Download Tattoos: A New Medical Tool? Christine Starkey Introduction After a

Tattoos: A New Medical Tool?
Christine Starkey
Introduction
After a routine visit, you leave your doctor’s office and head straight for a tattoo parlor. As
you wait you prick your finger to check your blood sugar level; it appears normal. Your
name is called and you have a seat in the tattooist’s chair. You hand the artist a piece of
paper. On it is not a drawing of the new ink you want, but instead it is a prescription. You
are here to receive a tattoo that will allow you to continuously monitor your glucose level
so you can finally stop pricking your fingers several times a day.
This fictional scenario could become reality in the near future, as the fields of
nanotechnology and biomedicine expand. Diabetes is a disease that currently affects 20
million adults in the United States [1]. The disease is characterized by high blood glucose
levels resulting from either the body’s inability to produce insulin or its inability to use its
own insulin [1]. Diabetics have to test their blood sugar levels multiple times a day, doing
so by drawing a drop of blood from a finger and testing it with a glucometer. Over the
lifetime of a diabetic the continuous use of testing strips and the need to replace meters can
become costly. Coupled with the pain from daily testing, this traditional method of blood
glucose monitoring has many drawbacks but is currently one of the few options available
to diabetics. Scientists are now looking to develop less invasive means of blood glucose
monitoring using currently existing technologies. They are turning to the age-old art of
tattooing to develop continuous blood glucose monitoring systems.
The History and Culture of Tattoos
For thousands of years, humans have been tattooing themselves for many different reasons
ranging from social or cultural identification to medical use. The Greek word stigma(ta)
indicated tattooing as we think of it today, the process of marking one’s skin permanently
with ink. Ancient Greeks associated tattooing with barbarians and other uncivilized types
of people. The Romans then adopted this connotation of tattoos and used tattoos to mark
their criminals and slaves[2]. This practice of tattooing as punishment and establishing
social roles continued through the Middle Ages [2].
Instead of tattoos as a means to delineate social roles, other cultures used tattoos
medicinally. The medicinal use of tattoos dates back to Europe in 3,300 BCE. The Tyrolean
Iceman, Ötzi, was found in the Ötztal Alps and is Europe’s oldest human mummy [3]. Ötzi’s
discovery gave scientists valuable information about the lives of humans during the Copper
Age, including what they ate, what they wore, how they lived, and how they treated
illnesses. Ötzi had 15 groups of tattoos covering his back and legs, made up of mainly
linear geometric designs.
These tattoos lie on or near classical acupuncture points,
suggesting a medical use [4]. Tattoos are currently used in medical practice as markers for
radiation treatment; they are used to guide the beam to the correct location and minimize
radiation exposure in unaffected areas.
Tattoos continue to exist in our culture as decorative pieces, social markers, and
storytellers. With the development of tattooing as a diabetic monitoring device, tattooing
can reenter common culture as a medical tool.
The Science of Tattoos
A tattoo is a picture or design on a person’s skin that is made through the insertion of ink
into the dermis layer of the skin. The dermis is the second layer of skin. Below the
epidermis, the dermal cells are more stable than the epidermis, allowing the tattoo to
remain in place and maintain its original colors [5]. To get the ink into the dermis, tattoo
artists use a tattoo machine. The machine drives a needle into the skin between 50 to
3,000 times per minute, and each time the needle enters the skin it deposits insoluble ink
[5]. (Tattoo machines would require an entire article for themselves, and the focus of this
article is on the tattoo ink that is injected by the machines.)
This insoluble ink is made up of a suspension of solid pigments in a liquid carrier [6]. As
tattooing has existed for over 5000 years, the composition of the pigments used in tattoo
ink has changed with time. Pigments are used instead of dyes in tattoos due to their
insolubility, meaning that the pigment will not dissolve in the human body. Originally
tattoo pigments were derived from animal or plant extracts; tattooists then moved to use
colored inorganic oxides and salts. Currently most modern tattoo artists use industrial
organic pigments [7]. These pigments are suspended in a wide variety of liquids, including:
water, witch hazel, alcohols, and surfactants [6]. The smallest pigments are black pigments
made up of carbon black; the largest pigments are titanium white, or TiO2. Green and blue
inks are made up of phthalocyanines, a blue-green aromatic compound [8]; red and yellow
ink contains azo pigments [9].
Azo pigments and phthalocyanines are both organic
pigments. Organic pigments are favored over inorganic pigments because of their tinting
strength, resistance to enzymatic degradation, dispersion, and cost effectiveness [7].
Organic compounds are generally defined as carbon containing compounds, and inorganic
compounds generally do not contain carbon, however, there are some exceptions to this
rule.
The market for tattoo ink is largely unregulated. The U.S. Food and Drug Administration
(FDA) currently considers tattoo ink to be a cosmetic [10]. This designation has lead to
limited regulation regarding the pigments and solvents used in tattoo ink, and currently the
FDA does not attempt to regulate pigments or color additives [10]. Manufacturers are not
legally required to disclose the composition of the ink they sell [7]. While this policy
protects the manufacturer’s proprietary formula, it does so at the potential expense of the
consumer. Tattoo inks made using inorganic compounds are still in use today, although
their use is not as widespread as before due to the shift to safer, organic pigments. These
inorganic pigments often consist of heavy metals, including lead molybdates and
cadmiums, in order to produce bright colors [11]. Heavy metal pigments can result in toxic
reactions.
Tattoos as Bioindicators
Researchers as MIT are working to create a new type of blood glucose monitor using
carbon nanotube technology. They plan to use carbon nanotubes coated with a polymer
that fluoresces in the presence of glucose, and through measurement of the amount of
fluorescence, determine the level of glucose in the blood.
The nanotubes would be
suspended in a saline solution, creating injectable ink with a lifetime of approximately six
months [15]. This ink would be used to create a tattoo for the patient using a regular tattoo
gun. The tattoo will be located in a discreet location, potentially the upper arm, where the
meter can be worn.
Nanotechnology is the manipulation of material on the nanoscale, or 1/1,000,000,000
meters, the size of atoms and molecules. When working at the nanoscale, materials begin
to exhibit quantum properties, leading to interesting new material interactions and
potential applications for nanotechnology.
The carbon nanotube is a structure made up of pure carbon arranged in a cylindrical
nanostructure that is only billionths of a meter wide, 100,000 times narrower than a
human hair [12]. Despite their size carbon nanotubes have astounding physical and
electronic properties. The Young’s modulus, a measure of the stiffness of a material, for
carbon nanotubes was 50 times that of steel. This impressive strength comes from the sp2
bonds between the carbon atoms [13].
Carbon nanotubes have strong conductive
properties, allowing them to carry a current density 1000 times greater than copper [14].
The carbon nanotubes act as a vehicle for the glucose-indicating polymer. The polymer is a
hydrogel, a network of hydrophilic polymer chains [16]. When exposed to glucose, the
polymers in the hydrogel crosslink with each other, causing the gel to swell. Increasing the
concentration of glucose increases the swelling of the hydrogel, resulting in a detectable
increase in fluorescence when activated by near-infrared light. A wearable meter detects
these slight changes in fluorescence as it simultaneously shines near-infrared light onto the
tattoo.
The potential dangers and drawbacks of carbon nanotubes are currently being studied to
determine their safety in human medical use. When evaluating a biomaterial for human
use many tests must be performed, including implantation tests, cytotoxicity tests,
carcinogenicity tests, and in vivo pharmacokinetic studies [17]. Implantation tests ensure
that no negative reaction arises from a foreign material after it is implanted in living tissue.
Cytotoxicity tests determine if a compound will have toxic effect on the surrounding cells
due to leaching [18]. Pharmacokinetic studies determine the fate of the compound once
administered to an organism, this includes how the compound is absorbed and distributed
within the body. All of these tests are in place to ensure that the patient is not adversely
harmed by the material used to treat them. Researchers performed a study using mice
with increased sensitivity to cancer causing agents to compare the carcinogenicity of
tattooed carbon nanotubes compared to the control of carbon black tattoo ink.
Surprisingly, the researchers found a lower incidence of cancer in mice tattooed with
carbon nanotubes than the mice tattooed with carbon black tattoo ink, a widespread tattoo
ink [17].
As previously noted, there are great benefits to replacing the traditional method of blood
glucose monitoring, the main benefits being reduced cost and reduced pain and
inconvenience for the patient. An additional benefit to using tattoos to monitor blood
glucose levels is the ability to continuously monitor those levels. A study was done
comparing patients that received continuous glucose monitoring to patients that received
normal monitoring with a blood glucose meter. They found that the patients using the
continuous monitoring had better glycemic control, meaning fewer fluctuations in their
blood glucose level, and an overall reduced baseline blood glucose level [19]. Fewer
glucose level swings and a lower baseline glucose level lead to better long-term health of
the patient.
The application of this technology in humans is still years away, as the researchers leading
this study must still improve the accuracy of their sensor and conduct animal trials. If the
technology is successful and graduates to human use, it could change the lives of many
diabetics, and also potentially be applied to other diseases.
Future applications of this technology could include continuous cholesterol monitoring by
measuring the level of lipids in the blood, detection of certain types of cancers, or early
detection of AIDS. Continuous monitoring of a wide variety of conditions will allow for
human health to improve as a whole. Maybe in the distant future all humans will receive a
tattoo that contains an array of nanotubes that can detect and alert the patient about
various illnesses and diseases, all before going to the doctor. This future tattoo will be
possible as the field of nanotechnology and biomedical engineering progress hand in hand.
Major hurdles to this advancement include numerous FDA regulations and clinical trials
that must be done before this ink can be rolled out as a medical device.
Also, the
development of a wearable meter that can withstand daily wear while maintaining
accuracy is critical.
Finally, overcoming the stigma of tattoos will lead to a wider
acceptance of tattoos as a medical device.
Sources
[1] Centers for Disease Control and Prevention, “Diabetes Report Card 2012,” US
Department of Health and Human Services: Atlanta, United States, 2012.
[2] J. Fisher, “Tattooing the Body, Marking Culture,” Body and Society, vol. 8, no. 4, 2002, pp.
91-107.
[3] A. Keller et al, “New insights into the Tyrolean Iceman’s origin and phenotype as
inferred by whole-genome sequencing,” Nature Communications, Feb. 2012, pp. 1-9.
[Online] Available: Nature Communications, doi: 10.1038/ncomms1701 [Accessed: 11
Mar. 2013].
[4] L. Dorfer et al, “A medical report from the stone age?,” The Lancet, Sept. 1999, p. 10231025. [Online]. Available: PubMed, doi: 10.1016/S0140-6736(98)12242-0 [Accessed:
11 Mar. 2013].
[5] T. Wilson, How Tattoos Work, HowStuffWorks.com, Apr. 2000. [Online]. Available:
http://health.howstuffworks.com/skin-care/beauty/skin-and-lifestyle/tattoo.htm
[Accessed: 11 Mar. 2013].
[6] L. Jarvis, “Tattoo Ink,” Chemical & Engineering News, vol. 85, no. 46, Dec. 2007, p. 52.
[Online]. Available: Chemical & Engineering News,
http://cen.acs.org/articles/85/i46/Tattoo-Ink.html [Accessed: 11 Mar. 2013].
[7] K. Poon, I. Dadour and A. McKinley, “In situ chemical analysis of modern organic tattoing
inks and pigments by micro-Raman spectroscopy,” Journal of Raman Spectroscopy, vol.
39, no. 9, Sept 2008, p. 1227-1237. [Online]. Available: Wiley Online Library, doi:
10.1002/jrs.1973 [Accessed: 11 Mar. 2013].
[8] M. Dahlen, “The Phthalocyanines: A New Class of Synthetic Pigments and Dyes,”
Industrial & Engineering Chemistry, vol. 31, no. 7, Jul. 1939, pp. 839-847. [Online].
Available: ACS Publications, doi: 10.1021/ie50355a12 [Accessed: 11 Mar. 2013].
[9] T. Hogsberg et al , “Tattoo inks in genera usage contain nanoparticles,” British Journal of
Dermatology, vol. 165, no. 6, Dec 2011, pp. 1210-1218. [Online]. Available: Wiley Online
Library, doi: 10.1111/j.1365-2133.2011.10561.x [Accessed: 11 Mar. 2013].
[10] Tattoos & Permanent Makeup, U.S. Food and Drug Administration, Aug. 2012. [Online].
Available:
http://www.fda.gov/Cosmetics/ProductandIngredientSafety/ProductInformation/ucm
108530.htm [Accessed: 11 Mar. 2013].
[11] Replacing Heavy-Metal Based Pigments, SpecialChem, Jul. 2009. [Online]. Available:
http://www.specialchem4polymers.com/resources/articles/article.aspx?id=3740
[Accessed: 11 Mar. 2013].
[12] Charging Ahead: Carbon Nanotubes Could Hold Long-Sought Battery Technology
Breakthrough, Scientific American, Apr. 2010. [Online[. Available:
http://www.scientificamerican.com/article.cfm?id=earth-talk-charging-ahead
[Accessed: 11 Mar. 2013].
[13] Carbon Nanotubes and Other Nanostructured Materials, American Institute of Chemical
Engineers, Jul 2011. [Online]. Available:
http://www.aiche.org/resources/chemeondemand/webinars/carbon-nanotubes-andother-nanostructured-materials [Accessed: 11 Mar. 2013].
[14] S. Hong and S. Myung, “Nanotube Electronics: A flexible approach to mobility,” Nature
Nanotechnology, vol. 2, Apr. 2007, pp. 207- 208. [Online]. Available: nature.com, doi:
10.1038/nnano.2007.89 [Accessed: 11 Mar. 2013].
[15] A. Trafton, “’Tattoo’ may help diabetics track their blood sugar,” MIT news, May 2010.
[Online]. Available: http://web.mit.edu/newsoffice/2010/glucose-tattoo-0528.html
[Accessed: 11 Mar. 2013].
[16] P. Barone et al, “Modulation of Single-Walled Carbon Nanotube Photoluminescence by
Hydrogel Swelling,” ACS Nano, vol. 3, no. 12, Nov. 2009, pp. 3869-3877. [Online].
Available: ACS Publications, doi:10.1021/nn901025x [Accessed: 11 Mar. 2013].
[17] S. Takanashi et al, “Carcinogenicity evaluation for the application of carbon nanotubes
as biomaterials in rashH2 mice,” Scientific Reports, vol. 2, no. 498, Jul. 2012. [Online].
Available: U.S. National Library of Medicine National Institutes of Health, doi:
10.1038/srep00498 [Accessed: 11 Mar. 2013].
[18] MicroMed Laboratories, Test Services, MicroMed Laboratories, 2013. [Online],
Available: http://www.micromedlabs.com/services/cytotoxicity.php [Accessed: 30
Apr. 2013].
[19] The Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study
Group, “Continuous Glucose Monitoring and Intensive Treatment of Type 1 Diabetes,”
The New England Journal of Medicine, vol. 359, Oct. 2008, pp. 1464-1476. [Online].
Available: The New England Journal of Medicine, doi: 10.1056/NEJMoa0805017
[Accessed: 11 Mar. 2013].