US-12616455-B2 - Hydrogel-enabled microfluidic sweat sequestering for wearable human-device interfaces

Abstract

Microfluidic devices are provided for continuous sampling of biological fluid for extended periods of time, e.g. for periods of time up to and including 10 days. The microfluidic devices can be made from porous hydrophilic substrate, e.g. hydrophilic paper substrates. The devices can include a collection pad, an evaporative pump, and a channel connecting the collection pad and the evaporative pump. Hydrogels at the collection pad can promote collection of sweat or other biological fluids from a subject, which in some aspects is assisted by the use of one or more microneedles on the substrate. An evaporative pump can provide for long periods of sampling by providing continual pumping, e.g. through the use of an evaporation pad where sampled fluid can evaporate.

Inventors

• Orlin D. Velev
• Timothy W. Shay
• Michael D. Dickey

Assignees

• NORTH CAROLINA STATE UNIVERSITY

Dates

Publication Date

20260505

Application Date

20180602

Claims (17)

1. 1 . A microfluidic device comprising: a porous hydrophilic substrate having both an upper surface and a lower surface, wherein the lower surface is configured to be in contact with skin, wherein the porous hydrophilic substrate comprising a collection pad, an evaporative pump, and a closed channel connecting the collection pad and the evaporative pump, wherein the collection pad is located only on the lower surface of the porous hydrophilic substrate, wherein the evaporative pump comprises an evaporation pad, wherein the evaporation pad comprises a first cellulosic substrate, wherein the evaporation pad is located only on the upper surface of the porous hydrophilic substrate, wherein the evaporation pad and the collection pad are located on opposite surfaces of the porous hydrophilic substrate, wherein a side of the closed channel is made of a second cellulosic substrate; and a hydrogel in contact with the upper surface of the porous hydrophilic substrate at the collection pad, wherein the porous hydrophilic substrate is between the hydrogel and the skin, wherein the hydrogel comprises a plurality of extractants.
2. 2 . The microfluidic device according to claim 1 , wherein the first cellulosic substrate is selected from the group consisting of paper, cellulose derivatives, woven cellulosic materials, and non-woven cellulosic materials, wherein the second cellulosic substrate is selected from the group consisting of paper, cellulose derivatives, woven cellulosic materials, and non-woven cellulosic materials.
3. 3 . The microfluidic device according to claim 2 , wherein the first cellulosic substrate is paper that is selected from the group consisting of filter paper, chromatography paper, card stock, vellum paper, printing paper, bond paper, blotting paper, drawing paper, tissue paper, paper towel, and nanocelluosic paper, wherein the second cellulosic substrate is paper that is selected from the group consisting of filter paper, chromatography paper, card stock, vellum paper, printing paper, bond paper, blotting paper, drawing paper, tissue paper, paper towel, and nanocelluosic paper.
4. 4 . The microfluidic device according to claim 2 , wherein the first cellulosic substrate is paper having a grammage of about 0.5 g/m 2 or more, wherein the second cellulosic substrate is paper having a grammage of about 0.5 g/m 2 or more.
5. 5 . The microfluidic device according to claim 1 , wherein the porous hydrophilic substrate has a thickness of about 0.05 mm to 0.5 mm.
6. 6 . The microfluidic device according to claim 1 , wherein the collection pad has a surface area of about 1 mm 2 to 100 mm 2 .
7. 7 . The microfluidic device according to claim 1 , wherein the closed channel has a width of about 100 μm to 1000 μm.
8. 8 . The microfluidic device according to claim 1 , wherein the closed channel has a height of about 5 μm to 500 μm.
9. 9 . The microfluidic device according to claim 1 , wherein the closed channel has a length of about 5 mm to 30 mm.
10. 10 . The microfluidic device according to claim 1 , wherein the evaporative pump comprises the evaporation pad has surface area of about 0.1 cm 2 to 10 cm 2 .
11. 11 . The microfluidic device according to claim 1 , wherein the evaporation pad has a surface area of about 0.1 cm 2 to about A max , wherein A max is calculated according to the following formula A ma ⁢ ⁢ x = ( Δ ⁢ ⁢ Ph ⁢ ⁢ κρ μ ⁢ ⁢ LH ) ⁢ w where ρ is a density of a fluid, L is a length of the closed channel, h is height of the closed channel, w is a width of the closed channel, μ is a viscosity of the fluid flowing through the closed channel, κ is a permeability of the fluid flowing through the channel, ΔP is a pressure drop over the length of the closed channel, and H is an evaporation flux of the evaporation pad.
12. 12 . The microfluidic device according to claim 11 , wherein the fluid is selected from the group consisting of sweat, interstitial fluid, extracellular fluid, blood, urine, saliva, tissue exudate, tissue transudate, and a combination thereof.
13. 13 . The microfluidic device according to claim 12 , wherein the fluid comprises a hydrophilic fluid.
14. 14 . The microfluidic device according to claim 1 , wherein the evaporation pad is a semicircular or radial segment evaporation pad composed of paper, extending radially from an end of the closed channel.
15. 15 . The microfluidic device according to claim 1 , wherein the hydrogel comprises a crosslinked network comprising one or more hydrophilic polymers or biopolymers.
16. 16 . A method of detecting an analyte in a fluid using a microfluidic device according to claim 1 , the method comprising placing the lower surface of the microfluidic device on the skin so that the collection pad is in contact with the skin, and measuring the analyte in the fluid by detecting the amount of analyte collected either in the closed channel or in the evaporative pump.
17. 17 . A microfluidic device comprising: a porous hydrophilic substrate, wherein the porous hydrophilic substrate is a single layer having both an upper surface and a lower surface, wherein the lower surface is configured to be in contact with skin, wherein the porous hydrophilic substrate comprising a collection pad, an evaporative pump, and a closed channel connecting the collection pad and the evaporative pump, wherein the evaporative pump comprises an evaporation pad, wherein the evaporation pad comprises a first cellulosic substrate, wherein a side of the closed channel is made of a second cellulosic substrate; and a hydrogel in contact with the upper surface of the porous hydrophilic substrate at the collection pad, wherein the porous hydrophilic substrate is between the hydrogel and the skin, wherein the hydrogel comprises a plurality of extractants; wherein the collection pad is located only on the lower surface of the porous hydrophilic substrate, wherein the evaporation pad is located only on the upper surface of the porous hydrophilic substrate, and wherein the evaporation pad and the collection pad are located on opposite surfaces of the porous hydrophilic substrate.

Description

CROSS-REFERENCE TO RELATED APPLICATION This application is the 35 U.S.C. § 371 national stage application of PCT Application No. PCT/US2018/035761, filed Jun. 2, 2018, which claims priority to, and the benefit of, U.S. provisional application entitled “HYDROGEL-ENABLED MICROFLUIDIC SWEAT SEQUESTERING FOR WEARABLE HUMAN-DEVICE INTERFACES” having Ser. No. 62/514,232, filed Jun. 2, 2017, both of which are hereby incorporated by reference in their entireties. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT This invention was made with government support under grant number 1160483 awarded by the National Science Foundation. The government has certain rights to this invention. TECHNICAL FIELD The present disclosure generally relates to microfluidic devices and uses thereof. BACKGROUND Wearable health monitors and activity monitors are among the most popular technology trends. Most of these devices utilize accelerometers and gyroscopes to obtain data on motion of the user and correlate that to physical activity. While these devices are great at tracking activity, patient health can only be inferred based off of movements. To obtain a very clear picture of a person's health, a biochemical test is usually performed. These tests are often performed on blood that has been drawn using a needle and then tested in a lab for various analytes. Blood sampling is invasive and very uncomfortable for the patient. Blood is not the only body fluid which can provide useful insight into the body's biochemical health. Sweat is a body fluid which is constantly released through the sweat glands. Sweat contains useful biochemical indicators such as glucose, lactate, cortisol and various ionic species. There remains a need for improved devices for analyzing analytes in sweat and other fluids that overcome the aforementioned deficiencies. SUMMARY Microfluidic devices and methods of using microfluidic devices are provided that overcome one or more of the aforementioned deficiencies. In various aspects, microfluidic devices are provided having a porous hydrophilic substrate having both an upper surface and a lower surface, the porous hydrophilic substrate having a reservoir/collection pad, an evaporative pump, and a channel, connecting the collection pad and the evaporative pump. In various aspects, a hydrogel is on the upper surface of the porous hydrophilic substrate at the collection pad, wherein the hydrogel includes a plurality of extractants. Extractants can include, for example, various salts or other solutes to create an osmotic pressure difference for pulling fluid into the hydrophilic substrate. The porous hydrophilic substrate can have a thickness of about 0.05 mm to 0.5 mm. The device can include one or more sensors such as optical sensors, electrochemical sensors, fluorescent sensors, colorimetric sensors, turbidimetric sensors, or a combination thereof, at a location along the channel. The sensors can provide monitoring of one or more analytes in a fluid in the channel. In various embodiments, the porous hydrophilic substrate include a cellulosic substrate. Suitable cellulosic substrates can include, for example, paper, cellulose derivatives, woven cellulosic materials, and non-woven cellulosic materials. Paper can include chromatography paper, card stock, filter paper, vellum paper, printing paper, wrapping paper, ledger paper, bank paper, bond paper, blotting paper, drawing paper, fish paper, tissue paper, paper towel, wax paper, or photography paper. Various weight papers can be used, for example paper having a grammage of about 0.5 g/m2 or more. Synthetic “non-woven” paper-like materials can be used as substitutes for natural material papers. The collection pad can have various dimensions suitable for the application needs. In some aspects, the collection pad has a surface area from about 1 mm2 to 100 mm2. The collection pad can be connected on one end to the channel, which can have a variety of dimensions. In some aspects, the channel has a width of about 100 μm to 1000 μm, a height of about 50 μm to 500 μm, a length of about 1 mm to 20 mm, or any combination thereof. A variety of channels can be used in various aspects described herein. In some aspects, the channel is a thin strip of paper or other porous hydrophilic material that connects the collection pad and the evaporative pump. In some aspects, the channel is a hydrophilic conduit in a paper or other hydrophobic substrate. For example, a paper or other porous substrate may include hydrophobic portions and one or more hydrophilic portions defining a conduit through the paper or other hydrophobic substrate. The device can include an evaporative pump to create a driving force for pumping a fluid through the channel. In some embodiments, the evaporative pump includes a paper or other evaporation pad having a surface area of about 0.1 cm2 to 10 cm2. In some aspects, the evaporative pump has a surface area of about 0.1 cm2 to about Amax, wherein Amax is