Tag Archives: nanoimprint lithography

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.

A rose by any other name: water pinning nanostructures and wettability

There are two items about rose petals as bioinspiration for research in this posting. The first being the most recent research where scientists in Singapore have made an ultrathin film modeled on rose petals. From an Aug. 13, 2014 news item on Nanowerk (Note: A link has been removed),

A*STAR [based in Singapore] researchers have used nanoimprinting methods to make patterned polymeric films with surface topography inspired by that of a rose petal, producing a range of transparent films with high water pinning forces (“Bioinspired Ultrahigh Water Pinning Nanostructures”).

An Aug. 13, 2014 A*STAR news highlight, which originated the news item, describes the nature of the research,

A surface to which a water droplet adheres, even when it is turned upside down, is described as having strong water pinning characteristics. A rose petal and a lotus leaf are both superhydrophobic, yet dissimilarities in their water pinning properties cause a water droplet to stick to a rose petal but roll off a lotus leaf. The two leaf types differ in their micro- and nanoscale surface topography and it is these topographical details that alter the water pinning force. The rose petal has almost uniformly distributed, conical-shaped microscale protrusions with nanoscale folds on these protrusions, while the lotus leaf has randomly distributed microscale protrusions.

The imprinted surfaces developed by Jaslyn Law and colleagues at the A*STAR Institute of Materials Research and Engineering and the Singapore University of Technology and Design have uniformly distributed patterns of nanoscale protrusions that are either conical or parabolic in shape. The researchers found that the water pinning forces on these continuously patterned surfaces were much greater than on non-patterned surfaces and surfaces composed of isolated nanopillared structures or nanoscale gratings. They could then achieve high water pinning forces by patterning the nanoprotrusions onto polymeric films with a range of different non-patterned hydrophobicities, including polycarbonate, poly(methyl methacrylate) and polydimethylsiloxane (see image).

“Other methods that recreate the water pinning effect have used actual rose petals as the mold, but unless special care is taken, there are likely to be defects and inconsistencies in the recreated pattern,” says co-author Andrew Ng. “While bottom-up approaches for making patterns — for example, laser ablation, liquid flame spray or chemical vapor deposition — are more consistent, these methods are limited in the types of patterns that can be used and the scale at which a substrate can be patterned.”

In contrast, nanoimprinting methods are capable of fabricating versatile and large-scale surfaces, and can be combined with roll-to-roll techniques, hence potentially enabling more commercial applications.

The patterned polycarbonate surfaces were also shown to reduce the ‘coffee-ring’ effect: the unevenly deposited film left behind upon the evaporation of a solute-laden droplet. This mitigation of the coffee-ring effect may assist microfluidic technologies and, more generally, the patterned surfaces could be used in arid regions for dew collection or in anti-drip applications such as in greenhouses.

The study which was published online in Dec. 2013, was featured in a Jan. 22, 2014 article by Katherine Bourzac for C&EN (Chemistry and Engineering News),

In the early morning, dew clings to rose petals; when the sun rises, the dewdrops act like tiny lenses, making diffraction patterns that attract pollinating insects, says Jaslyn Bee Khuan Law, a materials scientist at the Agency for Science, Technology, and Research (A*STAR), in Singapore. A drop of water will cling to a rose petal even when it’s tilted or held upside down. The petals can hold onto these droplets because their surfaces consist of closely packed conical structures a few micrometers across. These microscale surface patterns tweak the surface tension of the water droplets, causing them to cling to the petals.

But none of these fabrication methods are amenable to large-scale, low-cost manufacturing, preventing commercialization of the water-clinging surfaces. So Law turned to a specialty of her lab: nanoimprint lithography. This printing method utilizes metal or silicon drums molded with nanoscale features on their surfaces. When the molds are heated and pressed against sheets of plastic, the plastic is embossed with the nanoscale pattern. This roll-to-roll printing process resembles the way newspapers are printed. It’s capable of producing large-area films in a short amount of time.

Water droplets easily slid off plastic films patterned with simple nanoscale gratings; isolated nanoscale pillars hung onto water slightly better. But the films with the best properties consisted of tightly packed cones about 300 nm tall. Plastic patterned with these structures could hold onto water droplets as massive as 69 mg. The team could print a 110- by 65-mm sheet of this plastic film at a speed of 10 m per minute. Currently, the dimensions of the films are limited by the size of the premade molds, Law says.

While the Singapore group has made good progress on manufacturing these materials, very basic, vexing questions about how water clings to these surfaces remain, Hayes says. For example, very small changes in the surface’s roughness can switch it from water-pinning to super hydrophobic, and researchers don’t have a detailed understanding of why.

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

Bioinspired Ultrahigh Water Pinning Nanostructures by Jaslyn Bee Khuan Law, Andrew Ming Hua Ng, Ai Yu He, and Hong Yee Low. Langmuir, 2014, 30 (1), pp 325–331 DOI: 10.1021/la4034996 Publication Date (Web): December 20, 2013
Copyright © 2013 American Chemical Society

This paper appears to be open access (I was able to access it by clicking on the HTML option).

Finally, here’s an image supplied by the A*Star researchers to illustrate their work,

[downloaded from http://pubs.acs.org/doi/full/10.1021/la4034996]

[downloaded from http://pubs.acs.org/doi/full/10.1021/la4034996]

This second rose petal item comes from Australia and dates from Fall 2013. From a Sept. 18, 2013 news item on ScienceDaily,

A new nanostructured material with applications that could include reducing condensation in airplane cabins and enabling certain medical tests without the need for high tech laboratories has been developed by researchers at the University of Sydney [Australia].

“The newly discovered material uses raspberry particles — so-called because of their appearance — which can trap tiny water droplets and prevent them from rolling off surfaces, even when that surface is turned upside down,” said Dr Andrew Telford from the University’s School of Chemistry and lead author of the research recently published in the journal, Chemistry of Materials.

The ability to immobilise [pin] very small droplets on a surface is, according to Dr Telford, a significant achievement with innumerable potential applications.

A Sept. 17, 2013 University of Sydney news release, which originated the news item, provides more insight into the research where the scientists have focused on ‘raspberry particles’ which could also be described as the ‘conical structures’ mentioned in the A*STAR work to achieve what appear to be similar ends,

Raspberry particles mimic the surface structure of some rose petals.

“Water droplets bead up in a spherical shape on top of rose petals,” Dr Telford said. “This is a sign the flower is highly water repellent.”

The reasons for this are complex and largely due to the special structure of the rose petal’s surface. The research team replicated the rose petal by assembling raspberry particles in the lab using spherical micro- and nanoparticles.

The result is that water droplets bead up when placed on films of the raspberry particles and they’re not able to drip down from it, even when turned upside down.

“Raspberry particle films can be described as sticky tape for water droplets,” Dr Telford said.

This could be useful in preventing condensation issues in airplane cabins. It could also help rapidly process simple medical tests on free-standing droplets, with the potential for very high turnover of tests with inexpensive equipment and in remote areas.

Other exciting applications are under study: if we use this nanotechnology to control how a surface is structured we can influence how it will interact with water.

“This means we will be able to design a surface that does whatever you need it to do.

“We could also design a surface that stays dry forever, never needs cleaning or able to repel bacteria or even prevent mould and fungi growth.

“We could then tweak the same structure by changing its composition so it forces water to spread very quickly.

“This could be used on quick-dry walls and roofs which would also help to cool down houses.

“This can only be achieved with a very clear understanding of the science behind the chemical properties and construction of the surface,” he said.

The discovery is also potentially viable commercially.

“Our team’s discovery is the first that allows for the preparation of raspberry particles on an industrial scale and we are now in a position where we can prepare large quantities of these particles without the need to build special plants or equipment,” Dr Telford said.

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

Mimicking the Wettability of the Rose Petal using Self-assembly of Waterborne Polymer Particles by A. M. Telford, B. S. Hawkett, C. Such, and C. Neto. Chem. Mater., 2013, 25 (17), pp 3472–3479 DOI: 10.1021/cm4016386 Publication Date (Web): July 23, 2013
Copyright © 2013 American Chemical Society

This paper is behind a paywall.