Tag Archives: tattoos

Nanoscale tattoos for individual cells

It’s fascinating to read about a technique for applying ‘tattoos’ to living cells and I have two news items and news releases with different perspectives about this same research.

First out the door was the August 7, 2023 news item on ScienceDaily,

Engineers have developed nanoscale tattoos — dots and wires that adhere to live cells — in a breakthrough that puts researchers one step closer to tracking the health of individual cells.

The new technology allows for the first time the placement of optical elements or electronics on live cells with tattoo-like arrays that stick on cells while flexing and conforming to the cells’ wet and fluid outer structure.

“If you imagine where this is all going in the future, we would like to have sensors to remotely monitor and control the state of individual cells and the environment surrounding those cells in real time,” said David Gracias, a professor of chemical and biomolecular engineering at Johns Hopkins University who led the development of the technology. “If we had technologies to track the health of isolated cells, we could maybe diagnose and treat diseases much earlier and not wait until the entire organ is damaged.”

An August 7, 2023 Johns Hopkins University news release by (also on EurekAlert), which originated the news item, describes the research in an accessible fashion before delving into technical details,

Gracias, who works on developing  biosensor technologies that are nontoxic and noninvasive for the body, said the tattoos bridge the gap between living cells or tissue and conventional sensors and electronic materials. They’re essentially like barcodes or QR codes, he said.

“We’re talking about putting something like an electronic tattoo on a living object tens of times smaller than the head of a pin,” Gracias said. “It’s the first step towards attaching sensors and electronics on live cells.”

The structures were able to stick to soft cells for 16 hours even as the cells moved.

The researchers built the tattoos in the form of arrays with gold, a material known for its ability to prevent signal loss or distortion in electronic wiring. They attached the arrays to cells that make and sustain tissue in the human body, called fibroblasts. The arrays were then treated with  molecular glues and transferred onto the cells using an alginate hydrogel film, a gel-like laminate that can be dissolved after the gold adheres to the cell. The molecular glue on the array bonds to a film secreted by the cells called the extracellular matrix.

Previous research has demonstrated how to use hydrogels to stick nanotechnology onto human skin and internal animal organs. By showing how to adhere nanowires and nanodots onto single cells, Gracias’ team is addressing the long-standing challenge of making optical sensors and electronics compatible with biological matter at the single cell level. 

“We’ve shown we can attach complex nanopatterns to living cells, while ensuring that the cell doesn’t die,” Gracias said. “It’s a very important result that the cells can live and move with the tattoos because there’s often a significant incompatibility between living cells and the methods engineers use to fabricate electronics.”

The team’s ability to attach the dots and wires in an array form is also crucial. To use this technology to track bioinformation, researchers must be able to arrange sensors and wiring into specific patterns not unlike how they are arranged in electronic chips. 

“This is an array with specific spacing,” Gracias explained, “not a haphazard bunch of dots.”

The team plans to try to attach more complex nanocircuits that can stay in place for longer periods. They also want to experiment with different types of cells.

Other Johns Hopkins authors are Kam Sang Kwok, Yi Zuo, Soo Jin Choi, Gayatri J. Pahapale, and Luo Gu.

This looks more like a sea creature to me but it’s not,

Caption: False-colored gold nanodot array on a fibroblast cell. Credit: Kam Sang Kwok and Soo Jin Choi, Gracias Lab/Johns Hopkins University.[The measurement, i.e., what looks like a ‘u’ with a preceding tail, in the lower right corner of the image is one micron/one millionth add that to the ‘m’ and you have what’s commonly described as one micrometre.]

An August 10, 2023 news item on ScienceDaily offers a different perspective from the American Chemical Society (ACS) on this research,

For now, cyborgs exist only in fiction, but the concept is becoming more plausible as science progresses. And now, researchers are reporting in ACS’ Nano Letters that they have developed a proof-of-concept technique to “tattoo” living cells and tissues with flexible arrays of gold nanodots and nanowires. With further refinement, this method could eventually be used to integrate smart devices with living tissue for biomedical applications, such as bionics and biosensing.

An August 10, 2023 ACS news release (also on EurekAlert), which originated the news item, explains some of the issues with attaching electronics to living tissue,

Advances in electronics have enabled manufacturers to make integrated circuits and sensors with nanoscale resolution. More recently, laser printing and other techniques have made it possible to assemble flexible devices that can mold to curved surfaces. But these processes often use harsh chemicals, high temperatures or pressure extremes that are incompatible with living cells. Other methods are too slow or have poor spatial resolution. To avoid these drawbacks, David Gracias, Luo Gu and colleagues wanted to develop a nontoxic, high-resolution, lithographic method to attach nanomaterials to living tissue and cells.

The team used nanoimprint lithography to print a pattern of nanoscale gold lines or dots on a polymer-coated silicon wafer. The polymer was then dissolved to free the gold nanoarray so it could be transferred to a thin piece of glass. Next, the gold was functionalized with cysteamine and covered with a hydrogel layer, which, when peeled away, removed the array from the glass. The patterned side of this flexible array/hydrogel layer was coated with gelatin and attached to individual live fibroblast cells. In the final step, the hydrogel was degraded to expose the gold pattern on the surface of the cells. The researchers used similar techniques to apply gold nanoarrays to sheets of fibroblasts or to rat brains. Experiments showed that the arrays were biocompatible and could guide cell orientation and migration.

The researchers say their cost-effective approach could be used to attach other nanoscale components, such as electrodes, antennas and circuits, to hydrogels or living organisms, thereby opening up opportunities for the development of biohybrid materials, bionic devices and biosensors.

The authors acknowledge funding from the Air Force Office of Scientific Research, the National Institute on Aging, the National Science Foundation and the Johns Hopkins University Surpass Program.

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

Toward Single Cell Tattoos: Biotransfer Printing of Lithographic Gold Nanopatterns on Live Cells by Kam Sang Kwok, Yi Zuo, Soo Jin Choi, Gayatri J. Pahapale, Luo Gu, and David H. Gracias. Nano Lett. 2023, 23, 16, 7477–7484 DOI: https://doi.org/10.1021/acs.nanolett.3c01960 Publication Date:August 1, 2023 Copyright © 2023 American Chemical Society

This paper is behind a paywall.

Tattoo yourself painlessly

This is all at the microscale (for those who don’t know what micro means in this context, it’s one-millionth; specifically, the needles are measured in miilionths of a meter).

Caption: A magnified view of a microneedle patch with green tattoo ink. Credit: Georgia Tech

From a September 14, 2022 Georgia Institute of Technology (Georgia Tech) news release (also on EurekAlert),

Instead of sitting in a tattoo chair for hours enduring painful punctures, imagine getting tattooed by a skin patch containing microscopic needles. Researchers at the Georgia Institute of Technology have developed low-cost, painless, and bloodless tattoos that can be self-administered and have many applications, from medical alerts to tracking neutered animals to cosmetics.

“We’ve miniaturized the needle so that it’s painless, but still effectively deposits tattoo ink in the skin,” said Mark Prausnitz, principal investigator on the paper. “This could be a way not only to make medical tattoos more accessible, but also to create new opportunities for cosmetic tattoos because of the ease of administration.”

Prausnitz, Regents’ Professor and J. Erskine Love Jr. Chair in the School of Chemical and Biomolecular Engineering, presented the research in the journal iScience, with former Georgia Tech postdoctoral fellow Song Li as co-author.

Tattoos are used in medicine to cover up scars, guide repeated cancer radiation treatments, or restore nipples after breast surgery. Tattoos also can be used instead of bracelets as medical alerts to communicate serious medical conditions such as diabetes, epilepsy, or allergies.

Various cosmetic products using microneedles are already on the market — mostly for anti-aging — but developing microneedle technology for tattoos is new. Prausnitz, a veteran in this area, has studied microneedle patches for years to painlessly administer drugs and vaccines to the skin without the need for hypodermic needles.

“We saw this as an opportunity to leverage our work on microneedle technology to make tattoos more accessible,” Prausnitz said. “While some people are willing to accept the pain and time required for a tattoo, we thought others might prefer a tattoo that is simply pressed onto the skin and does not hurt.” 

Transforming Tattooing

Tattoos typically use large needles to puncture repeatedly into the skin to get a good image, a time-consuming and painful process. The Georgia Tech team has developed microneedles that are smaller than a grain of sand and are made of tattoo ink encased in a dissolvable matrix.

“Because the microneedles are made of tattoo ink, they deposit the ink in the skin very efficiently,” said Li, the lead author of the study.

In this way, the microneedles can be pressed into the skin just once and then dissolve, leaving the ink in the skin after a few minutes without bleeding.  

Tattooing Technique

Although most microneedle patches for pharmaceuticals or cosmetics have dozens or hundreds of microneedles arranged in a square or circle, microneedle patch tattoos imprint a design that can include letters, numbers, symbols, and images. By arranging the microneedles in a specific pattern, each microneedle acts like a pixel to create a tattoo image in any shape or pattern.

The researchers start with a mold containing microneedles in a pattern that forms an image. They fill the microneedles in the mold with tattoo ink and add a patch backing for convenient handling. The resulting patch is then applied to the skin for a few minutes, during which time the microneedles dissolve and release the tattoo ink. Tattoo inks of various colors can be incorporated into the microneedles, including black-light ink that can only be seen when illuminated with ultraviolet light.

Prausnitz’s lab has been researching microneedles for vaccine delivery for years and realized they could be equally applicable to tattoos. With support from the Alliance for Contraception in Cats and Dogs, Prausnitz’s team started working on tattoos to identify spayed and neutered pets, but then realized the technology could be effective for people, too.

The tattoos were also designed with privacy in mind. The researchers even created patches sensitive to environmental factors such as light or temperature changes, where the tattoo will only appear with ultraviolet light or higher temperatures. This provides patients with privacy, revealing the tattoo only when desired.

The study showed that the tattoos could last for at least a year and are likely to be permanent, which also makes them viable cosmetic options for people who want an aesthetic tattoo without risk of infection or the pain associated with traditional tattoos. Microneedle tattoos could alternatively be loaded with temporary tattoo ink to address short-term needs in medicine and cosmetics.

Microneedle patch tattoos can also be used to encode information in the skin of animals. Rather than clipping the ear or applying an ear tag to animals to indicate sterilization status, a painless and discreet tattoo can be applied instead.

“The goal isn’t to replace all tattoos, which are often works of beauty created by tattoo artists,” Prausnitz said. “Our goal is to create new opportunities for patients, pets, and people who want a painless tattoo that can be easily administered.”

Prausnitz has co-founded a company called Micron Biomedical that is developing microneedle patch technology, bringing it further into clinical trials, commercializing it, and ultimately making it available to patients. 

Prausnitz and several other Georgia Tech researchers are inventors of the microneedle patch technology used in this study and have ownership interest in Micron Biomedical. They are entitled to royalties derived from Micron Biomedical’s future sales of products related to the research. These potential conflicts of interest have been disclosed and are overseen by Georgia Institute of Technology. 

You can see what they mean when they claim this is not competitive with the work you’ll see from a tattoo artist,

Heart tattoo: microneedle patch (above) and tattoo on skin (below).Credit: Song Li, Georgia Tech

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

Microneedle patch tattoos by Song Li, Youngeun Kim, Jeong Woo Lee, Mark R. Prausnitz. iScience DOI:https://doi.org/10.1016/j.isci.2022.105014 Published: September 14, 2022

This paper is open access.

The company mentioned in the news release, Micron Biomedical can be found here.

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.

Needle-free tattoos, smart and otherwise

Before getting to the research news from the University of Twente (Netherlands), there’s this related event which took place on April 18, 2019 (from the Future Under Our Skin webpage (on the University of Twente website) Note: I have made some formatting changes,

Why this event?

Our skin can give information about our health, mood and surroundings. Medical and recreational tattoos have decorated humans for centuries. But we can inject other materials besides ink, such as sensing devices, nano- or bio-responsive materials. With the increased percentage of tattooed population in recent years new health challenges have emerged; but is also a unique possibility to “read from our own skin”, beyond an artistic design. 
 
We have invited scientists, innovators, entrepreneurs, dermatologists, cosmetic permanent make-up technicians, tattoo artists, philosophers, and other experts. They will share with us their vision of the current and future role our skin has for improving the quality of life.

Open Event

This event is open to students, citizens in general as well as societal and governmental organisations around the different uses of our skin. The presence of scientists, medical doctors, tattoo artists and industry representatives is guaranteed. Then, we will all explore together the potential for co-creation with healthy citizens, patients, entreprises and other stakeholders.


If you want to hear from experts and share your own ideas, feel free to come to this Open Event!
 
It is possible to take the dish of the day (‘goed gevulde noedels met kippendij en satésaus en kroepoek’) in restaurant The Gallery (same building as DesignLab) at own costs (€7,85). Of course it is also possible to eat à la carte in Grand Café 

Wanneer: : 18 april 2019
Tijd: :17:30 – 20:00
Organisator: University of Twente
Locatie: Design Lab University of Twente
Hengelosestraat 500
7521 AN Enschede

Just days before, the University of Twente announced this research in an April 16, 2019 news item on Naowerk (Note: A link has been removed),

A tattoo that is warning you for too many hours of sunlight exposure, or is alerting you for taking your medication? Next to their cosmetic role, tattoos could get new functionality using intelligent ink. That would require more precise and less invasive injection technique.

Researchers of the University of Twente now develop a micro-jet injection technology that doesn’t use needles at all. Instead, an ultrafast liquid jet with the thickness of a human hair penetrates the skin. It isn’t painful and there is less waste.

In their new publication in the American Journal of Physics (“High speed imaging of solid needle and liquid micro-jet injections”), the scientists compare both the needle and the fluid jet approach.

Here’s an image provided by the researchers which illustrates the technique they have developed,

Working principle of needle-free injection: laser heating the fluid.The growing bubble pushes out the fluid (medicine or ink) at very high speed. Courtesy: University of Twente

An April 15, 2019 University of Twente press release, which originated the news item, provides more detail about tattoos and the research leading to ‘need-free’ tattoos,

Ötzi the Iceman already had, over 5000 years ago, dozens of simple tattoos on his body, apparently for pain relief. Since the classic ‘anchor’ tattoo that sailors had on their arms, tattoos have become more and more common. About 44 million Europeans wear one or more of them. Despite its wider acceptance in society, the underlying technique didn’t change and still has health risks. One or more moving needles put ink underneath the skin surface. This is painful and can damage the skin. Apart from that, needles have to be disposed of in a responsible way, and quite some ink is wasted. The alternative that David Fernández Rivas and his colleagues are developing, doesn’t use any needles. In their new paper, they compare this new approach with classic needle technology, on an artificial skin material and using high speed images. Remarkably, according to Fernández Rivas, the classic needle technology has never been subject of research in such a thorough way, using high speed images.

Fast fluid jet

The new technique employs a laser for rapidly heating a fluid that is inside a microchannel on a glass chip. Heated above the boiling point, a vapour bubble forms and grows, pushing the liquid out at speeds up to 100 meter per second (360 km/h). The jet, about the diameter of a human hair, is capable of going through human skin. “You don’t feel much of it, no more than a mosquito bite”, say Fernandez Rivas.

The researchers did their experiments with a number of commercially available inks. Compared to a tattoo machine, the micro-jet consumes a small amount of energy. What’s more important, it minimizes skin damage and the injection efficiency is much higher, there is no loss of fluids. And there is no risk of contaminated needles. The current microjet is a single one, while tattooing is often done using multiple needles with different types or colours of ink. Also, the volume that can be ‘delivered’ by the microjet has to be increased. These are next steps in developing the needle-free technology.

Skin treatment

In today’s medical world, tattoo-resembling techniques are used for treatment of skin, masking scars, or treating hair diseases. These are other areas in which the new technique can be used, as well as in vaccination. A challenging idea is using tattoos for cosmetic purposes and as health sensors at the same time. What if ink is light-sensitive or responds to certain substances that are present in the skin or in sweat?

On this new approach, scientists, students, entrepreneurs and tattoo artists join a special event ‘The future under our skin’, organized by David Fernandez Rivas.

Research has been done in the Mesoscale Chemical Systems group, part of UT’s MESA+ Institute.

Here’s a link to an d a citation for the paper,

High speed imaging of solid needle and liquid micro-jet injections by Loreto Oyarte Gálveza, Maria Brió Pérez, and David Fernández Rivas. Journal of Applied Physics 125, 144504 (2019); Volume 125, Issue 14 DOI: 10.1063/1.5074176 https://doi.org/10.1063/1.5074176 Free Published Online: 09 April 2019

This paper appears to be open access.

Nanoparticles from tattoo inks circulate through your body

English: Tattoo of Hand of Fatima,. Model: Casini. Date: 4 July 2017, 18:13:41. Source : Own work. Author: Stephencdickson.

For those who like their news in video format, there’s this Canadian Broadcasting Corporation (CBC) news item broadcast on Sep. 11, 2017 (after the commercials),

For those who like text and more detail, scientists at the European Synchrotron Radiation Facility (ESRF) have produced a study of the (at the nanoparticle scale) inks in tattoos. From a Sept. 12, 2017 news item on phys.org,

The elements that make up the ink in tattoos travel inside the body in micro and nanoparticle forms and reach the lymph nodes, according to a study published in Scientific Reports on 12 September [2017] by scientists from Germany and the ESRF, the European Synchrotron, Grenoble (France). It is the first time researchers have found analytical evidence of the transport of organic and inorganic pigments and toxic element impurities as well as in depth characterization of the pigments ex vivo in tattooed tissues. Two ESRF beamlines were crucial in this breakthrough.

A Sept. 12, 2017 ESRF press release (also on EurkeAlert), which originated the news item, explains further,

The reality is that little is known about the potential impurities in the colour mixture applied to the skin. Most tattoo inks contain organic pigments, but also include preservatives and contaminants like nickel, chromium, manganese or cobalt. Besides carbon black, the second most common ingredient used in tattoo inks is titanium dioxide (TiO2), a white pigment usually applied to create certain shades when mixed with colorants. Delayed healing, along with skin elevation and itching, are often associated with white tattoos, and by consequence with the use of TiO2. TiO2 is also commonly used in food additives, sun screens and paints. Scientists from the ESRF, the German Federal Institute for Risk Assessment, Ludwig-Maximilians University, and the Physikalisch-Technische Bundesanstalt have managed to get a very clear picture on the location of titanium dioxide once it gets in the tissue. This work was done on the ESRF beamlines ID21 and ID16B.

drawing tattookinetics.jpg

Translocation of tattoo particles from skin to lymph nodes. Upon injection of tattoo inks, particles can be either passively transported via blood and lymph fluids or phagocytized by immune cells and subsequently deposited in regional lymph nodes. After healing, particles are present in the dermis and in the sinusoids of the draining lymph nodes. Credits: C. Seim.

The hazards that potentially derive from tattoos were, until now, only investigated by chemical analysis of the inks and their degradation products in vitro. “We already knew that pigments from tattoos would travel to the lymph nodes because of visual evidence: the lymph nodes become tinted with the colour of the tattoo. It is the response of the body to clean the site of entrance of the tattoo. What we didn’t know is that they do it in a nano form, which implies that they may not have the same behaviour as the particles at a micro level. And that is the problem: we don’t know how nanoparticles react”, explains Bernhard Hesse, one of the two first authors of the study (together with Ines Schreiver, from the German Federal Institute for Risk Assessment) and ESRF visiting scientist.

titaniumdistribution.jpg

Particle mapping and size distribution of different tattoo pigment elements.  a, d) Ti and the Br containing pigment phthalocyanine green 36 are located next to each other. b, e) Log scale mappings of Ti, Br and Fe in the same areas as displayed in a) and d) reveal primary particle sizes of different pigment species. c, f) Magnifications of the indicated areas in b) and e), respectively. Credits: C. Seim.

X-ray fluorescence measurements on ID21 allowed the team to locate titanium dioxide at the micro and nano range in the skin and the lymphatic environment. They found a broad range of particles with up to several micrometres in size in human skin, but only smaller (nano) particles transported to the lymph nodes. This can lead to the chronic enlargement of the lymph nodes and lifelong exposure. Scientists also used the technique of Fourier transform infrared spectroscopy to assess biomolecular changes in the tissues in the proximity of the tattoo particles.

ESRF16_Tattoo-1low.jpg

Ines Schreiver doing experiments on ID16B with Julie Villanova. Credits: B. Hesse.

Altogether the scientists report strong evidence for both migration and long-term deposition of toxic elements and tattoo pigments as well as for conformational alterations of biomolecules that are sometimes linked to cutaneous adversities upon tattooing.

Then next step for the team is to inspect further samples of patients with adverse effects in their tattoos in order to find links with chemical and structural properties of the pigments used to create these tattoos.

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

Synchrotron-based ν-XRF mapping and μ-FTIR microscopy enable to look into the fate and effects of tattoo pigments in human skin by Ines Schreiver, Bernhard Hesse, Christian Seim, Hiram Castillo-Michel, Julie Villanova, Peter Laux, Nadine Dreiack, Randolf Penning, Remi Tucoulou, Marine Cotte, & Andreas Luch. Scientific Reports 7, Article number: 11395 (2017) doi:10.1038/s41598-017-11721-z Published online: 12 September 2017

This paper is open access.

Temporary tattoos mark the spot for surgery

Presumably they used markers of some kind before deciding on tattoos to mark the spot for surgeons.  Here’s more on the latest about temporary tattoos from a Dec. 21, 2016 news item on phys.org,

Tattoos aren’t just for body art. They can have medical applications, too. Doctors are using them on patients to mark an area for future treatment—particularly for non-melanoma skin cancer such as basal cell carcinoma—but the inks can cause problems. Now scientists have developed a better solution. In the journal ACS Nano, they report a new ink that glows only under certain light conditions and can disappear altogether after a period of time.

A Dec.21, 2016 American Chemical Society news release (also on EurekAlert), which originated the news item, describes the research and the reason for it in more detail,

Patients diagnosed with skin cancer typically have to wait up to three months between a biopsy confirming their condition and treatment. Doctors can mark the spot for possible future treatment using carbon graphite, India ink or fluorescent dye. But these pigments permanently color the skin, and can require laser or surgical removal after a patient has undergone surgery. They can also cause inflammation and discomfort at the site of the tattoo. Kai Chen, Gary S. Chuang, Hsian-Rong Tseng and colleagues wanted to develop a safer, more patient-friendly option.

The researchers created a time-limited pigment by cross-linking fluorescent supramolecular nanoparticles. Under ambient lighting, the nanoparticles are invisible, which would avoid unwanted markings in a patient’s skin. But the pigment glows under light shining at a wavelength of 465 nanometers, so doctors would be able to use a special light to see the dye. Testing in mice showed that tattoos created with these nanoparticles didn’t cause inflammation and lasted for three months. This would be long enough to mark a spot from biopsy through treatment for a non-melanoma patient.

The researchers have provided an image illustrating their work,

Temporary tattoo. Courtesy: ACS Nano

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

Cross-Linked Fluorescent Supramolecular Nanoparticles as Finite Tattoo Pigments with Controllable Intradermal Retention Times by Jin-sil Choi, Yazhen Zhu, Hongsheng Li, Parham Peyda, Thuy Tien Nguyen, Mo Yuan Shen, Yang Michael Yang, Jingyi Zhu, Mei Liu, Mandy M. Lee, Shih-Sheng Sun, Yang Yang, Hsiao-hua Yu, Kai Chen, Gary S. Chuang, and Hsian-Rong Tseng. ACS Nano, Article ASAP DOI: 10.1021/acsnano.6b06200 Publication Date (Web): November 30, 2016.

Copyright © 2016 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.

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.

Skin as art and as haptic device

I stumbled across an essay, Nano-Bio-Info-Cogno Skin by Natasha Vita-More on the IEET (Institute for Ethics & Emerging Technologies) website newly republished on Mar. 19, 2012. (The essay was originally published Jan. 19, 2009 on the Nanotechnology Now website.) No matter the date, it has proved quite timely in light of Nokia’s (Finnish telephone company) application to patent magnetic tattoos. From the Vibrating tattoo alerts patent filed by Nokia in US  March 20, 2012 story on the BBC News online,

Vibrating magnetic tattoos may one day be used to alert mobile phone users to phone calls and text messages if Nokia follows up a patent application.

The Finnish company has described the idea in a filing to the US Patent and Trademark Office.

It describes tattooing, stamping or spraying “ferromagnetic” material onto a user’s skin and then pairing it with a mobile device.

It suggests different vibrations could be used to create a range of alerts.

The application is dated March 15, 2012. From United States Patent Application no. 20120062371 (abstract),

1. An apparatus comprising: a material attachable to skin, the material capable of detecting a magnetic field and transferring a perceivable stimulus to the skin, wherein the perceivable stimulus relates to the magnetic field.

2. An apparatus according to claim 1, wherein the material comprises at least one of a visible image, invisible image, invisible tattoo, visible tattoo, visible marking, invisible marking, visible marker, visible sign, invisible sign, visible label, invisible label, visible symbol, invisible symbol, visible badge and invisible badge.

3. An apparatus according to claim 1, wherein the perceivable stimulus comprises vibration.

4. An apparatus according to claim 1, wherein the magnetic field originates from an electronic device and relates to digital content stored in the electronic device.

5. An apparatus according to claim 1, wherein the perceivable stimulus is related to the magnetic field.

6. An apparatus according to claim 1, wherein the perceivable stimulus relates to a time variation of at least one of a magnetic field pulse, height, width and period.

7. An apparatus according to claim 1, wherein the magnetic field originates from a remote source.

8. An apparatus according to claim 7, wherein the perceivable stimulus relates to digital content of the remote source.

If you want the full listing, there are 13 more claims for a total of 21 listed in the abstract. Nokia’s initial plans are to create a material that you’d wear, the notion of tattoos arises later in the application according to Vlad Bobleanta in his March 15, 2012 article for unwiredview.com. He describes the potential tattoos is some detail,

The tattoo would be applied using ferromagnetic inks. The ink material would first be exposed to high temperatures to demagnetize it. Then the tattoo would be applied. You’ll apparently be able to choose the actual image you want as the tattoo. The procedure is identical to that of getting a ‘normal’ tattoo – only the ink is special.

After the tattoo has been applied, you’ll need to magnetize it. That means bringing the tattooed area in the close proximity of an external magnet, and going “several times over this magnet to magnetize the image material again”. The tattoo will then have enhanced sensitivity towards external alternating magnet fields, and will basically function the same way the aforementioned material attached to your skin did. Only in a more permanent fashion, so to speak.

I suggest reading Bobleanta’s article as he includes diagrams of the proposed tattoo, fabric, and fingernail applications. Yes, this could be attached to your fingernails.

Getting back to Vita-More’s essay, she was exploring the integration of nanotechnology, biotechnology, cognitive and neuro sciences (nano-bio-info-cogno- or NBIC) as applied to skin (from the essay),

NBIC is a far cry from the biological touch, taste and smell of our skin because it suggests a cold, mechanical and invasive integration. While the cognitive and neuro sciences are a bit more familiar from a biological viewpoint, they too suggest tampering with our thoughts and probing our privacy. Nonetheless, the enhancement of our human skin is not only lifesaving; it offers new textures, sensations and smells which will have their own sensorial capabilities. [emphasis mine]

New sensorial capabilities certainly evokes Nokia’s proposed magnetic tattoo. She also comments from an artist’s perspective,

What does this mean for designers and media artists? From the perspective of my own artistic practice, it means that it is natural that humans integrate with other types of organisms, that we will evolve with other types of systems, and that this evolution is essential for our future.

The idea of fusing skin with technology is not new as you can see from Vita-More’s essay and countless science fiction stories, as well, there’s research of this kind being done globally. For example, there’s research on electronic tattoos as I noted in my Aug. 12, 2011 posting (and you can find more references elsewhere online). However, these magnetic tattoos represent the first time I’ve seen interest from a commercial enterprise.