Interstitial Fluid

Where biology first becomes measurable

Many biological signals become visible in interstitial fluid (ISF) before they become measurable in blood. For decades, scientists have understood its value. Access has been the challenge.

Why ISF matters

Interstitial fluid surrounds and connects the cells that make up human biology. Proteins, peptides, metabolites, nucleic acids, and other signaling molecules enter ISF directly from nearby tissues.

ISF serves as the primary biological environment surrounding cells and facilitates the exchange of molecular signals between tissues and the circulatory system.¹ ²

Blood: What you currently measure

¹Friedel, M., Thompson, I. A., Kasting, G., Polsky, R., Cunningham, D., Soh, H. T., & Heikenfeld, J. (2023). Opportunities and challenges in the diagnostic utility of dermal interstitial fluid. Nature Biomedical Engineering, 7(12), 1541-1555.

²Blood is 8% of body weight Cleveland Clinic https://my.clevelandclinic.org/health/body/24836-blood 


³Samant, P. P., & Prausnitz, M. R. (2018). Mechanisms of sampling interstitial fluid from skin using a microneedle patch. Proceedings of the National Academy of Sciences, 115(18), 4583–4588.

The limitation was never the biology.
The limitation was access.

1628

William Harvey demonstrates blood circulation, transforming medicine's understanding of systemic biology.¹

1870’s

Scientists identify extracellular and interstitial fluid, recognizing a biological environment surrounding every cell.²

1950s–1990s

Microdialysis, wick techniques, and suction blister methods provide early access to ISF for research applications.³

1999

First FDA-approved continuous glucose monitor demonstrates the clinical utility of ISF-based monitoring.⁴

2000s

Microneedle and patch-based technologies expand access to ISF through minimally invasive sampling.⁵

2018

The interstitium gains widespread scientific attention as an extensive fluid-filled tissue network.⁶

Today

Research across oncology, neuroscience, immunology, metabolic disease, and drug development continues to expand our understanding of ISF biology.⁷

Biology Was
Never the Question

For nearly 150 years, scientists have recognized the biological importance of interstitial fluid. The challenge was not biology—it was access.

  1. Harvey, W. (1628/1847). On the motion of the heart and blood in animals (R. Willis, Trans.). London: Sydenham Society.
  2. Starling, E. H. (1896). On the absorption of fluids from the connective tissue spaces. Journal of Physiology, 19(4), 312–326.
  3. Ungerstedt, U. (1991). Microdialysis—Principles and applications for studies in animals and man. Journal of Internal Medicine, 230(4), 365–373.
  4. Klonoff, D. C. (2005). Continuous glucose monitoring: roadmap for 21st century diabetes therapy. Diabetes care, 28(5), 1231-1239.
  5. Samant, P. P., & Prausnitz, M. R. (2018). Mechanisms of sampling interstitia fluid from skin using a microneedle patch. Proceedings of the National Academy of Sciences, 115(18), 4583–4588.
  6. Benias, P. C., Wells, R. G., Sackey-Aboagye, B., et al. (2018). Structure and distribution of an unrecognized interstitium in human tissues. Scientific Reports, 8, 4947.
  7. Samant, P. P., Niedzwiecki, M. M., Raviele, N., Walker, D. I., Mena-Lapaix, J., Jones, D. P., Miller, G. W., & Prausnitz, M. R. (2020). Sampling interstitial fluid from human skin using a microneedle patch. Science Translational Medicine, 12(571), eaaw0285.

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CTnT

CEA

IL-6

MMP-9

Biology Looks Different in ISF

Some biological signals remain localized to the tissue where they originate. Others become diluted, altered, or fall below detectable levels by the time they reach systemic circulation.
ISF provides access to biology that may otherwise remain difficult to detect.

ISF provides access to biology occurring within tissue microenvironments that may be difficult to observe through blood alone.

Published studies have reported that ISF may provide access to:

¹ Samant, P. P., & Prausnitz, M. R. (2018). Mechanisms of sampling interstitial fluid from skin using a microneedle patch. Proceedings of the National Academy of Sciences, 115(18), 4583–4588.
² Samant, P. P., Niedzwiecki, M. M., Raviele, N., Walker, D. I., Mena-Lapaix, J., Jones, D. P., Miller, G. W., & Prausnitz, M. R. (2020). Sampling interstitial fluid from human skin using a microneedle patch. Science Translational Medicine, 12(571), eaaw0285.

p-Tau217

CTnT

CEA

IL-6

MMP-9

Proven applications of ISF

Drug Development

PK/PD monitoring and measurement of tissue-level drug exposure and biological response.

Oncology

Accessing tumor biology beyond what blood alone can reveal.

Metabolic & Cardiac
Monitoring

Continuous measurement of glucose, cardiac injury, and stress biomarkers through ISF.

Neuroscience

Measuring neurological and neuroinflammatory signals closer to their source.

For decades, ISF has demonstrated value across multiple fields.

Explore the science of ISF

The Access Challenge 

The value of ISF was understood decades ago.
Access remained the challenge. KIFFIK was built to change that.

The K-EXP™ platform enables repeat access to interstitial fluid through a non-invasive approach designed for longitudinal biological monitoring.

Discover how the K-EXP™ platform enables repeat access to ISF. Because understanding biology requires more than measuring blood alone. It requires access to biology closer to where it happens.