Tag Archives: medical tattoos

Gold nanoparticle tattoo changes medical diagnostics?

The tattoos are in fact implantable sensors. Here’s more from an April 6, 2021 news item on ScienceDaily,

The idea of implantable sensors that continuously transmit information on vital values and concentrations of substances or drugs in the body has fascinated physicians and scientists for a long time. Such sensors enable the constant monitoring of disease progression and therapeutic success. However, until now implantable sensors have not been suitable to remain in the body permanently but had to be replaced after a few days or weeks. On the one hand, there is the problem of implant rejection because the body recognizes the sensor as a foreign object. On the other hand, the sensor’s color which indicates concentration changes has been unstable so far and faded over time. Scientists at Johannes Gutenberg University Mainz (JGU) have developed a novel type of implantable sensor which can be operated in the body for several months. The sensor is based on color-stable gold nanoparticles that are modified with receptors for specific molecules. Embedded into an artificial polymeric tissue, the nanogold is implanted under the skin where it reports changes in drug concentrations by changing its color.

An April 6, 2021 Johannes Gutenberg Universitaet Mainz press release (also on EurekAlert), which originated the news item, provides more detail about the proposed tattoo/implantable sensors,

Implant reports information as an “invisible tattoo”

Professor Carsten Sönnichsen’s research group at JGU has been using gold nanoparticles as sensors to detect tiny amounts of proteins in microscopic flow cells for many years. Gold nanoparticles act as small antennas for light: They strongly absorb and scatter it and, therefore, appear colorful. They react to alterations in their surrounding by changing color. Sönnichsen’s team has exploited this concept for implanted medical sensing.

To prevent the tiny particles from swimming away or being degraded by immune cells, they are embedded in a porous hydrogel with a tissue-like consistency. Once implanted under the skin, small blood vessels and cells grow into the pores. The sensor is integrated in the tissue and is not rejected as a foreign body. “Our sensor is like an invisible tattoo, not much bigger than a penny and thinner than one millimeter,” said Professor Carsten Sönnichsen, head of the Nanobiotechnology Group at JGU. Since the gold nanoparticles are infrared, they are not visible to the eye. However, a special kind of measurement device can detect their color noninvasively through the skin.

In their study published in Nano Letters, the JGU researchers implanted their gold nanoparticle sensors under the skin of hairless rats. Color changes in these sensors were monitored following the administration of various doses of an antibiotic. The drug molecules are transported to the sensor via the bloodstream. By binding to specific receptors on the surface of the gold nanoparticles, they induce color change that is dependent on drug concentration. Thanks to the color-stable gold nanoparticles and the tissue-integrating hydrogel, the sensor was found to remain mechanically and optically stable over several months.

Huge potential of gold nanoparticles as long-lasting implantable medical sensors

“We are used to colored objects bleaching over time. Gold nanoparticles, however, do not bleach but keep their color permanently. As they can be easily coated with various different receptors, they are an ideal platform for implantable sensors,” explained Dr. Katharina Kaefer, first author of the study.

The novel concept is generalizable and has the potential to extend the lifetime of implantable sensors. In future, gold nanoparticle-based implantable sensors could be used to observe concentrations of different biomarkers or drugs in the body simultaneously. Such sensors could find application in drug development, medical research, or personalized medicine, such as the management of chronic diseases.

Interdisciplinary team work brought success

Sönnichsen had the idea of using gold nanoparticles as implanted sensors already in 2004 when he started his research in biophysical chemistry as a junior professor in Mainz. However, the project was not realized until ten years later in cooperation with Dr. Thies Schroeder and Dr. Katharina Kaefer, both scientists at JGU. Schroeder was experienced in biological research and laboratory animal science and had already completed several years of research work in the USA. Kaefer was looking for an exciting topic for her doctorate and was particularly interested in the complex and interdisciplinary nature of the project. Initial results led to a stipend awarded to Kaefer by the Max Planck Graduate Center (MPGC) as well as financial support from Stiftung Rheinland-Pfalz für Innovation. “Such a project requires many people with different scientific backgrounds. Step by step we were able to convince more and more people of our idea,” said Sönnichsen happily. Ultimately, it was interdisciplinary teamwork that resulted in the successful development of the first functional implanted sensor with gold nanoparticles.

The researchers have provided an image which illustrates several elements described in the press release,

Caption: Gold nanoparticles embedded in a porous hydrogel can be implanted under the skin and used as medical sensors. The sensor is like an invisible tattoo revealing concentration changes of substances in the blood by color change. Credit: ill./©: Nanobiotechnology Group, JGU Department of Chemistry

Here’s a link to and a citation for the paper,

Implantable Sensors Based on Gold Nanoparticles for Continuous Long-Term Concentration Monitoring in the Body by Katharina Kaefer, Katja Krüger, Felix Schlapp, Hüseyin Uzun, Sirin Celiksoy, Bastian Flietel, Axel Heimann, Thies Schroeder, Oliver Kempski, and Carsten Sönnichsen. Nano Lett. 2021, XXXX, XXX, XXX-XXX DOI: https://doi.org/10.1021/acs.nanolett.1c00887 Publication Date:March 30, 2021 © 2021 The Authors. Published by American Chemical Society

This paper is behind a paywall.

Tattoos that detect glucose levels

Temporary tattoos with a biomedical function are a popular topic and one of the latest detects glucose levels without subjecting a person with diabetes to pin pricks. From a Jan. 14, 2015 news item on ScienceDaily,

Scientists have developed the first ultra-thin, flexible device that sticks to skin like a rub-on tattoo and can detect a person’s glucose levels. The sensor, reported in a proof-of-concept study in the ACS [American Chemical Society] journal Analytical Chemistry, has the potential to eliminate finger-pricking for many people with diabetes.

A Jan. 14, 2015 ACS news release on EurekAlert, which originated the news item, describes the current approaches to testing glucose and the new painless technique,

Joseph Wang and colleagues in San Diego note that diabetes affects hundreds of millions of people worldwide. Many of these patients are instructed to monitor closely their blood glucose levels to manage the disease. But the standard way of checking glucose requires a prick to the finger to draw blood for testing. The pain associated with this technique can discourage people from keeping tabs on their glucose regularly. A glucose sensing wristband had been introduced to patients, but it caused skin irritation and was discontinued. Wang’s team wanted to find a better approach.

The researchers made a wearable, non-irritating platform that can detect glucose in the fluid just under the skin based on integrating glucose extraction and electrochemical biosensing. Preliminary testing on seven healthy volunteers showed it was able to accurately determine glucose levels. The researchers conclude that the device could potentially be used for diabetes management and for other conditions such as kidney disease.

There is a Jan. 14, 2015 University of California at San Diego news release (also on EurekAlert) describing the work in more detail,

Nanoengineers at the University of California, San Diego have tested a temporary tattoo that both extracts and measures the level of glucose in the fluid in between skin cells. …

The sensor was developed and tested by graduate student Amay Bandodkar and colleagues in Professor Joseph Wang’s laboratory at the NanoEngineering Department and the Center for Wearable Sensors at the Jacobs School of Engineering at UC San Diego. Bandodkar said this “proof-of-concept” tattoo could pave the way for the Center to explore other uses of the device, such as detecting other important metabolites in the body or delivering medicines through the skin.

At the moment, the tattoo doesn’t provide the kind of numerical readout that a patient would need to monitor his or her own glucose. But this type of readout is being developed by electrical and computer engineering researchers in the Center for Wearable Sensors. “The readout instrument will also eventually have Bluetooth capabilities to send this information directly to the patient’s doctor in real-time or store data in the cloud,” said Bandodkar.

The research team is also working on ways to make the tattoo last longer while keeping its overall cost down, he noted. “Presently the tattoo sensor can easily survive for a day. These are extremely inexpensive—a few cents—and hence can be replaced without much financial burden on the patient.”

The Center “envisions using these glucose tattoo sensors to continuously monitor glucose levels of large populations as a function of their dietary habits,” Bandodkar said. Data from this wider population could help researchers learn more about the causes and potential prevention of diabetes, which affects hundreds of millions of people and is one of the leading causes of death and disability worldwide.

People with diabetes often must test their glucose levels multiple times per day, using devices that use a tiny needle to extract a small blood sample from a fingertip. Patients who avoid this testing because they find it unpleasant or difficult to perform are at a higher risk for poor health, so researchers have been searching for less invasive ways to monitor glucose.

In their report in the journal Analytical Chemistry, Wang and his co-workers describe their flexible device, which consists of carefully patterned electrodes printed on temporary tattoo paper. A very mild electrical current applied to the skin for 10 minutes forces sodium ions in the fluid between skin cells to migrate toward the tattoo’s electrodes. These ions carry glucose molecules that are also found in the fluid. A sensor built into the tattoo then measures the strength of the electrical charge produced by the glucose to determine a person’s overall glucose levels.

“The concentration of glucose extracted by the non-invasive tattoo device is almost hundred times lower than the corresponding level in the human blood,” Bandodkar explained. “Thus we had to develop a highly sensitive glucose sensor that could detect such low levels of glucose with high selectivity.”

A similar device called GlucoWatch from Cygnus Inc. was marketed in 2002, but the device was discontinued because it caused skin irritation, the UC San Diego researchers note. Their proof-of-concept tattoo sensor avoids this irritation by using a lower electrical current to extract the glucose.

Wang and colleagues applied the tattoo to seven men and women between the ages of 20 and 40 with no history of diabetes. None of the volunteers reported feeling discomfort during the tattoo test, and only a few people reported feeling a mild tingling in the first 10 seconds of the test.

To test how well the tattoo picked up the spike in glucose levels after a meal, the volunteers ate a carb-rich meal of a sandwich and soda in the lab. The device performed just as well at detecting this glucose spike as a traditional finger-stick monitor.

The researchers say the device could be used to measure other important chemicals such as lactate, a metabolite analyzed in athletes to monitor their fitness. The tattoo might also someday be used to test how well a medication is working by monitoring certain protein products in the intercellular fluid, or to detect alcohol or illegal drug consumption.

This reminds me a little of the Google moonshot project concerning health diagnostics. Announced in Oct. 2014, that project involved swallowing a pill containing nanoparticles that would circulate through your body monitoring your health and recongregating at your wrist so a band worn there could display your health status (Oct. 30, 2014 article by Signe Brewster for GigaOm). Experts welcomed the funding while warning the expectations seemed unrealistic given the current state of research and technology. This temporary tattoo seems much better grounded in terms of the technology used and achievable results.

Here’s a link to and a citation for the paper,

Tattoo-Based Noninvasive Glucose Monitoring: A Proof-of-Concept Study by Amay J. Bandodkar, Wenzhao Jia, Ceren Yardımcı, Xuan Wang, Julian Ramirez, and Joseph Wang. Anal. Chem., 2015, 87 (1), pp 394–398 DOI: 10.1021/ac504300n Publication Date (Web): December 12, 2014

Copyright © 2014 American Chemical Society

This appears to be an open access paper.

My latest posting posting on medical tattoos (prior to this) is an Aug. 13, 2014 post about a wearable biobattery.

A tattoo that’s a biobattery and a sensor?

It’s going to be an American Chemical Society (ACS) 248th meeting kind of week as yet another interesting piece of scientific research is bruited (spread) about the internet. This time it’s all about sweat, exercise, and biobatteries. From an Aug. 13, 2014 news item on Nanowerk,

In the future, working up a sweat by exercising may not only be good for your health, but it could also power your small electronic devices. Researchers will report today that they have designed a sensor in the form of a temporary tattoo that can both monitor a person’s progress during exercise and produce power from their perspiration.

An Aug. 13, 2014 ACS news release on EurekAlert, which originated the news item, describes the inspiration (as opposed to perspiration) for this technology,

The device works by detecting and responding to lactate, which is naturally present in sweat. “Lactate is a very important indicator of how you are doing during exercise,” says Wenzhao Jia, Ph.D.

In general, the more intense the exercise, the more lactate the body produces. During strenuous physical activity, the body needs to generate more energy, so it activates a process called glycolysis. Glycolysis produces energy and lactate, the latter of which scientists can detect in the blood.

Professional athletes monitor their lactate levels during performance testing as a way to evaluate their fitness and training program. In addition, doctors measure lactate during exercise testing of patients for conditions marked by abnormally high lactate levels, such as heart or lung disease. Currently, lactate testing is inconvenient and intrusive because blood samples must be collected from the person at different times during the exercise regime and then analyzed.

The news release goes on to describe the research process which resulted in a temporary tattoo that could be used to power small scale electronics,

Jia, a postdoctoral student in the lab of Joseph Wang, D.Sc., at the University of California San Diego, and her colleagues developed a faster, easier and more comfortable way to measure lactate during exercise. They imprinted a flexible lactate sensor onto temporary tattoo paper. The sensor contained an enzyme that strips electrons from lactate, generating a weak electrical current. The researchers applied the tattoo to the upper arms of 10 healthy volunteers. Then the team measured the electrical current produced as the volunteers exercised at increasing resistance levels on a stationary bicycle for 30 minutes. In this way, they could continuously monitor sweat lactate levels over time and with changes in exercise intensity.

The team then went a step further, building on these findings to make a sweat-powered biobattery. Batteries produce energy by passing current, in the form of electrons, from an anode to a cathode. In this case, the anode contained the enzyme that removes electrons from lactate, and the cathode contained a molecule that accepts the electrons.

When 15 volunteers wore the tattoo biobatteries while exercising on a stationary bike, they produced different amounts of power. Interestingly, people who were less fit (exercising fewer than once a week) produced more power than those who were moderately fit (exercising one to three times per week). Enthusiasts who worked out more than three times per week produced the least amount of power. The researchers say that this is probably because the less-fit people became fatigued sooner, causing glycolysis to kick in earlier, forming more lactate. The maximum amount of energy produced by a person in the low-fitness group was 70 microWatts per cm2 of skin.

“The current produced is not that high, but we are working on enhancing it so that eventually we could power some small electronic devices,” Jia says. “Right now, we can get a maximum of 70 microWatts per cm2, but our electrodes are only 2 by 3 millimeters in size and generate about 4 microWatts — a bit small to generate enough power to run a watch, for example, which requires at least 10 microWatts. So besides working to get higher power, we also need to leverage electronics to store the generated current and make it sufficient for these requirements.”

Biobatteries offer certain advantages over conventional batteries: They recharge more quickly, use renewable energy sources (in this case, sweat), and are safer because they do not explode or leak toxic chemicals.

“These represent the first examples of epidermal electrochemical biosensing and biofuel cells that could potentially be used for a wide range of future applications,” Wang says.

The ACS has made a video about this work available,

It seems to me this tattoo battery could be used as a self-powered monitoring device in a medical application for heart or lung disease.

University of Toronto’s (Canada) smiley face tattoo/sensor

Researchers at the University of Toronto have created a medical sensor that can be applied to the skin like a temporary tattoo.

University of Toronto Scarborough student Vinci Hung helped create the smiley face sensor shown here in the box at upper right (photo by Ken Jones)

The Dec. 3, 2012 news item on ScienceDaily notes,

A medical sensor that attaches to the skin like a temporary tattoo could make it easier for doctors to detect metabolic problems in patients and for coaches to fine-tune athletes’ training routines. And the entire sensor comes in a thin, flexible package shaped like a smiley face.

“We wanted a design that could conceal the electrodes,” says Vinci Hung, a PhD candidate in the Department of Physical & Environmental Sciences at UTSC [University of Toronto Scarborough], who helped create the new sensor. “We also wanted to showcase the variety of designs that can be accomplished with this fabrication technique.”

The Dec. 3, 2012 University of Toronto news release by Kurt Kleiner, which originated the news item, provides details about how the sensor/tattoo is fabricated and how it functions on the skin,

The new tattoo-based solid-contact ion-selective electrode (ISE) is made using standard screen printing techniques and commercially available transfer tattoo paper, the same kind of paper that usually carries tattoos of Spiderman or Disney princesses. In the case of the smiley face sensor, the “eyes” function as the working and reference electrodes, and the “ears” are contacts to which a measurement device can connect.

The sensor Hung helped make can detect changes in the skin’s pH levels in response to metabolic stress from exertion. Similar devices, called ion-selective electrodes (ISEs), are already used by medical researchers and athletic trainers. They can give clues to underlying metabolic diseases such as Addison’s disease, or simply signal whether an athlete is fatigued or dehydrated during training. The devices are also useful in the cosmetics industry for monitoring skin secretions.

But existing devices can be bulky, or hard to keep adhered to sweating skin. The new tattoo-based sensor stayed in place during tests, and continued to work even when the people wearing them were exercising and sweating extensively. The tattoos were applied in a similar way to regular transfer tattoos, right down to using a paper towel soaked in warm water to remove the base paper.

To make the sensors, Hung and her colleagues used a standard screen printer to lay down consecutive layers of silver, carbon fibre-modified carbon and insulator inks, followed by electropolymerization of aniline to complete the sensing surface.

By using different sensing materials, the tattoos can also be modified to detect other components of sweat, such as sodium, potassium or magnesium, all of which are of potential interest to researchers in medicine and cosmetology.

You can find the reserchers’ article in the Royal Society’s Analyst journal,

Tattoo-based potentiometric ion-selective sensors for epidermal pH monitoring
Amay J. Bandodkar ,  Vinci W. S. Hung ,  Wenzhao Jia ,  Gabriela Valdés-Ramírez ,  Joshua R. Windmiller ,  Alexandra G. Martinez ,  Julian Ramírez ,  Garrett Chan ,  Kagan Kerman and Joseph Wang in Analyst, 2013,138, 123-128 DOI: 10.1039/C2AN36422K

The article is open access but you do need to register for a free account with the Royal Society’s RSC [ublishing platform.