U.S. patent application number 15/697264 was filed with the patent office on 2018-03-15 for system of injectable fully-monolithic wireless bio-sensing.
The applicant listed for this patent is Verily Life Sciences LLC. Invention is credited to Peng Cong, Alireza Dastgheib, Sean Korhummel, Stephen O'Driscoll, Kannan Sankaragomathi, Jiang Zhu, You Zou.
Application Number | 20180075267 15/697264 |
Document ID | / |
Family ID | 61558759 |
Filed Date | 2018-03-15 |
United States Patent
Application |
20180075267 |
Kind Code |
A1 |
O'Driscoll; Stephen ; et
al. |
March 15, 2018 |
SYSTEM OF INJECTABLE FULLY-MONOLITHIC WIRELESS BIO-SENSING
Abstract
Systems are provided for a wireless system-on-chip (SoC) with
integrated antenna, power harvesting, and biosensors. An
illustrative SoC can have a dimension of 200 .mu.m.times.200
.mu.m.times.100 .mu.m to allow painless injection. Such small
device size is enabled by: a 13 .mu.m.times.20 .mu.m 1 nA current
reference, optical clock recovery, low voltage inverting dc-dc to
enable use of higher quantum efficiency diodes, on-chip resonant
antenna, and an array-scanning reader.
Inventors: |
O'Driscoll; Stephen; (San
Francisco, CA) ; Zou; You; (Redwood City, CA)
; Korhummel; Sean; (San Carlos, CA) ; Cong;
Peng; (Burlingame, CA) ; Sankaragomathi; Kannan;
(San Mateo, CA) ; Dastgheib; Alireza; (Mountain
View, CA) ; Zhu; Jiang; (Cupertino, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Verily Life Sciences LLC |
South San Francisco |
CA |
US |
|
|
Family ID: |
61558759 |
Appl. No.: |
15/697264 |
Filed: |
September 6, 2017 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62393078 |
Sep 11, 2016 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/14532 20130101;
A61B 5/1473 20130101; G06K 19/07773 20130101; A61B 2562/028
20130101; H02M 3/07 20130101; A61B 2560/0219 20130101; G06K 19/0709
20130101; A61B 5/0031 20130101; G06K 7/10316 20130101 |
International
Class: |
G06K 7/10 20060101
G06K007/10; H02M 3/07 20060101 H02M003/07; G06K 19/07 20060101
G06K019/07; G06K 19/077 20060101 G06K019/077 |
Claims
1. A system-on-chip (SoC) sensing system, the system comprising: a
measurement reader having at least one reader antenna for
transmitting a signal to a SoC, the measurement reader being not
located on the SoC; and the SoC comprising: a receiving antenna for
receiving the signal transmitted from the at least one reader
antenna; a power supply subsystem powered by the signal received by
the receiving antenna, the power supply subsystem comprising a
plurality of diodes; a clock recovery subsystem powered by the
signal received by the receiving antenna, the clock recovery system
comprising a set of diodes; and a sensor subsystem, the sensor
subsystem generating a digital signal for modulating the signal
transmitted by the measurement reader
2. The system of claim 1, wherein the sensor subsystem includes an
electrochemical sensor.
3. The system of claim 1, wherein the sensor subsystem includes a
light sensor.
4. The system of claim 1, wherein the sensor subsystem includes a
capacitance sensor.
5. The system of claim 1, wherein the SoC has a dimension equal to
or less than 200 .mu.m.times.200 .mu.m.times.100 .mu.m.
6. The system of claim 1, wherein the SoC is injected into a skin
at a depth ranging from about 1 mm to about 4 mm.
7. The system of claim 1, wherein the power supply include a charge
pump.
8. The system of claim 1, wherein the SoC further comprising a
current reference having a switched capacitor reference.
9. The system of claim 1, wherein the SoC further comprising a
DC-to-DC low voltage converter.
10. The system of claim 1, wherein the signal transmitted by the
measurement reader is an optical signal in a range of radio
frequency.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is related to and claims the benefit
of priority of U.S. Provisional Application No. 62/393,078, filed
Sep. 11, 2016, entitled "SYSTEM OF INJECTABLE FULLY-MONOLITHIC
WIRELESS BIO-SENSING", the full disclosure which is incorporated
herein in its entirety.
BACKGROUND
Technical Field
[0002] The present disclosure generally relates to the field of
systems for system-on-chip (SoC). More particularly, and without
limitation, the disclosed embodiments relate to systems for
injectable wireless smart sensing SoC.
Background Description
[0003] A SoC generally refers to an integrated circuit (IC) that
integrates all components of a computer or other electronic system
into a single chip. The SoC may comprise digital, analog,
mixed-signal, and/or radio-frequency functions that are all on a
single chip substrate. SoCs have various applications including
mobile electronics, medical devices, and bio-sensing.
[0004] As an exemplary application, SoCs may be used to monitor
health metrics of a person and/or animal. Conventionally, for
example, skin hydration and body glucose levels have been monitored
using needles in the skin because the skin is a vital organ from
which many health metrics may be garnered. But, those needles can
cause discomfort and impinge on users' lifestyle.
SUMMARY
[0005] There is a need for systems and methods for ongoing
monitoring that need to be unobtrusive and not require or reduce
maintenance. To this end, monolithic injectable wireless smart
sensing SoCs according to the present disclosure may fulfill these
requirements. The embodiments of the present disclosure provide
systems for SoC bio-sensing. According to an exemplary embodiment
of the present disclosure, the system may include: an SoC, and a
measurement reader having at least one reader antenna for
transmitting a signal to the SoC. In an illustrative embodiment,
the measurement reader is not located on the SoC. The SoC in some
embodiments may comprise: a receiving antenna for receiving the
signal transmitted from the at least one reader antenna; a power
supply subsystem powered by the signal received by the receiving
antenna; a clock recovery subsystem powered by the signal received
by the receiving antenna; and a sensor subsystem. In exemplary
embodiments, the power supply subsystem may include a plurality of
diodes. Further, the clock recovery subsystem in some embodiments
may include a set of diodes. And the sensor subsystem may generate
a digital signal for modulating the signal transmitted by the
measurement reader antenna.
BRIEF DESCRIPTION OF THE DRAWINGS
[0006] FIG. 1 shows a schematic representation of a monolithic
injectable bio-sensing system according to embodiments of the
present disclosure.
[0007] FIGS. 2A-2D show testing of diodes and a schematic
representation of a charge pump circuitry used in the system of
FIG. 1, according to embodiments of the present disclosure.
[0008] FIGS. 3A-3C show a schematic representation of a clock
recovery circuitry used in the system of FIG. 1, according to
embodiments of the present disclosure.
[0009] FIGS. 4A-4D show schematic representations of an on-chip
antenna and a reader antenna used in the system of FIG. 1,
according to embodiments of the present disclosure.
[0010] FIGS. 5A-5C show a schematic illustration for an exemplary
SoC bio-sensing system with an electrochemical sensor for glucose
monitoring, according to embodiments of the present disclosure.
[0011] FIGS. 6A-6C show a graphical illustration of the exemplary
SoC bio-sensing system and associated performance of the system,
according to embodiments of the present disclosure.
[0012] FIG. 7 shows photos of an exemplary die for fabricating a
SoC bio-sensing system, according to embodiments of the present
disclosure.
DETAILED DESCRIPTION
[0013] The disclosed embodiments relate to systems for injectable
wireless sensing SoCs. Advantageously, the exemplary embodiments
allow for a monolithic injectable wireless smart sensing SoC to be
designed and injected painlessly into a skin. The SoC is such small
(for example, less than or equal to 250 .mu.m on each side) that it
is not visible once injected. Embodiments of the present disclosure
may be implemented in a SoC system, e.g., a glucose bio-sensing
system. Alternatively, embodiments of the present disclosure may be
implemented in a method for fabricating a SoC bio-sensing
system.
[0014] In some embodiments of the present disclosure, the SoC
bio-sensing system may be injected in the skin at depths ranging
from about 1 mm to about 4 mm depending on applications. Although
various SoC bio-sensing systems may be fabricated, some embodiments
may be powered by a reader, which is placed above the skin when a
measurement is to be made. Other embodiments are powered by ambient
light for example, to power UV exposure recording.
[0015] In some embodiments, a wireless SoC with integrated antenna,
power harvesting, and biosensors, and small dimension (e.g., 200
.mu.m.times.200 .mu.m.times.100 .mu.m) is provided to allow
painless injection. The small device size may be enabled by, for
example, a 13 .mu.m.times.20 .mu.m 1 nA current reference, an
optical clock recovery, a low voltage inverting DC-DC to enable use
of higher quantum efficiency diodes, an on-chip resonant antenna,
and an array scanning reader.
[0016] In some embodiments, in-vivo power and data transfer is
demonstrated and linear glucose concentration recordings are
provided. Innovative circuit designs are provided to achieve the
small size and monolithic integration. Further, a glucose-sensing
embodiment of a SoC bio-sensing system may be provided.
[0017] Reference will now be made in detail to embodiments and
aspects of the present disclosure, examples of which are
illustrated in the accompanying drawings. Elements in the drawings
are not necessarily drawn to scale.
[0018] FIG. 1 is a block diagram of a SoC 100 according to one
embodiment of the present application. As shown in FIG. 1, SoC 100
may include a subsystem 110 (a top panel other than dashed boxes
illustrated in FIG. 1) showing a scheme to harvest clock and power;
an on-chip antenna 150; and various different sensing schemes
showed in dashed boxes.
[0019] Subsystem 110 may in illustrative embodiment comprise five
44 .mu.m.times.44 .mu.m on-chip diodes 102 that are used for a main
power supply, and four 44 .mu.m.times.44 .mu.m diodes 104 of which
two (104a and 104b) each for a clock recovery supply and an input
respectively. The clock and power in subsystem 110 may, for
example, be harvested from an amplitude modulated optical signal
transmitted by a measurement device reader (referred to as "reader"
herein). It is contemplated that other signal diodes may be
used.
[0020] The reader may transmit a radio frequency (RF) signal. Each
sensor interface (i.e., various sensing schemes) generates a
digital signal which modulates a load across an impedance of
on-chip antenna 150 and thus modulates a reflected RF signal
backscattered to the reader.
[0021] In an exemplary embodiment, a sensing scheme may be for an
electrochemical sensor 120 as shown in FIG. 1. In another
embodiment, a sensing scheme may be for a light sensor 130 as shown
in FIG. 1. Alternatively, a sensing scheme in FIG. 1 may be for a
capacitance sensor 140.
[0022] As shown in FIG. 1, subsystem 110 may be powered by an
optical signal transmitted by the reader. In some embodiments, two
major design choices for optical powering are which wavelength of
light and which on-chip diodes to use. A diode test structure 200
(referred to as "structure 200" herein) as shown in FIG. 2A, was
built to evaluate the two major design choices. Quantum
efficiencies of diodes tested in structure 200 are measured and
plotted as depicted in a first panel 210 of FIG. 2B. As can be
seen, Psub-to-nwell diodes were the most efficient irrespective of
wavelength, and thus, Psub-to-nwell diodes (i.e., D3) may be chosen
for photovoltaic harvesting. Furthermore, first panel 210 shows
higher quantum efficiency at visible wavelengths than in near-IR
(infrared).
[0023] In addition, optical transmission versus wavelength was
evaluated for numerous porcine skin samples. Results for two
representative samples are shown in a second panel 220 of FIG. 2B
indicating a better transmission in near-IR. This indicates there
is a tradeoff between skin-transmission versus diode quantum
efficiency.
[0024] Furthermore, a maximum permissible exposure (MPE) is not
uniform across this tested spectrum as shown in a third panel 230
of FIG. 2B. A fourth panel 240 of FIG. 2B shows an available
electrical power when operating at the MPE using diodes in this
process that is calculated based on the three plots in first panel
210, second panel 220 and third panel 230. Fourth panel 240 also
shows that wavelength 900 nm results in the maximum available power
on-chip.
[0025] While the Psub-to-nwell diodes generate greater available
power, they may generate a lower open-circuit voltage than the
other diode options. In some embodiments, an input light energy the
voltage generated may be -0.3 V. Generating +0.6 V and +1.0 V to
supply various on-chip circuits is challenging, not least in the
first stage circuits in which the substrate is the most positive
potential (for example, 0 V vs -0.3 V).
[0026] In some embodiments, a DC-DC converter may be used to
resolve the above challenge. An exemplary charge pump subsystem 250
is illustrated in FIG. 2C and includes a 3.times. clock-boosting
circuit that generates a clock swing with a peak-to-peak swing of
0.9 V (+0.3 V to -0.6 V) to drive charge pump switches. In this
example, all NMOS in the clock booster sit in deep Nwells connected
to ground. Switches in the charge pump stages are realized using
PMOS transistors, such that deep Nwell NMOS switches are avoided to
save area. Switches are bootstrapped using voltages from the
successive stages that use the scheme shown in subsystem 250.
Nwells of the PMOS are tied to nodes with high capacitance to avoid
dropping of the boostrapped gate due to photocurrent of the
Nwell-Psub parasitic diode of the PMOS switches. In some
embodiments, a top metal optical shield reduces leakage in the
parasitic photodiodes. In this example, the input capacitances can
be 13 .mu.m.times.4 .mu.m of MIM (110 pF) per stage input and the
per stage output capacitances are 18 .mu.m.times.22 .mu.m of MIM
and MOM per stage output (1.9 pF total per stage). The entire
circuit occupies 88 .mu.m.times.88 .mu.m. A plot 260 of FIG. 2D
shows a measured output voltage versus a load current for a charge
pump driven by five 44 .mu.m.times.44 .mu.m on-chip diodes through
3 mm of free space and 1.8 mm of tissue from a 4 mW/mm.sup.2
source. As shown in plot 260, the charge pump efficiency at 100 nA
load is 37%.
[0027] In some embodiments, a current reference may be essential
for sensing and current control. A conventional supply independent
1 nA reference may take up a 92 .mu.m.times.92 .mu.m area, which
may be equivalent to one quarter of a total permitted SoC area.
[0028] To overcome disadvantages of the conventional approach
discussed above, in some embodiments, a switched capacitor
reference instead of a conventional physical resistor is used as
illustrated in a block diagram 310 of FIG. 3B. In block 310,
transistors M5-M8 form a conventional reference. But, a switched
capacitor circuit formed by transistors M9 and M10 and a capacitor
C1 is applied instead to provide the required resistance. In this
example, capacitor C1 is chosen as 20 fF to minimize area whilst
ensuring the capacitance is very large with respect to non-linear
variations in the switch input capacitance. Startup branch M1-M4
consumes 15 nA at startup and less than 1 pA (e.g., worst case).
Pseudoresistor M13 and capacitor C3 form a low pass filter to
suppress ripple from the switched capacitor. A simulated output
ripple is less than 0.15% across corners as the supply voltage
varies from 0.4 V to 1 V. A total area of the switched capacitor
circuit may be about 13 .mu.m.times.20 .mu.m, 32 times less than a
conventional resistor alone which would be used in the conventional
approach.
[0029] Further shown in FIG. 3C is a plot 320 depicting a plot of
measured output current versus input clock frequency. As shown in
plot 320, a target current of 1 nA is achieved at an input
frequency of 0.8 MHz, and the variation of current with frequency
is seen to be linear over more than two decades of frequency.
Therefore, the output current can be tuned by varying the input
clock frequency which gives flexibility to overcome process
variations.
[0030] A crystal reference for clock generation would be many times
larger than the device. The current reference may require a clock
input so clock generation cannot depend on the current reference.
Instead, the light transmitted to power the SOC may be
amplitude-modulated by the reader. A schematic diagram 300 of an
illustrative clock recovery circuit is illustrated in FIG. 3A. In
this example, two 44 .mu.m.times.44 .mu.m N-Well to P-sub diodes
D1, are used to generate a supply voltage for the clock recovery
circuit. The supply voltage generated is negative, for example,
from -0.3 V to -0.4 V. The modulated signal is recovered from an
identical diode D2, which is high-pass filtered by a resistor R1
and a capacitor C2 and amplified by the subsequent inverter. The
exemplary first inverter is connected in unity-gain feedback. The
first stage could be self-biased using a pseudo-resistor and
contribute gain, but even with metal light shielding residual light
would cause photogeneration in the pseudo-resistor and saturate the
inverter. Therefore, in this exemplary design, unity-gain feedback
is used for the first stage, but establishes bias for the
subsequent stages. Dedicated metal shielding layers on the top of
the circuit are employed to reduce offset in the inverter. Metal
shielding layers above the circuit may be employed to reduce
photo-induced inverter offset. In this example, all NMOS may be
deep N-Well with bulk tied to negative voltage source supply
(-Vss). The circuit (excluding D1, 2) may occupy 33 .mu.m.times.33
.mu.m and consumes 45 nA from a -0.35 V supply. In some
embodiments, the nominal operating frequency is 1 MHz and the
circuit recovers clocks from 0.1 MHz to 2 MHz.
[0031] In some embodiments, 2.4 GHz is chosen as an operating
frequency for a RF link since an on-chip antenna (also referred to
as a receive antenna herein) may be sub-mm sized, which is small
compared to the range while being embedded in a lossy tissue. An
exemplary on-chip antenna 400 is illustrated in FIG. 4A. For this
on-chip antenna, multiple turns over many metal layers give an
electrically long structure close to self-resonance thus saving
area of matching components and increasing B-field sensitivity. A
25 .mu.m.times.10 .mu.m MIM capacitor may be used to fine tune. A
plot 410 in FIG. 4B illustrates a plot of resulting antenna
impedance versus frequency obtained from antenna 400.
[0032] A reader antenna may not be very large compared to a receive
antenna in order to maximize link gain making alignment difficult.
In some embodiments, a scanning reader antenna array may be used as
a reader as illustrated in a diagram 420 in FIG. 4C making
alignment easier. As shown in diagram 420 each external antenna
element 422 is a hexagon having a diameter of about 3.6 mm and the
reader scans through each element 422 to find a best link. Light is
transmitted through holes in the middle of each antenna element
422. Power received for RF-powered SoCs at 1.4 mm depth in chicken
skin is illustrated a plot 430 in FIG. 4D. To produce plot 430, RX
power is measured on an illustrative chip variant. Plot 430 shows
power versus position moving along a diameter of the array at 1.4
mm depth in chicken skin. A scanning link may be used for
communication in the optically-powered versions and to power
RF-powered versions.
[0033] An illustrative electrochemical sensing system is
illustrated in a schematic diagram 500 of FIG. 5A according to some
embodiments of the present application. As shown in diagram 500,
the electrochemical sensing system may be implemented on a larger
die to accommodate bond pads. The die may be affixed to a 1.5
mm.times.0.7 mm glass slide on which a 200 .mu.m.times.200 .mu.m
electrochemical sensor is patterned and functionalized and a
potentiostat input is wire bonded to the sensor as shown in FIG.
5A. Such a electrochemical sensor demonstrates the system
functionality of a SoC and the feasibility of glucose measurement
with such a small sensor. In some embodiments, a SoC may be formed
with through-silicon vias and sensors may be fabricated on a
backside of the SoC. For example, a schematic diagram 510 of FIG.
5B shows a monolithic glucose sensor with electrode pattern on a
bottom side of IC and connected to circuitry through TSVs
(through-silicon vias).
[0034] In an illustrative embodiment, a glass slide device is
placed in a custom flow cell and controlled concentrations of
glucose in saline solution and powered by the reader, which reads
the backscatter demodulated ADC output. That recorded ADC output is
plotted versus glucose concentration in an illustrative process, as
shown in plot 530 of FIG. 5C. A good linearity between ADC output
and glucose concentration is observed.
[0035] In some embodiments, light sensing systems may be fabricated
similarly as the above electrochemical sensing system, which may
rely on a source-coupled oscillator to generate the clock and may
have higher power consumption.
[0036] In some embodiments, capacitance-sensing systems may be
fabricated similarly as the above electrochemical sensing system,
which may rely on a source-coupled oscillator to generate the clock
and may have higher power consumption.
[0037] In some embodiments, a SoC device may be coated with a
bio-compatible package. A photo 600 of FIG. 6A demonstrates a
successful powering and reading at 2 mm depth in-vivo in rabbits
using a SoC device coated with the bio-compatible package. Due to
an extremely small size, the SoC device can be injected into the
skin of a subject with relative ease and with minimal to no pain. A
photo 610 of FIG. 6B shows an exvivo SEM image of a SoC device
injected into a porcine leg.
[0038] Table 620 of FIG. 6C summarizes further performance
information and characteristics of such SoC device for glucose
sensing.
[0039] FIG. 7 shows photo 700 of a die for fabricating SoC
according to some embodiments of the present application. As shown
in photo 700, an antenna top layer 702 is visible as a 5 .mu.m
wide, 200 .mu.m.times.200 .mu.m square around the perimeter of the
die. Nine squares 704 corresponding to the nine 44 .mu.m.times.44
.mu.m diodes used for photovoltaic (PV) harvesting of clock and
power are visible along the top, left and bottom side of the die.
Further, a metal visible above the other circuits is for light
shielding. In some embodiments, methods for fabricating the above
SoCs may be performed.
[0040] The foregoing description has been presented for purposes of
illustration. It is not exhaustive and is not limited to precise
forms or embodiments disclosed. Modifications and adaptations of
the embodiments will be apparent from consideration of the
specification and practice of the disclosed embodiments. For
example, the described implementations include hardware
and/software, but systems and methods consistent with the present
disclosure can be implemented as hardware alone. In addition, while
certain components have been described as being coupled to one
another, such components may be integrated with one another or
distributed in any suitable fashion.
[0041] Moreover, while illustrative embodiments have been described
herein, the scope includes any and all embodiments having
equivalent elements, modifications, omissions, combinations (e.g.,
of aspects across various embodiments), adaptations and/or
alterations based on the present disclosure. The elements in the
claims are to be interpreted broadly based on the language employed
in the claims and not limited to examples described in the present
specification or during the prosecution of the application, which
examples are to be construed as nonexclusive.
[0042] The features and advantages of the disclosure are apparent
from the detailed specification, and thus, it is intended that the
appended claims cover all systems and methods falling within the
true spirit and scope of the disclosure. As used herein, the
indefinite articles "a" and "an" mean "one or more." Similarly, the
use of a plural term does not necessarily denote a plurality unless
it is unambiguous in the given context. Words such as "and" or "or"
mean "and/or" unless specifically directed otherwise. Further,
since numerous modifications and variations will readily occur from
studying the present disclosure, it is not desired to limit the
disclosure to the exact construction and operation illustrated and
described, and accordingly, all suitable modifications and
equivalents may be resorted to, falling within the scope of the
disclosure.
[0043] Other embodiments will be apparent from consideration of the
specification and practice of the embodiments disclosed herein. It
is intended that the specification and examples be considered as
example only, with a true scope and spirit of the disclosed
embodiments being indicated by the following claims.
* * * * *