Recent Advances in Two-Dimensional MXene-Based Electrochemical Biosensors for Sweat Analysis

Abstract

Sweat, a biofluid secreted naturally from the eccrine glands of the human body, is rich in several electrolytes, metabolites, biomolecules, and even xenobiotics that enter the body through other means. Recent studies indicate a high correlation between the analytes' concentrations in the sweat and the blood, opening up sweat as a medium for disease diagnosis and other general health monitoring applications. However, low concentration of analytes in sweat is a significant limitation, requiring high-performing sensors for this application. Electrochemical sensors, due to their high sensitivity, low cost, and miniaturization, play a crucial role in realizing the potential of sweat as a key sensing medium. MXenes, recently developed anisotropic two-dimensional atomic-layered nanomaterials composed of early transition metal carbides or nitrides, are currently being explored as a material of choice for electrochemical sensors. Their large surface area, tunable electrical properties, excellent mechanical strength, good dispersibility, and biocompatibility make them attractive for bio-electrochemical sensing platforms. This review presents the recent progress made in MXene-based bio-electrochemical sensors such as wearable, implantable, and microfluidic sensors and their applications in disease diagnosis and developing point-of-care sensing platforms. Finally, the paper discusses the challenges and limitations of MXenes as a material of choice in bio-electrochemical sensors and future perspectives on this exciting material for sweat-sensing applications.

Keywords: diagnostic; glucose monitoring; point-of-care; wearable sensor.

Figure 1

(a) Schematic representation of the average density of sweat glands in the different parts of the human body(glands/cm²). (b) Approximate range of analytes’ concentrations present in the sweat. Reproduced with permission from Ref. [60]. Copyright 2019 Elsevier.

Figure 2

(a) Schematic illustration of the synthesis process of Ti₃AlC₂. Reproduced with permission from Ref. [85] Copyright 2011 John Wiley and Sons. (b) X-ray diffraction pattern of Mo₂Ga₂C film before and after HF etching. Reproduced with permission from Ref. [86]. Copyright 2015 Elsevier.

Figure 3

(a) Schematic representation of the etching mechanism at elevated temperature and their high exfoliation. (b) XRD pattern of exfoliated material at different temperatures and reduced intensity at high–temperature etching of MX80 indicates deterioration of crystallinity. (c) BET isotherm studies confirm the increase in surface area with high–temperature etching. (d) Raman spectra of exfoliated MXene at different temperatures were high–intensity peaks observed for MX80, indicating the defects introduced at high–temperature etching. Reproduced from Ref. [99] with permission from the Royal Society of Chemistry.

Figure 4

(a) Schematics show the flexible sensor’s fabrication process. (b) The preparation process of the microfluidic patch. (c) Integration of MXene–based sensor to microfluidic patch. (d) Schematic overview of the proposed flexible wearable sensor. (e) Cross–sectional view of the sensor on the skin. (f) The electrochemical oxidation reaction of glucose on the MXene. (g) CV response of Pt/Ti₃C₂ MXene coated on GCE. (h) CV response of Pt/Ti₃C₂–fabricated flexible wearable sensor. The figure is reproduced with permission from [180]. The copyright year is 2023 American Chemical Society.

Figure 5

(a) Schematic illustration of layer-by-layer assembled multiplexed electrochemical sensor mounted on the skin containing various analyte-templated patterns designed on thin polyethylene terephthalate (PET) substrate. (b) bi-HEB patch mounted at the chest to monitor sweat glucose, temperature, and pH simultaneously. (c) Schematic representation of layer-by-layer fabrication process of the bi-HEB patch from top to bottom. Reproduced with permission from Ref. [73]. Copyright 2022 John Wiley and Sons.

Figure 6

(a) Photograph of wearable sweat monitoring patch connected to a portable electrochemical analyzer that supplies power and can wirelessly communicate the body’s status with mobile phones via Bluetooth. (b) Skin–attached wearable sweat sensor. (c) Graphical data of on–body test cycling resistance profile. (d) Chronoamperometric response of pH changes and glucose sensor before and after a meal. (e) pH response at different times during exercise. (f) The electrochemical response of lactate sensor at different times during exercise. (g) Comparison of pH level and glucose after a meal with three different sensors. (h) Comparison of pH levels at different times during exercise. (i) Comparison of lactate sensor responses at different exercise times with different lactate sensors. Reproduced with permission from Ref. [184]. Copyright 2019 John Wiley and Sons.

Figure 7

(a) Picture of flexible MXene/ZnO TPs/Gox composite electrode at strain range of 0–35%. (b) Working performance of fabricated sensor at applied strains (electrode current density vs applied strains) graph. (c) Photograph of skin–attachable sensor functioning for monitoring of glucose in sweat. (d) Graph of current density changes in composite material under sweet consumption for glucose detection. Reprinted with permission from Ref. [186]. (e) SWASV response of composite material–based fabricated electrode for 300 ppb Cu (II) ion on normal and bending mode. (f) Photographs of bending processes of the fabricated electrode. Reproduced with permission from Ref. [187]. Copyright 2020, American Chemical Society.

Figure 8

(a) Schematic illustration of the fabrication of counter and reference electrodes, surface modification, and electrochemical deposition of gold nanoparticles on the surface of the electrode. (b) Immobilization process. Reproduced with permission from Ref. [71]. Copyright 2022 Elsevier.

Figure 9

(a) Schematic illustration of the operating mechanism of wearable, wireless, battery–free integrated electrochemical sensing patch (valinomycin is a selective K⁺ carrier and naturally has specific permeability to K⁺). (b) Steps involved in electrode fabrication. (c) Sensor fabrication process. (d) CV study bare carbon, carbon/MWCNTs, carbon/MXene, and carbon/MWCNTs/MXene. (e) EIS Nyquist analysis. Reproduced with the permission form. Ref. [77]. Copyright 2020 Elsevier.

Figure 10

(a) Digital photograph of wearable pH sensor with a lithium-ion battery, mini–type potentiometer, and F–Ti₃C₂T_x/PANI material. (b) Continuously monitored real–time pH in human male and female volunteers. (c) Comparison of F–Ti₃C₂T_x/PANI sensor with ex situ electrochemical workstation and pH meter results. (d) Schematic illustration of F–Ti₃C₂T_x/PANI electrochemical behavior. Reproduced with permission from Ref. [192]. Copyright 2022 American Chemical Society.