Opportunities and challenges in the diagnostic utility of dermal interstitial fluid

Thompson, Ian Andrew Paul; Kasting, Gerald B.; Polsky, Ronen; Cunningham, David; Soh, H. Tom; Heikenfeld, Jason

doi:10.1038/s41551-022-00998-9

Cited by 136 publications

(140 citation statements)

References 129 publications

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“…ISF is readily available in the dermis and hypodermis of the skin where almost all analytes found in blood can also be found in ISF. 2 Even though ISF presents an opportunity to continuously monitor proteins, several fundamental challenges (Fig. 1) related to biology present themselves including:…”

Section: Biologymentioning

confidence: 99%

“…First, with respect to biology, it is yet to be confirmed with significant accuracy how large proteins (similar to or greater than the molecular weight of albumin) partition from blood to dermal ISF, leading to unknown correlations between protein levels in blood vs ISF. 2 Furthermore, it is unclear how external stimuli from insertion of sensors into the body will affect protein transport between blood and ISF (i.e., inflammatory response). Second, technologically, it is unknown if affinity-based sensing mechanisms such as redox-modified aptamers can accurately measure any type of protein in ISF over the multi-day to multi-week time scale needed for meaningful health status assessments.…”

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confidence: 99%

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Perspective—The Feasibility of Continuous Protein Monitoring in Interstitial Fluid

et al. 2023

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Real-time continuous monitoring of proteins in-vivo holds great potential for personalized medical applications. Unfortunately, a prominent knowledge gap exists in the fundamental biology regarding protein transfer and correlation between interstitial fluid and blood. In addition, technological sensing will require affinity-based platforms that cannot be robustly protected in-vivo and will therefore be challenged in longevity, fouling, and sensitivity over multi-day to week timelines. Here we use electrochemical aptamer-based sensors as a model system to discuss further research necessary to achieve continuous protein sensing.

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Section: Biologymentioning

confidence: 99%

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confidence: 99%

Perspective—The Feasibility of Continuous Protein Monitoring in Interstitial Fluid

et al. 2023

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“…1,2 Interstitial fluid (ISF), a biofluid mainly present in the dermis, contains various electrolytes (e.g., Na + , K + , and Cl -), 3,4 and their intradermal concentrations correlate with those in plasma. [5][6][7] Previous studies have shown that the change in the Na + concentration serves as the indicator of dehydration and electrolyte imbalance, 8,9 and the Na + /K + ratio reflects the prevalence of hypertension. 10 Therefore, monitoring of electrolytes in ISF could provide valuable information for health management and point-of-care diagnosis.…”

Section: Main Bodymentioning

confidence: 99%

Porous Microneedle-Based Potentiometric Sensor for Intradermal Electrolyte Monitoring

et al. 2023

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A porous microneedle (PMN)-based potentiometric ion sensor for transdermal monitoring of electrolytes in the interstitial fluid was developed. The carbon coating with an ionselective membrane was formed on half of the needle tip as the working electrode, while the Ag/AgCl reference electrode was mounted on the PMN chip. This design of a single needletype configuration allows lower invasive transdermal sensing than the conventional system with multiple needle electrodes. The fabricated potentiometric sensor showed the near-Nernstian responses to Na + concentration in the excised pig skin, demonstrating the applicability for monitoring intradermal electrolytes.

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“…2). In addition, we perform measurements in interstitial fluids (ISF), which we believe is more practical than invasive blood sampling for future healthcare applications [32]. We demonstrate this capability in a freely moving rat with both the sensing probes and electronics implanted under the skin to prevent the animals from chewing off the device.…”

Section: Wireless Monitoring Of Small Molecules In a Freely Moving An...mentioning

confidence: 99%

Wireless Monitoring of Small Molecules on a Freely-Moving Animal using Electrochemical Aptamer Biosensors

Chien

Baker

Gates

et al. 2022

2022 IEEE Biomedical Circuits and Systems Conference (BioCAS)

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This paper introduces a wireless electrochemical sensing system for in vivo small-molecule sensing using reagent-less structure-switching aptamers. The system consists of a 65-nm CMOS electrochemical sensing circuit with an on-chip waveform generator, a Bluetooth microcontroller (MCU), and a battery, which allow for robust wireless recording in a freely moving animal. The device can perform data acquisition every 10 seconds, including wireless data transfer, and consumes an average current of 3mA after duty cycling. Multiple steps in the data processing for noise reduction are discussed. Real-time sensing of infused kanamycin concentration in the interstitial fluids (ISF) using "wire" electrodes is demonstrated on a freely moving rat with the device implanted under the skin. The paper also compares the results at different sensing locations and identifies the difference in their diffusion rates. Finally, the authors suggest that the technology can be adapted for monitoring other molecules using DNA aptamers of different sequences.

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Opportunities and challenges in the diagnostic utility of dermal interstitial fluid

Cited by 136 publications

References 129 publications

Perspective—The Feasibility of Continuous Protein Monitoring in Interstitial Fluid

Perspective—The Feasibility of Continuous Protein Monitoring in Interstitial Fluid

Porous Microneedle-Based Potentiometric Sensor for Intradermal Electrolyte Monitoring

Wireless Monitoring of Small Molecules on a Freely-Moving Animal using Electrochemical Aptamer Biosensors

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