal electrode distance, D.sub.max,
where the minimal electrode distance D.sub.min is a distance (e.g.,
D in FIG. 1B) of said two electrodes 121 and 122 when the torso
sensor system is in a non-stretched state (FIG. 1B), and the
maximal electrode distance D.sub.max is a distance (e.g., D2 in
FIG. 1CD) of said two electrodes 121 and 122 when the torso sensor
system is in a maximally stretched state along the distance
direction 101 (FIG. 1D).
[0144] As shown in FIG. 1H, the sensor member 123 also includes,
but is not limited to, an instrumentation amplifier (e.g., Inst.
Amp) electrically coupled to the two electrodes 121 and 122,
adapted for eliminating the need for input impedance matching and
thus making the amplifier particularly suitable for use in
measurement and test equipment, and an anti-aliasing filter (AAF)
electrically couple to the instrumentation amplifier and used
before a signal sampler to restrict the bandwidth of a signal to
approximately or completely satisfy the Nyquist-Shannon sampling
theorem over the band of interest.
[0145] Referring to FIG. 1H, the plurality of electronic components
120 also includes a system on a chip (SoC) 124 that includes, but
is not limited to, a microprocessor unit, e.g., CPU, a near-field
communication (NFC) interface, e.g., NFC ISO 15693 interface,
general-purpose input/output (GPIO) ports, one or more temperature
sensors (Temp. sensor), and analog-to-digital converters (ADCs) in
communication with each other, for receiving data from the sensor
member 123 and processing the received data.
[0146] Still referring to FIG. 1H, the plurality of electronic
components 120 includes a transceiver 125 coupled to the SoC 124
for wireless data transmission and wireless power harvesting. In
the exemplary embodiment, the transceiver 125 comprises a loop
antenna tuned to compliance with the NFC protocol and configured to
allow simultaneous wireless data transmission and wireless power
harvesting through a single link.
[0147] In addition, referring back to FIG. 1B, the torso sensor
system 110 also includes a microfluidic chamber (channel) 145
formed between the tissue-facing surface 148 and the plurality of
electronic components 120 in the elastomeric encapsulation member
and is configured to mechanically isolate the plurality of
electronic components 120 from a skin surface of a patient during
use. In one embodiment, the microfluidic chamber 145 is at least
partially filled with at least one of an ionic liquid and a gel.
For example, in the embodiment shown in FIG. 1A, the ionic liquid
in microfluidic channel 145 contains blue dye for visualization
purposes. Furthermore, two through openings 146 and 147 are defined
in the microfluidic channel 145 such that during use the electrodes
121 and 122 are operably in epidermal contact with the skin surface
of the patient through the opening 147 and 147, respectively, for
measuring the ECG signals.
[0148] In one embodiment, the encapsulation layer further comprises
channels or conduits configured to facilitate sweat evaporation
during use. In another embodiment, the encapsulation layer is
optically transparent so as to be compatible with visual inspection
of underlying tissue. In certain embodiments, the encapsulation
layer is configured to electrically isolate the first sensor system
from an electroshock applied to the mammal subject. In one
embodiment, the encapsulation layer comprises a flame retardant
material.
[0149] In one exemplary embodiment shown in FIGS. 1B, 1E and 1H,
the extremity sensor system 150 is also a wireless, battery-free
sensor system for recording PPG data and skin temperature and
includes a plurality of electronic components 160 and a plurality
of flexible and stretchable interconnects 170 electrically
connecting to different electronic components, and an elastomeric
encapsulation member (including layers 181, 182 and 183 shown in
the bottom panel of FIG. 1B) at least partially surrounding the
plurality of electronic components 160 and the plurality of
flexible and stretchable interconnects 170 to form a tissue-facing
surface 188 and an environment-facing surface 189. The elastomeric
encapsulation member is formed of a silicone elastomer, or the
like.
[0150] The plurality of flexible and stretchable interconnects 170
are serpentine interconnects as shown in FIG. 1B. Other forms of
flexible and stretchable interconnects such as zigzag interconnects
can also be utilized to practice the invention. The plurality of
flexible and stretchable interconnects 170 is formed of any
conductive material including a metal material such as Au, Ag, Cu,
etc.
[0151] The plurality of electronic components 160 includes a sensor
member for measuring the physiological parameters such as PPG data.
As shown in FIG. 1H, the sensor member 163 includes a PPG sensor
located within a sensor footprint, which has an optical source
having an infrared (IR) light emitting diode (LED) 161 and a red
LED 162, and an optical detector (PD) electrically coupled to the
IR LED 161 and the red LED 162. The sensor member 163 also
includes, but is not limited to, an LED driver electrically coupled
to the two electrodes 161 and 162 for driving the IR LED 161 and
the red LED 162, and a trans Z amplifier electrically coupled to
the PD.
[0152] Referring to FIG. 1H, the plurality of electronic components
160 also includes a system on a chip (SoC) 164 that includes, but
is not limited to, a microprocessor unit, e.g., CPU, a near-field
communication (NFC) interface, e.g., NFC ISO 15693 interface,
general-purpose input/output (GPIO) ports, one or more temperature
sensors (Temp. sensor), and analog-to-digital converters (ADCs) in
communication with each other, for receiving data from the sensor
member 163 and processing the received data.
[0153] Still referring to FIG. 1H, the plurality of electronic
components 160 includes a transceiver 165 coupled to the SoC 164
for wireless data transmission and wireless power harvesting. In
the exemplary embodiment, the transceiver 165 comprises a loop
antenna tuned to compliance with the NFC protocol and configured to
allow simultaneous wireless data transmission and wireless power
harvesting through a single link.
[0154] In addition, referring back to FIG. 1B, the extremity sensor
system 150 also includes a microfluidic chamber (channel) 185
formed between the tissue-facing surface 188 and the plurality of
electronic components 160 in the elastomeric encapsulation member
and is configured to mechanically isolate the plurality of
electronic components 160 from a skin surface of the patient during
use. In one embodiment, the microfluidic chamber 185 is at least
partially filled with at least one of an ionic liquid and a gel.
For example, in the embodiment shown in FIG. 1B, the ionic liquid
in microfluidic channel 185 contains blue dye for visualization
purposes.
[0155] In one embodiment, the encapsulation layer further comprises
channels or conduits configured to facilitate sweat evaporation
during use. In another embodiment, the encapsulation layer is
optically transparent so as to be compatible with visual inspection
of underlying tissue. In certain embodiments, the encapsulation
layer is configured to electrically isolate the second sensor
system from an electroshock applied to the mammal subject. In one
embodiment, the encapsulation layer comprises a flame retardant
material.
[0156] In operation, the torso sensor system 110 (ECG EES 110) and
the extremity sensor system 150 (PPG EES 150) are in wireless
communication with a reader system 190, alternatively, a
microcontroller unit (MCU), having an antenna 195. Specifically,
the RF loop antennas 125 and 165 in both the torso sensor system
110 (ECG EES 110) and the extremity sensor system 150 (PPG EES 150)
are in wireless communication with the antenna 195 and serve dual
purposes in power transfer and in data communication, as shown in
FIG. 1H. In one embodiment, the reader system 190 also includes,
but is not limited to, an NFC ISO 15693 reader, a circular buffer
and a Bluetooth Low Energy (BLE) interface, which are configured
such that data can be continuously streamed at rates of up to 800
bytes/s with dual channels, which is orders of magnitude higher
than those previously achieved in NFC sensors. A key to realizing
such high rates is in minimizing the overhead associated with
transfer by packaging data into 6 blocks (24 Bytes) in the circular
buffer. Here, reading occurs with an NFC host interfaced to a
microcontroller in a BLE system configured with this type of
customized circular buffer decoding routine shown in FIG. 21. The
primary antenna 195 connects to the host system for simultaneous
transfer of RF power to the ECG EES 110 and the PPG EES 150. As
such, the apparatus can operate at vertical distances of up to 25
cm, through biological tissues, bedding, blankets, padded
mattresses, wires, sensors and other materials found in NICU
incubators, for full coverage wireless operation in a typical
incubator. BLE radio transmission then allows transfer of data to a
personal computer, tablet computer or smartphone with a range of up
to 20 m. Connections to central monitoring systems in the hospital
can then be established in a straightforward manner.
[0157] In certain embodiments, the apparatus 100 may have an alarm
device (not shown) for providing at least one of an optical alert
and an audio alert when a physiological parameter is out of a
pre-defined range. In one embodiment, the alarm device is at least
one of an on-board device and an off-board device.
[0158] In another embodiment as shown in FIG. 1I, the first sensor
system 210 and the second sensor system 250 are similar to the
first sensor system 110 and the second sensor system 150 shown in
FIG. 1H, except that each of the first sensor system 210 and the
second sensor system 250 further comprises a battery 205 for
provide power to said sensor system, and a power management unit/IC
(PMIC) 206 electrically coupled with the battery 205, the SoC
224/264 and the transceiver (antenna) 195. The power management
unit 206 operably involves dual power operation mode from primary
wireless power transfer and the secondary battery 205 for
portability. In addition, the sensor member (or sensor circuit) 223
of the first sensor system (ECG EES) 210 also includes optional
electrode for fECG measurement and 6 axial inertial measurement
unit (IMU) for seismocardiography (SCG) and respiratory rate
measurement on the top of an ECG analog front end (AFE). The sensor
member (or sensor circuit) 263 of the second sensor system (PPG
EES) 250 also includes also a PPG AFE and 6 axial IMU for motion
artifact reduction algorithm. The SoC 224/264 of each of the first
sensor system 210 and the second sensor system 250 further
comprises a down-sampler and BLE radio. Each of the power
management unit 206 and the sensor members 223 and 263 is
controlled by BLE SoC 224/264.
[0159] In certain embodiments, the battery 205 is a rechargeable
battery operably recharged with wireless recharging. In one
embodiment, the plurality of electronic components of each of the
first sensor system 210 and the second sensor system 250 further
comprises a failure prevention element that is a short-circuit
protection component or a battery circuit (not shown) to avoid
battery malfunction.
[0160] In certain embodiments, each of the first sensor system
110/210 and the second sensor system 150/250 is radio translucent
and thermally stable so that each of the first sensor system and
the second sensor system is compatible with medical imaging
including X-ray, CT and/or MRI imaging. According to the invention,
with the specific advantage of having a lower radiological
shadowing effect, the small thin sensors allow for less
perturbation of CT/X-ray imaging. In addition, the sensors generate
minimal heat during MRIs allowing for them to remain on body during
this imaging modality.
[0161] In certain embodiments, each of the first sensor system
110/210 and the second sensor system 150/250 is formed to be
stretchable and bendable.
[0162] In certain embodiments, each of the first sensor system
110/210 and the second sensor system 150/250 is formed in a
multi-layer structure to mechanically isolate mechanically stiff
components in a mechanical island configuration to accommodate
bending, twisting or stretching without fracture or substantial
degradation of an operating parameter.
[0163] In certain embodiments, each of the first sensor system
110/210 and the second sensor system 150/250 is configured to
conformally attach to a skin surface in a conformal contact without
an adhesive, wherein a contact force is generated by Van der Waals
interaction between the tissue facing surface of each of the first
sensor system and the second sensor system and a skin surface
during use.
[0164] In certain embodiments, the adhesive-free conformal contact
comprises a wrapped geometry, the sensor member of at least one of
the first sensor system and the second sensor system further
comprises a fastener connected to an external surface of the
encapsulation layer to fasten the sensor member in the wrapped
geometry to a mammal subject.
[0165] In one embodiment, each of the first sensor system and the
second sensor system further comprises an adhesive layer operably
attached to the tissue-facing surface of the encapsulation layer,
wherein the adhesive layer has a pattern of perforations through
open regions.
[0166] In certain embodiments, at least one of the first sensor
system 110/210 and the second sensor system 150/250 comprises a
dynamic baseline control module configured to automatically
compensate for mammal subject-to-mammal subject variability and
generate an effective driving current to ensure sufficient
signal-to-noise and avoid saturation. In one embodiment, the
driving current is supplied to an LED to generate an optimized
light intensity provided to an underlying mammal subject
region.
[0167] In certain embodiments, each of the first sensor system
110/210 and the second sensor system 150/250 is encapsulated with a
thin film of silicone elastomer so that said sensor system is
waterproof.
[0168] In certain embodiments, each of the first sensor system
110/210 and the second sensor system 150/250 has a thickness less
than or equal 3 mm.
[0169] In certain embodiments, each of the first sensor system
110/210 and the second sensor system 150/250 has a Young's modulus
less than or equal to 1 GPa.
[0170] As disclosed above, two sensor systems are utilized to
measure the physiological parameters of a mammal subject. In
certain aspects, the invention is not limited the two sensor
systems. Instead, one sensor system that is discussed above can
also be used to measure the physiological parameters. Furthermore,
three or more of these sensor systems, each of which is
time-synchronized to each other, and spatial separately attached on
a respective position of a mammal subject, can also be used to
measure the physiological parameters of the mammal subject. In one
embodiment, at least one of the three or more sensor systems is a
conformable torso sensor system configured to attach and conform to
a torso region of the mammal subject, and at least one of the three
or more sensor systems is a conformable torso sensor system
configured to attach and conform to a torso region of the mammal
subject.
[0171] Referring now to FIGS. 10A-10I, a process for making a
sensor system including a plurality of electronic components 1041
and a plurality of interconnects 1021 and 1022 electrically
connecting to the plurality of electronic components 1041 is shown
according to one embodiment of the invention. In exemplary
embodiment, the process starts with the steps of (a) forming an
elastomeric layer 1010 of an elastomeric material, e.g., PDMS, on a
substrate 1001 (FIG. 10A); (b) forming a first electrically
conductive film 1020 on the elastomeric layer 1010 (FIGS. 10B-10C),
(c) lithographically patterning the interconnects 1021 in the first
electrically conductive film 1020 (FIGS. 10C-10D); (d) assembling
the plurality of electronic components 1041 onto the patterned
interconnects 1021 (FIGS. 10E-10F); and (e) encapsulating an entire
area of the assembled electronic components 1041 onto the patterned
interconnects 1021 with the elastomeric material, e.g. PDMS (FIG.
10G), followed by detaching from the substrate 1001 (FIG. 10G), to
fabricate the sensor system.
[0172] In one embodiment, the elastomeric material comprises PDMS
or other elastomers.
[0173] In one embodiment, the electrically conductive film is
formed of an electrically conductive material including a metal
material comprises Au, Ag, or Cu.
[0174] In one embodiment, said forming the electrically conductive
film comprises laminating a double layered film 1020 and 1022 of
the electrically conductive material on the elastomeric layer 1010
(FIG. 10B); and removing a top layer 1022 of the double layered
film (FIG. 10C).
[0175] In one embodiment, said assembling the plurality of
electronic components 1041 onto the patterned interconnects 1021
comprises connecting a second electrically conductive film 1025 for
a bridge and a light source to the patterned interconnects 1021
(FIG. 10F).
[0176] In one embodiment, the method further includes forming a
microfluidic chamber 1035 below the plurality of electronic
components 1041 (FIGS. 10H-10I).
[0177] In one embodiment, said forming the microfluidic chamber
1035 comprises attaching a layer 1030 of the elastomeric material
having the microfluidic chamber 1035 defined therein to the bottom
surface of the elastomeric layer 1010.
[0178] In another embodiment, the method further includes injecting
a blended solution of at least one of ionic liquid and silica gel
into the microfluidic chamber 1035.
[0179] In yet another embodiment, the method further includes
forming a silicone layer 1002 on the bottom of the sensor system
(FIG. 10I).
[0180] In addition, the invention also relates to a method of
non-invasively measuring physiological parameters of a mammal
subject. In one embodiment, the method includes conformally
contacting a first sensor system at a torso region of the mammal
subject and a second sensor system at a limb or appendage region of
the mammal subject, respectively, wherein the first sensor system
and the second sensor system are spatially separated by a distance,
and configured to measuring a torso physiological parameter and an
extremity physiological parameter, respectively; and continuously
wirelessly transmitting the time synchronized measured torso
physiological parameter and extremity physiological parameter to an
external reader, thereby non-invasively measuring the physiological
parameters of the mammal subject.
[0181] In one embodiment, the distance between the first sensor
system and the second sensor system is adjustable between a minimum
distance and a maximum distance.
[0182] In one embodiment, the physiological parameter is obtained
from electrical sensing by electrodes; and oxygen sensing by a
plethysmograph.
[0183] In one embodiment, the method further includes applying a
hydrogel between the first sensor system and the second sensor
system and underlying tissue of the mammal subject.
[0184] In another embodiment, the method further includes measuring
at least one additional physiological parameter related to
temperature; movement; spatial position; sound; and blood
pressure.
[0185] In yet another embodiment, the method further includes
determining a mammal subject and region-specific optimized driving
voltage provided to an optical light source; and powering an LED
optical light source with the optimized driving voltage, thereby
ensuring the LED optical light source intensity provides sufficient
signal to an optical detector without saturating the optical
detector.
[0186] In one aspect, the invention relates to a non-transitory
tangible computer-readable medium storing instructions which, when
executed by one or more processors, cause the above-disclosed
method.
[0187] It should be noted that all or a part of the methods
according to the embodiments of the invention is implemented by
hardware or a program instructing relevant hardware.
[0188] Yet another aspect of the invention provides a
non-transitory computer readable storage medium/memory which stores
computer executable instructions or program codes. The computer
executable instructions or program codes enable a computer or a
similar computing apparatus to complete various operations in the
above disclosed method of non-invasively measuring physiological
parameters of a mammal subject. The storage medium/memory may
include, but is not limited to, high-speed random access
medium/memory such as DRAM, SRAM, DDR RAM or other random access
solid state memory devices, and non-volatile memory such as one or
more magnetic disk storage devices, optical disk storage devices,
flash memory devices, or other non-volatile solid state storage
devices.
[0189] Certain aspects of the invention also relate to an
epidermal-mountable device for monitoring physiological parameters
of a patient comprising at least two electronically-coupled sensor
systems. Each sensor system comprises a plurality of electronic
components, including an antenna for wireless transmissions from a
sensor to an external reader; an interconnect that electrically
interconnects different electronic components; an elastomeric
encapsulation layer that surrounds the plurality of electronic
components and interconnect to form a bottom tissue-facing surface
and a top environment-facing surface; wherein each of the at least
two electronically-coupled sensor systems are configured to conform
to spatially separate positions on a patient.
[0190] In certain embodiments, the interconnect is a flexible and
stretchable interconnect that electrically interconnects different
strain-sensitive electronic components.
[0191] In certain embodiments, the flexible and stretchable
interconnects comprise serpentine interconnects.
[0192] In certain embodiments, the first sensor system is a
conformable torso sensor system configured to epidermally-mount and
conform to a torso region; and the second sensor system is a
conformable extremity sensor system configured to epidermally mount
and conform to a limb or an appendage region.
[0193] In certain embodiments, the extremity sensor system
comprises a main circuit component configured to wrap around an
appendage in a wrapping direction to mount to the appendage during
use; and a sensor that is mechanically decoupled and spatially
separated from, and electronically connected to, the main circuit
component, and that extends in a different direction than the
wrapping direction to mount to a sensor region that is spatially
distinct from the wrapped portion during use.
[0194] In certain embodiments, the sensor is a PPG sensor
comprising an optical source and an optical detector located within
a sensor footprint that is less than or equal to 5 mm.sup.2.
[0195] In certain embodiments, the PPG sensor mounts to an
appendage region such as a foot or a nail with an adhesive and the
main circuit component is configured to mount to an appendage such
as an ankle without an adhesive.
[0196] In certain embodiments, the device further comprises a
temperature sensor mechanically decoupled and spatially separated
from, and electronically connected to, the main circuit
component.
[0197] In certain embodiments, at least one of the sensor systems
further comprise a microfluidic chamber positioned between the
tissue-facing surface and the plurality of electronic components
configured to mechanically isolate the plurality of electronic
components from a skin surface during use.
[0198] In certain embodiments, the conformable torso sensor system
electronic components comprise electrodes for electrocardiogram
generation.
[0199] In certain embodiments, the conformable torso sensor system
electronic components further comprise one or more of a three-axis
accelerometer for position monitoring; and a temperature sensor for
measuring temperature.
[0200] In certain embodiments, the conformable extremity sensor
system electronic components comprise an optical detector for
measuring oxygen level in tissue underlying the conformable limb
sensor system by pulse oximetry. In certain embodiments, the
extremity sensor is configured to conformally mount to any of a
limb region of all four limbs, forehead, chest, back, abdomen for
tissue oxygen determination. In certain embodiments, the
conformable extremity sensor system electronic components further
comprise an optical light source, such as a light emitting diode,
and an optical detector.
[0201] In certain embodiments, the conformable extremity sensor
system electronic components further comprise a three-axis
accelerometer for position or movement monitoring; and a
temperature sensor for measuring temperature.
[0202] In certain embodiments, the sensor systems are configured to
measure a physiological parameter selected from one or more of the
group consisting of heart activity, including stroke volume,
ejection fraction; oxygenation level; temperature; patient
movement; patient position; breathing parameter; blood pressure;
and a biomechanical perturbation.
[0203] In certain embodiments, each of the sensor systems has a
footprint area less than or equal to 10 cm.sup.2.
[0204] In certain embodiments, each of the sensor systems have a
thickness less than or equal 3 mm.
[0205] In certain embodiments, the device wirelessly communicates
with an externally-positioned reader and is wirelessly powered.
[0206] In certain embodiments, the device is configured to
conformally mount to a skin surface without an adhesive, wherein a
contact force is generated by Van der Waals interaction between the
bottom surface and a skin surface during use.
[0207] In certain embodiments, the device has a peel force from the
skin selected from a range that is greater than 0 Newton and less
than 1 Newton.
[0208] In certain embodiments, the device further comprises an
adhesive layer connected to the bottom tissue-facing surface of the
encapsulation layer, wherein the adhesive layer has a pattern of
perforations.
[0209] In certain embodiments, the bottom encapsulation layer
comprises channels or conduits configured to facilitate sweat
evaporation during use.
[0210] In certain embodiments, the device is configured to measure
a plurality of physiological parameters from a neonate.
[0211] In certain embodiments, each of the limb and extremity
sensor system have a Young's modulus less than or equal to 1
GPa.
[0212] In certain embodiments, the device is capable of undergoing
a strain of up to 20% and bending radius as small as 5 mm without
fracture.
[0213] In certain embodiments, the measurement of the physiological
parameter is continuous for an extended time period that is greater
than 4 hours.
[0214] In certain embodiments, the device further comprises a
hydrogel positioned between the bottom-tissue facing surface and a
tissue surface during use.
[0215] In certain embodiments, the conformal contact is
adhesive-free.
[0216] In certain embodiments, the adhesive-free conformal contact
comprises a wrapped geometry, the sensor member of at least one of
the first sensor system and the second sensor system further
comprises a fastener connected to an external surface of the
encapsulation layer to fasten the sensor member in the wrapped
geometry to a patient.
[0217] In certain embodiments, the extremity sensor system
comprises an optical unit for photoplethysmography on a nail of an
individual that is mechanically isolated from a main circuit
component comprising a microprocessor and a wireless
transmitter.
[0218] In certain embodiments, the sensors are conformable to a
skin surface and configured as a soft wrap for circumferential
mounting to a limb region.
[0219] In certain embodiments, the limb region corresponds to a
hand or a foot of a neonate.
[0220] In certain embodiments, each of the sensors have a footprint
less than or equal to 9 cm.sup.2.
[0221] In certain embodiments, the device further comprises a
battery to power the sensors, and the elastomeric encapsulation
layer is electrically insulative to electrically isolate the
battery from a patient during use.
[0222] In certain embodiments, the encapsulation layer electrically
isolates the sensor from an electroshock applied to a patient,
including under an applied cardiac defibrillation stimulus.
[0223] In certain embodiments, the device further comprises a
failure prevention element that is a short-circuit protection
component or a battery circuit to avoid battery malfunction.
[0224] In certain embodiments, the elastomeric encapsulation layer
comprises a flame retardant material.
[0225] In certain embodiments, the device further comprises a
multi-layer structure to mechanically isolate mechanically stiff
components in a mechanical island configuration to accommodate
bending, twisting and/or stretching without fracture or substantial
degradation of an operating parameter.
[0226] In certain embodiments, the pair of sensor systems
wirelessly communicate time-synchronized data to an external
reader, including for pulse arrival time and pulse transit time to
determine blood pressure.
[0227] In certain embodiments, the device has a continuous stream
rate that is greater than or equal to 600 bytes/second.
[0228] In certain embodiments, the device further comprises further
comprises an external reader wirelessly connected to the pair of
sensor systems to display and/or record wirelessly transmitted data
from each of the sensors of the sensor systems.
[0229] In certain embodiments, the device further comprises further
comprises a microprocessor operably connected to the sensors for
on-board real-time data processing, analytics and adaptive gain
modulation.
[0230] In certain embodiments, the antenna is a magnetic loop
antenna for wireless power generation.
[0231] In certain embodiments, the device further comprises a loop
antenna.
[0232] In certain embodiments, the device further comprises further
comprises a rechargeable battery for wireless recharging.
[0233] In certain embodiments, the at least two sensor systems
together have a peak current consumption of less than 3 mA.
[0234] In certain embodiments, the encapsulation layer is optically
transparent and sensor systems have open regions for visual
inspection of underlying tissue without monitor removal from
skin.
[0235] In certain embodiments, the device is radio translucent and
thermally stable for medical imaging without device removal during
medical imaging.
[0236] In certain embodiments, spacing between the pair of sensor
systems is adjustable.
[0237] In certain embodiments, the device further comprises further
comprises an alarm for a physiological parameter that is out of a
user-defined normal range.
[0238] In certain embodiments, the alarm is an optical alert and/or
an audio alert on-board or off-board the device.
[0239] In certain embodiments, the microfluidic chamber has a
volume that is less than or equal to 1 mL.
[0240] In certain embodiments, the microfluidic chamber is at least
partially filled with a liquid or a gel.
[0241] In certain embodiments, the microfluidic chamber is at least
partially filled with a blended solution of an ionic fluid and a
silica gel.
[0242] In certain embodiments, the device further comprises a
dynamic baseline control module to automatically compensate for
patient-to-patient variability and generate an effective driving
current to ensure sufficient signal-to-noise and avoid
saturation.
[0243] In certain embodiments, the driving current is supplied to
an LED to generate an optimized light intensity provided to an
underlying patient region.
[0244] Certain aspects of the invention further includes method of
non-invasively monitoring a physiological parameter of a patient,
comprising the steps of providing the above-disclosed device;
conformally contacting the sensor systems at spatially separated
regions of the patient; continuously wirelessly transmitting a time
synchronized measured torso physiological parameter and extremity
physiological parameter to an external reader; thereby
non-invasively monitoring a physiological parameter of a
patient.
[0245] In certain embodiments, the conformal contact is without an
adhesive and the conformal contact has a duration of at least 8
hours.
[0246] In certain embodiments, the method further comprises
applying a hydrogel between the device and underlying tissue.
[0247] In certain embodiments, the physiological parameter is
obtained from electrical sensing by microelectrodes; and oxygen
sensing by a plethysmograph.
[0248] In certain embodiments, the method further comprises
measuring at least one additional physiological parameter that is
related to temperature; movement; spatial position; sound; or blood
pressure.
[0249] In certain embodiments, the method further comprises
determining a patient and region-specific optimized driving voltage
provided to an optical light source; powering an LED optical light
source with the optimized driving voltage; thereby ensuring the LED
optical light source intensity provides sufficient signal to an
optical detector without saturating the optical detector.
[0250] Certain aspects of the invention also disclose a device for
measuring a physiological parameter comprising a main circuit
component having a microprocessor and a wireless transmitter; a
sensor that is mechanically decoupled and spatially separated from,
and electronically connected to, the main circuit component; an
encapsulation layer that encapsulates the main circuit component
and the sensor; wherein during use the device is configured to
mount to a patient surface and is completely wireless.
[0251] In certain embodiments, the device further comprises a
flexible and stretchable interconnect that electronically connects
the sensor to the main circuit.
[0252] In certain embodiments, the device further comprises a
laterally extending wrap region configured to wrappably mount the
main circuit component to a patient during use without an adhesive
layer between the encapsulation layer and skin; and a sensor
extending sensor region configured to mount the sensor in a
direction independent of a wrap direction.
[0253] In certain embodiments, the sensor is configured to mount to
a foot region or a toenail and the main circuit component around an
ankle region.
[0254] In certain embodiments, the sensor is a PPG sensor.
[0255] According to the invention, among other things, relevant
differences of the invented sensor systems from conventional sensor
systems include: an ultra-low profile form factor with fully
wireless functionality. This enables in-hospital and post-discharge
monitoring without any wires. Furthermore, the form factor and
encapsulation avoid use of harsh adhesives, so that, if necessary,
ultra-low adhesives may be used, which is important for
ultra-fragile skin and the entire device is compatible with common
medical imaging techniques (CT, XR and MRI). Multiple measurements
of a vital sign with different sensor platforms increases accuracy
and reliability while decreasing risk of false-positives. The
platform is versatile, characterized in that many different
physiological parameters can be measured, including, but not
limited to, the ones listed above. The digital nature of the sensor
systems makes them particularly compatible with various software
methodologies, including advanced analytics for predictive
algorithms.
[0256] Provided herein are also methods of monitoring one or more
physiological parameters using any of the devices or systems
described herein. Also provided are devices for carrying out any of
the methods described herein.
[0257] These and other aspects of the present invention are further
described below. Without intent to limit the scope of the
invention, examples according to the embodiments of the present
invention are given below. Note that titles or subtitles may be
used in the examples for convenience of a reader, which in no way
should limit the scope of the invention. Moreover, certain theories
are proposed and disclosed herein; however, in no way they, whether
they are right or wrong, should limit the scope of the invention so
long as the invention is practiced according to the invention
without regard for any particular theory or scheme of action.
Example 1
Dual Wireless Epidermal Electronic Systems with In-Sensor Analytics
for Neonatal Intensive Care
[0258] Existing vital sign monitoring systems in the neonatal
intensive care unit (NICU) fail to offer a safe, patient-centric
mode of operation, largely due to the necessity of multiple wires
connected to rigid electrodes with strongly adherent interfaces to
the skin to ensure good contact. Here, we introduce a pair of
ultrathin, skin-like electronic sensors whose coordinated operation
bypasses limitations of existing technologies. The enabling
advances in engineering science include designs that support (1)
wireless, battery-free operation, (2) real-time, in-sensor data
analytics, (3) time-synchronized, continuous data streaming, (4)
soft mechanics and light adhesive interfaces to the skin and (5)
compatibility with advanced medical imaging techniques used in the
NICU. Studies on neonates admitted to operating NICUs demonstrate
performance capabilities that exceed those of the most advanced
clinical-standard monitoring systems.
[0259] Continuous recording and real-time graphical display of
vital signs is essential for critical care. Each year in the U.S.,
approximately 300,000 neonates, including a large fraction with
exceptionally fragile health status due to severe prematurity and
very low birth weight (<1500 g), are admitted to neonatal
intensive care units (NICUs). Existing monitoring systems for the
NICU require multiple electrode/sensor interfaces to the skin, with
hard-wired connections to separately located base units that may be
stand alone or wall-mounted for heart rate (HR), respiratory rate
(RR), temperature, blood oxygenation (SpO.sub.2) and blood pressure
(BP). Although such technologies are essential to clinical care,
the associated web of wires greatly complicates even the most basic
bedside tasks such as turning a neonate from prone to supine. This
hardware also interferes with emergency clinical interventions and
radiological studies, and impedes therapeutic skin-to-skin contact,
colloquially known as kangaroo mother care, between parents and
their infant. Most significantly, the adhesives that couple these
wired electrodes to the fragile skin of the neonates are a frequent
cause of iatrogenic injuries and subsequent scarring.
[0260] A fully wireless alternative that eliminates mechanical
stresses and potentially reduces injury-risk, and that deploys
effectively on the full range of gestational ages encountered in
the NICU would represent a significant advance over the existing
standard of care. While textile-based sensors are of interest,
these technologies retain wired connections across the body and
their inability to support an intimate connection to the skin
precludes reliable operation at clinical-grade levels of accuracy,
particularly with motion. Recent advances in materials science and
biomedical engineering serve as the basis for devices that have an
ideal, skin-like form factor. Although such systems can support
various types of biophysical measurements of physiological health,
significant additional advances are needed to meet the challenging
requirements of the NICU, where comprehensive, continuous sensing
with wireless functionality, clinical-grade measurement fidelity,
and mechanical form factors that eliminate risk of harm to
exceptionally fragile neonatal skin are essential.
[0261] In certain aspects, the invention discloses a wireless,
battery-free vital signs monitoring system that exploits a bi-nodal
pair of ultrathin, low-modulus measurement modules, each referred
to as an epidermal electronic system (EES), capable of softly and
non-invasively interfacing onto neonatal skin. Among other things,
five essential advances include: (1) techniques for simultaneous
wireless power transfer, low noise sensing and high speed data
communications via a single link based on magnetic inductive
coupling at a radio frequency band that has negligible absorption
in biological tissues, (2) efficient algorithms for real-time data
analytics, signal processing and dynamic baseline modulation
implemented in the highly constrained computing resources available
on the sensor platforms themselves, (3) strategies for
time-synchronized, continuous streaming of wireless data from two,
separately located devices, (4) mechanics designs and strategies in
interface adhesion that minimize the risk of iatrogenic skin injury
to fragile neonatal skin, and (5) optimized layouts that enable
visual inspection of underlying tissue of the skin interface, and
radiolucent electrical configurations that allow magnetic resonance
imaging (MRI) and X-ray imaging (XR). Successful pilot phase
demonstrations on neonates with gestational ages ranging from 28
weeks to full-term in two, tertiary-level NICUs establish
quantitative equivalency to clinical standards.
[0262] In addition to advanced capabilities in monitoring, the
skin-like profile and fully wireless nature of these platforms
offer direct therapeutic value by reducing the barriers for
skin-to-skin contact between parent and child. The result enables
spontaneous interactions with neonates not further encumbered by
ventilator support or central vascular lines. Studies indicate that
such skin-to-skin contact reduces neonatal mortality, risk of
severe infection, and hypothermia while increasing the rate of
weight gain and head circumference growth.
Sensor Designs, System Configurations and Wireless, Battery-Free
Modes of Operation
[0263] FIG. 1B presents schematic representations of an epidermal
system comprising two wireless, sensor systems (epidermal
electronic systems (EES)) that, when used together in a
time-synchronized fashion, constitute an overall bi-nodal platform
capable of reconstructing full vital signs information. The
time-synchronized aspect of the sensor systems is also generally
referred herein as the sensor systems being "electronically
coupled". The epidermal system is, of course, compatible with more
than two sensor systems. The electronic layer in each EES
incorporates a collection of thin, narrow serpentine metal traces
(Cu, 50-100 .mu.m in width, 5 .mu.m in thickness) that interconnect
multiple, chip-scale integrated circuit components. One EES mounts
on the chest to record electrocardiograms (ECGs; FIG. 1B, top)
through skin-interfaced electrodes that comprise filamentary metal
mesh microstructures in fractal geometries; the other mounts on an
extremity, such as the base of the foot, to record
photoplethysmograms (PPGs; FIG. 1B, bottom) by reflection mode
measurements. A microfluidic chamber filled with a non-toxic ionic
liquid (e.g., 1-ethyl-3-methylimidazolium ethyl sulfate
[EMIM][EtSO.sub.4], Sigma-Aldrich) between the electronics and the
lower encapsulation layer mechanically strain-isolates the systems
from the fragile skin of the neonate. A thin film of silicone
elastomer encapsulates the top, the bottom and the sides, to enable
operation even when completely immersed in water as shown in FIGS.
8A-8B.
[0264] In addition to the electronics, each EES incorporates a
magnetic loop antenna (FIGS. 9A-9B) tuned to compliance with near
field communication (NFC) protocols and configured to allow
simultaneous wireless data transmission and wireless power delivery
through a single link. The low conductivity of the ionic liquid
allows stable electrical operation in this RF environment. Details
of the methods for fabrication are described below and shown in
FIGS. 10A-10I. The resulting bi-nodal system captures and
continuously transmits ECG, PPG and skin temperature from each EES.
From these data, HR, heart rate variability (HRV), RR, SpO.sub.2
and a surrogate of systolic blood pressure (BP) can be extracted,
as discussed subsequently.
[0265] The images shown in FIG. 1C highlight the overall size and
the ultrathin, soft form factor of these systems. Finite element
analysis and experimental results indicate that these devices can
bend to radii that are much smaller (6.4 mm and 5 mm, respectively;
FIGS. 11A-11B) than required (>about 140 mm and >about 50 mm
for the chest and foot, respectively, depending on gestational age)
to interface with the chest and the limb of each neonate, without
adverse mechanical effects on the device or skin. The
electromagnetic properties of both the ECG EES and PPG EES undergo
negligible changes when stretched and bent in this manner, thus
ensuring robust wireless operation mode for data transmission and
power harvesting, as shown in FIGS. 12A-12C and 13A-13C, including
during with on a moving patient, such as aneonate. Stretching the
ECG EES uniaxially by up to 16% (FIG. 1C) and the PPG EES up to 13%
results in strains in the electronics and antenna structures that
remain below the limits for plastic deformation (about 0.3%; FIGS.
14A-14B, 15A-15E and 16A-16E). Even with 20% stretching the changes
in the inductance, Q factor and resonant frequency of the antennas
are minimal (<5%), as shown in FIGS. 17A-17C and 18A-18C. FIG.
1E illustrates a PPG EES with its red LED activated, captured with
and without external illumination.
[0266] Images shown in FIGS. 1F-1G compare clinical standard
technologies (FIG. 1F) to the invented devices (FIG. 1G), as
deployed on a realistic model of a neonate. Existing systems
require a collection of separate electrodes, sensors and
limb-strapped systems paired to base units with hard-wired
connections. ECG requires three adhesive-backed electrodes with
adjoining wires to monitor HR, HRV and RR. Commonly used electrodes
for this purpose (e.g., 3M Red Dot.TM., 3M Company) may require
additional adhesives that further increase the risk of skin injury.
Measurements of SpO.sub.2 rely on limb-based devices for PPG (e.g.,
NLCS Neo SpO.sub.2 sensor, Masimo.RTM.), typically wrapped around
the entire foot, with an additional wired interface. Continuous
measurements of skin temperature, necessary to monitor for signs of
hypothermia, involve another adhesive-backed sensor (e.g.,
HNICU-22, DeRoyal.RTM.) and adjoining wire. Collectively, then,
vital signs monitoring in the conventional manner demands at least
four electrodes and one limb-deployed device, with five wires for
external connection to yield HR, HRV, RR, skin temperature, and
SpO.sub.2.
[0267] The block diagram shown in FIG. 1H summarizes the system
architecture and overall wireless operation of the systems
introduced here. The ECG EES includes two epidermal electrodes, an
instrumentation amplifier, analog filters, an inverting amplifier,
and an NFC system-on-a-chip (SoC) (FIG. 19). The PPG EES includes a
pair of small-scale LEDs that emit in the red (640 nm) and IR (940
nm), a photodiode, LED drivers, an external power circuit, analog
filters, an inverting amplifier, and an NFC SoC (FIG. 20). A 14-bit
analog-to-digital converter (ADC) operating at a sampling frequency
of 200 Hz on the SoCs digitizes the signals captured by each
module. The RF loop antennas in both the ECG EES and PPG EES serve
dual purposes in power transfer and in data communication.
[0268] Since the standard NFC protocol at 13.56 MHz supports only
low speed, low fidelity applications in contactless payments,
wireless identification and others, significant modification in
both the transponder and host reader systems at ISO15693 were
required to enable data transfer rates sufficient for NICU
monitoring (hundreds of Hz). The results enable continuous
streaming of data at rates of up to 800 bytes/s with dual channels,
which is orders of magnitude larger than those previously achieved
in NFC sensors. A key to realizing such high rates is in minimizing
the overhead associated with transfer by packaging data into 6
blocks (24 Bytes) in a circular buffer. Here, reading occurs with
an NFC host interfaced to a microcontroller in a Bluetooth Low
Energy (BLE) system configured with this type of customized
circular buffer decoding routine shown in FIG. 21. The primary
antenna connects to the host system for simultaneous transfer of RF
power to the ECG EES and the PPG EES. Operation is possible at
vertical distances of up to 25 cm, through biological tissues,
bedding, blankets, padded mattresses, wires, sensors and other
materials found in NICU incubators, for full coverage wireless
operation in a typical incubator. BLE radio transmission then
allows transfer of data to a personal computer, tablet computer or
smartphone with a range of up to 20 m. Connections to central
monitoring systems in the hospital can then be established in a
straightforward manner.
Low Modulus Mechanics, Soft Interface Adhesion and Implications for
Neonatal Skin Safety
[0269] The essential mechanics of these systems decrease risks for
skin injury relative to existing clinical standards. The global
incidence of skin breakdown in hospitalized neonates ranges between
31-45%, with medical devices and associated adhesives being a major
iatrogenic cause. Additionally, pressure-related skin injuries
occur in 26% of hospitalized infants <3 months of age with 80%
directly related to medical devices, where PPG modules are the most
common culprit. By age 7, more than 90% of children previously
cared for in the NICU exhibit residual scars secondary to
monitoring probes, adhesives and invasive medical interventions.
Premature neonates are particularly high-risk given that their
epidermis and dermis is 40-60% thinner than adult skin with
incomplete cornification, greater trans-epidermal water loss and
evaporative heat loss, decreased mechanical strength, and greater
propensity to scar. The inherently thin, soft physical properties
of the sensors reported here allow for significantly reduced skin
contact stresses and adhesion via van der Waals forces alone, and
without at least strong conventional adhesives. The result lowers
the risk of iatrogenic skin injury in premature neonates by
reducing the need for additional adhesives. The devices shown in
FIG. 1B have effective moduli in the range of 200-300 kPa (FIG. 2A)
and induce minimal normal and shear stresses at the skin interface
associated with natural motions of the neonate. The mechanical
decoupling afforded by the microfluidic channel decreases these
stresses by up to a factor of 2.5 (FIG. 2B), relative to otherwise
similar designs without the microfluidics.
[0270] Experimental and theoretical studies reveal the fundamental
aspects of soft adhesion in these systems. Simulations that use the
cohesive zone model (FIG. 23) allow quantitative examination of the
mechanics associated with removal of conventional adhesives (e.g.,
Argyle.TM. Hydrogel Adhesive Baby Tape Strips, Covidien) and EES
devices (modeled as an effective medium; FIGS. 2C-2D) from surfaces
with mechanical properties reflective of neonatal skin. The
differences between the magnitudes of deformations induced in the
skin, at identical peel forces, are notable (FIG. 2C). The forces
at steady-state peeling rates are different by approximately a
factor of about 10 (FIG. 2D), with reductions in the maximum von
Mises stress on the skin by a factor of 4.3. Experimental testing
on adult skin (FIGS. 2E-2F) shows similar behaviors, including a
significant reduction in peel force (about 1000%, FIG. 24) of an
EES relative to that of a traditional adhesive. Analysis of these
experimental results defines the adhesion energy at the interface
between the EES and skin, i.e. G=16 N/m.
[0271] The presence of the microfluidic channel, as shown in FIG.
25C, serves a role in determining the adhesion properties of the
EES, as shown in FIG. 2G. At steady-state (>2 s), the peel
forces (F) with and without the microfluidics are approximately the
same, consistent with a scaling relationship that depends only on G
and the width of the device, W, as F=G.times.W. In other words, the
adhesion energy defines the steady-state peeling force. At the
initiation of peeling, however, in the non-steady state regime when
the forces on the skin are most important, the cohesive strength
determines the force. Specifically, the interface starts to
delaminate when the normal stress reaches about 20 kPa (FIG. 2G,
inset). The microfluidic channel reduces the effective modulus of
the EES and, as a consequence, increases the ability of the device
to deform under applied force. The consequent reduction in the size
of the cohesive zone at the delamination front (FIGS. 26A-26B)
decreases the peel force for the same peak stress (cohesive
strength).
[0272] Further reductions can be achieved by the addition of
perforations through the open regions of the EES platform, as shown
in FIGS. 27B-27D for different patterns of holes. FIG. 2H
highlights the peel force, the primary driver of epidermal
stripping in fragile neonatal skin, as a function of time during
peeling for a regular triangular pattern of holes (diameter D=200
.mu.m). The force scales simply with 1-.alpha. (FIGS. 28A-28C),
i.e., the area of contact between the EES and the skin. This
scaling also applies to other patterns of holes (e.g., FIGS.
29A-29C and 30A-30C for square patterns without and with 45.degree.
rotation, respectively). For sufficiently small holes (e.g., 200
.mu.m, or less than 250 .mu.m), the relation between the peel force
and time depends only on 1-.alpha. and is approximately independent
of pattern. Oscillations in the force only appear for holes larger
that the characteristic size of the cohesive zone (about 500 .mu.m
as in FIG. 2I). An optimized approach to reducing interface
stresses and peel forces, therefore, combines microfluidic channel
structures with small perforation holes, the latter of which can be
naturally accommodated within the open network designs
characteristic of epidermal electronics (FIG. 1B).
Compatibility with Medical Imaging Techniques Used in the NICU
[0273] These open design layouts, taken together with certain
favorable electromagnetic characteristics of the antennas and
interconnects, also greatly improve compatibility with medical
imaging and clinical inspections relative to existing clinical
monitoring hardware. Magnetic resonance imaging (MRI) is one type
of imaging modality that is essential in the NICU, due to its
ability to deliver precise assessment of white matter, gray matter,
and posterior fossa abnormalities with functional capabilities that
exceed those of ultrasound. The EES platforms described here
exploit designs that minimize disturbances in the time dependent
magnetic fields associated with MRI scanning, thereby reducing
distortions and shadowing artifacts in the final images and
eliminating any parasitic heating from magnetically induced eddy
currents. Calculations of the gradients of the magnetic field
density near electrodes with different structures (mesh, solid and
commercial electrodes, see FIG. 36B) on biological tissues in a 3 T
MRI scanner reveal the underlying effects. The results show that
mesh electrodes induce the weakest disturbance to the magnetic
field among mesh (layout of FIG. 1C), solid (i.e. no mesh) and
commercial electrodes with similar overall sizes and geometries
(FIGS. 3A and 3C) for both the in plane |.gradient.pB| and
out-of-plane gradient |.gradient.zB| of the magnetic field density.
The maximum value of |.gradient.pB| for the mesh electrode is
roughly a factor of three times smaller than that of the commercial
electrode (FIG. 3E); |.gradient.zB| is four times smaller (FIG.
3F). The mesh design, of course, also has significant advantages in
its soft, flexible mechanics and associated benefits in interfacial
stresses and adhesion.
[0274] Additional simulations guide selection of designs that
ensure that the resonant frequencies of the EES have no overlap
with the working frequencies of typical MRI scanners (64 MHz, 128
MHz, 298 MHz and 400 MHz for 1.5, 3, 7 and 9.4 T MRI scanners,
respectively, FIG. 3G), thereby avoiding large gradients of the
magnetic field density (FIGS. 3B, 3D and 38). Similar simulations
for the PPG EES indicate gradients of the magnetic field density
that are smaller than those for the ECG EES (FIGS. 39A-39B). These
features allow the devices to remain in place on neonates
undergoing MRI imaging, thereby mitigating the risk of injury and
complications with removal and re-adhesion.
[0275] Experiment and simulation results also yield information on
parasitic heating during an MRI scan. Full three-dimensional
multi-physics modeling shows that, at the end of single scan for
0.5 ms, the copper layer of an ECG EES undergoes heating by only
1.degree. C. (FIG. 3H). The resultant maximum temperature change at
the skin interface is 0.04.degree. C., far below the threshold for
sensation, due to the insulating effects of the PDMS and the
microfluidic channel. The maximum change in temperature occurs
about 0.24 s (FIGS. 3H and 40A-40B) after initiating the scan. This
time scale is on the same order as that for heat conduction (0.1 s)
in the microfluidic channel (FIGS. 40A-40B).
[0276] Experimental measurements support these findings. FIG. 3I
shows the change of temperature during an MRI scan (3 T MAGNETOM
Prisma, Siemens Healthineers), measured on a sample of phantom skin
at a location underneath the ECG EES near the loop antenna and
adjacent to the device. The results show a temperature difference
of about 0.1.degree. C. FIG. 3J presents measurements in the middle
region of the ECG EES where the values of |.gradient.zB| and
|.gradient.pB|, are comparable to those of the bare phantom skin.
Simulation results for the PPG EES suggest even smaller changes in
temperature than those for the ECG EES (FIGS. 41A-41B). Additional
testing with another MRI system (9.4 T Bruker Biospec MRI system,
Bruker BioSpin Corporation) and an ECG EES placed over cadaveric
rat tissue (FIG. 3K) show no observable magnetically induced
displacement forces or torques and no measurable changes in
temperature. The results meet FDA requirements for an "MRI-safe"
label for medical devices. Actual imaging results indicate that the
ECG EES causes much less shadowing and image distortion compared to
a conventional NICU ECG electrode (FIG. 3L).
[0277] Beyond benefits in MRI, the EES eliminates radiopaque wires,
thereby improving evaluation by XR imaging, a modality required for
90% of low-birth weight neonates (26). Experimental results show
that an ECG EES placed over the same tissue in a rodent model
imaged using a CT/XR system (nanoScan PET/CT, Mediso) exhibits
improved radiolucency in comparison to standard ECG electrodes and
wires (FIGS. 3M-3N). The optical transparency of the silicone and
the open mesh designs of the electronics and antenna structures
also provide direct visual access to the skin and tissue beneath
the sensor (FIG. 48), thereby negating the need to remove the
sensor to monitor the underlying skin for signs of infection or
irritation.
Real-Time Measurements, In-Sensor Analytics, Data Transmission and
Display for Neonatal Critical Care
[0278] Exploiting this collection of attractive electronic,
mechanical and radiolucent properties for practical use in a NICU
environment requires in-sensor processing and data analytics to
reduce bandwidth requirements on wireless transmission and to
ensure operational robustness. For example, computational
facilities on the NFC SoC of the ECG EES can support a streamlined
version of the Pan-Tompkins algorithm for accurate, on-board
analysis of the QRS complex of ECG signals in real-time to yield HR
and HRV on a beat-to-beat basis. FIG. 4A summarizes an approach
that starts with digital bandpass filter (f.sub.c1=5 Hz,
f.sub.c2=15 Hz) to attenuate the noise. Differentiating and
squaring the resulting data yields the slope of QRS peaks and
prevents false peak detection associated with the T wave. Applying
a moving average and a dynamic threshold identifies a running
estimate of the R peak and the magnitude of the noise. Automatic
adjustments of the threshold rely on these estimates for the
preceding beat cycle (FIGS. 44A-44F). The R-to-R intervals
determined in this way yield the instantaneous HR. Simultaneous
recordings obtained using a clinical standard system, henceforth
referred to as `gold` standard data, validate the ECG module
hardware and in-sensor analytics, via measurements on a healthy
adult volunteer (FIGS. 4B-4C). The ECG signals and computed HR
values from these two platforms show no measurable differences.
Periodic modulations of the amplitude of the R peak define the RR
(FIG. 4D), which also agrees with the gold standard (visual
counting by a physician in this case; FIG. 4E). Measurements of
skin temperature rely on sensors internal to the NFC SoC in each
EES, where transmission at a sampling frequency of 1 Hz is
sufficient for monitoring purposes. The low thermal mass of the EES
and the small thickness of the substrate layer (PDMS; 50 .mu.m in
thickness) separates the SoC from the skin to ensure fast thermal
response times and excellent thermal coupling, respectively.
Comparisons against readings from a thermometer (Fisherbrand.TM.
13202376, Fisher Scientific) serve as means to calibrate the sensor
(FIG. 4F) via testing in a water bath (FIG. 45). Thermal images
captured with an IR camera (FLIR A325SC, FLIR Systems) during
operation indicate negligible heating associated with the
electronics or the antenna structures (FIG. 4G). FIG. 4H shows
temperature readings from ECG EES for 60 s. Comparison tests of
this system against FDA cleared monitoring equipment (Dash 3000, GE
Healthcare) on healthy adult volunteers (n=3) show excellent
agreement for HR (mean difference=0.1, standard deviation=2.55,
both in bpm) and RR (mean difference=0.3, standard deviation=0.95,
both in bpm) as shown in FIGS. 4I-4J, respectively.
[0279] The PPG EES relies on similar NFC protocols, but with
in-sensor analytic methods that not only reduce requirements on
transmission bandwidth but also provide, when used in conjunction
with adaptive circuits, crucial functionality for stable operation.
Specifically, the processing in this case can enable (i) dynamic
baseline control to ensure that the input to the ADC on the NFC SoC
lies within the linear response range and (ii) real-time
calculation of SpO.sub.2 from the PPG traces (FIG. 5A). Here, the
processing begins with application of a moving average filter to
the photodetector response from the red and IR LEDs. When the
larger of these two averaged PPG amplitudes (typically that
associated with the IR response) lies outside of a range that is
optimal for the ADC (0.25-0.7 V), a programmable difference
amplifier with voltage dividers at V+ dynamically adjust the
baseline level. The circuit shown in FIG. 5B demonstrates the
operation where the governing equation is
V tr = - R f R s .times. V pre + ( 1 + R f R s ) .times. V + ( 1 )
##EQU00001##
where V.sub.tr is the voltage output of the amplifier, V.sub.pre is
the voltage of the input signal, R.sub.s is the input resistance,
R.sub.f is the feedback resistance. The voltage divider at V.sub.+
with resistor R.sub.d1 and R.sub.d2 governs following equation with
Vref of 1.8V
V + = R d .times. 2 .times. V r .times. e .times. f R d .times. 2 +
R d .times. 1 .times. ( a 0 1 .times. 6 + a 1 8 + a 2 4 + a 3 2 ) (
2 ) ##EQU00002##
[0280] Sixteen different baseline states can be accessed via
activation of binary values from four general purpose input output
pins (a.sub.0, a.sub.1, a.sub.2, a.sub.3) on the SoC (FIG. 46),
applied through an R-2R resistor ladder. FIG. 5C shows dynamic
control of the output voltage (V.sub.tr) of a sinusoidal input
signal (frequency=50 mHz, amplitude=40 mV, V.sub.offset=-30 mV).
Starting with the default setting of the GPIO ports (a.sub.0,
a.sub.1, a.sub.2, a.sub.3; all high, or 1111), the baseline level
automatically adjusts to lower levels associated as the value of
V.sub.tr drifts above the upper boundary of the specified voltage
range, and vice versa as V.sub.tr falls below the lower boundary.
The result maintains V.sub.tr in the allowed range. FIG. 5D
summarizes the operation in an actual PPG recording. Without this
type of real-time, in-sensor processing (IR Non in FIG. 5D) robust
operation would be impossible: PPG signals would quickly drift
outside of the narrow operating range of the ADC due to
patient-to-patient variations in skin pigmentation and unavoidable,
time-dependent fluctuations in optical scattering that result from
micro-motions relative to underlying blood vessels and subdermal
structures.
[0281] Calculating SpO.sub.2 involves determining the ratio
(R.sub.oa) between the alternating and direct components of the PPG
signals according to
R o .times. a = A .times. C R .times. E .times. D D .times. C R
.times. E .times. D / A .times. C IR D .times. C IR ( 3 )
##EQU00003##
for data from the red and IR LEDs (FIG. 5E). An empirical
calibration formula determined by comparison to an FDA-cleared
fingertip oximeter measurement (MightySat Fingertip Oximeter,
Masimo.RTM.) converts the R.sub.oa to SpO.sub.2 (FIG. 5F). Time
dependent variations of SpO.sub.2 determined in this manner appear
in FIG. 5G with demonstration in a decrease with a breath hold in
an adult volunteer.
[0282] Beyond re-capitulation of well-established vital signs, the
time synchronized outputs from the ECG EES and the PPG EES allow
for determination of advanced physiological parameters that are of
high clinical value but not regularly collected in routine practice
in NICUs. A key example is the measurement of pulse arrival time
(PAT), defined by the time lapse between the maximum fiducial point
in the ECG signal (R peak) and the corresponding minimal fiducial
point in the PPG signal at valley as in FIG. 5H, as a direct
correlate to systolic blood pressure. Blood pressure is an
essential physiological marker of perfusion, autonomic function,
and vascular tone for critically ill newborns. Cuff-based blood
pressure measurements with sphygmomanometers fail to provide a
continuous measurements, overestimate blood pressure in premature
neonates, and pose a direct risk for pressure-related injuries.
While arterial lines offer a continuous measurement of blood
pressure in neonates, these invasive interventions can cause
thrombosis, hematomas, infection, and even death. Thus, the ability
to capture PAT non-invasively and continuously would be of high
clinical value in the NICU with prior reports providing evidence
that PAT correlates with blood pressure in infants. The
Moens-Korteweg equation provides a linear relationship between PAT
and BP. Measurements of 1/PAT performed in processing of ECG and
PPG data in the host (FIGS. 47A-47B), together with corresponding
values of systolic BP captured using a sphygmomanometer on a
healthy adult during a period of rest after exercising (running at
6 miles per hour for 15 minutes), exhibit the expected linear
relationship (FIG. 5I). A calibration plot with a linear fit
appears in FIG. 5J. The bi-nodal configuration of the system
naturally yields not only a surrogate marker of BP but also
temperatures at two different locations (trunk and limb), to
improve monitoring for hypothermia and provide a noninvasive method
to track peripheral perfusion. In current clinical practice,
measurements of skin temperature are typically limited to a single
body location due to the need to minimize wired connections and
adhesive interfaces to the skin. Comparison tests of this system
against FDA cleared monitoring equipment (Dash 3000, GE Healthcare)
on healthy adult volunteers (n=3) show excellent agreement for
SpO.sub.2 (mean difference=0.3, standard deviation=1.37, both in %)
as shown in FIG. 5K. FIG. 5L illustrates the ability with an ECG
EES and PPG EES to capture differential skin temperature between
the torso and peripheral limbs.
Pilot Studies in NICUs and Validation Against Clinical
Standards
[0283] Preliminary testing of the EES system in both healthy
neonates (n=3) and premature infants in two tertiary level NICUs
demonstrates feasibility and measurement validity. FIGS. 6A-6C,
highlight deployment in a healthy term neonate with an ECG EES and
a PPG EES mounted on the chest and the foot, respectively, where
van der Waals forces govern the mechanical interface to the skin,
with minimal mechanical, mass or thermal load (FIG. 6A; 38 weeks
3/7 gestational age, 2.75 kg birth weight). The silicone
encapsulation also enables reliable operation of the systems when
completely immersed in water (FIGS. 8A-8B), thereby supporting
compatibility with NICU incubators commonly set at humidity above
80% to maintain temperature homeostasis and prevent dehydration in
premature neonates.
[0284] FIG. 6B illustrates the use in a mode that facilitates
physical contact between parent and child, which is difficult or
impossible to replicate with hard-wired conventional systems. FIG.
6C shows an alternative mounting location, where the ECG EES
resides on the back of the neonate to facilitate chest-to-chest
skin interaction, while highlighting the intimate contact with the
skin, even while naturally deformed and wrinkled. In FIGS. 6D-6E,
the sensor system is on a neonate admitted in the NICU,
highlighting intimate contact of the ECG EES to the skin, even with
motion and position adjustment. An additional example of
skin-to-skin contact in a chest-to-chest position is in FIG. 6E,
with the PPG EES on the upper limb to illustrate another option for
placement. Representative results of continuous recordings are in
FIG. 6F for the neonate presented in FIG. 6A. Calculated HR,
SpO.sub.2, and RR compare favorably against gold standard equipment
(Intellivue MX800, Philips). The temperature and PAT data appear
alone given the absence of a comparator system (FIG. 6G).
[0285] Concomitant deployment with standard of care monitors
(Intellivue MX800, Philips; Table 1) shows excellent agreement in
HR, RR, and SpO.sub.2 (FIGS. 7A-7C) in n=3 neonates ranging in
gestational age from 28 to 40 weeks admitted to the NICU. The mean
difference is -0.17 beats per minute for HR, 0.76 breathes per
minute for respiratory rate, and 1.02% for SpO.sub.2. Advanced
physiological parameters such as PAT and continuous differential
skin temperature are also shown (FIGS. 7D-7G). Additional studies
in n=18 neonates admitted in the NICU with gestational ages as low
as 28 weeks and weights as low as 1470 g, using related device
platforms with on-board power supply to facilitate testing, further
validate the operation and applicability across a large cohort of
subjects (FIGS. 49A-49C, Table 1) with excellent agreement with
gold-standard monitoring equipment (Intellivue MX800, Philips).
[0286] Beyond efficacy and safety, the eventual diffusion of
medical technologies depends on economic considerations. Table 2
outlines cost structures associated with all aspects of device
construction, ranging from components, to fabrication processing
fees and encapsulation materials. The results suggest costs (ECG
EES and PPG EES) of less than $20 USDs per unit at scaled
production. Full compatibility with autoclave sterilization (2540E,
Heidolph) enables safe re-use (FIGS. 43A-43D) and further improved
economics, with potential to facilitate deployment in low and
middle income countries in the context of global health.
TABLE-US-00001 TABLE 1 Clinical characteristics of neonates
admitted in the NICU and tested with the battery-free, dual EES
system using both battery-free modality (n = 3) and battery-powered
version (n = 18). Subject Gestational Age (Weeks) Ethnicity
Clinical Validation of Wireless, Battery-Free ECG EES and PPG EES
System in the Neonatal Intensive Care Unit 1 28 Hispanic 2 29
Caucasian 3 40 Asian Clinical Validation of Wireless,
Battery-Embedded ECG EES and PPG EES System in the Neonatal
Intensive Care Unit 1 41 Hispanic 2 34 South Asian 3 40 Caucasian 4
39 African American 5 36 African American 6 35 Caucasian 7 41
Caucasian 8 38 South Asian 9 37 Caucasian 10 38 Caucasian 11 34
Caucasian 12 34 Caucasian 13 40 Caucasian 14 33 Caucasian 15 33
Caucasian 16 28 Hispanic 17 36 African American 18 39 African
American
TABLE-US-00002 TABLE 2 Estimation of the costs of the ECG EES and
PPG EES. Component Cost Determination Passive Components $0.30 per
sensor given about 30 passive components per device at $0.01 per
passive component Active Components $3.79 per RF unit $3.19 for the
instrumentation amplifier (only ECG EES) $4.7 for
photodiode/LEDs/rectifier/buck converter (only PPG EES) $1.25 for
the voltage feedback amplifier Silicon PDMS $127.64 for 100 devices
Encapsulation (10 g/device) ($63.82/0.5 kg) (PDMS, Silbione)
Silbione $88.10 for 100 devices High Tack Silicone (5 g/device)
($39.95/8 oz) Gel. A-4717-1 Subtotal: $215.74 for 100 devices/$2.16
per device Ionic Liquid $2.58 per devices (0.7 g of ionic fluid per
device) Dual Copper Sheet $4.60 per device ($947/50 Sheets)
Cleanroom ($18/hr) $180 for 100 devices (10 devices/hr) Fabrication
Costs Harrick Plasma Cleaner $475 for 100 devices
(Photolithography, ($19/hr) (4 devices/hr) E-beam, RIE) Subtotal:
$6.55 per device Total $17.96 (ECG EES)/$19.47 (PPG EES) per
device
[0287] The battery-free, wireless power transfer strategies
described here offer advantages in form factor for extremely low
birth weight neonates less than 27 weeks of gestational age,
although the device requirements for proximity to a primary antenna
is less than ideal. Strategies that implement small batteries for
operation when wireless power is unavailable, or those that exploit
multiple primary antennas can be pursued. The devices may further
integrate additional sensors to measure parameters such as
transcutaneous CO.sub.2 and O.sub.2, ballistocardiography, motion
and crying time.
[0288] The NICU represents one of the most challenging environments
to develop new medical technologies given the extreme fragility of
the population, and the high acuity of care. The results reported
here follow from a collection of advances in engineering science,
to establish the basis for a wireless, skin-like technology that
not only reproduces comprehensive vital signs monitoring
capabilities currently provided by invasive, wired systems but that
also adds multi-point sensing of temperature and continuous
tracking of blood pressure. These sensors explicitly address the
unique needs of the NICU due to their high mechanical compliance
and non-invasive skin adhesive interface, their water resistance,
and their compatibility with essential medical imaging and
inspection. Further clinical validation and testing may lead to
broad adoption in both high-resource and low-resource settings.
[0289] Fabrication: the fabrication involves a combination of
semiconductor processing steps, lamination procedures, transfer
printing processes and chip placement and solder bonding. Addition
of a thin layer of PDMS layer bonded around the perimeter of the
device and the electrodes allowed filling with an ionic liquid
using a syringe to form the microfluidic channel. A coating of a
soft silicone material on the bottom layer provides a light
adhesive surface.
[0290] Sensor assessment: the primary antenna (size of 32
cm.times.34 cm; FIGS. 22A-22B) connected to the host system for
simultaneous transfer of RF power to the ECG EES and the PPG EES.
The low current consumption of these platforms (about 450 .mu.A and
5 mA as peak current, respectively) can be satisfied by RF power (5
W; compliant to EN 50364; standard for human exposure) at vertical
distances of up to 25 cm through biological tissues, bedding,
blankets, padded mattresses, wires, sensors and other materials
found in NICU incubators, and across lateral areas of 32
cm.times.34 cm, for full coverage wireless operation in a typical
incubator.
[0291] The primary antenna was pre-embedded within existing NICU
incubators. Sensors were placed on the skin without skin
preparation for the neonate thereafter. Data was transmitted,
collected, and stored for further data analysis on a table PC
(e.g., Surface Pro 4, Microsoft.RTM.).
Fabrication of the Metal Coil and Interconnectors and the
Microfluidic Channel
[0292] A double layered copper (Cu) foil (18/5 .mu.m thick, Oak
Mitsui MicroThin Series) provided the material for the NFC coil and
interconnectors (FIGS. 8A-8B). After lamination of this Cu foil
onto the PDMS (Sylgard 184, Dow-Corning; 10:1 weight ratio) coated
glass slide, with the 5 .mu.m thick Cu side down and 18 .mu.m side
up, the Cu foil was peeled off by hands. The NFC coil and
interconnectors was micro-patterned by photolithography
(photoresist AZ P4620, AZ Electronic Materials; spin-casting at
3000 rpm for 30 sec, soft baking on a hot plate at 110.degree. C.
for 3 min, UV irradiance for 500 mJ/cm.sup.2, and development for
about 50 sec with developer AZ 400K/DI water solution of 1:3 volume
ratio), and wet etching (CE-100 copper etchant, Transense; about 2
min with frequent rinsing by DI water). Photoresist was removed
with acetone, IPA, and DI water rinse. After the native Cu oxide on
the surface was eliminated by using oxide remover (Flux,
Worthington), electrical circuit components were assembled with
indium/silver soldering paste (about 130.degree. C., 1 min). The
whole area of the ECG EES and PPG EES was encapsulated by a low
modulus silicone elastomer after the second metal layer (e.g.,
bridge and red/IR LED part), the back side insulated by a thin PDMS
coating, was connected with the first metal interconnectors.
[0293] For the microfluidic channel, photolithography defined SU-8
mold (photoresist SU-8 2100, MicroChem; spin-casting at 3000 rpm
for 30 sec, soft baking on a hot plate at 65.degree. C. for 3 min
and 95.degree. C. for 20 min, UV irradiance for 380 mJ/cm.sup.2,
post exposure baking on a hot plate at 65.degree. C. for 3 min and
95.degree. C. for 10 min, development for about 20 min with SU-8
developer, IPA rinsed, and hard baking at 120.degree. C. for 30
min). Spin-casting polytetrafluoroethylene (PTFE, Sigma-Aldrich;
thickness of about 100 nm) at 3000 rpm for 30 sec and baking at
110.degree. C. for 5 min formed a thin antiadhesive layer on the
SU-8 mold. An additional spin casting on top of the mold and curing
at room temperature for 24 hours yielded a bottom PDMS (Sylgard
184, Dow-Corning; 10:1 weight ratio) substrate. Delamination from
the SU-8 mold allowed sample placement on a glass substrate with
the feature side facing up. Next, a thin film of a fluoropolymer (1
.mu.m, OSCoR 2312 photoresist solution, Orthogonal INC) spincast on
a PDMS substrate and then thermally annealed (50.degree. C. for 1
min) yields a low energy coating.
[0294] After exposure to oxygen plasma generated at low power (8.5
W) RF at 500 mTorr (Plasma Cleaner PDC-32G, Harrick Plasma) for 20
sec, the upper part (electronic layer encapsulated by PDMS) and the
lower part (thin PDMS layer with microfluidic channel) was aligned
and bonded. Finally, the bottom side was covered with a Silbione
layer and a syringe with a micro-needle injected a blended solution
(82:18, volume ratio) of ionic liquid (1-ethyl-3-methylimidazolium
ethyl sulfate [EMIM][EtSO.sub.4], Sigma-Aldrich) and silica gel
(high-purity grade, pore size 6 nm, 200-425 mesh particle size,
Sigma-Aldrich) into the microfluidic channel.
Mechanical Simulations
[0295] The commercial software ABAQUS (ABAQUS Analysis User's
Manual 2010, V6.10) was used to study mechanics of the devices and
to optimize the design layouts. The objectives are to ensure that
(1) the interfacial normal and shear stresses on the skin are below
the low somatosensory perception of the device on the human skin;
and (2) the strain in the copper layers is below the elastic limit
such that no plastic yielding occurs. The PDMS (elastic modulus 500
kPa and Poisson's ratio 0.5), Silbione (elastic modulus 3 kPa and
Poisson's ratio 0.5) and ionic liquid were modeled by hexahedron
elements (C3D8R) while the stiff copper (elastic modulus 119 GPa
and Poisson's ratio 0.34) film was modeled by composite shell
elements (S4R). The positions of the chips and the widths of
serpentine interconnects were optimized to satisfy the competing
requirements from mechanics and electromagnetical designs. For
example, narrow interconnects improve the elasticity
stretchability, but lead to the undesired increase in the
electrical resistance. An iterative optimization process was
adopted to carefully balance these competing requirements and other
mechanical and electromagnetical considerations. The positions of
the chips were optimized to avoid entanglement of interconnects and
contact between components. The minimum work of adhesive Gmin
required to prevent device delamination from the stretched skin was
also shown in FIG. 35. For stretching less than 20%, Gmin is small
such that the van der Waals force between the devices and skin is
enough to provide this adhesion (16 N/m), i.e., without the need of
any adhesives.
Electromagnetic Simulations
[0296] A finite element method was used in the electromagnetic
simulations to determine the inductance, Q factor and the
scattering parameters S11 of the ECG EES and PPS EES in undeformed
and deformed states. The simulations were performed using the
commercial software Ansys HFSS (Ansys HFSS 13 User's guide, Ansys
Inc. 2011), where the lumped port was used to obtain the scattering
parameters S11 and port impendence Z. An adaptive mesh (tetrahedron
elements) together with a spherical surface (1000 mm in radius) as
the radiation boundary, was adopted to ensure computational
accuracy. The inductance (L) and Q factor (Q) (shown in FIGS.
9A-9B) were obtained from L=Im{Z}/(2.pi.f) and Q=|Im{Z}/Re{Z}|,
where Re{Z}, Im{Z} and f represent the real and imaginary part of
the Z and the frequency, respectively. For 20% stretching of the
loop antennas of the ECG EES and PPG EES, the changes of the
inductance, Q factor and resonant frequency are less than 5% (FIGS.
17A-17C and 18A-18C). For bending radii >about 140 mm for the
chest and >about 50 mm for the foot, the inductance, Q factor
and resonant frequencies are approximately unchanged (FIGS. 12A-12C
and 13A-13C).
Simulation for Peel Test
[0297] The commercial software ABAQUS (ABAQUS Analysis User's
Manual 2010, V6.10) was also used to study peel force of
conventional adhesive (elastic modulus 5 MPa and Poisson's ratio
0.5), and EES adhesive with/without the ionic liquid layer (FIGS.
25A-25C), and with different patterns of holes (FIGS. 27A-27D). The
adhesion energy of the interface between the phantom skin and
EES/conventional adhesives obtained from experiments were 16 N/m
and 175 N/m, respectively. The cohesive strengths .sigma..sub.0
were estimated as 20 kPa and 50 kPa for the EES adhesive and
conventional adhesive, respectively, from FIG. 2E. The peeling
velocity was 0.53 mm/s, from experiments. The cohesive zone model
is shown in FIG. 23.
Simulations of Electromagnetics Associated with MRI Imaging
[0298] The finite element method was used to determine the magnetic
fields. The simulations were performed using a commercial software
(Ansys HFSS 15 User's guide, Ansys Inc. 2012), where adaptive mesh
(tetrahedron elements) together with a spherical surface (2000 mm
in radius) as the radiation boundary, was adopted to ensure
computational accuracy. The in-plane gradient of the magnetic field
density underneath the electrodes (FIGS. 3A and 3E) was obtained
from
|.gradient.pB|=[(.differential.B/.differential.x).sup.2+(.differential.B/-
.differential.y).sup.2].sup.1/2 and
|.gradient..sub.zB|=|.differential.B/.differential.z| with a
working frequency of 128 MHz, where B is the magnitude of the
magnetic field density, and x, y, z, are the orthogonal coordinates
of in the electrode plane.
Simulations for Thermal Load of EES Sensors
[0299] The commercial software ABAQUS (ABAQUS Analysis User's
Manual 2010, V6.10) was used to study the temperature change of the
skin for one-time MRI scan. The oscillating magnetic field density
in MRI is B=20 .mu.T, and the working time for one-time scan of MRI
is 0.5 ms. The received power of the ECG EES from the
electromagnetic simulation is imported into ABAQUS for thermal
analysis. The convective heat transfer coefficient of air is 6
W/(m.sup.2K). Except for Cu, the hexahedron elements (DC3D8) were
used, whereas thin Cu layer was modeled by the shell elements
(DS4). The minimal mesh size was 1/10 of the thickness (10 .mu.m)
of the ionic layer, and the mesh convergence of the simulation was
ensured. The thermal conductivity, heat capacity and mass density
used in the simulations are 0.35 Wm.sup.-1K.sup.-1, 2135
Jkg.sup.-1K.sup.-1 and 1490 kgm.sup.-3 for the skin; 0.15
Wm.sup.-1K.sup.-1, 1510 Jkg".sup.1K.sup.-1 and 1000 kgm.sup.-3 for
PDMS; 0.15 Wm.sup.-1K.sup.-1, 2200 Jkg".sup.1K.sup.-1 and 1100
kgm.sup.-3 for ionic liquid; 0.15 Wm.sup.-1K.sup.-1, 1460
Jkg.sup.-1K.sup.-1 and 970 kgm.sup.-3 for Silbione; and 386
Wm.sup.-1K.sup.-1, 383 Jkg.sup.1K.sup.-1 and 8954 kgm.sup.-3 for
Cu, respectively.
Example 2
Advanced Physiological Monitors for Neonatal Care
[0300] The apparatuses and methods provided herein have
applications including, but not limited to: critical care
monitoring in neonatal intensive care units; critical care
monitoring in pediatric intensive care units; critical care
monitoring in neonatal/pediatric cardiac care units; critical care
monitoring in neonatal/pediatric neocritical care units;
post-discharge home monitoring for high-risk neonates; critical
care monitoring in adults; home monitoring for medical recovery;
and monitoring for rehabilitation care.
[0301] The advantages of the apparatuses and methods include
foundational concepts of skin-like, multi-modal sensors enabled by
advances in in-sensor analytics and time-synchronized, multi-nodal
wireless operation. This offers the ability to significantly
improve the efficacy and safety of vital signs monitoring for
newborns in neonatal intensive care units.
[0302] Ultra-low noise operation enables capture of low-power
physiological signals such as fetal heart rate or miniscule
movements of the chest wall reflective of breathing in a premature
neonate.
[0303] Apparatuses may include two separate but software linked
(e.g., "electronically-coupled") sensor systems: a chest-deployed
unit with ECG, skin temperature, and seismocardiograhy, and a
limb-based unit with photoplethysmography for pulse oximetry.
[0304] Further embodiments include the deployment of multiple
sensors at various locations dependent on the clinical use case.
For instance, during skin-to-skin or "kangaroo care" where a baby
is placed on the mom's chest, the ECG sensors can be placed on the
back or flank of the neonate.
[0305] Advanced software function and interoperability enabling
cloud storage, remote login, and secure communication. Further
capabilities include the integration of third-party sensors,
wearables, and other hardware systems.
[0306] Design features that enable immediate deployability in NICUs
include: Radiolucency that is compatible to CT and XR imaging; MRI
compatibility; and optically transparent design allows for clinical
evaluation of the skin directly beneath sensor negating the need
for removal that can be damaging to fragile skin.
[0307] Safety features that drastically decrease the risk of
iatrogenic injury and support therapeutic skin-to-skin contact
include: The soft, mechanical nature of the sensor itself enables
intimate skin coupling without the need of powerful adhesives. The
removal of traditional electrodes and sensors with adhesives lead
to skin stripping and iatrogenic injuries including permanent
scarring. The devices and systems provided herein exhibit peel
forces orders of magnitude lower than existing systems. Soft, thin,
wearable nature allows for skin-to-skin contact that is
unobstructed between mother and baby.
[0308] Advanced physiological monitoring capabilities that exceed
current standard of care capabilities includes: continuous
measurement of skin temperature at multiple locations of the
neonate; thus, this allows for the development of novel metrics of
peripheral perfusion; lows for calculation of pulse arrival time
and pulse transit time--these measures are surrogate markers of
blood pressure but can be measured continuously and non-invasively.
A high-frequency 3-axis accelerometer within the sensor system can
be placed directly on the chest enabling continuous, wearable
seismocardiography (SCG) of neonates. This enables continuous
recording of heart sounds, and assessment of chest wall movements
with breathing for more accurate respiratory rate. The apparatuses
may enable correlation of SCG with stroke volume and ejection
fraction measured by echocardiography. The accelerometer also
allows analysis of a baby's position including when a baby is
upright. This can be used to quantify important parameters such as
how long a baby is being held for kangaroo care, being fed,
resting, crying and the like. The output of the sensor can be used
to determine whether a baby has sustained an injury that is
consistent with non-accidental trauma (e.g., child abuse).
[0309] The multi-nodal (and multi-modal) aspect of the devices
provided herein facilitate at least dual measurement systems to
capture accurate respiratory rate. The measurement of respiratory
rate derived through the ECG via impedance pneumonography is often
times inaccurate and overestimates the true respiratory rate.
Herein, we describe the ability to measure chest wall movement to
derive respiratory rate along with traditional impedance
pneumonography.
[0310] Each sensor system may have a form factor in a patch-like
geometry that occupies a small surface area (less than 2.0
cm.times.4.0 cm) that facilitates placement on a premature
neonate.
[0311] Embodiments include: where the form factor includes a single
chest unit sensor with all electronics and vital sign monitoring
functionality; where the electrode spacing or sensor elements are
adjustable; the ability to create alarms based on pre-programmed or
physician specified inputs. These alarms include both visual and
audio notifications. These notifications can be displayed on an
external display unit or onboard the sensor itself (either via an
onboard LED or sound).
[0312] A sensor system having an optical unit for the
photoplethysmograph may be located on the infant's nail (toenail or
fingernail).
[0313] The sensors may be wrapped circumferentially around a limb
or body structure and fastened with a mechanical mechanism (e.g.,
hook in loop, clasps, buttons, magnets).
[0314] Embodiments include where the pulse oximeter unit is placed
on various locations of the body to derive a measure location
specific pulse oximetry. Locations include, but are not limited to,
all 4 limbs, chest, back, abdomen, forehead.
[0315] Embodiments include where the same power management and
antennae schema is applied to Bluetooth rather than NFC.
[0316] Embodiments include the sensors having an onboard
battery--but wireless charging is implemented in instances where a
wireless power source is detected which simultaneously powers the
sensor and charges the battery.
[0317] Here we report foundational concepts for a wireless,
battery-free vital signs monitoring system that exploits an at
least bi-nodal pair of ultrathin, low-modulus measurement modules,
each referred to here as an epidermal electronic systems (EES),
capable of gently and non-invasively interfacing onto the skin of
neonates, even at gestational ages that approach the limit of
viability. The materials choices and device architectures leverage
the most advanced concepts in soft electronic systems, with modes
of operation that follow from four essential advances reported
here: (1) techniques for simultaneous wireless power transfer, low
noise sensing and data communications via a single link based on
magnetic inductive coupling at a radio frequency band that has
negligible absorption in biological tissues, (2) efficient
algorithms for real-time data analytics, signal processing and
dynamic baseline modulation implemented in the highly constrained
computing resources available on the sensor platforms themselves,
(3) strategies for time-synchronized, continuous streaming of
wireless data from two, separately located devices and (4) fully
transparent and radiolucent designs that enable visual inspection
of underlying tissue of the skin interface, and magnetic resonance
(MRI) and X-ray imaging (XR) of the neonate. The resulting systems
are qualitatively smaller in size, lighter in weight and less
adhesive to the skin than clinical standard hardware, with
potential for costs that are orders of magnitude lower. Other
embodiments of the sensor include the coupling of Bluetooth
communication and small embedded batteries.
[0318] FIG. 1B presents schematic representations of the two
wireless, EES that, when used together in a time-synchronized
fashion, constitute an overall bi-nodal platform capable of
reconstructing full vital signs information. The electronic layer
in each EES incorporates a collection of thin, narrow serpentine
metal traces (Cu, 50-100 .mu.m in width, 5 .mu.m in thickness) that
interconnect multiple, chip-scale circuit components, including
passives (resistors, capacitors, inductors) and actives (infrared
and red light emitting diodes (LEDs), photodiodes (PDs),
system-on-a-chip (SoC) components with power harvesting, radio
frequency (RF) communication, microcontroller, analog-to-digital
conversion and general input/output functionality). One EES mounts
on the chest to record electrocardiograms (ECGs; FIG. 1B top panel)
through skin-interfaced electrodes that consist of filamentary
metal mesh microstructures in fractal geometries; the other mounts
on the base of the foot to record photoplethysmograms for pulse
oximetry (PPGs; FIG. 1B bottom panel) by reflection mode optical
measurements. A microfluidic chamber filled with a non-toxic ionic
liquid (1-ethyl-3-methylimidazolium ethyl sulfate
[EMIM][EtSO.sub.4], Sigma-Aldrich) between the electronics and the
lower encapsulation layer mechanically strain-isolates the system
from the fragile skin of the neonate. In addition to the
electronics, each EES incorporates a magnetic loop antenna
(inductance, Q-factor, and S11 at 13.56 MHz are 3.88 .mu.H, 10.65,
and -26.54 for the ECG module and 0.84 .mu.H, 7.12, and -23.07 for
the PPG module, respectively) tuned to compliance with NFC
protocols, and configured to allow simultaneous wireless data
transmission and wireless power delivery through a single link. The
low conductivity of the ionic liquid allows stable electrical
operation in this RF environment. The resulting bi-nodal system
captures and continuously transmits ECG, PPG and skin temperature
(from each EES), HR, heart rate variability (HRV), RR, SpO.sub.2
and a surrogate of systolic blood pressure (BP), as discussed
subsequently.
[0319] The images shown in FIG. 1C highlight the overall size and
the ultrathin, soft form factor of these systems. Stretching the
ECG EES uniaxially by up to 15% (FIG. 1D) induces interfacial
normal and shear stresses on the skin that lie below the threshold
for human sensation (about 20 kPa). Similarly low levels of stress
result from stretching of the PPG EES up to 13%. In both cases,
deformations result in strains in the electronics and antenna
structures that are beneath the limits for plastic deformation
(about 0.3%). The thin geometry, exceptionally low modulus
mechanics and minimal interfacial stresses enable reliable coupling
to the skin of the neonate based on weak, van der Waals forces
alone, thereby eliminating the need for skin adhesives. FIG. 1E
shows pictures of the PPG EEG with red LED activated, captured with
and without external illumination.
[0320] Because the standard NFC protocol at 13.56 MHz supports only
low speed, low fidelity applications in contactless payments,
wireless identification and others, significant optimization is
necessary in both the transponder and host reader systems at
ISO15693 to enable required data transfer rates for NICU monitoring
(hundreds of Hz). These optimizations enable continuous streaming
of data at rates of up to 800 bytes/s with dual channels, which is
orders of magnitude larger than previously reported NFC sensing
devices and represents a first example of bi-nodal,
time-synchronized operation. A key is in minimizing the overhead
associated with transfer by packaging data into 6 Blocks (24 Bytes)
in a circular buffer. Here, reading occurs with an NFC host
(LRM1002, Feig Electronics) interfaced to a microcontroller (MCU,
ARM.RTM. Cortex.TM.-M4F) in a Bluetooth Low Energy (BLE) system
(SoC, nRF52832, Nordic Semiconductor) configured this type of
customized circular buffer decoding routine. The receiver antenna
(size of 32 cm.times.34 cm) connects to the host system for
simultaneous transfer of RF power to the ECG EES and the PPG EES.
The low current consumption of these platforms (about 450 .mu.A and
2 mA as peak current, respectively) can be satisfied by RF power (5
W; compliant to EN 50364; standard for human exposure) at vertical
distances of up to 25 cm, through biological tissues, bedding,
blankets, padded mattresses, wires, sensors and other materials
found in NICU isolettes, and across lateral areas of 32 cm.times.34
cm, for full coverage wireless operation in a typical incubator.
The BLE radio allows transmission of data to a personal computer,
tablet computer or smartphone with a range of up to 20 m. Further
software embodiments would enable direct communication and
telemetry with legacy systems in the NICU including electronic
medical records.
[0321] In-sensor processing and data analytics further reduce
bandwidth requirements on wireless transmission and greatly improve
the robustness in operation. For example, computational facilities
on the NFC SoC of the ECG EES can support a streamlined version of
the Pan-Tompkins algorithm for accurate, on-board analysis of the
QRS complex of ECG signals in real-time to yield HR, HRV, and RR on
a beat to beat basis. FIG. 50A summarizes an approach that starts
with a finite impulse response (FIR) digital bandpass filter (fc1=5
Hz, fc2=15 Hz) to attenuate the noise outside the passband.
Differentiating and squaring the resulting data yields the slope of
QRS peaks and prevents false peak detection associated with the T
wave. Applying a moving average (N=30) and a dynamic threshold
identifies a running estimate of the R peak and the magnitude of
the noise. Automatic adjustments of the threshold rely on these
estimates for the preceding beat cycle. The R to R intervals
determined in this way yield the instantaneous HR. Simultaneous
recordings obtained using a clinical standard system, henceforth
referred to as `gold` standard data, validate the ECG module
hardware and in-sensor analytics, per measurements on a healthy
adult volunteer (FIGS. 50B-50C). The ECG signals and computed HR
values from these two platforms show no measurable differences.
Periodic modulations of the amplitude of the R peak define the RR
(FIG. 50D), which also agrees with the gold standard (visual
counting by a physician in this case; FIG. 50E).
[0322] Measurements of skin temperature rely on sensors internal to
the NFC SoC in each EES, where transmission at a sampling frequency
of 1 Hz is sufficient for monitoring purposes. The exceptionally
low thermal mass of the EES and the small thickness of the
substrate layer (PDMS; 50 .mu.m in thickness) that separates the
SoC from the skin ensure fast thermal response times and excellent
thermal coupling, respectively. Comparisons against readings from
an FDA-approved thermometer serve as means to calibrate the sensor
(FIG. 50F) via testing in a water bath. Thermal images captured
with an IR camera (FLIR A325SC, FLIR Systems) during operation
indicate negligible heating associated with the electronics or the
antenna structures (FIG. 50G). FIG. 50H shows temperature readings
from ECG EES for 60 seconds after calibrated against thermometer.
Simultaneous measurements of temperature on the chest and foot,
which follow naturally from the bi-nodal nature of the system, can
be clinically important as described subsequently.
[0323] The PPG EES relies on similar NFC protocols, but with
in-sensor analytic methods that not only reduce requirements on
transmission bandwidth but also provide, when used in conjunction
with adaptive circuits, crucial functionality for stable operation.
Specifically, the processing in this case enables (i) dynamic
baseline control to ensure that the input to the ADC on the NFC SoC
lies within the linear response range and (ii) real-time
calculation of SpO.sub.2 from the PPG traces (FIG. 51A). Here, the
processing begins with application of a moving average filter
(N=15; 100 ms) to the photodetector response from the red and IR
LEDs. When the larger of these two averaged PPG amplitudes,
typically that associated with the IR response, lies outside
boundary at the voltage of 0.2 V and 0.7 V, a programmable
difference amplifier (FIG. 51B) with voltage dividers at V+
dynamically controls the baseline level according to:
V.sub.tr=-Z.sub.fi.sub.PD+(1+Z.sub.f/R.sub.s)V.sub.+=-R.sub.f/((jwR.sub.-
fC.sub.f+1))i.sub.PD+(1+R.sub.f/R.sub.s)V.sub.+ (4)
where V.sub.tr is output of the amplifier, Z.sub.f is impedance of
feedback loop, R.sub.s is series resistance, C.sub.f is feedback
capacitor, R.sub.f is feedback resistor, i.sub.PD is current output
of photodiode and,
V.sub.+=V.sub.ddR.sub.d2/(R.sub.d2+a2(4R.sub.g+R.sub.d1)+a1(2R.sub.g+R.s-
ub.d1)+a0(R.sub.g+R.sub.d1)). (5)
[0324] Four different baseline levels can be accessed via
activation of three GPIO outputs (a0, a1, a2). FIG. 51C shows
dynamic control of the output voltage (VADC) of a sinusoidal input
signal (frequency=50 mHz, amplitude=35 mV, V.sub.offset=-30 mV).
Starting with the default setting (LV3), the baseline level
automatically adjusts to lower levels associated with VADC above
the boundary, and vice versa with VADC below it, thereby
maintaining VADC in an allowed range. FIG. 51D summarizes the
operation in an actual PPG recording. Without this type of
real-time, in-sensor processing (IR.sub.Non in FIG. 51D) robust
operation would be impossible: PPG signals would quickly drift
outside of the narrow operating range of the ADC due to
patient-to-patient variations in skin pigmentation and unavoidable,
time-dependent fluctuations in optical scattering that result from
micromotions relative to underlying blood vessels and subdermal
structures.
[0325] Calculating SpO.sub.2 involves determining the ratio
(R.sub.oa) between the alternating component and the direct
component of PPG signals according to the following equation
R.sub.oa((AC.sub.RED)/DC.sub.RED)/(AC.sub.IR/DC.sub.IR) (6)
for data from the red and IR LEDs (FIG. 51E). A peak detection
algorithm plays a central role in determining the peak and valley
points for accurate calculation of R.sub.oa. Peaks and valleys
correspond to the locations at which the slope turns from positive
to negative and vice versa, respectively. A 200 ms refractory
period imposed after detection of a peak prevents false negatives
from the dicrotic notch feature characteristic of normal PPG
waveforms. An empirical calibration formula determined by
comparison to a gold standard measurement (MightySat Fingertip
Oximeter, Masimo) converts the R.sub.oa to SpO.sub.2 (FIG. 51F).
Time dependent variations of SpO.sub.2 determined in this manner
appear in FIG. 51G. The rapid drop and recovery result from a
breath hold.
[0326] The time synchronized outputs from the ECG EES and the PPG
EES allow determination of the pulse arrival time (PAT), as defined
by the time lapse between the maximum fiducial point in the ECG
signal (R peak) and the corresponding minimal fiducial point in the
PPG signal at valley as in (FIG. 51H). Literature studies support a
quantitative correspondence between PAT and systolic BP.
Specifically, the Moens-Korteweg equation provides a linear
relationship between PAT and BP. For real-time data analysis,
processing of ECG and PPG data in the host (i) time-stamps each
wirelessly transmitted data point with the local clock of each EES,
where these local clocks sync with a global clock based on the
high-frequency clock of the BLE SoC, thereby providing time
synchronization (ii) applies a cubic spline interpolation to the
ECG and PPG data to obtain an equivalent 1 kHz version for improved
timing accuracy, (iii) computes time differences to yield PAT
values for each beat cycle and (iv) imposes a moving average on
these PAT values over a 1-minute period to reduce the noise.
Measurements of 1/PAT performed in this manner, together with
corresponding values of systolic BP captured using a
sphygmomanometer on a healthy subject during a period of rest after
exercising (running at 6 miles per hour for 15 minutes), exhibit
the expected linear relationship (FIG. 51I). A calibration plot
with a linear fit appears in FIG. 51J.
[0327] A full demonstration of the wireless bi-nodal system on a
neonate (38 wks 3/7, 2.75 kg) validates the performance a clinical
environment. Here, the NFC antenna for power transfer and data
communication lies beneath the mattress inside an incubator (FIG.
6A). An ECG and a PPG EES softly mount on the chest and the dorsum
of the foot, respectively, where van der Waals forces govern the
mechanical interface to the skin, with minimal mechanical, mass or
thermal load (FIG. 6A). FIG. 6B demonstrates use in a mode that
facilitates skin-to-skin contact between parent and child, as a
form of therapeutic touch that is nearly impossible to replicate
with hard-wired conventional systems. FIG. 6C shows an alternative
location of an ECG EES on the back of a neonate to demonstrate
another mounting locations to promote skin-to-skin interaction. The
magnified image in FIG. 6D highlights the intimate contact with the
skin while naturally deformed and wrinkled. Results of continuous
recordings are in FIG. 6E. FIG. 6E demonstrates deployment of a PPG
EES on back of hand for a neonate with dark skin color. Calculated
HR, SpO.sub.2, and RR compare favorably against gold standards. The
temperature and PAT data appear alone due to the absence of a
temperature probe or arterial line during the experiments (FIG.
6G). Sphygmomanometer cuffs represent a direct risk for
pressure-related injuries in premature neonates and are highly
inaccurate in low-birth weight neonates. Measurements of
temperature are typically limited to a single body location due to
the need to minimize wired connections and adhesive interfaces to
the skin. The bi-nodal configuration of the system presented here
naturally yields not only a surrogate marker of BP but also
temperatures at two different locations (trunk and limb), to
improve monitoring for hypothermia and provide a noninvasive method
to track peripheral perfusion. Additional demonstrations in the
NICU with related devices indicate similar performance on neonates
with gestational ages as low as 28 weeks and weights as low as 1470
g.
[0328] FIG. 52A demonstrates important user-centric design aspects
that enable the ECG EES and PPG EES to operate seamlessly within
NICUs. The greatest risk of skin stripped is secondary to adhesives
removal of electrodes--our experimental results suggests that the
van der Waals adhesion forces that still allow for intimate skin
coupling are 20 times weaker than those associated with
conventional NICU adhesives (FIG. 52B). The drastically lower peel
forces associated with the removal of the ECG EES and PPG EES
presented here would dramatically reduce the risk of skin-related
iatrogenic injuries. Medical imaging, and direct nursing and
physician evaluation of skin integrity are standard, essential
procedures in the NICU. The optical transparency provides nurses
and physicians with direct visual access to the skin and tissue
beneath the sensor (FIG. 6D) without the need for removal as a
routine means to examine for signs of infection or skin breakdown.
The elimination of wires, which are radiopaque, improves the
evaluation of X-ray images, which are required for 90% of low-birth
weight neonates. MRI-compatibility is an additional important
design consideration, as this imaging modality enables precise
assessment of white matter, gray matter, and posterior fossa
abnormalities, with functional capabilities that exceed those of
ultrasound. FIGS. 52C-52D show the MRI images in sagittal and axial
planes, respectively. When the ECG EES is placed overlying
cadaveric chicken tissue in a clinical MRI system (7 T MRI Bruker
PharmaScan MRI system), there were no observable magnetically
induced displacement force and torque, or measurable levels of
RF-induced heating--these features are required by the FDA to
enable an "MRI-safe" label. (Adding information for X-ray and CT in
the future). The encapsulation within a silicone elastomer enables
operation even when completely immersed in water--this allows for
full functionality when operating in a neonatal incubators that are
commonly set at >80% humidity or higher to maintain temperature
homeostasis and prevent dehydration in premature neonates.
[0329] A hardware modification for further enhancement in
functionality including 6-axial inertial movement unit (IMU;
3-axial accelerometer and 3-axial gyroscope; BMI160, Bosch
Sensortec), a Bluetooth SoC with 32-bit ARM Cortex-M4F
microprocessor (nRF52832, Nordic Semiconductor), and on-board flash
memory (S25FS512, Cypress). FIG. 1I shows the schematic of the
hardware modification. The IMU unit enables seismocardiography on
the chest when deployed in the ECG EES, thereby providing
mechano-acoutic information of the heart including heart sounds for
echocardiogram and periodic vibration from breathing for accurate
respiratory rate. Deployed in the PPG EES, the IMU serves as a
feedback-controlled motion artifact reduction algorithm to
compensate the vulnerability of PPG signals being prone to motion
artifact. Acceleration and orientation information obtained from
two IMUS on the chest and foot, respectively, provides posture
information of baby. The posture pattern accessed from the IMU is
further analyzed through machine learning based algorithm to
identify Kangaroo Mother Care (KMC). The ECG EES also enables
maternal/fetal measurement from both fetal electrocardiography
(fECG) and mechano-acoustic movement of fetus. The algorithm for
fECG extraction is based on singular value decomposition that
compares the pattern weights in raw ECG signal. The maternal ECG
corresponds to the greatest weight, while the fetal ECG the second
greatest. After identifying peaks of maternal ECG (mECG) and weight
pattern is obtained by singular value decomposition, fECG can be
isolated by removing components having the greatest pattern values.
Mechano-acoustic movement of fetus can also give fetal heart rate
(fHR).
[0330] While certain embodiment of the sensor systems are purely
wirelessly powered, other embodiments of the sensor systems with
onboard power when a neonate or infant is moved away from the
inductive antennae are disclosed. Furthermore, a hardware
modification is also disclosed to include a secondary power supply
plan using a small battery embedded in the sensors through power
supply and management units with three mechanisms: (1) charging
battery when wireless power transfer (WPT) is activated, sensed
through WPT sensing circuit, (2) activating primary power source
through WPT that continuously supplies power to the sensors via
full wave rectifier and voltage regulator, (3) activating secondary
power supply based battery when wireless power transfer is not
sensed. Extremely low-power nature of our sensors is achieved by
optimizing power management using both on-board memory and
down-sampled real-time wireless transmission such that the raw data
is stored into flash memory while power demanding real-time
transmission event is effectively duty cycled to minimized power
consumption without loss of signal quality. The outcome is
facilitating 24-hour battery power operation using small
non-magnetic embedded battery (12 mAh, 9 mm.times.9 mm.times.3 mm
(W.times.L.times.H)) without affecting the overall dimension or
thickness of the sensor significantly.
[0331] FIG. 53 shows the underlying software enables
interoperability with third party platforms, according to one
embodiment of the invention. Further capabilities include cloud
storage in a HIPAA complaint manner. The receiver may be a tablet,
smartphone, or existing vital signs monitor.
[0332] Also, further software innovations to the sensor systems
according embodiments of the invention distinguish this invention
from prior works. Currently, the wireless sensors each communicate
via Bluetooth Low Energy (BLE) with mobile devices (e.g.,
Microsoft.RTM. SurfacePro and Samsung.RTM. smartphones). Software
enables continued transmission of captured data to a cloud-based
server. The cloud will decouple a neonate's data from the mobile
devices by centralizing the data with an HIPAA-compliant data
storage (Amazon Simple Storage) and database (Amazon Relational
Database). It will also provide opportunities to integrate with
existing systems including Electronic health record (EHR) and
Hospital information system (HIS) with GE Healthcare MUSE eDoc
Connect. By utilizing the cloud's computation nodes with
General-purpose computing on graphics processing units (GPGPU) and
Field-programmable gate array (FPGA), the platform can perform
accelerated real-time analytics and machine learning, and provide a
base to do distributed computation on cloud clusters with big-data
engines such as Apache Spark. By developing interfaces to the
server via Representational State Transfer (REST) Application
programming interface (API) and web interface, authorized doctors
and researchers will have a secure remote access to the data and
tools to execute post-hoc analysis. Relevant parameters for
in-clinical care use include 24-hour battery power operation, cloud
integration, and a web-interface.
[0333] FIG. 54 shows an example of a user interface, according to
one embodiment of the invention. Wireless wearable sensors that are
discoverable are shown on the left panel. Beyond the sensors
themselves, our user interface and base displays can also be used
to deliver therapeutic benefit. For instance, musical therapy has
been shown to be beneficial to neonatal brain development and
neonatal stress relief. Existing displays and monitoring systems
are only capable of alarms. Also available on the user interface is
an avatar that can depict the patient position, such as on the
back, side or front.
[0334] The foregoing description of the exemplary embodiments of
the present invention has been presented only for the purposes of
illustration and description and is not intended to be exhaustive
or to limit the invention to the precise forms disclosed. Many
modifications and variations are possible in light of the above
teaching.
[0335] The embodiments were chosen and described in order to
explain the principles of the invention and their practical
application so as to activate others skilled in the art to utilize
the invention and various embodiments and with various
modifications as are suited to the particular use contemplated.
Alternative embodiments will become apparent to those skilled in
the art to which the present invention pertains without departing
from its spirit and scope. Accordingly, the scope of the present
invention is defined by the appended claims rather than the
foregoing description and the exemplary embodiments described
therein.
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