Flexible systems, devices and methods for epidermal monitoring of analytes and biomarkers in fluids on skin

Patent metadata

Field	Value
Publication number	US-2020337641-A1
Application number	US-201816760431-A
Country	US
Kind code	A1
Filing date	Nov 2, 2018
Priority date	Nov 2, 2017
Publication date	Oct 29, 2020
Grant date	—

Abstract

Disclosed are devices, systems and methods for epidermal monitoring of a fluid on skin. In some aspects, a device includes an electrochemical sensor comprising two or more electrodes disposed on a first flexible substrate; a microfluidic device comprising a second flexible substrate coupled to the first substrate and structured to include (i) a channel in a first cavity of the second substrate, (ii) one or more holes that connect to the channel and provide one or more inlets, and (iii) a reservoir connected to the channel, in which the electrochemical sensor is aligned with the reservoir; and an adhesion layer coupled to the microfluidic device and attachable to skin, and the device being operable to detect a biomarker in a fluid in secreted by the skin into the microfluidic device.

First claim

What is claimed is:

1 . A wearable electrochemical sensor device, comprising:
a first flexible substrate including an electrically insulating material; two or more electrodes disposed on the first flexible substrate; a second flexible substrate coupled to the first flexible substrate on a first side of the second flexible substrate, the second substrate including an electrically insulating material and wherein the second substrate is structured to include (i) a channel that recedes from the surface of the first side of the second flexible substrate, (ii) a first set of one or more holes on a second side of the second flexible substrate that connect to a first region of the channel to provide one or more inlets, (iii) a cavity intersecting the channel beyond the first region to provide a reservoir, (iv) a second set of one or more holes that connect to a second region of the channel opposite the first region to provide one or more outlets, wherein the two or more electrodes on the first flexible substrate are aligned with the reservoir of the second flexible substrate; and an adhesion layer coupled to the second substrate and attachable to skin, the adhesion layer structured to include one or more openings arranged on the adhesion layer to align with the one or more inlets, wherein, when the device is electrically coupled to an electronics unit and adhered to the skin of a user, the device is operable to detect a biomarker in a fluid secreted from the skin of the user into the device.

2 . The device of claim 1 , wherein the reservoir further comprises one or more pillars to support the first flexible substrate.

3 . The device of claim 1 , wherein a first electrode of the two or more electrodes having a surface that includes a catalyst or a reactant corresponding to an analyte in the fluid, and wherein a second electrode of the two or more electrodes is disposed on the first flexible substrate in a location separated from the first electrode, the first electrode and second electrode operable to measure an electrical signal corresponding to a redox reaction including a chemical substance and the analyte at the first electrode and second electrode.

4 . The device of claim 1 , wherein the electronics unit is electrically coupled to the wearable electrochemical sensor device via electrical interconnects, the electronics unit configured to supply electrical energy to at least some of the two or more electrodes.

5 . The device of claim 4 , wherein the electronics unit includes:
a signal conditioning circuit to amplify signals detected by the electrochemical sensor device, a data processing unit including a processor and memory to process data based on the measured signals, and a wireless communications unit to wirelessly transmit the processed signals to an external device.

6 . The device of claim 5 , wherein the wireless communications unit includes a Bluetooth Low-Energy (BLE) chipset.

7 . The device of claim 1 , wherein one or both of the first flexible substrate and the second substrate comprises polydimethylsiloxane (PDMS).

8 . The device of claim 1 , wherein the first flexible substrate, the second substrate and the adhesion layer are configured as three circular, flexible layers having a diameter in a range of 1 cm to 10 cm.

9 . The device of claim 1 , further comprising a biofuel cell, wherein the device includes the electronics unit electrically coupled to the two or more electrodes via electrical interconnects and the biofuel cell, the biofuel cell configured to supply electrical energy to the two or more electrodes for electrochemical detection of the biomarker in the fluid.

10 . The device of claim 9 , wherein the biofuel cell is a microfluidic biofuel cell including:
an anodic reservoir containing a first catalyst capable of oxidizing a component of the fluid secreted from the skin of the user and generating an electron, wherein the first catalyst is an enzyme; a cathodic reservoir containing a second catalyst capable of reducing an oxidant by accepting the electron generated in the anodic reservoir, wherein the second catalyst is an enzyme; and an external circuit that connects the anodic and cathodic reservoirs, wherein the electron generated in the anodic reservoir travels through the external circuit and into the cathodic reservoir, wherein when the first and second catalysts are in contact with the fluid secreted from the skin of the user a chemical reaction occurs resulting in a signal representative of a level of the biomarker in the fluid secreted by the skin of the user.

11 . The device of claim 1 , wherein the device is operable to obtain one or more of amperometric measurements, potentiometric measurement, or square-wave voltammetric measurements.

12 . The device of claim 1 , wherein the reservoir can fill with the fluid secreted from the skin of the user in less than 5 minutes.

13 . The device of claim 1 , wherein the device enables a constant, rapid fluid transport to the reservoir.

14 . The device of claim 1 , wherein the device can simultaneously detect two or more biomarkers.

15 . The device of claim 1 , wherein the device is resilient to mechanical deformations, wherein the mechanical deformations include bending, stretching, compressing, and/or twisting.

16 . The device of claim 1 , wherein the device is stable to repeated use for at least 5 days.

17 . The device of claim 1 , wherein the biomarker is one or more of an electrolyte, glucose, lactate, a pro-inflammatory cytokine, an anti-inflammatory cytokine, a catecholamine, a neuropeptide, and/or a protein.

18 . The device of claim 17 , wherein the electrolyte is one or more of sodium, potassium, chloride, bicarbonate, calcium, phosphate, magnesium, copper, zinc, iron, manganese, molybdenum, copper, and chromium.

19 . The device of claim 1 , wherein the two or more electrodes are ion-selective electrodes selected from the group consisting of sodium, potassium, chloride, bicarbonate, calcium, phosphate, magnesium, copper, zinc, iron, manganese, molybdenum, copper, and chromium ion-selective electrodes.

20 . A method for detecting a biomarker in a fluid on skin of a user, the method comprising:
capturing, by a wearable electrochemical sensor device adhered to the skin of the user, a fluid secreted from the skin of the user in one or more inlets of the wearable electrochemical sensor device; transferring, through a channel of the wearable electrochemical device, the captured fluid to a reservoir of the wearable electrochemical sensor device; measuring one or more biomarkers present in the fluid secreted from the skin of the user, the measuring including electrochemically detecting the one or more biomarkers using two or more electrodes positioned in the reservoir of the wearable electrochemical sensor device; and directing the fluid secreted from the skin of the user out of the reservoir to expel from the device, whereby fresh fluid secreted from the skin of the user is transferred in the reservoir of the wearable electrochemical sensor device for continuous electrochemical detection.

21 . The method of claim 20 , wherein adhesion of the wearable electrochemical sensor device to the skin of the user provides a pressure sufficient for the wearable electrochemical sensor device to direct the fluid secreted by the skin of the user to the reservoir without the application an external pressure.

22 . The method of claim 20 , wherein the electrochemical sensor d

Assignees

• Univ California

Inventors

• Wang Joseph
• Moreto Juliane Sempionatto
• Kurniawan Jonas Felipe
• Galan Aida Martin
• Kim Jayoung
• Campbell Alan
• Moreto Jose Roberto

Classifications

• A61B2562/164

  the sensor is mounted in or on a conformable substrate or carrier · CPC title

• A61B2560/0214

  of power generation or supply · CPC title

• A61B5/1486

  using enzyme electrodes, e.g. with immobilised oxidase · CPC title

• A61B5/1477

  non-invasive · CPC title

• A61B5/14546

  for measuring analytes not otherwise provided for, e.g. ions, cytochromes · CPC title