Implantable Biosensor and Methods of Use Thereof

Abstract

Disclosed herein is an analyte sensing device capable of continuously monitoring metabolic levels of a plurality of analytes. The device comprises an external unit, which, for example, could be worn around the wrist like a wristwatch or could be incorporated into a cell phone or PDA device, and an implantable sensor platform that is suitable, for example, for implantation under the skin. The external device and the internal device are in wireless communication. In one embodiment, the external device and the internal device are operationally linked by a feedback system. In one embodiment, the internal device is encapsulated in a biocompatible coating capable of controlling the local tissue environment in order to prevent/minimize inflammation and fibrosis, promote neo-angiogenesis and wound healing and this facilitate device functionality.

1 . An analyte sensing device comprising:
 an external control unit and an implantable sensor platform in wireless optical two-way operable communication, wherein the implantable sensor platform can pass though a bore of a needle,
 wherein the implantable sensor platform comprises, in operable communication, 
 a photovoltaic device to receive optical power from the external control unit to serve as a power source for powering said implantable sensor platform, 
 an optical receiver for detecting signals produced by the external control unit, 
 a plurality of sensor elements deposited on a surface of the implantable sensor platform and operable for sensing one or more analytes,
 wherein the plurality of sensor elements have one or more working electrodes, a reference electrode and a counter electrode in contact with the surface they are deposited on such that the electrodes do not delaminate when exposed to body fluids, 
 
 an interfacing circuit, for providing operating parameters to the electrodes of the plurality of sensor elements and controlled feedback for the operation of the plurality of sensor elements, wherein the plurality of sensor elements generates a sensor output signal having a sensor output signal magnitude proportional to the amount of analyte present,
 wherein the interfacing circuit comprises at least one potentiostat, 
 
 a signal processing circuit interfaced with the sensor output signal, wherein the signal processing circuit converts the sensor output signal of the plurality of sensor elements to digital pulses having a pulse frequency, 
 wherein the pulse frequency is determined by the sensor output signal magnitude and wherein changes in the pulse frequency are proportional to changes in the analyte levels, wherein the digital pulses are transmitted to the external unit, 
 a switching mode selector configured to cause the implantable sensor platform to perform at least one of an initialization function, a power level check function, a potentiostat circuit reconfiguration function for analyte level measurement, an implantable sensor selection function, and an implantable sensor calibration function, 
 one or more optical components for facilitating wavelength selection, transmission and/or reflection, and 
 a biocompatible coating surrounding at least a portion of the implantable sensor platform,
 wherein said biocompatible coating comprises a drug and is designed to control the timed release of the drug, 
 
 wherein the external control unit comprises, in operable communication, 
 an optical source suitable for powering the photovoltaic device of the implantable sensor platform, 
 a receiver suitable for receiving one or more digital pulses from the implantable sensor platform and processing the one or more digital pulses to determine the analyte levels, 
 an optical transmitter suitable to transmit one or more optical pulses to the optical receiver of the implantable sensor platform, wherein the optical pulse relays instructions to the switching mode selector to cause the implantable sensor platform to perform at least one of the initialization function, the power level check function, the potentiostat circuit reconfiguration function, the sensor selection for analyte level measurement function, the implantable sensor selection function and the implantable sensor calibration function, 
 an integrated circuit for processing and displaying the analyte levels, wherein the integrated circuit is in operable communication with the receiver, 
 a microcontroller comprising a program code, programmable memory, and means to display output and communicate with other devices, means of interfacing with the receiver, optical source and optical transmitter, to establish an operable communication with the implantable sensor platform, 
 a power supply to power the external unit, 
 one or more optical components providing wavelength selection, transmission or reflection functions, and 
   a miniaturized camera to align the implantable sensor platform with the optical components of the external control unit.   
     
     
         2 . The analyte sensing device of  claim 1 , wherein the implantable sensor platform comprises a first sub-chip, a second sub-chip and a third sub-chip in operable communication, wherein
 the first sub-chip includes,
 the photovoltaic device, 
 a transmitter configured to transmit information in the form of digital pulses to the external unit, and 
 the optical receiver configured to receive instructions from the external unit; 
   the second sub-chip includes,
 the interfacing circuits including initialization, sensor select, and sensor calibration, 
 the potentiostat and signal processing circuits, and 
 the transmitter configured to wirelessly transmit digital pulses; and 
   the third sub-chip includes the plurality of sensor elements.   
     
     
         3 . The analyte sensing device of  claim 2 , wherein the first sub-chip, second sub-chip and third sub-chip are integrated via at least one of through-Silicon-vias, partial-Silicon-vias and interconnects. 
     
     
         4 . The analyte sensing device of  claim 1 , wherein the interfacing circuit includes a voltage control logic unit and the signal processing circuit includes a potentiostat and an analog to digital converter. 
     
     
         5 . The analyte sensing device  claim 1 , wherein the plurality of sensor elements are configured to monitor at least one of the plurality of analytes. 
     
     
         6 . The analyte sensing device of  claim 5 , further comprising sensor-select and potentiostat circuits that sequentially address the plurality of sensor elements. 
     
     
         7 . The analyte sensing device of  claim 1 , further comprising a digital-to-RF converter circuit and an antenna, wherein the digital-to-RF converter circuit is configured to receive and convert the digital pulses from the output of the signal processing unit into a wireless radio frequency(RF) signal responsive to the analytes, and wherein the antenna is configured to transmit the RF signal to the external unit. 
     
     
         8 . The analyte sensing device of  claim 7 , wherein the external unit includes an external RF receiver configured to receive the RF signal. 
     
     
         9 . The analyte sensing device of  claim 1 , further comprising a transducer configured to receive and convert the digital pulses at the output of signal processing unit into a wireless ultrasound signal responsive to the analytes. 
     
     
         10 . The analyte sensing device of  claim 9 , wherein the external unit includes an external ultrasound receiver configured to receive the wireless ultrasound signal. 
     
     
         11 . The analyte sensing device of  claim 1  wherein the miniaturized camera is used to implant the implantable sensor platform under the skin using a needle based insertion device. 
     
     
         12 . An analyte sensing device comprising:
 an external control unit and an implantable sensor platform in wireless optical two-way operable communication, wherein the implantable sensor platform can pass though a 14 gauge or smaller bore needle,   wherein the implantable sensor platform comprises sub-chip # 1 , sub-chip # 2  and sub-chip # 3  and a biocompatible coating surrounding at least a portion of the sensor platform,   wherein sub-chip # 1  comprises:   a photovoltaic device that powers the sub-chip # 1 , sub-chip # 2  and sub-chip # 3 ,   a first optical receiver to receive instructions from a mode select unit located in the external control unit via an external unit optical transmitter, wherein the external unit optical transmitter is located in the external control unit, and   a second optical receiver for providing information regarding light intensity received from light-emitting diodes located in the external control unit;   wherein the first and second optical receivers operate at wavelengths such that the first and second optical receivers do not interfere with each other,   a sensor platform transmitter configured to transmit digital pulses, relaying information selected from sensor output, calibration, potentiostat check, or solar power level check received from a driver located on subchip # 2 ,   one or more coatings providing wavelength selection, transmission or reflection functions,   wherein sub-chip # 2  comprises:   a plurality of interfacing circuits selected from initialization circuits, sensor select circuits, and sensor calibration circuits,   a potentiostat,   a signal processing circuit,   a logic circuit, a demultiplexer, a multiplexer, and the driver to enable transmission of feedback signals selected from a level of radiation intensity received by the photovoltaic device, a reference voltage of the potentiostat, or a sensor reading, and   wherein the driver on subchip # 2  transmits a plurality of digital pulses to the sensor platform transmitter located on subchip # 1  and transmits digital pulses using transmitter selected from wireless RF and ultrasound,   wherein sub-chip # 3  comprises a plurality of sensor elements operable for sensing of one or more analytes,
 and wherein the plurality of sensor elements has one or more working electrodes, a reference electrode and a counter electrode, wherein the one or more working electrodes, reference electrode and counter electrodes are in contact with the surface they are deposited on in a way that they do not delaminate when exposed to body fluids, 
   wherein the plurality of sensor elements are in contact with the potentiostat and other circuits located on subchip # 2 ,   wherein sub-chip # 1 , sub-chip # 2  and sub-chip # 3  are electrically interconnected using through-silicon-vias or partial-silicon-vias and interconnects and integrated in a manner to operate in the presence of body fluids;   wherein the external control unit comprises, in operable communication, an optical source comprising light-emitting diodes and laser diodes, wherein the optical source powers the photovoltaic device on sub-chip # 1 ,   a third receiver for receiving digital pulses from the sensor platform transmitter on subchip # 1  of the implantable sensor platform,   wherein the signal processing circuit converts a sensor element output signal to digital pulses,   wherein the sensor platform transmitter converts the digital pulses to RF and ultrasound pulses,   wherein the frequency of the digital pulses is determined by the sensor element output signal which is controlled by an analyte level in the body fluids,   wherein the external unit optical transmitter transmits one or more optical pulses to the first optical receiver, wherein the one or more optical pulse relays instructions to sub-chip # 2  for the switching, multiplexing, demultiplexing and logic circuits of sub-chip # 2  to provide at least one function wherein the at least one function includes an initialization function, a power check function, a potentiostat circuit reconfiguration for analyte level measurement function, an implantable sensor selection function, and an implantable sensor calibration function,   an integrated circuit for processing and displaying an electrical pulse, wherein the integrated circuit is in operable communication with an optical receiver,   a microcontroller comprising a program code; programmable memory; a means to display the output and communicate with other devices; a means of interfacing with the optical source, a receiver located in the external control unit receiving digital pulses from RF or ultrasound transducer serving as transmitter and an optical transmitter located in the external control unit operating at 800-1000 nanometers,   a power supply to power the external control unit,   one or more optical components providing wavelength selection, transmission, or reflection functions, and   a miniaturized camera to align the implantable sensor platform with the optical components of the external control unit,   wherein the miniaturized camera is used to assist in inserting the implantable sensor platform under the skin using a 14 gauge or smaller needle.   
     
     
         13 . An implantable sensor platform delivery device for delivering an implantable sensor platform into the body of living being, comprising:
 an actuator,   a plunger, and   a needle cannula having a hollow cannula bore that extends the length of the cannula, wherein the hollow cannula bore is sized and shaped to moveably contain the implantable sensor platform   wherein the actuator is associated with the plunger and wherein the plunger is configured to be moveably located within the hollow cannula bore, such that when the implantable sensor platform and the plunger is located within the hollow cannula bore, movement of the actuator causes movement of the plunger.