Biomarkers and Detection Platforms for Human Health and Performance Monitoring: A Review

Abstract

Human health and performance monitoring (HHPM) is imperative to provide information necessary for protecting, sustaining, evaluating, and improving personnel in various occupational sectors, such as industry, academy, sports, recreation, and military. While various commercially wearable sensors are on the market with their capability of "quantitative assessments" on human health, physical, and psychological states, their sensing is mostly based on physical traits, and thus lacks precision in HHPM. Minimally or noninvasive biomarkers detectable from the human body, such as body fluid (e.g., sweat, tear, urine, and interstitial fluid), exhaled breath, and skin surface, can provide abundant additional information to the HHPM. Detecting these biomarkers with novel or existing sensor technologies is emerging as critical human monitoring research. This review provides a broad perspective on the state of the art biosensor technologies for HHPM, including the list of biomarkers and their physiochemical/physical characteristics, fundamental sensing principles, and high-performance sensing transducers. Further, this paper expands to the additional scope on the key technical challenges in applying the current HHPM system to the real field.

Keywords: biosensor technologies; human health and performance biomarkers; human health and performance monitoring.

Figure 1

Human status monitoring through the biomarker detection strategies including biomarkers, sensing principles, transducers, and practical issues.

Figure 2

Biochemical sensing principles for detecting biomarker in body fluid. a) (1–5) Biorecognition elements. Reproduced with permission.^{[ 56 ]} Copyright 2017, IOP Publishing. b) Ionophores. Reproduced with permission.^{[ 59 ]} Copyright 2016, Elsevier.

Figure 3

Physical sensing principles for measuring various biomarkers on skin. a) Resistance temperature detector (RTD) for skin temperature. Reproduced with permission.^{[ 92 ]} Copyright 2012, IOP Publishing. b) 2‐wire conductance measuring principle for skin conductance. Reproduced with permission.^{[ 102 ]} Copyright 2013, Elsevier. c) Indentation method for skin hardness. Reproduced with permission.^{[ 105 ]} Copyright 2006, IOP Publishing. d) Photoplethysmography (PPG) for pulse wave. Reproduced with permission.^{[ 106 ]} Copyright 2017, JMIR Publication. e) Closed chamber method for sweat rate. Reproduced with permission.^{[ 110 ]} Copyright 2008, Elsevier.

Figure 4

Transducers for biochemical sensing. a) Electrochemical impedance spectroscopy (EIS). Reproduced with permission.^{[ 114 ]} Copyright 2018, MDPI. b) Sensing efficacy improvement using antifouling self‐assembled monolayers for the real‐time biomarker monitoring in an ambulatory rat. Reproduced with permission.^{[ 122 ]} Copyright 2017, National Academy of Sciences. c) Field‐effect transistors (FETs). Reproduced with permission.^{[ 127 ]} Copyright 2020, American Chemical Society. d) Graphene‐based FETs characterized in physiologically relevant environments (an artificial sweat with various ionic concentrations of the electrolyte). Reproduced with permission.^{[ 135 ]} Copyright 2020, American Chemical Society. e) Quartz crystal microbalance (QCM). Reproduced with permission.^{[ 141 ]} Copyright 2004, CIGR Journal. f) Cantilever. Reproduced with permission.^{[ 148 ]} Copyright 2012, Elsevier. g) A 3D printed cantilever platform to overcome reproducibility and fabrication complexity issues. Reproduce with permission. Copyright 2017, American Chemical Society. h) Surface plasmon resonance (SPR). Reproduced with permission.^{[ 149 ]} Copyright 2002, Springer Nature. i) A plasmonic sensing probe with tilted fiber Bragg grating imprinted on optical silica fibers. Reproduced with permission.^{[ 161 ]} Copyright 2019, Elsevier. j) Colorimetric measurement. Reproduced with permission.^{[ 167 ]} Copyright 2020, Elsevier. k) Microfluidic colorimetric detection reservoirs for the determination of multiple biomarker concentrations. Reproduced with permission.^{[ 164 ]} Copyright 2016, AAAS.

Figure 5

Flexible substrate‐based biomarker sensing platforms. a) Epidermal electronic systems to measure thermal properties of human skin. Reproduced with permission.^{[ 173 ]} Copyright 2018, Wiley‐VCH. b) Physical biomarker sensors targeting pressure related to human skin by microfluidics‐based diaphragm pressure sensor. Reproduced with permission.^{[ 187 ]} Copyright 2017, Wiley‐VCH. c) Tattoo‐type sensors utilizing a sweat‐based epidermal enzymatic biosensor for the assessment of Vitamin C levels. Reproduced with permission.^{[ 196 ]} Copyright 2020, American Chemical Society.

Figure 6

Body fluid manipulation techniques. a) Iontophoretic delivery of a chelating agent for breaking apart the tight junctions through sequestration of calcium, increasing the flux of analytes in conjunction with reverse iontophoresis. Reproduced with permission.^{[ 205 ]} Copyright 2018, PLoS. b) Hollow needles with substantially greater extraction of ISF due to the inherent flow restrictions with any polymer‐based methodology. Reproduced with permission.^{[ 20 ]} Copyright 2018, Springer Nature.

Figure 7

Integration designs of multimodal platforms for reducing measuring site. a) Physical/chemical sensor arrays where electrodes for a conductivity sensor were patterned in the middle of each electrode for glucose and pH sensing applications, showing the fabrication of the multimodal sensors placed on a surface of the small diameter needle. Reproduced with permission.^{[ 213 ]} Copyright 2020, Elsevier. b) Reduced size of stress monitoring patch with a size comparable to that of a stamp, while measuring multiple physical biomarkers such as skin temperature, skin conductance and pulse wave. Reproduced with permission.^{[ 214 ]} Copyright 2016, Springer Nature. c) Specific design of a probe that enabled three different biomarker measurements where the specially designed truncated hollow cone probe efficiently contained a force sensor above a conductance sensor with a sweat rate sensor placed inside the hollow probe. Reproduced with permission.^{[ 215 ]} Copyright 2019, MDPI.

Figure 8

The use of add‐ons for improving accuracy and stability. a) Integration of a force regulator with a PPG sensor contact force between the skin and a PPG sensor constantly for the consistent and stable PPG measurement results independent of body movements. Reproduced with permission.^{[ 277 ]} Copyright 2018, AIP Publishing. b) Integration of a micro‐sized RTD type temperature sensor next to several sensing modules to compensate measurement results depending on the temperature. Reproduced with permission.^{[ 75 ]} Copyright 2016, Springer Nature. c) Integration of temperature, humidity and pH sensors to obtain more accurate glucose measurement results where the three additional elements were monolithically integrated with the glucose‐sensing element on the flexible substrate. Reproduced with permission.^{[ 68 ]} Copyright 2017, AAAS.

Figure 9

The strategies for improving sensor recovery time and continuous measurement. a) Self‐recovering gas sensors by using CNTs as both the sensing element and heater, significantly improving baseline drift and response time. Reproduced with permission.^{[ 221 ]} Copyright 2018, Royal Society of Chemistry. b) Paper‐based microfluidic skin patches where channels are patterned and radially arranged with different lengths to realize the discrete real‐time measurement of sweat secretion. Reproduced with permission.^{[ 226 ]} Copyright 2019, Springer Nature. c) Sweat collection through microchannels where the passive valves were used for chronometric collection of sweat, resulting in time‐dynamic analysis of sweat analysis using galvanic stopwatches. Reproduced with permission.^{[ 227 ]} Copyright 2019, Wiley‐VCH.

Figure 10

Wireless power and energy harvesting for biosensors. a) Near field communication (NFC) as a power supply system that was integrated with the skins thermal property sensing element. Reproduced with permission.^{[ 232 ]} Copyright 2018, Wiley‐VCH. b) Self‐powered conformal skin sensors based on the flexible photovoltaics where an organophotovaltaic (OPV) power source was integrated with a sensing element in the form of an electrochemical transistor to measure cardiac signals from human skin. Reproduced with permission.^{[ 234 ]} Copyright 2018, Springer Nature. c) Electronic skin based on a nanofiber triboelectric nanogenerator (TENG) that serves as an energy harvester converting mechanical energy into electricity based on the coupling effect of contact electrification and electrostatic induction. Reproduced with permission.^{[ 235 ]} Copyright 2020, AAAS. d) Battery‐free, perspiration‐powered electronic skin (PPES) that harvests energy from human sweat by using lactate biofuel cells (BFCs). Reproduced with permission.^{[ 236 ]} Copyright 2020, AAAS. e) Protein nanowire‐based power generation from ambient humidity. Reproduced with permission.^{[ 237 ]} Copyright 2020, Springer Nature.

Figure 11

Product strategy for reconfigurable and cost‐effective manufacturing via module elements. The product type is divided into an oxygen mask platform and a band‐type platform, where a universal monitoring system is equipped. The universal monitoring system consists of sensor modules (body fluid‐, breath‐, or skin surface‐based), processor/add‐ons, and power source. Each module element can be customized to be inserted into the universal monitoring system, depending on the target applications (airmen, ground soldiers/first responders, athletes, and cyber operators) and their environmental conditions.