Accessing analytes in biofluids for peripheral biochemical monitoring


Peripheral biochemical monitoring involves the use of wearable devices for minimally invasive or noninvasive measurement of analytes in biofluids such as interstitial fluid, saliva, tears and sweat. The goal in most cases is to obtain measurements that serve as surrogates for circulating analyte concentrations in blood. Key technological developments to date include continuous glucose monitors, which use an indwelling sensor needle to measure glucose in interstitial fluid, and device-integrated sweat stimulation for continuous access to analytes in sweat. Further development of continuous sensing technologies through new electrochemical sensing modalities will be a major focus of future research. While there has been much investment in wearable technologies to sense analytes, less effort has been directed to understanding the physiology of biofluid secretion. Elucidating the underlying biology is crucial for accelerating technological progress, as the biofluid itself often presents the greatest challenge in terms of sample volumes, secretion rates, filtration, active analyte channels, variable pH and salinity, analyte breakdown and other confounding factors.

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Fig. 1
Fig. 2: Characteristics of the glands and biofluids discussed in this Review.
Fig. 3: Correlation between blood glucose and ISF glucose measured on different devices.
Fig. 4: Correlation between different bioanalytes in the blood and saliva and examples of different devices for analyzing saliva.
Fig. 5: Sweat data for glucose.
Fig. 6: Sweat stimulation approaches.


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Authors at the University of Cincinnati and Eccrine Systems would like to acknowledge support from the Air Force Research Labs (USAF contract #FA8650-16-C-6760). The University of Cincinnati authors further acknowledge support from the National Science Foundation (EPMD award #ECCS-1608275), the Ohio Federal Research Network (PO FY16-049; WSARC-1077-700), Eccrine Systems and the industrial members of the Center for Advanced Design and Manufacturing of Integrated Microfluidics (NSF I/UCRC award #IIP-1738617).

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J.H. led the organization and revision of the manuscript, and all other others contributed to the writing. A.J led the local structure section; B.F. the ISF section; S. Granger and S. Gaitonde the saliva section; J.H., G.B. and B.K. the sweat section; and J.H. the introduction and discussion sections.

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Correspondence to Andrew Jajack.

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Competing interests

J.H. is the Chief Science Officer and cofounder of Eccrine Systems, Inc., which is commercializing sweat biosensing technology. B.F. is an employee of Abbott Diabetes Care, which produces and markets the FreeStyle Libre Flash Glucose Monitoring System. S. Granger and S. Gaitonde are employees of Salimetrics LLC, which commercializes saliva biosensing devices.

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Heikenfeld, J., Jajack, A., Feldman, B. et al. Accessing analytes in biofluids for peripheral biochemical monitoring. Nat Biotechnol 37, 407–419 (2019).

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