Biosensing Tattoos Your Mother Would Approve Of

By Stephanie Baringer

Imagine this: you are at a family gathering and your mom sees your newest tattoo and starts to interrogate you on the purpose of your new ink masterpiece. In a mix of excitement and internalized teenage angst you exclaim, “But mom, you don’t understand! This tattoo could save my life!” Maybe that is a bit dramatic, but not improbable for those with chronic diseases and the recent biotechnological development of biosensing tattoo ink.

Over half of adults in the United States suffer from at least one chronic disease1. As an example, chronic liver diseases affect nearly 100 million Americans and include alcoholic liver disease, hepatitis B and C, non-alcoholic fatty liver disease, and hemochromatosis2. Additionally, approximately 37 million Americans have diabetes, a disease in which the pancreas does not properly produce insulin in order to regulate blood glucose levels3. In studies of chronic disease, less than half of participants have their disease under control4, suggesting that the majority of those with a chronic disease worsen over time due to direct and indirect mismanagement of their disease. Disease mismanagement can be due to environmental factors, such as access to healthcare, financial constraints, and/or inaccurate prognosis information.

In order to effectively treat and guide disease management of a chronic disease, patients and their physicians need to understand how the affected system is functioning through the use of a biomarker monitoring tool. The use of such tools is common, with nearly half of all medical tests ordered worldwide being for disease monitoring purposes5. For example, patients with and physicians treating chronic liver disease need to know blood levels of albumin (a protein indicative of liver failure when present at high levels) to determine if the patient’s liver is failing. Additionally, those with diabetes often measure their blood sugar levels to determine whether, and in what quantity, they need to take insulin or glucose tablets to stabilize blood glucose levels.

Despite the need for fast and accurate disease monitoring, current tools can be invasive, expensive, and/or inaccurate. Blood tests are required to measure albumin levels in chronic liver disease, but consistent monitoring is disruptive to the patient’s life. At-home testing for blood-sugar levels is available, but this can be costly over time. An average diabetic can spend nearly $1,500 on supplies (most of which are to monitor blood sugar levels) in a single year6.  Moreover, patients’ life circumstances change over time, leading to more difficult disease monitoring consistency. A permanent and relatively inexpensive monitoring tool – such as a tattoo – would greatly increase the monitoring ability for a disease.

Biosensing tattoo inks are being called a potential revolutionary tool in at-home health monitoring7. The inks are similar to routine colorimetric assays run in any laboratory, but in this case, the laboratory is the human body itself, and the inks can provide information in real time! The chemical properties of the inks result in a color change under specific conditions. When these inks are placed under the skin, as is the case with tattoos, they are able to detect changes to the local environment. Under the dermis, the compounds in the ink can interact with the interstitial fluid the fluid composed of cell waste and by-products, such as lipids, proteins, and electrolytes8 that occupies the space between cells and is a point of fluid exchange between cells and blood arteries. The sampling of biomarkers, such as sodium, potassium, magnesium, bicarbonate, small proteins, pH, and glucose, from the interstitial fluid for disease monitoring has been shown to be just as accurate as sampling from blood8. Biosensing inks provide the opportunity for high quality, real-time diagnostic results within minutes that more and more researchers are attempting to take advantage of for monitoring a variety of diseases.

Dermal Abyss, a collaboration between researchers at Massachusetts Institute of Technology and Harvard Medical School, kicked off biosensing ink development in 20169. The group developed biosensing inks to detect pH changes, glucose levels, and sodium levels in ex vivo skin; of these, their pH sensor was deemed the most promising9. Later, in 2019, scientists at the Technical University of Munich in Germany announced their successful development of similar biosensing inks to measure pH, glucose, and albumin levels10. The Munich researchers used ex vivo pig skin to mimic various pathological states and test their inks’ ability to detect acid-base homeostasis, diabetes, and liver failure (Figure 1). Not only did they succeed on the biochemical side, demonstrating a system in which their inks accurately report on conditions of interest, but they also worked with tech developers to create a smartphone app able to quantify with incredible accuracy the biomarkers based on the color of the ink10. The most recent advancement to biosensing tattoos came in 2021, when another research group tattooed live mice with inks, and were able to accurately measure pH, uric acid, glucose, and temperature11.

Figure 1 from Yetisen et al.: Biosensing inks can be used in tattoos to accurately detect changes in pH, glucose, and albumin in ex vivo skin. A smartphone app can then be used to semi-quantify the ink measurements and provide real-time health data.

The future of biosensing tattoos is an open door, with endless possibilities for diverse applications. One group developed a cellular ink to aid in detecting cancer-related hypercalcemia12. Others in the field are exploring how tattoos could deliver vaccinations composed of peptides that easily aggregate, taking advantage of the abundance of antigen-presenting cells in the dermis8,13 to generate a location-specific immune response. The biggest limitation to biosensing tattoo studies is that none have been performed on live human skin. Many experimental inks used have only been used in experiments on ex vivo tissue with a single endpoint measurement, and thus have not tested the dyes’ ability to continuously measure respective biomarkers. The human body also has a robust immune response to the trauma inflicted when getting a tattoo14 and it is unclear how this could impact the functionality of the inks.

Regardless of these barriers, the possibility of a permanent biosensor to aid in the management of chronic disease could certainly be enough for many to justify getting another tattoo. Imagine adding a pop of color to your next piece that informed you about your liver function or blood sugar levels. Knowledge of dramatic changes to either measurement could save a person’s life. At least, the life-saving ability of biosensing tattoos can be deemed the purpose of the new ink those in the future may get. Who knows, maybe moms everywhere would approve.

TL:DR

  • Self-monitoring a chronic disease is crucial to the management of the disease
  • Biosensing tattoo inks are able to accurately measure biomarkers in the dermis, such as albumin, glucose, and pH, and readouts can be quantified with a smartphone app
  • Biosensing tattoos could be game changing for those managing a chronic disease

References

1.         Boersma, P. Prevalence of Multiple Chronic Conditions Among US Adults, 2018. Prev. Chronic Dis. 17, (2020).

2.         How Many People Have Liver Disease? American Liver Foundation https://liverfoundation.org/about-your-liver/facts-about-liver-disease/how-many-people-have-liver-disease/.

3.         CDC. Type 2 Diabetes. Centers for Disease Control and Prevention https://www.cdc.gov/diabetes/basics/type2.html (2022).

4.         Javors, J. R. & Bramble, J. E. Uncontrolled chronic disease: patient non-compliance or clinical mismanagement? Dis Manag 6, 169–178 (2003).

5.         Glasziou, P., Irwig, L. & Mant, D. Monitoring in chronic disease: a rational approach. BMJ 330, 644–648 (2005).

6.         The Cost of Diabetes | ADA. https://diabetes.org/about-us/statistics/cost-diabetes.

7.         Calsbeek, J. Permanent Tattoos as Biosensors: The Future of Health Monitoring? UC Davis Biotechnology Program https://biotech.ucdavis.edu/blog/permanent-tattoos-biosensors-future-health-monitoring (2020).

8.         Pazos, M. D. et al. Tattoo Inks for Optical Biosensing in Interstitial Fluid. Advanced Healthcare Materials 10, 2101238 (2021).

9.         Project Overview ‹ DermalAbyss: Possibilities of Biosensors as a Tattooed Interface. MIT Media Lab https://www.media.mit.edu/projects/d-Abyss/overview/.

10.       Yetisen, A. K. et al. Dermal Tattoo Biosensors for Colorimetric Metabolite Detection. Angewandte Chemie International Edition 58, 10506–10513 (2019).

11.       He, R. et al. A Colorimetric Dermal Tattoo Biosensor Fabricated by Microneedle Patch for Multiplexed Detection of Health-Related Biomarkers. Adv Sci (Weinh) 8, e2103030 (2021).

12.       Tastanova, A. et al. Synthetic biology-based cellular biomedical tattoo for detection of hypercalcemia associated with cancer. Sci Transl Med 10, eaap8562 (2018).

13.       Pokorná, D. et al. Vaccination with human papillomavirus type 16-derived peptides using a tattoo device. Vaccine 27, 3519–3529 (2009). 14.       drdoppelt. Tattoos: What’s Happening Under Your Skin. Southeastern Dermatology https://www.drdoppe

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