Wireless sensing platform for multi-analyte sensing

Abstract

Monitoring of one or more key indicators can provide powerful insights into operation and state of different physical systems. For example, continuous monitoring of multiple analyte in body will allow for detailed insights into personal health and will allow for preventative health management. In this application, we present an ultra-small scale wireless sensing platform capable of long-term wireless in-vivo sensing. The key for extreme miniaturization lies in ultra-low-power compact design and lithographic integration of key system components. The key to low cost is using standard technologies and scalable manufacturing. For example, using standard semiconductor technologies for sensing, processing and wireless operation paves way to a low-cost integrated wireless sensing technology. Modern semiconductor technologies provide the capability to provide low-power and yet powerful electronics functionality in a small (mm-scale) size and wireless operation at high frequency. Furthermore, these technologies also present the possibility of integrating different components through wafer-scale lithographic integration. This application presents optimal design and processing methods for a small wireless multi-analyte sensing platform that can be used to monitor multiple analyte such as glucose, lactate, Urea and other physicochemical quantities and operates wirelessly. The design techniques and processing methods presented in this application can be used for a multitude of other applications and are not limited to those described here.

1 .- 21 . (canceled) 
     
     
         22 . An implantable wireless sensor system comprising:
 A) a transceiver configured to receive information from an implantable sensing device via a resonant circuit, said transceiver including 1) a microcontroller or microprocessor, 2) battery, and 3) an antenna;   B) an implantable sensing device with an integrated telemetry unit configured to operate as part of a resonant circuit comprising a capacitor bank, a switch and an on-chip antenna structure formed in the top 3 metal layers of a CMOS stack,   wherein the implantable sensing device communicates to the transceiver by having the on-chip antenna and the transceiver antenna in resonance, changing the impedance of the on-chip antenna creating a mismatch between the external transceiver antenna and the on-chip antenna, and picking up the resulting signal reflection at the transceiver.   
     
     
         23 . The implantable wireless sensor system of  claim 22 , wherein the antenna is circular. 
     
     
         24 . The implantable wireless sensor system of  claim 22 , wherein the impedance of the antenna of the implantable sensing device is changed by using a switch which closes the on-chip antenna or by switching in or out parallel capacitance. 
     
     
         25 . The implantable wireless sensor system of  claim 22 , wherein the implantable sensing device further comprises: 1) a sensing element including one or more electrodes which generates a signal representative of analyte concentration, 2) an analyte signal acquisition and processing unit that receives signals from the sensing element, 3) and a wireless power harvesting unit connected and providing power to the device, while sharing the on-chip antenna structure of the telemetry unit, wherein the sensing element, analyte signal acquisition and processing unit, and wireless power harvesting unit are monolithically integrated with the telemetry element. 
     
     
         26 . The implantable wireless sensor system of  claim 22 , wherein the implantable sensing device is located on a single CMOS die with a thickness of 30 microns to 250 microns, length of 500 to 10,000 microns, and width of 200 microns to 4,000 microns. 
     
     
         27 . An integrated sensor circuit comprising one or more electrodes,
 wherein each electrode comprises a conductive surface and at least one conductive surface is surface patterned to increase a contact area of the electrode with square or rectangular pillars from 2 to 5 microns on each side with heights of 2 to 5 microns,   wherein the core of a square or rectangular pillar is formed at a CMOS foundry in a top most metal and the core of a square pillar formed in the top most metal is coated with a noble metal.   
     
     
         28 . The integrated sensor circuit as in  claim 27 , wherein one or more electrode materials are etched and then coated with a more stable and suitable material using photolithography and selective etching chemistries. 
     
     
         29 . An integrated sensor circuit comprising:
 several electrodes including a shared counter electrode; a shared reference electrode; and multiple working electrodes;   a power management unit with a reference generator which generates a reference voltage;   a sensor signal acquisition unit with a distributed potentiostat containing a plurality of op-amps;   wherein the shared counter electrode and shared reference electrode are connected by an op-amp of the distributed potentiostat to hold the reference electrode at a defined voltage potential; and   the multiple working electrodes each have their own op-amp of the distributed potentiostat converting each sensor redox current into a respective voltage considering the reference voltage of the reference generator.   
     
     
         30 . The integrated sensor circuit of  claim 29  wherein the voltage of the multiple working electrodes is provided to a single analog-to-digital converter individually via time multiplexing. 
     
     
         31 . The integrated sensor circuit of  claim 29 , wherein the integrated sensor circuit is located on a single CMOS die with a thickness of 30 microns to 150 microns, length of 500 to 10,000 microns, and width of 200 microns to 4,000 microns. 
     
     
         32 . The integrated sensor circuit of  claim 29 , wherein a working electrode surface contains a noble metal and the working electrode is surface patterned to increase a contact surface area of the electrode. 
     
     
         33 . The integrated sensor circuit of  claim 32 , wherein the noble metal is platinum. 
     
     
         34 . The integrated sensor circuit of  claim 29 , coated with a hydrogel inclusive of a cross linking agent, an enzyme, and a proteinaceous material. 
     
     
         35 . The integrated sensor circuit of  claim 34 , wherein the cross linking agent is glutaraldehyde, the enzyme is glucose oxidase (GOx), and the proteinaceous material is Serum Albumin (SA). 
     
     
         36 . The integrated sensor circuit of  claim 29 , wherein the integrated sensor circuit is partially covered with a polymeric coating at a thickness between 0.25 to 10 microns and configured to allow oxygen to pass through but hinder glucose diffusion. 
     
     
         37 . The integrated sensor circuit of  claim 36 , wherein the polymeric coating contains polyurethane. 
     
     
         38 . An integrated sensor circuit at least partially covered with a polymeric coating, said integrated sensor circuit comprising:
 several electrodes made using lithographic processing including multiple counter electrodes; multiple reference electrodes; and multiple working electrodes;   a power management unit with at least one reference generator to generate at least one reference voltage; and   a sensor signal acquisition unit with multiple potentiostats and at least one analog-to-digital converter;   wherein the multiple working electrodes each have their own potentiostat converting each sensor current into a respective voltage considering the reference voltage of the corresponding reference generator.   
     
     
         39 . The integrated sensor circuit as in  claim 38 , in which all reference voltages for redox reactions are equal. 
     
     
         40 . The integrated sensor circuit as in  claim 38 , in which different reference voltages are required for different redox reactions.