U.S. patent application number 11/747598 was filed with the patent office on 2008-07-17 for microchip reservoir devices using wireless transmission of power and data.
This patent application is currently assigned to MICROCHIPS, INC.. Invention is credited to Dennis Ausiello, Michael J. Cima, Stephen J. Herman, Robert S. Langer, John T. Santini, Norman F. Sheppard.
Application Number | 20080172043 11/747598 |
Document ID | / |
Family ID | 22901160 |
Filed Date | 2008-07-17 |
United States Patent
Application |
20080172043 |
Kind Code |
A1 |
Sheppard; Norman F. ; et
al. |
July 17, 2008 |
MICROCHIP RESERVOIR DEVICES USING WIRELESS TRANSMISSION OF POWER
AND DATA
Abstract
Devices and methods are provided for wirelessly powering and/or
communicating with implanted medical devices used for the
controlled exposure and release of reservoir contents, such as
drugs or sensors. The device may include a substrate having a
plurality of reservoirs containing reservoir contents for release
or exposure; and a rechargeable or on-demand power source
comprising a local component which can wirelessly receive power
from a remote transmitter wherein the received power can be used,
directly or following transduction, to activate the release or
exposure of the reservoir contents.
Inventors: |
Sheppard; Norman F.; (New
Ipswich, NH) ; Santini; John T.; (North Chelmsford,
MA) ; Herman; Stephen J.; (Andover, MA) ;
Cima; Michael J.; (Winchester, MA) ; Langer; Robert
S.; (Newton, MA) ; Ausiello; Dennis;
(Wellesley Hill, MA) |
Correspondence
Address: |
SUTHERLAND ASBILL & BRENNAN LLP
999 PEACHTREE STREET, N.E.
ATLANTA
GA
30309
US
|
Assignee: |
MICROCHIPS, INC.
Bedford
MA
|
Family ID: |
22901160 |
Appl. No.: |
11/747598 |
Filed: |
May 11, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
09975672 |
Oct 10, 2001 |
7226442 |
|
|
11747598 |
|
|
|
|
60239222 |
Oct 10, 2000 |
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Current U.S.
Class: |
604/891.1 |
Current CPC
Class: |
A61M 5/14 20130101; A61K
9/0097 20130101; A61B 5/318 20210101; A61K 9/0009 20130101; A61M
2205/0244 20130101; A61K 9/0051 20130101; A61M 5/14276 20130101;
A61B 5/14539 20130101; A61M 2210/1042 20130101; A61B 1/041
20130101; A61M 2210/0612 20130101; A61M 2205/3523 20130101; A61B
5/369 20210101 |
Class at
Publication: |
604/891.1 |
International
Class: |
A61M 5/00 20060101
A61M005/00 |
Claims
1. A medical device comprising: an implantable component which
comprises a substrate having a plurality of discrete reservoirs
which contain reservoir contents for selective release or exposure;
a rechargeable or on-demand power source which comprises a local
component which is physically coupled to the implantable component,
wherein the local component can wirelessly receive power from a
remote transmitter; and actuation electronics to selectively
control and direct the power from the local component to
selectively open the reservoirs to release or expose the reservoir
contents.
2. The device of claim 1, wherein the reservoir contents comprises
a sensor or component thereof.
3. The device of claim 1, wherein the remote transmitter transmits
the power in the form of electromagnetic energy or mechanical
energy.
4. The device of claim 3, wherein the remote transmitter transmits
electromagnetic energy selected from radio frequency signals,
microwave signals, infrared signals, ultraviolet signals, and
combinations thereof.
5. The device of claim 3, wherein the remote transmitter transmits
the mechanical energy in the form of acoustic energy.
6. The device of claim 1, wherein the power source comprises a
rechargeable power storage unit.
7. The device of claim 6, wherein the rechargeable power storage
unit comprises a capacitor or a rechargeable battery.
8. The device of claim 6, wherein the rechargeable power storage
unit further comprises a coil for the receipt of electromagnetic
energy, a photocell, a hydrophone, or a combination thereof.
9. The device of claim 1, wherein the power source comprises an
on-demand power unit.
10. The device of claim 1, wherein the power source comprises both
an on-demand power unit and a rechargeable power storage unit.
11. The device of claim 1, wherein the actuation electronics
comprises components selected from the group consisting of
multiplexers, demultiplexers, signal generators, signal
oscillators, amplifiers, switches, potentiostats, and combinations
thereof.
12. The device of claim 1, further comprising a local controller
for controlling the actuation electronics.
13. The device of claim 12, wherein the local controller comprises
a microprocessor.
14. The device of claim 12, wherein the local controller or a
component thereof receives signals from a biosensor.
15. The device of claim 12, further comprising a telemetry system
for the wireless transfer of data between the implantable component
and a remote controller.
16. The device of claim 15, wherein the implantable component
comprises a receiver comprising a component selected from the group
consisting of photocells, photodiodes, phototransistors, and
ultrasonic receivers.
17. The device of claim 15, wherein the remote controller comprises
a light-emitting diode, a laser, or an ultrasonic transmitter.
18. The device of claim 13 wherein the reservoir contents comprise
a drug.
19. The device of claim 1, wherein the implantable component
further comprises a discrete reservoir cap positioned over the
reservoir contents in each reservoir and release or exposure of the
reservoir contents is controlled by disintegration of the reservoir
cap.
20. The device of claim 19, wherein the reservoir cap comprises a
metal film.
21. The device of claim 203 wherein the substrate comprises
silicon.
22. An implantable device for the controlled release or exposure of
reservoir contents in a human or animal comprising: a substrate
having a plurality of discrete reservoirs which contain reservoir
contents for selective release or exposure; a power component which
converts mechanical or chemical energy from the body of the human
or animal into power which can be used to activate the release or
exposure of the reservoir contents; and actuation electronics to
selectively control and direct the power from the power component
to selectively open the reservoirs to release or expose the
reservoir contents.
23. The device of claim 22, wherein the power component transduces
a mechanical force produced by motion of the body or a part thereof
into the power.
24. The device of claim 22, wherein the component comprises a
biofuel cell which generates the power by chemically reacting a
molecule present in the body.
25. The device of claim 22, wherein the reservoir content comprises
a sensor or component thereof.
26. The device of claim 22, wherein the reservoir contents
comprises a drug.
27. The device of claim 22, wherein the substrate further comprises
a plurality of discrete reservoir caps positioned over the
reservoir contents and release or exposure of the reservoir
contents is controlled by disintegration of the reservoir caps.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This is a divisional of U.S. application Ser. No.
09/975,672, filed Oct. 10, 2001, which is incorporated herein by
reference in its entirety. Priority is claimed to U.S. Provisional
Application No. 60/239,222, filed Oct. 10, 2000.
BACKGROUND OF THE INVENTION
[0002] This invention relates to miniaturized devices for the
controlled exposure or release of molecules such as drugs and/or
secondary devices such as sensors.
[0003] Microchip devices for chemical and drug delivery and for
controlled exposure of reservoir contents have been described in
detail in U.S. Pat. No. 5,797,898; U.S. Pat. No. 6,123,861; PCT WO
01/64344; and PCT WO 01/35928. One group of embodiments of these
microchip devices provides active release or exposure of the
contents of a reservoir in the substrate of the device. "Active" is
used to refer to those embodiments in which release or exposure is
initiated at a particular time by the application of a stimulus to
the device or a portion of the device.
[0004] An important application for these active microchip devices
is to serve as an implantable device for the delivery of drugs in
the body of humans and animals, for the treatment or diagnosis of
disease. Due to its small size, the microchip device may be
implanted in the body in a variety of locations, including, but not
limited to, under the skin and in the peritoneal cavity. The device
may also be ingested for drug delivery or content exposure
throughout the gastrointestinal tract. Flexibility of implant
location and site variation are particularly important, for example
when local, rather than systemic, administration is desired.
Currently available implantable drug delivery devices such as pumps
may be too large for use in many of locations in the body.
[0005] U.S. Pat. No. 5,797,898 to Santini, et al., describes
powering the active microchip devices using pre-charged power
sources (e.g., pre-charged micro-batteries), which can be
integrated with the microchip and its associated electronics. Such
a pre-charged micro-battery can be a thin film battery fabricated
on the microchip substrate itself, or it can exist as a separate
component that is connected to the microchip substrate through
interconnects and packaging. Such power sources generally must
store all the power required during the operating lifetime of the
microchip device. If it cannot store all of the required power
during the intended useful life of the microchip device, then the
depleted battery must be replaced with a new battery. However, such
replacement typically is impractical or undesirable for an
implanted device. It would therefore be advantageous to avoid the
need for battery replacement. Furthermore, conventional means of
powering an implantable device may be unsuitable for a variety of
implanted devices, particularly for all possible implant
locations.
[0006] U.S. Pat. No. 5,797,898 also describes incorporating a
pre-programmed microprocessor into the active microchip device to
control which reservoirs are activated and when they are activated.
The microprocessor is disclosed as being fabricated onto the back
of the microchip substrate. It would be advantageous to be able to
alter the programming after implantation in order to make the
microchip device more flexible and adaptable to various
applications, particularly implant applications.
[0007] It is therefore an object of the present invention to
provide devices and methods for reducing or eliminating the need
for pre-charged power sources for active release microchip
devices.
[0008] It is another object of the present invention to provide
devices and methods for avoiding explantation of implanted
microchip devices for the purpose of replacing or recharging the
device's power source or for the purpose of reprogramming the
device's microprocessor.
[0009] It is a further object of the present invention to provide
additional means for powering and communicating with microchip drug
delivery and sensing devices.
[0010] These and other objects, features, and advantages of the
present invention will become apparent upon review of the following
detailed description of the invention taken in conjunction with the
drawings and the appended claims.
SUMMARY OF THE INVENTION
[0011] Devices, systems, and methods are provided for wirelessly
powering and/or communicating with microchip devices used for the
controlled exposure and release of reservoir contents, such as
drugs, reagents, and sensors.
[0012] In a preferred embodiment, the system for the controlled
release or exposure of reservoir contents comprises (1) a microchip
device comprising a substrate having a plurality of reservoirs
containing reservoir contents for release or exposure; and (2) a
rechargeable or on-demand power source comprising a local component
which can wirelessly receive power from a remote transmitter;
wherein the received power can be used, directly or following
transduction, to activate said release or exposure of the reservoir
contents. These systems advantageously do not require a power
storage unit to be physically connected to or integrated into the
microchip device. For example, the local component can be adapted
to receive power from an electromagnetic energy source, such as
radio frequency signals or a laser, and/or from a sonic energy
source, such as an ultrasound generator. The system optionally can
include a rechargeable power storage unit, such as a capacitor or
rechargeable battery. However, it need not store all of the power
required for the operating life of the microchip, since additional
power can wirelessly be transmitted and received when needed (i.e.
on-demand). The rechargeable power storage unit can include, for
example, a coil for the receipt of electromagnetic energy, a
photocell, a hydrophone, or a combination thereof.
[0013] The system may further include actuation electronics, local
controllers, and a telemetry system. Actuation electronics, such as
multiplexers/demultiplexers, selectively control and direct the
power to selectively open the reservoirs. The local controller can
control the actuation electronics, and may include microprocessors,
read only memory, random access memory, clocks, analog input/output
devices, digital input/output devices, programmable logic circuits,
and combinations thereof. A telemetry system wirelessly transfers
data (e.g., a signal) between the microchip device and a remote
controller.
[0014] In another preferred embodiment, the system for the
controlled release or exposure of reservoir contents comprises (1)
a microchip device comprising a substrate a plurality of reservoirs
containing reservoir contents for release or exposure; and (2) a
telemetry system for the wireless transfer of data between the
microchip device and a remote controller. The system can further
comprise actuation electronics to selectively open the reservoirs,
as well as a local controller (which typically would be in wireless
communication with the remote controller of the telemetry system)
for controlling the actuation electronics.
[0015] The data transfer can be accomplished using a first coil in
the microchip device to inductively couple electromagnetic energy
to a corresponding coil in the remote controller. Alternatively,
the transfer may utilize various kinds of transmitters and
receivers. For example, the microchip device can comprise a
receiver which includes photocells, photodiodes, phototransistors,
and/or ultrasonic receivers, where the remote controller comprises
a light-emitting diode (LED), a laser, and/or an ultrasonic
transmitter. For example, LED's can be fabricated on or in the
microchip device, wherein the LED can be used to transmit energy or
data to other components of the system, such as external/internal
transmitters or remote controllers using light of varying
wavelengths.
[0016] It should be noted that the wireless transmission of power
and the wireless transmission of data can be transmitted to the
microchip device in the same signal and then separated
appropriately in the microchip device.
[0017] The microchip device systems can be used in a variety of
applications. A preferred application is the controlled delivery of
a drug, chemical reagent, or biosensor to sites within the body of
a human or animal. In one example, the microchip device is adapted
for implantation onto or in the eye of a human or animal, and the
remote controller and/or power source comprises an ophthalmic
laser. In another example, the microchip device is adapted for oral
administration, and the remote controller comprises a radio
frequency transmitter.
[0018] The system also has a variety uses that are not limited to
implantation. For example, the reservoir contents may include a
sensor for detecting a chemical or biological molecule at the site
in which the microchip is placed, and the telemetry system
transmits a status of the sensor detection to the remote
controller. Such a site could be in vivo or in vitro. The chemical
or biological molecule could, for example, be associated with a
chemical or biological weapon, and the system used in an early
warning/detection system.
[0019] In a preferred variation of the embodiments described above,
each reservoir can have a reservoir cap positioned on the reservoir
over the reservoir contents, wherein release or exposure of the
reservoir contents is controlled by diffusion through or
disintegration of the reservoir cap. The reservoir cap can be an
anode, such that upon application of an electric potential between
a cathode and the anode the reservoir cap is oxidized to facilitate
its disintegration, thereby exposing the reservoir contents to a
surrounding fluid.
[0020] The reservoir content preferably is a drug, a biosensor, or
a combination thereof.
BRIEF DESCRIPTION OF THE FIGURES
[0021] FIG. 1 is a schematic showing the primary components of a
system for the wireless transmission of power or data to or from a
microchip device for the release or exposure of reservoir
contents.
[0022] FIG. 2(a) illustrates one embodiment of a configuration of a
microchip system for drug release into the eye that is equipped for
power and data transmittal by laser, and FIG. 2(b) illustrates a
process of using an ophthalmic laser to transmit power and data to
a drug delivery implant in the eye.
[0023] FIG. 3 is a diagram illustrating how a microchip device can
be activated at a specific location in the gastrointestinal tract
based on the location of a drug delivery microchip relative to an
RF transmitter.
DETAILED DESCRIPTION OF THE INVENTION
[0024] Devices, systems, and methods have been developed for
wirelessly powering and/or communicating with microchip devices
used for the controlled exposure and release of reservoir contents,
such as drugs, reagents, and sensors.
[0025] The Microchip Device Systems
[0026] The systems include a microchip device, along with means for
wirelessly delivering power (i.e. energy) to the microchip device,
means for wirelessly transferring data between the microchip device
and a remote controller, or both means. [0027] The Microchip
Device
[0028] The microchip device is described in U.S. Pat. No. 5,797,898
and No. 6,123,861, both to Santini, et al., and PCT WO 01/64344, WO
01/41736, WO 01/35928, and WO 01/12157, which are hereby
incorporated by reference in their entirety. Each microchip device
includes a substrate having a plurality of reservoirs containing
reservoir contents for release or exposure. In a preferred
embodiment, each reservoir has a reservoir cap positioned on the
reservoir over the reservoir contents, wherein release or exposure
of the reservoir contents is controlled by diffusion through or
disintegration of the reservoir cap. The reservoir cap can be an
anode, such that upon application of an electric potential between
a cathode and the anode the reservoir cap is oxidized to facilitate
its disintegration, thereby exposing the reservoir contents to a
surrounding fluid.
[0029] In another embodiment, the reservoir cap includes an
electrically- or thermally-responsive polymer whose integrity or
porosity can be modulated (i.e. increased or decreased) upon
application of electrical energy to the reservoir cap (e.g., for
the electrically responsive polymer) or to a nearby resistor (e.g.,
for the thermally responsive polymer). Similarly, the reservoir cap
can include or be formed of a polymer having a porosity that can be
modulated by application of electromagnetic energy, acoustic
energy, or a particular chemical species (e.g., for chemical
actuation) provided by the microchip device or other source.
[0030] The microchip reservoir contents can be essentially any
chemical or miniature device. In a preferred embodiment, the
chemical is a therapeutic, prophylactic, or diagnostic agent. (The
term "drug" is used herein to refer any of these agents.) Preferred
drug delivery applications include potent compounds, including both
small and large (i.e. macro) molecules, such as hormones, steroids,
chemotherapy medications, vaccines, gene delivery vectors, and some
strong analgesic agents. An example of a diagnostic agent is an
imaging agent such as a contrast agent. Other molecules that can be
released include fragrances and flavoring agents.
[0031] The reservoir contents also can be catalyst (e.g., zeolites,
enzymes), one or more reagents, or a combination thereof. In
another embodiment, the reservoir content includes a secondary
device such as a sensor and sensing component, e.g., a biosensor.
Examples of sensing components include components utilized in
measuring or analyzing the presence, absence, or change in a
chemical or ionic species, electromagnetic or thermal energy (e.g.,
light), or one or more physical properties (e.g., pH, pressure) at
a site. The contents may either be released from or remain
immobilized in the reservoir, depending on the particular
application. Individual reservoirs may contain multiple types of
chemicals, multiple types of devices, or combinations of devices
and chemicals.
[0032] The microchip devices can be made and assembled using
microfabrication methods known in the art, particularly those
methods described and referenced in U.S. Pat. No. 5,797,898 and No.
6,123,861, both to Santini, et al., and in PCT WO 01/64344, WO
01/41736, WO 01/35928, and WO 01/12157. [0033] Wireless Powering
Means/On-Demand Power Sources
[0034] Means of supplying power to active-release microchip devices
include the use of a precharged power source (which contain all of
the power required for operation over the life of the microchip
device), a source that can be periodically recharged, and an
on-demand power source. The latter two power sources are
preferred.
[0035] The microchip device typically includes a transducer for
receiving energy wirelessly transmitted to the device, circuitry
for directing or converting the received power into a form that can
be used or stored, and if stored, a storage device, such as a
rechargeable battery or capacitor. Therefore in preferred
embodiments, the system for the controlled release or exposure of
reservoir contents includes a microchip device and a rechargeable
or on-demand power source. The on-demand power source
advantageously does not require that a power storage unit to be
physically connected to or integrated into the microchip device.
The rechargeable power source (i.e. the rechargeable power storage
unit) can store power, but advantageously need not store all of the
power required for the operating life of the microchip. The
rechargeable power source and on-demand power sources can both be
included in a single microchip device, as it is common for a system
having an on-demand power source to include a power storage unit,
such as a capacitor or battery.
[0036] The systems described herein preferably are provided with a
means for monitoring the state of any power storage unit. As power
is used or depleted from the storage device, additional power can
wirelessly be transmitted to and received by the rechargeable power
storage unit when needed. Rechargeable power sources provide a
means of extending the operating life of the microchip device
beyond that possible with pre-charged storage cells or
non-rechargeable systems.
[0037] Systems and techniques for on-demand power by wireless
transmission, which can be adapted for use with the microchip
devices described herein, are disclosed, for example, in U.S. Pat.
No. 6,047,214 to Mueller, et al.; U.S. Pat. No. 5,841,122 to
Kirchhoff; U.S. Pat. No. 5,807,397 to Barreras; and U.S. Pat. No.
5,324,316. The systems typically involve a receiver and a
transmitter of one or more forms of energy. The rechargeable or
on-demand power source preferably includes a local component which
can wirelessly receive power from a remote transmitter. As used
herein, the term "local" refers to being local to the microchip
device (rather than remote), and includes, but is not limited to,
having the local component attached to the microchip device, such
as by fabrication onto the substrate.
[0038] The local component can be adapted to receive power by a
variety of means. For example, the local component can be adapted
to receive power from an electromagnetic (EM) energy source, or an
acoustic (i.e. sonic) energy or other mechanical energy source.
Electromagnetic energy refers to the full spectral range from x-ray
to infrared. Representative examples of useful EM energy forms
include radio frequency signals and laser light. A representative
example of a useful form of acoustic energy is ultrasound. In
various embodiments, the rechargeable power storage unit can
include, for example, a coil for the receipt of electromagnetic
energy, or a means for transducing other types of energy, such as a
photocell, a hydrophone, or a combination thereof. Additional
components may include a means of power conversion such as a
rectifier, a power storage unit such as a battery or capacitor, and
an electric potential/current controller (i.e.
potentiostat/galvanostat).
[0039] The microchip device also can include a component to convert
mechanical or chemical energy from the body of the human or animal
into power (i.e. energy) which can be used to activate release or
exposure of the reservoir contents. For example, components
comprising accelerometers and gyroscopes, can be used to convert
motion of a body into electrical energy. Similarly, an implanted
transducer can convert heartbeats into useful energy, as currently
is done with some pacemaker designs. See, e.g., U.S. Pat. No.
5,713,954. In another embodiment power is generated/converted from
a chemical energy source. For example, the microchip can comprises
a biofuel cell which generates the power by chemically reacting a
molecule present in the body. Examples of these fuel cells are
described for example in Palmore & Whitesides, "Microbial and
Enzymatic Biofuel Cells," Enzymatic Conversion of Biomass for Fuel
Production, ACS Symposium Series 566:271-90 (1994); Kano &
Ikeda, "Fundamentals and practices of mediated
bioelectrocatalysis," Analytical Sci., 16(10): 1013-21 (2000); and
Wilkenson, Autonomous Robots, 9(2): 99-111 (2000). In a typical
embodiment, the implanted device would have an immobilized enzyme
which would react with a biological molecule to cause electron
transfer, thereby causing an electric current to flow. Possible
useful biological molecules include triphosphates, such as ATP, and
carbohydrates, such as sugars, like glucose.
[0040] Many of these components (except for the external energy
transmission source) may be fabricated on the microchip ("on-chip"
components) using known MEMS fabrication techniques, which are
described, for example, in Madou, Fundamental of Microfabrication
(CRC Press, 1997) or using known microelectronics processing
techniques, which are described, for example, in Wolf & Tauber,
Silicon Processing for the VLSI Era (Lattice Press, 1986). Each of
these components (except the external energy transmission source)
also may exist as discrete, "off the shelf" microelectronic
components that can be connected to the microchip devices through
the use of hybrid electronic packaging or multi-chip modules
(MCMs). An active-release microchip device with the capability of
receiving power through wireless means also can be composed of a
combination of "on-chip" components and "off the shelf"
components.
[0041] The particular power needs of the microchip device will
depend on the application for and the specific design of the
microchip device. Examples of design factors include the size
requirements and anticipated operating life of the device. The
particular devices and techniques for transmitting power will
likely depend on the selected sites for the microchip device and
remote transmitter. For example, for an implanted microchip, the
body tissue will affect the transmission of power from an
externally located transmitter. For example, inductively coupled
electromagnetic energy typically penetrates body tissues to a
limited extent; however, sonic energy, e.g., ultrasound, is readily
transmitted through tissue and bodily fluids. As another example,
although light (e.g., visible light) is generally not transmitted
through tissue, it may be easily transmitted through the aqueous
and vitroeous humor of the eye. However, other electromagnetic
radiation, for example x-rays, may readily be transmitted through
tissue, depending primarily upon the wavelength of the
radiation.
[0042] In one form, the system provides remote recharging of a
battery for powering a microchip device.
[0043] In one embodiment having an in vivo rechargeable power
storage unit, the power storage unit is separate from the other in
vivo electronic components and communicates with them by wire or by
in vivo telemetry. See for example, the implantable heart apparatus
and energy transfer systems described in PCT WO 01/37926 and WO
01/28629.
[0044] The system may further include a telemetry system to
wirelessly transfers data (e.g., a signal) between the microchip
device and a remote controller or between components of the
microchip device. [0045] Wireless Communication Means/Telemetry
System
[0046] Means for sending and receiving data using wireless
technology are similar to those described for the wireless
transmission of power. In a preferred embodiment, the system for
the controlled release or exposure of reservoir contents includes a
microchip device and a telemetry system for the wireless transfer
of data between the microchip device and a remote controller.
Generally, the telemetry system includes a transmitter and a
receiver. A transmitter can be included in the remote controller,
the microchip device, or both when data is transferred in both
directions (to/from the microchip device), when the receiver is
included in the microchip device, the remote controller, or both,
respectively. As used herein, the "remote controller" therefore can
include a transmitter, a receiver, or both.
[0047] Generally, the telemetry (i.e. the transmitting and
receiving) is accomplished using a first coil to inductively couple
electromagnetic energy to a matching/corresponding second coil. The
means of doing this are well established, with various modulation
schemes such as amplitude or frequency modulation used to transmit
the data on a carrier frequency. The choice of the carrier
frequency and modulation scheme will depend on the location of the
device and the bandwidth required, among other factors. Other data
telemetry means also may be used. Examples include optical
communication, where the receiver is in the form of a photocell,
photodiode, and/or phototransistor, and where the transmitter a
light-emitting diode (LED) or laser. For example, an LED could be
fabricated into the silicon microchip substrate, either inside or
outside of the reservoirs, by using or adapting techniques such as
those described in Barillo, et al., "A porous silicon LED based on
a standard BCD technology", Optical Materials 17(1-2): 91-94
(2001). Optical telemetry techniques are further described, for
example, in U.S. Pat. No. 6,243,608. For telemetry through soft
tissue of the body, acoustic (i.e. sonic) energy, such as
ultrasound energy, may be used as a means of communication. See,
e.g., U.S. Pat. No. 6,140,740. One skilled in the art can adapt
these known telemetry means for use with a microchip device to
optimize power and data exchange. For example, one can account for
impedance matching with tissue and receptive field and other
factors for optimizing ultrasound transmission.
[0048] In various embodiments, the microchip device is provided
with a receiver that accepts commands and data from the remote
controller, and may be used to actuate a reservoir, to request
status information about the state of the system or an event log,
or to reprogram the controller operating system (e.g., the internal
firmware). In an embodiment in which the microchip device is
implanted in a human or animal, the remote controller can include a
means of display and/or actuation that can be used by the physician
or patient to operate and monitor the microchip device. For
example, the microchip may wirelessly transmit to a remote
controller, comprising a receiver, information about the battery
condition and the location and number of reservoirs used and
remaining. Additional support circuitry may be used to interface to
biosensors or other types of devices such as pacemakers or
defibrillators. [0049] Other Components and Features of the
Systems
[0050] It should be noted that the wireless transmission of power
and the wireless transmission of data can be transmitted to the
microchip device in the same signal and then separated
appropriately in the microchip device.
[0051] The systems described herein may further include actuation
electronics and local controllers. Actuation electronics
selectively control and direct the power to the desired reservoirs.
The actuation electronics contains circuitry to condition the power
in a form that is needed for opening the reservoirs. For example,
this circuitry may include signal generators/oscillators, voltage
or current sources, amplifiers, and/or switches. For metal film
reservoir caps, the actuation electronics preferably includes a
potentiostat. Representative types of actuation electronics include
potentiostat/voltage sources, galvanostat/current sources,
multiplexers, and demultiplexers. In a preferred embodiment, the
actuation electronics preferably includes a demultiplexer to route
the power to the desired reservoirs. The demultiplexer may be
integrated on the microchip or may be a separate chip or electrical
component.
[0052] The local controller can control the actuation electronics
and typically is responsible for operation of the device. The
complexity of the controller will depend on the particular
application of the microchip. The controller generally is either a
microprocessor-based system or a dedicated logic circuit with a
finite number of operational states. In the case of a
microprocessor system, there preferably is a microprocessor, memory
(read-only and random-access), clock, analog input/output devices,
and digital input/output devices. The memory generally will contain
a set of instructions to be executed by the microprocessor. These
instructions can include routines to actuate the reservoirs, to
receive commands or data from the remote controller, to transmit
information to the remote controller, and to measure and interpret
signals from devices such as sensors. A controller based on a
dedicated logic circuit may be controlled by the receipt of
commands or data in the form of an encoded (voltage) signal. See,
e.g., U.S. Pat. No. 5,324,316, which describes using a dedicated
logic circuit as a controller of an implantable microstimulator.
The components of the controller system may be integrated as part
of the microchip on the same substrate, or may be separate local
components.
Use of the Microchip Devices and Systems
[0053] The microchip device systems can be used in a wide variety
of applications. The applications can be ex vivo or in vitro, but
more preferably are for in vivo applications, particularly
following non- or minimally-invasive implantation.
[0054] Preferred applications for using the devices and systems
include the controlled delivery of a drug (i.e. a therapeutic,
prophylactic, or diagnostic agent) to sites within the body of a
human or animal, biosensing, or a combination thereof. The
microchip systems are especially useful for drug therapies in which
it is desired to control the exact amount, rate, and/or time of
delivery of the drug. Preferred drug delivery applications include
the delivery of potent compounds, including both small and large
molecules, such as hormones, steroids, chemotherapy medications,
vaccines, gene delivery vectors, and some strong analgesic
agents.
[0055] The microchips can be implanted via surgical procedures or
injection, or swallowed, and can deliver many different drugs, at
varying rates and varying times. In one example, the microchip
device is adapted for implantation onto or in the eye of a human or
animal, and the remote controller comprises an ophthalmic laser. In
another example, the microchip device is adapted for oral
administration, and the remote controller comprises a radio
frequency transmitter.
[0056] In another preferred embodiment, the microchip device
includes one or more biosensors (which may be sealed in reservoirs
until needed for use) that are capable of detecting and/or
measuring signals within the body of a patient. As used herein, the
term "biosensor" includes, but is not limited to, sensing devices
that transduce the chemical potential of an analyte of interest
into an electrical signal, as well as electrodes that measure
electrical signals directly or indirectly (e.g., by converting a
mechanical or thermal energy into all electrical signal). For
example, the biosensor may measure intrinsic electrical signals
(EKG, EEG, or other neural signals), pressure, temperature, pH, or
loads on tissue structures at various in vivo locations. The
electrical signal from the biosensor can then be measured, for
example by a microprocessor/controller, which then can transmit the
information to a remote controller, another local controller, or
both. For example, the system can be used to relay or record
information on the patient's vital signs or the implant
environment, such as blood gases, drug concentration, or
temperature.
[0057] The system also has a variety uses that are not limited to
implantation. For example, the reservoir contents may include a
sensor for detecting a chemical or biological molecule at the site
in which the microchip is placed, and the telemetry system
transmits a status of the sensor detection to the remote
controller. Such a site could be in vivo or in vitro. The chemical
or biological molecule could, for example, be associated with a
chemical or biological weapon, and the system used in an early
warning/detection system.
[0058] Active microchip devices may be controlled by local
microprocessors or remote control. Biosensor information may
provide input to the controller to determine the time and type of
activation automatically, with human intervention, or a combination
thereof The microchip devices have numerous in vivo, in vitro, and
commercial diagnostic applications. The microchips are capable of
delivering precisely metered quantities of molecules and thus are
useful for in vitro applications, such as analytical chemistry and
medical diagnostics, as well as biological applications such as the
delivery of factors to cell cultures.
[0059] The present invention can best be understood with reference
to the following non-limiting examples.
EXAMPLE 1
Chemical Releasing Microchip with Electrochemical Actuation and RF
Power Transmission
[0060] An electrochemically actuated microchip device having
reservoirs covered by thin film gold reservoir caps can be
fabricated using the processes described in U.S. Pat. No.
6,123,861. The reservoirs contain drug or other molecules for
release. Application of an electric potential of approximately 1.0
volt (with respect to a saturated calomel reference electrode) in
the presence of chloride ions would cause the reservoir caps to
oxide and disintegrate, releasing the material stored in the
reservoir. An on-demand power and control system would include an
RF generating and a transmission source in an external controller
unit. The microchip device would include a receiver coil (i.e. an
inductor), an optional power converter (rectifier, regulator), a
power storage unit (e.g., a capacitor, micro-battery), optional
potentiostat or galvanostat circuitry (if electric potential or
current modulation is required), a demultiplexer, a timer, and a
microprocessor.
[0061] When release from a particular reservoir is desired, an RF
signal is (wirelessly) transmitted to the reservoir-containing
microchip device. The RF signal would induce an AC electric current
in the receiver coil. This RF generated AC current can be rectified
to DC current and directed to a unit for power storage, or if the
electric current/corrosion behavior of the reservoir cap is well
characterized, then the current can be sent directly to the anode
reservoir cap covering the particular reservoir from which release
is desired. In some cases, the received power is directed through a
galvanostat or potentiostat to modulate the current or to produce a
specific electric potential (relative to a reference electrode) at
the reservoir cap. The electric current or potential is directed to
the correct reservoir by a microprocessor-controlled demultiplexer.
The microprocessor can be coupled with memory and a timer to enable
timed dose regimens to be stored on-chip. The microprocessor then
can direct power from the power storage unit or directly from the
AC to DC converter to the correct reservoir in a particular release
pattern programmed into the memory.
[0062] The release pattern also could be controlled in a wireless
manner via commands sent from a remote controller over a telemetry
system. Alternatively, the delivery of the drug or other molecule
could be controlled by feedback from a biosensor located on or near
the microchip, and interfaced to the controller.
[0063] This example may be better understood with reference to FIG.
1, which is a schematic that illustrates the primary components and
the flow of power and data in a typical wireless microchip
system.
EXAMPLE 2
Microchip for the Selective Exposure of Reservoir Contents with
Thermal Activation and RF Power Transmission
[0064] A microchip device similar to that described in Example 1
can be made with reservoirs containing catalysts for reactions
and/or sensors for chemical and biological agent detection, wherein
power transmitted by wireless methods can be used to open the
reservoirs to selectively expose the contents. In this embodiment,
electromagnetic energy is transmitted to a receiver coil located on
or connected to the microchip device. The induced AC current can be
rectified to DC current to charge a storage battery or capacitor,
or sent directly to resistors located on, near, or inside the
reservoirs that are to be opened. Current passing through the
resistor will cause a temperature rise in the resistor and
surrounding area. The rise in temperature can cause the reservoir
cap material to disintegrate, melt, or phase change and selectively
expose the sensor or catalyst. Alternatively, a temperature rise
inside the reservoir can result in a rise in pressure inside the
reservoir that may cause the reservoir cap to rupture, exposing the
contents of the reservoir to the surrounding environment. As in
Example 1, the direction of the power to the proper reservoir is
accomplished through the use of a demultiplexer controlled by a
preprogrammed microprocessor, remote control, or biosensor.
EXAMPLE 3
Microchip for Release of Drug to the Eye Using Laser Actuation
[0065] Lasers are used routinely in eye surgeries and other eye
procedures for the treatment of conditions such as diabetic
retinopathy, retinal detachments, age-related macular degeneration.
Some conditions, notably macular degeneration, can be treated with
periodic administration of medication delivered to the eye; however
currently available means for doing so, such as injections, are
difficult. To overcome such difficulties, an implantable microchip
device can be provided to deliver doses of one or more types of
medication to the eye on a periodic basis for an extended period of
time. As the power requirements for electrochemically actuated
silicon microchip devices with thin film gold reservoir caps are
sufficiently small, the power can be wirelessly supplied, for
example, via an ophthalmic laser. The ophthalmic laser also could
be used to wirelessly communicate instructions to the implanted
microchip device. Both power and data can be transmitted, for
example, by modulating the signal that will carry the power; the
modulation information to be communicated to the implanted
microchip device.
[0066] Such an implantable wireless ocular delivery system would
typically include (1) the drug-containing microchip with its local
controller, external interfaces, power conversion electronics, and
actuation electronics; and (2) the ophthalmic laser. The external
interface and power conversion electronics typically would include
a photocell to receive the incident light energy, circuitry to
generate the needed voltage, storage means such as a capacitor or
battery, and circuitry to decode information transmitted by
modulating the laser input. The controller typically would be a
microprocessor with associated support circuitry such as a memory
and a clock, although a dedicated integrated circuit may work for
some embodiments. Electronics required to actuate electrochemical
microchips typically would include means for controlling the
electrode potential, such as a potentiostat or galvanostat, and a
demultiplexer to direct the potential to the desired reservoir. If
desired, the system would provide feedback, for example, to confirm
the successful delivery of a dose. This information could be
transmitted back to the operator or to a computer monitoring
system, either optically by using a light-emitting diode (LED) or
by other modes of wireless transmission, such as RF. FIG. 2A
illustrates one possible configuration of the microchip device
configuration, wherein microchip device 10 includes an array of
reservoirs 12 containing drug to be released, power conversion,
actuation electronics and local controller area 14, photocell 16,
LED or wireless telemetry transmitter 18.
[0067] An ophthalmologist could initiate drug release and
communication with eye-implanted microchips by directing an
ophthalmic laser toward the appropriate portion of the microchip in
the patient's eye. See FIG. 2B, which illustrates an eye 20 with
optic nerve 21, wherein microchip device 28 is implanted at the
back of the interior of the eye. An ophthalmic laser 30 directs
power and data via laser light 32 through cornea 22, lens 24, and
vitreous humor 26, to power and communicate with the implanted
microchip device 28. Many ophthalmologists are already skilled in
the use of such lasers, so these procedures could be readily
performed.
EXAMPLE 4
Orally Administered Microchips for Drug Delivery Having Proximity
Actuation
[0068] A potential advantage of orally administered, drug delivery
microchips or sensors is that they can be activated at a specific
time or at a specific location in the gastrointestinal tract. Such
control over the time and location of release can be achieved using
pre-programmed microprocessors, remote control systems (e.g.
wireless systems), or biosensors. One method of initiating drug
release or exposure of a sensor at a particular location in the
gastrointestinal tract would involve using a remote, wireless
system of control that was highly location dependent. For example,
a patient that just swallowed an orally administered microchip
could wear a small RF transmitter on their belt. The filed produced
by the RF transmitter would be designed to localize the power at a
specific location in the gastrointestinal tract. Multiple coils or
antennas could be used to more precisely locate the field so that
its signal could only be detected at the desired location. The
microchip would travel through the gastrointestinal (GI) tract
until it reached a position where it could detect the signal from
the transmitter.
[0069] As in Example 1, the microchip would receive power from the
RF transmitter and could release drug or expose internal sensors.
The position of release or exposure in the gastrointestinal tract
would be controlled by the nature of the signal coming from the RF
transmitter (i.e. strength of signal), the positioning of the
transmitter (for example, its position on the patient's belt), and
the distance between the microchip and the transmitter (which is
based on how far the microchip has traveled in the gastrointestinal
tract).
[0070] This process is illustrated in FIG. 3, which shows a
microchip device 50A at a first location (i.e. the stomach) in the
GI tract, the microchip device 50B at a second location (i.e. the
colon), and RF transmitter 54 having an RF signal range shown by
dashed line 56. As the device passes through the GI tract, it moves
from position 50A, which is outside the RF signal range 56, to
position 50B, which is inside RF signal range 56 and can be powered
by the signal from RF transmitter 54.
EXAMPLE 5
Microchips Designed to Minimize Medical Errors
[0071] The inclusion of a microprocessor, memory, and a timer also
can help decrease the potential for drug overdoses or the
administration of the wrong drugs to patients. Safety protocols can
be stored in the memory and continuously checked by the
microprocessor to prohibit (i) the release of too much drug to a
patient over a particular time interval, and/or (ii) the
simultaneous release of two or more incompatible drugs. In
addition, the microchip can store in memory the exact amount of
drug delivered, its time of delivery, and the amount of drug
remaining in the microchip. This information can be transmitted
using wireless technology (for implants) or using standard computer
connections (for external, in-line, or intravenous systems) to the
physician or to a central monitoring system on a real-time basis.
This allows the physician to remotely monitor the patient's
condition.
[0072] Modifications and variations of the methods and devices
described herein will be obvious to those skilled in the art from
the foregoing detailed description. Such modifications and
variations are intended to come within the scope of the appended
claims.
* * * * *