Tag Archives: microneedles

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.

Better recording with flexible backing on a brain-computer interface (BCI)

This work has already been patented, from a March 15, 2022 news item on ScienceDaily,

Engineering researchers have invented an advanced brain-computer interface with a flexible and moldable backing and penetrating microneedles. Adding a flexible backing to this kind of brain-computer interface allows the device to more evenly conform to the brain’s complex curved surface and to more uniformly distribute the microneedles that pierce the cortex. The microneedles, which are 10 times thinner than the human hair, protrude from the flexible backing, penetrate the surface of the brain tissue without piercing surface venules, and record signals from nearby nerve cells evenly across a wide area of the cortex.

This novel brain-computer interface has thus far been tested in rodents. The details were published online on February 25 [2022] in the journal Advanced Functional Materials. This work is led by a team in the lab of electrical engineering professor Shadi Dayeh at the University of California San Diego, together with researchers at Boston University led by biomedical engineering professor Anna Devor.

Caption: Artist rendition of the flexible, conformable, transparent backing of the new brain-computer interface with penetrating microneedles developed by a team led by engineers at the University of California San Diego in the laboratory of electrical engineering professor Shadi Dayeh. The smaller illustration at bottom left shows the current technology in experimental use called Utah Arrays. Credit: Shadi Dayeh / UC San Diego / SayoStudio

A March 14, 2022 University of California at San Diego news release (also on EurekAlert but published March 15, 2022), which originated the news item, delves further into the topic,

This new brain-computer interface is on par with and outperforms the “Utah Array,” which is the existing gold standard for brain-computer interfaces with penetrating microneedles. The Utah Array has been demonstrated to help stroke victims and people with spinal cord injury. People with implanted Utah Arrays are able to use their thoughts to control robotic limbs and other devices in order to restore some everyday activities such as moving objects.

The backing of the new brain-computer interface is flexible, conformable, and reconfigurable, while the Utah Array has a hard and inflexible backing. The flexibility and conformability of the backing of the novel microneedle-array favors closer contact between the brain and the electrodes, which allows for better and more uniform recording of the brain-activity signals. Working with rodents as model species, the researchers have demonstrated stable broadband recordings producing robust signals for the duration of the implant which lasted 196 days. 

In addition, the way the soft-backed brain-computer interfaces are manufactured allows for larger sensing surfaces, which means that a significantly larger area of the brain surface can be monitored simultaneously. In the Advanced Functional Materials paper, the researchers demonstrate that a penetrating microneedle array with 1,024 microneedles successfully recorded signals triggered by precise stimuli from the brains of rats. This represents ten times more microneedles and ten times the area of brain coverage, compared to current technologies.

Thinner and transparent backings

These soft-backed brain-computer interfaces are thinner and lighter than the traditional, glass backings of these kinds of brain-computer interfaces. The researchers note in their Advanced Functional Materials paper that light, flexible backings may reduce irritation of the brain tissue that contacts the arrays of sensors. 

The flexible backings are also transparent. In the new paper, the researchers demonstrate that this transparency can be leveraged to perform fundamental neuroscience research involving animal models that would not be possible otherwise. The team, for example, demonstrated simultaneous electrical recording from arrays of penetrating micro-needles as well as optogenetic photostimulation.

Two-sided lithographic manufacturing

The flexibility, larger microneedle array footprints, reconfigurability and transparency of the backings of the new brain sensors are all thanks to the double-sided lithography approach the researchers used. 

Conceptually, starting from a rigid silicon wafer, the team’s manufacturing process allows them to build microscopic circuits and devices on both sides of the rigid silicon wafer. On one side, a flexible, transparent film is added on top of the silicon wafer. Within this film, a bilayer of titanium and gold traces is embedded so that the traces line up with where the needles will be manufactured on the other side of the silicon wafer. 

Working from the other side, after the flexible film has been added, all the silicon is etched away, except for free-standing, thin, pointed columns of silicon. These pointed columns of silicon are, in fact, the microneedles, and their bases align with the titanium-gold traces within the flexible layer that remains after the silicon has been etched away. These titanium-gold traces are patterned via standard and scalable microfabrication techniques, allowing scalable production with minimal manual labor. The manufacturing process offers the possibility of flexible array design and scalability to tens of thousands of microneedles.  

Toward closed-loop systems

Looking to the future, penetrating microneedle arrays with large spatial coverage will be needed to improve brain-machine interfaces to the point that they can be used in “closed-loop systems” that can help individuals with severely limited mobility. For example, this kind of closed-loop system might offer a person using a robotic hand real-time tactical feedback on the objects the robotic hand is grasping.  

Tactile sensors on the robotic hand would sense the hardness, texture, and weight of an object. This information recorded by the sensors would be translated into electrical stimulation patterns which travel through wires outside the body to the brain-computer interface with penetrating microneedles. These electrical signals would provide information directly to the person’s brain about the hardness, texture, and weight of the object. In turn, the person would adjust their grasp strength based on sensed information directly from the robotic arm. 

This is just one example of the kind of closed-loop system that could be possible once penetrating microneedle arrays can be made larger to conform to the brain and coordinate activity across the “command” and “feedback” centers of the brain.

Previously, the Dayeh laboratory invented and demonstrated the kinds of tactile sensors that would be needed for this kind of application, as highlighted in this video.

Pathway to commercialization

The advanced dual-side lithographic microfabrication processes described in this paper are patented (US 10856764). Dayeh co-founded Precision Neurotek Inc. to translate technologies innovated in his laboratory to advance state of the art in clinical practice and to advance the fields of neuroscience and neurophysiology.

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

Scalable Thousand Channel Penetrating Microneedle Arrays on Flex for Multimodal and Large Area Coverage BrainMachine Interfaces by Sang Heon Lee, Martin Thunemann, Keundong Lee, Daniel R. Cleary, Karen J. Tonsfeldt, Hongseok Oh, Farid Azzazy, Youngbin Tchoe, Andrew M. Bourhis, Lorraine Hossain, Yun Goo Ro, Atsunori Tanaka, Kıvılcım Kılıç, Anna Devor, Shadi A. Dayeh. Advanced Functional Materials DOI: https://doi.org/10.1002/adfm.202112045 First published (online): 25 February 2022

This paper is open access.

Microneedle patch from Sweden

Strictly speaking this isn’t a ‘nano’ story but this work from Sweden provides a complement and contrast to the Australian nanopatch I mentioned in a post earlier today (Dec. 16, 2016). From a Dec. 12, 2016 news item on Nanowerk,

It’s only a matter of time before drugs are administered via patches with painless microneedles instead of unpleasant injections. But designers need to balance the need for flexible, comfortable-to-wear material with effective microneedle penetration of the skin. Swedish researchers say they may have cracked the problem.

In the recent volume of PLOS ONE (“Flexible and Stretchable Microneedle Patches with Integrated Rigid Stainless Steel Microneedles for Transdermal Biointerfacing”), a research team from KTH Royal Institute of Technology in Stockholm reports a successful test of its microneedle patch, which combines stainless steel needles embedded in a soft polymer base – the first such combination believed to be scientifically studied. The soft material makes it comfortable to wear, while the stiff needles ensure reliable skin penetration.

A Dec. 12, 2016 KTH Royal Institute of Technology press release, which originated the news item, describes exactly the limitation that the scientists are trying to surmount,

Unlike epidermal patches, microneedles penetrate the upper layer of the skin, just enough to avoid touching the nerves. This enables delivery of drugs, extraction of physiological signals for fitness monitoring devices, extracting body fluids for real-time monitoring of glucose, pH level and other diagnostic markers, as well as skin treatments in cosmetics and bioelectric treatments.

Frank Niklaus, professor of micro and nanofabrication at KTH, says that practically all microneedle arrays being tested today are “monoliths”, that is, the needles and their supporting base are made of the same – often hard and stiff – material. While that allows the microneedles to penetrate the skin, they are uncomfortable to wear. On the other hand, if the whole array is made from softer materials, they may fit more comfortably, but soft needles are less reliable for penetrating the skin.

“To the best of our knowledge, flexible and stretchable patches with arrays of sharp and stiff microneedles have not been demonstrated to date,” he says.

They actually tested two variations of their concept, one which was stretchable and slightly more flexible than the other. The more flexible patch, which has a base of molded thiol-ene-epoxy-based thermoset film, conformed well to deformations of the skin surface and each of the 50 needles penetrated the skin during a 30 minute test.

A successful microneedle product could have major implications for health care delivery. “The chronically ill would not have to take daily injections,” says co-author Niclas Roxhed, who is research leader at the Department of Micro and Nano Systems at KTH.

In addition to addressing people’s reluctance to take painful shots, microneedles also offer a hygiene benefit. The World Health Organization estimates that about 1.3 million people die worldwide each year due to improper handling of needles.

“Since the patch does not enter the bloodstream, there is less risk of spreading infections,” Roxhed says.

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

Flexible and Stretchable Microneedle Patches with Integrated Rigid Stainless Steel Microneedles for Transdermal Biointerfacing by Mina Rajabi, Niclas Roxhed, Reza Zandi Shafagh, Tommy Haraldson,  Andreas Christin Fischer, Wouter van der Wijngaart, Göran Stemme, Frank Niklaus. PLOS [Public Library of Science] http://dx.doi.org/10.1371/journal.pone.0166330 Published: December 9, 2016

This paper is open access.