Tag Archives: David Gracias

Nanoscale tattoos for individual cells

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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.”

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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.

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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.

Small boxes in your bloodstream

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The boxes in question self-assemble although why anyone would consider the image of small boxes in one’s bloodstream appealing escapes me. Well, we are talking about engineers and mathematicians so perhaps it’s understandable. From the April 23, 2012 news item on Nanowerk,

… now, interdisciplinary research by engineers at Johns Hopkins University in Baltimore, Md., and mathematicians at Brown University in Providence, R.I., has led to a breakthrough showing that higher order polyhedra can indeed fold up and assemble themselves.

“What is remarkable here is not just that a structure folds up on its own, but that it folds into a very precise, three-dimensional shape, and it happens without any tweezers or human intervention,” says David Gracias, a chemical and biomolecular engineer at Johns Hopkins. “Much like nature assembles everything from sea shells to gem stones from the bottom up, the idea of self-assembly promises a new way to manufacture objects from the bottom up.”

Here’s a video from the US National Science Foundation about the work being done by David Gracias and his colleague at Brown University, mathematician Govind Menon,

Miles O’Brien of the NSF’s Science Nation magazine notes in his April 23, 2012 article that there are many applications for these structures,

Imagine thousands of precisely structured, tiny, biodegradable, boxes rushing through the bloodstream en route to a sick organ. Once they arrive at their destination, they can release medicine with pinpoint accuracy. That’s the vision for the future. For now, the more immediate concern is getting the design of the structures just right so that they can be manufactured with high yields.

“Our process is also compatible with integrated circuit fabrication, so we envision that we can use it to put silicon-based logic and memory chips onto the faces of 3-D polyhedra. Our methodology opens the door to the creation of truly three-dimensional ‘smart’ and multi-functional particles on both micro- and nano- length scales,” says Gracias.

Here’s more about the structures themselves, as mentioned in the video and in O’Brien’s article,

Menon’s team at Brown began designing these tiny 3-D structures by first flattening them out. They worked with a number of shapes, such as 12-sided interconnected panels, which can potentially fold into a dodecahedron shaped container. “Imagine cutting it up and flattening out the faces as you go along,” says Menon. “It’s a two-dimensional unfolding of the polyhedron.”

And not all flat shapes are created equal; some fold better than others. “The best ones are the ones which are most compact. There are 43,380 ways to fold a dodecahedron,” notes Menon.

The researchers developed an algorithm to sift through all of the possible choices, narrowing the field to a few compact shapes that easily fold into 3-D structures. Menon’s team sent those designs to Gracias and his team at Johns Hopkins who built the shapes, and validated the hypothesis.

“We deposit a material in between the faces and the edges, and then heat them up, which creates surface tension and pulls the edges together, fusing the structure shut,” explains Gracias. “The angle between adjacent panels in a dodecahedron is 116.6 degrees and in our process, pentagonal panels precisely align at these remarkably precise angles and seal themselves; all on their own.”

As noted earlier, I’m not thrilled with the idea of tiny boxes in my bloodstream but, analogy aside, the medical applications are appealing. As for Gracias’ smart and multifunctional particles, I look forward to hearing more about them.

3-D and self-assembly

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Here’s an intriguing approach to self-assembly for manufacturing purposes from scientists at Brown and Johns Hopkins Universities, respectively. From the Dec. 7, 2011 news item on Nanowerk,

In a paper published in the Proceedings of National Academy of Sciences (“Algorithmic design of self-folding polyhedra”), researchers from Brown and Johns Hopkins University determined the best 2-D arrangements, called planar nets, to create self-folding polyhedra with dimensions of a few hundred microns, the size of a small dust particle. The strength of the analysis lies in the combination of theory and experiment. The team at Brown devised algorithms to cut through the myriad possibilities and identify the best planar nets to yield the self-folding 3-D structures. Researchers at Johns Hopkins then confirmed the nets’ design principles with experiments.

Here’s the magnitude of the problem these scientists were solving (from the news item),

Material chemists and engineers would love to figure out how to create self-assembling shells, containers or structures that could be used as tiny drug-carrying containers or to build 3-D sensors and electronic devices.

There have been some successes with simple 3-D shapes such as cubes, but the list of possible starting points that could yield the ideal self-assembly for more complex geometric configurations gets long fast. For example, while there are 11 2-D arrangements for a cube, there are 43,380 for a dodecahedron (12 equal pentagonal faces). Creating a truncated octahedron (14 total faces – six squares and eight hexagons) has 2.3 million possibilities.

Associate professor of applied mathematics at Brown University, Govind Menon, says (from the news item),

“The issue is that one runs into a combinatorial explosion. … How do we search efficiently for the best solution within such a large dataset? This is where math can contribute to the problem.”

Here’s how they solved the problem (from the news item),

 

“Using a combination of theory and experiments, we uncovered design principles for optimum nets which self-assemble with high yields,” said David Gracias, associate professor in of chemical and biomolecular engineering at Johns Hopkins and a co-corresponding author on the paper.

“In doing so, we uncovered striking geometric analogies between natural assembly of proteins and viruses and these polyhedra, which could provide insight into naturally occurring self-assembling processes and is a step toward the development of self-assembly as a viable manufacturing paradigm.”

“This is about creating basic tools in nanotechnology,” said Menon, co-corresponding author on the paper. “It’s important to explore what shapes you can build. The bigger your toolbox, the better off you are.” While the approach has been used elsewhere to create smaller particles at the nanoscale, the researchers at Brown and Johns Hopkins used larger sizes to better understand the principles that govern self-folding polyhedra.

The news item on Nanowerk features more details, a video of a self-assembling dodecahedron, and an image of various options for 2-D nets that can be used to create 3-D shapes.

“Using a combination of theory and experiments, we uncovered design principles for optimum nets which self-assemble with high yields,” said David Gracias, associate professor in of chemical and biomolecular engineering at Johns Hopkins and a co-corresponding author on the paper. “In doing so, we uncovered striking geometric analogies between natural assembly of proteins and viruses and these polyhedra, which could provide insight into naturally occurring self-assembling processes and is a step toward the development of self-assembly as a viable manufacturing paradigm.”
“This is about creating basic tools in nanotechnology,” said Menon, co-corresponding author on the paper. “It’s important to explore what shapes you can build. The bigger your toolbox, the better off you are.”
While the approach has been used elsewhere to create smaller particles at the nanoscale, the researchers at Brown and Johns Hopkins used larger sizes to better understand the principles that govern self-folding polyhedra.