Transdermal sensing of analytes in interstitial fluid and associated data transmission systems

Abstract

Provided are transdermal microneedle-based devices for sensing the presence and concentration of analytes such as electrolytes, biomarkers, drugs, and proteins in interstitial fluid. Also provided are methods and systems to transmit the data obtained by wired or wireless connection to a receiver and to relay the data to the user or a clinician.

1 . An apparatus for testing interstitial fluid in a subject comprising a disposable integrated micro-sensing unit and an applicator,
 wherein the micro-sensing unit comprises a plurality of hollow transdermal microneedles, a microfluidics chamber, a vent, and one or more sensors in the microfluidics chamber capable of detecting the presence or concentration of one or more analytes;   and wherein the applicator comprises a switch capable of initiating the testing event, circuitry for processing data from the sensors, and circuitry for wirelessly transmitting data that result from the testing to a receiver.   
     
     
         2 . The apparatus of  claim 1  wherein the micro-sensing unit further comprises a reference electrode, a pH sensor, a temperature sensor, electronic circuitry to control the testing, a casing, and electrical contacts. 
     
     
         3 . The apparatus of  claim 2  further comprising a substrate, wherein the substrate and microneedles are formed in a first material; the analyte sensors, reference electrode, pH and temperature sensors, and electronic control circuitry are formed in one or more additional material(s) and placed over the substrate; and the first and additional materials may be the same or different. 
     
     
         4 . The apparatus of  claim 3  wherein the microfluidics chamber is a cavity formed by a spacer between the substrate and the additional material(s), a cavity formed by the casing, or a cavity in a block of material comprising the microneedles. 
     
     
         5 . The apparatus of  claim 2  wherein the microneedles, microfluidics chamber, analyte sensors, reference electrode, pH and temperature sensors, and electronic control circuitry are formed in a monolithic block of silicon. 
     
     
         6 . The apparatus of  claim 1  wherein the sensor(s) are conductivimetric, voltammetric, or amperometric. 
     
     
         7 . The apparatus of  claim 1  wherein the interior width of the hollow portion of the microneedles is less than 1 mm, the interior length, width, and height of the microfludics chamber are each from 10 μm to 2 mm, the length and width of the micro-sensing unit are each from 0.5 mm to 10 mm, and the thickness of the micro-sensing unit is from 0.5 mm to 5 mm. 
     
     
         8 . The apparatus of  claim 1  wherein the applicator comprises a battery and electronic circuitry to power the micro-sensing unit. 
     
     
         9 . A method for detecting the presence or concentration of one or more analytes in the interstitial fluid of a subject, comprising
 providing to a user a testing apparatus comprising a disposable integrated micro-sensing unit and an applicator,
 wherein the micro-sensing unit comprises a plurality of hollow transdermal microneedles, a microfluidics chamber, a vent, and one or more sensors in the microfluidics chamber capable of detecting the presence or concentration of the one or more analytes; 
 and wherein the applicator comprises a switch capable of initiating the testing event, circuitry for processing data from the sensors, and circuitry for wirelessly transmitting data that result from the testing to a receiver; 
   providing a receiver running a software application configured to receive and optionally to further transmit the data, wherein the receiver is a computer, smart phone, smart watch, tablet computing device, or wearable computing device;   applying the micro-sensing unit to the skin of the subject such that the microneedles contact interstitial fluid in the subject;   actuating the switch and thereby initiating a testing event, wherein the execution of the testing event and transmission of the data proceed under full automatic control without further intervention by the user;   collecting data from the sensor(s), processing the data, and transmitting the processed data to the receiver; and   analyzing the data in the software application.   
     
     
         10 . The method of  claim 9  further comprising communicating the results of the testing to the user in real time. 
     
     
         11 . The method of  claim 9  wherein the user is the subject. 
     
     
         12 . The method of  claim 9  wherein the user initiates the testing event by actuating the switch on the applicator. 
     
     
         13 . The method of  claim 9  wherein the software application is further configured to actuate the switch on the applicator, and wherein the user instructs the software to initiate the testing event. 
     
     
         14 . The method of  claim 9  wherein the software application controls or directs the testing event. 
     
     
         15 . The method of  claim 9  wherein the receiver further transmits the data to a server. 
     
     
         16 . The method of  claim 9  wherein the micro-sensing unit further comprises a reference electrode, a pH sensor, a temperature sensor, electronic circuitry to control the testing, a casing, and electrical contacts. 
     
     
         17 . The method of  claim 16  wherein the micro-sensing unit further comprises a substrate, and wherein the substrate and microneedles are formed in a first material; the analyte sensors, reference electrode, pH and temperature sensors, and electronic control circuitry are formed in one or more additional material(s) and placed over the substrate; and the first and additional materials may be the same or different. 
     
     
         18 . The method of  claim 17  wherein the microfluidics chamber is a cavity formed by a spacer between the substrate and the additional material(s), a cavity formed by the casing, or a cavity in a block of material comprising the microneedles. 
     
     
         19 . The method of  claim 16  wherein the microneedles, microfluidics chamber, analyte sensors, reference electrode, pH and temperature sensors, and electronic control circuitry are formed in a monolithic block of silicon. 
     
     
         20 . The method of  claim 9  wherein the sensor(s) are conductivimetric, voltammetric, or amperometric.