Recent Advances in Wearable Biosensors for Non-Invasive Detection of Human Lactate

Abstract

Lactate, a crucial product of the anaerobic metabolism of carbohydrates in the human body, is of enormous significance in the diagnosis and treatment of diseases and scientific exercise management. The level of lactate in the bio-fluid is a crucial health indicator because it is related to diseases, such as hypoxia, metabolic disorders, renal failure, heart failure, and respiratory failure. For critically ill patients and those who need to regularly control lactate levels, it is vital to develop a non-invasive wearable sensor to detect lactate levels in matrices other than blood. Due to its high sensitivity, high selectivity, low detection limit, simplicity of use, and ability to identify target molecules in the presence of interfering chemicals, biosensing is a potential analytical approach for lactate detection that has received increasing attention. Various types of wearable lactate biosensors are reviewed in this paper, along with their preparation, key properties, and commonly used flexible substrate materials including polydimethylsiloxane (PDMS), polyethylene terephthalate (PET), paper, and textiles. Key performance indicators, including sensitivity, linear detection range, and detection limit, are also compared. The challenges for future development are also summarized, along with some recommendations for the future development of lactate biosensors.

Keywords: flexible substrates; lactate detection; non-invasive; wearable biosensors.

Figure 3

Preparation process and characterization of electrochemical biosensors for lactate detection: (a) A fully integrated wireless eyeglasses-based biosensor platform for monitoring lactate in sweat in real time. Reprinted with permission from ref. [40]. Copyright 2017 Royal Society of Chemistry. (b) A wearable lactate biosensor fabricated by in-situ preparation of PB sensing membrane incorporated with rGO and urchin-like Au NPs on flexible SPCE. Reprinted with permission from ref. [65]. Copyright 2022 Elsevier. (c) Electrochemical sensor for detecting lactate using the wires as substrate. Reprinted with permission from ref. [39]. Copyright 2020 Nature Publishing Group. (d) Electrochemical biosensor prepared by electrospinning for detecting lactate in human sweat. Reprinted with permission from ref. [53]. Copyright 2021 Elsevier. (e) Coupling of silk fibroin nanofibrils enzymatic membrane with ultra-thin PtNPs/Graphene film to acquire long and stable on-skin sweat lactate sensing. Reprinted with permission from ref. [72]. Copyright 2021 Wiley-VCH. (f) Electrochemical sensor for enzymatic lactate detection based on laser-scribed graphitic carbon. Reprinted with permission from ref. [73]. Copyright 2022 Elsevier.

Figure 5

Preparation process and characterization of optical biosensors for lactate detection: (a) A soft, flexible, and stretchable microfluidic system for colorimetric analysis of lactate concentration. Reprinted with permission from ref. [102]. Copyright 2016 American Association for the Advancement of Science. (b) An electrogenerated chemiluminescent biosensor based on a g-C₃N₄-hemin nanocomposite and HGNPs for the detection of lactate. (A) ECL responses of the biosensor to lactate with different concentrations. (B) The curve of the linear relationship between ECL signal intensity and the concentration of lactate. Reprinted with permission from ref. [105]. Copyright 2014 Royal Society of Chemistry. (c) A flexible MIP-ECL sensor for epidermal analyte detection. (A) The synthesis of Ru-PEI@SiO₂. (B) The fabrication of a flexible MIP-ECL sensor. (i) Galvanic conversion of Ag NWs/PDMS to an Au NT/PDMS electrode. (ii) Immobilization of HLNs on an Au NT electrode. (iii) UV-vis light-induced polymerization to form a target-imprinted MIP layer on HLNs/Au NTs. (iv) Elution of flexible MIP-ECL sensors. (v) Epidermal analyte detection. Reprinted with permission from ref. [106]. Copyright 2019 Royal Society of Chemistry. (d) A wearable permeable sweat sampling patch for sweat lactate detection. Reprinted with permission from ref. [109]. Copyright 2021 American Chemical Society. (e) A textile-based microfluidic device integrated SERS technology and colorimetric assay as a multifunctional sweat sensor. Reprinted with permission from ref. [113]. Copyright 2022 Elsevier. (f) A novel 3D titania dioxide nanotube/alginate hydrogel scaffold used to detect lactate in sweat. Reprinted with permission from ref. [114]. Copyright 2021 American Chemical Society.

Figure 6

Preparation process and characterization of semiconductor biosensors for lactate detection: (a) Nickel oxide thin-film field-effect transistor based on radio frequency. Reprinted with permission from ref. [117]. Copyright 2017 Elsevier. (b) An extended-gate type OFET for lactate detection in aqueous media. Reprinted with permission from ref. [121]. Copyright 2015 Elsevier. (c) An organic voltage amplifier for lactate sensor on flexible plastic foil. Reprinted with permission from ref. [123]. Copyright 2020 WILEY-VCH. (d) OECT used as highly sensitive lactate sensors by modifying the gate electrode with LOx and poly(n-vinyl-2-pyrrolidone) -capped Pt NPs. (A) Schematic diagram of lactate sensor based on OECT integrated with microfluidic channel (LOx solution was used instead of GOx solution). (B) Gate electrode modification of device. (C) Transfer curve and corresponding transconductance curve of an OECT. (D) Output curve of OECT. Reprinted with permission from ref. [128]. Copyright 2016 WILEY-VCH. (e) A cumulative mode OECT prepared using n-type polymers. Reprinted with permission from ref. [131]. Copyright 2018 American Association for the Advancement of Science. (f) FECTs based on multi-walled carbon nanotube and PPy composites for noninvasive lactate sensing. Reprinted with permission from ref. [132]. Copyright 2020 Springer. (g) An organically modified sol-gel solid electrolyte for printed OECT-based lactate biosensor. Reprinted with permission from ref. [134]. Copyright 2015 Springer.

Figure 7

Preparation process and characterization of self-powered biosensors for lactate detection: (a) A self-powered piezoelectric biosensor based on enzyme/ZnO nanoarrays. (A) The fabrication process of the electronic skin. (B) The piezoelectric impulse of the piezoelectric biosensor. (C) The piezoelectric output voltage and response of the piezoelectric biosensor in different concentration of lactate. (D) The detection limit and the resolution of the piezoelectric lactate biosensor. (E) Optical images of the electronic skin. (F) The electronic skin for detecting lactate. Reprinted with permission from ref. [135]. Copyright 2017 American Chemical Society. (b) A self-powered piezoelectric biosensing textiles based on PVDF/T-ZnO. Reprinted with permission from ref. [136]. Copyright 2019 MDPI. (c) MFC as a self-powered lactate sensor that can be used to monitor sweat lactate. Reprinted with permission from ref. [144]. Copyright 2019 IEEE Proceedings. (d) A self-powered lactate biosensor fabricated from porous carbon film (modified with LOx). Reprinted with permission from ref. [145]. Copyright 2019 Elsevier.

Figure 8

Biosensors for lactate detection based on different substrate materials: (a–e) Biosensors for detecting lactate based on PDMS. Reprinted with permission from ref. [55,109,149,150,152]. Copyright 2019 IEEE Proceedings. Copyright 2017 American Chemical Society. Copyright 2021 American Chemical Society. Copyright 2021 Elsevier. Copyright 2021 Wiley-VCH. (f–h) Biosensors for detecting lactate based on PET. Reprinted with permission from ref. [38,75,153]. Copyright 2014 Royal Society of Chemistry. Copyright 2020 IEEE Sensor Journal. Copyright 2019 Advancement of Science. (i,j) Biosensors for detecting lactate based on paper. Reprinted with permission from ref. [30,155]. Copyright 2021 Elsevier. Copyright 2021 MDPI. (k,l) Biosensors for detecting lactate based on fabric. Reprinted with permission from ref. [76,157]. Copyright 2021 Elsevier. Copyright 2022 Elsevier.

Figure 1

Biosensors for lactate detection in human biofluid. Reprinted with permission from ref. [16]. Copyright 2021 Elsevier. Reprinted with permission from ref. [17]. Copyright 2019 Elsevier. Reprinted with permission from ref. [18]. Copyright 2016 WILEY-VCH. Reprinted with permission from ref. [19]. Copyright 2020 MDPI.

Figure 2

Schematic of the working principles for different types of electrochemical biosensors: (a) Amperometry (WE: Work Electrode, RE: Reference Electrode, CE: Counter Electrode), (b) Potentiometry, (c) Conductometry. Reprinted with permission from ref. [46]. Copyright 2019 Annual Reviews.

Figure 4

Schematic of the working principles for different types of optical biosensors: (a) Passive, (b) Photoluminescence (R*: the excited state species), (c) Electroluminescence (A*: the excited state). Reprinted with permission from ref. [86]. Copyright 2007 Elsevier.