Tag Archives: microneedles

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.