Tiny, wireless antennas use light to monitor cellular communication

But devices that record electrical signals in cell cultures and other liquid environments often use wires to connect each electrode on the device to its own amplifier. Since there are only limited wires to connect to the device, this limits the number of recording sites and thus the information that can be collected from the cells.

MIT researchers have now developed a biosensing technology that requires no wires. Instead, tiny wireless antennas use light to detect tiny electrical signals.

Small electrical changes in the surrounding liquid environment change the way the antenna scatters light. Using an array of tiny antennas, each one-hundredth the width of a human hair, researchers can measure the electrical signals exchanged between cells with extremely high spatial resolution.

The devices are durable enough to record signals continuously for more than 10 hours, helping biologists understand how cells communicate in response to changes in their environment. In the long term, these scientific insights could pave the way for diagnostic advances, stimulate the development of targeted therapies, and enable more precise evaluation of new treatments.

“Being able to record the electrical activity of cells with high throughput and high resolution is still a real problem. We need to try some innovative ideas and alternative methods,” said Benoît Desbiolles, a former postdoc at the MIT Media Lab and lead author of the paper. said.

Jad Hanna, a visiting student in the Media Lab, co-authored the paper. Former visiting student Raphael Ausilio; former postdoc Marta JI Airaghi Leccardi; Yang Yu, scientist at Raith America, Inc.; senior author Deblina Sarkar, career development assistant professor at AT&T Media Lab and MIT Center for Neurobiological Engineering, and Nano-Cyber Head of ​netic Biotrek Laboratory. The research was published today in scientific progress.

“Bioelectricity is the basis of cellular function and different life processes. However, accurately recording such electrical signals has been challenging,” Sarkar said. “The organic electrical scattering antenna (OCEAN) we developed can wirelessly record electrical signals from thousands of recording sites at the same time with micron-level spatial resolution. This can create unprecedented opportunities for understanding signal changes in basic biology and disease states, and for screening diseases. opportunity.

photobiosensing

The researchers set out to design a biosensing device that would require no wires or amplifiers. This device would be easier to use for biologists unfamiliar with electronic instrumentation.

“We wanted to know if we could make a device that converts electrical signals into light, and then use an optical microscope (the kind found in every biology lab) to detect these signals,” Debiolles said.

Initially, they used a special polymer called PEDOT:PSS to design nanoscale sensors containing tiny gold wires. The gold nanoparticles are supposed to scatter light—a process that will be induced and modulated by the polymer. But the results were inconsistent with their theoretical model.

The researchers tried removing the gold, and surprisingly, the results were more consistent with the model.

“It turns out that what we measured was not a signal from the gold, but from the polymer itself. This was a very surprising but exciting result. We developed an organic electrical scattering antenna based on this discovery, ” he said.

Organic electrical scattering antenna (OCEAN) consists of PEDOT:PSS. When there is electrical activity nearby, the polymer attracts or repels positive ions from the surrounding liquid environment. This changes its chemical structure and electronic structure, changing an optical property called its refractive index, which changes the way it scatters light.

When the researchers shine light onto the antenna, the intensity of the light it scatters back changes in proportion to the electrical signals present in the liquid.

By arranging thousands or even millions of tiny antennas, each just 1 micron across, into arrays, researchers can use optical microscopes to capture scattered light and measure electrical signals from cells at high resolution. Because each antenna is an independent sensor, researchers do not need to pool the contributions of multiple antennas to monitor electrical signals, which is why OCEAN can detect signals with micron resolution.

OCEAN arrays are suitable for in vitro studies and are designed to culture cells directly on top of them and place them under a light microscope for analysis.

“Growing” antennas on wafers

Key to these devices is the precision with which researchers fabricate the arrays at the MIT.nano facility.

They started with a glass substrate and deposited a layer of conductive material on top, followed by insulating material, each layer being optically transparent. They then used a focused ion beam to cut hundreds of nanometer-sized holes into the top layer of the device. This special type of focused ion beam enables high-throughput nanofabrication.

“This instrument is basically like a pen and you can etch anything with 10 nanometer resolution,” he said.

They immersed the wafer in a solution containing the polymer precursor building blocks. By applying an electric current to the solution, the precursor material is attracted to the holes on the wafer, and the mushroom-shaped antenna “grows” from the bottom up.

The entire manufacturing process is relatively fast, and researchers can use this technology to create wafers with millions of antennas.

“This technology can be easily adapted, so it is fully scalable. The limiting factor is the number of antennas we can image simultaneously,” he said.

The researchers optimized the size of the antenna and adjusted its parameters so that it could achieve sensitivity high enough to monitor signals with voltages as low as 2.5 millivolts in simulation experiments. The signals sent by neurons for communication are usually around 100 millivolts.

“Because we took the time to really dig into and understand the theoretical models behind this process, we can maximize the sensitivity of the antenna,” he said.

Oceans can also respond to changing signals in just a few milliseconds, allowing them to record electrical signals with rapid dynamics. Going forward, the researchers hope to test these devices with real cell cultures. They also hope to reshape the antenna so that it can penetrate cell membranes, allowing for more precise signal detection.

Additionally, they want to investigate how the ocean can be integrated into nanophotonic devices, which manipulate light at the nanometer scale, for use in next-generation sensors and optical devices.

This research was funded in part by the National Institutes of Health and the Swiss National Science Foundation.