Monitoring electrical signals in biological systems helps scientists understand how cells communicate, which can aid in the diagnosis and treatment of conditions like arrhythmia and Alzheimer's.
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 respective amplifier. Because only so many wires can be connected to the device, this restricts the number of recording sites, limiting the information that can be collected from cells.
MIT researchers have now developed a biosensing technique that eliminates the need for wires. Instead, tiny, wireless antennas use light to detect minute electrical signals.
Small electrical changes in the surrounding liquid environment alter how the antennas scatter the light. Using an array of tiny antennas, each of which is one-hundredth the width of a human hair, the researchers could measure electrical signals exchanged between cells, with extreme spatial resolution.
The devices, which are durable enough to continuously record signals for more than 10 hours, could help biologists understand how cells communicate in response to changes in their environment. In the long run, such scientific insights could pave the way for advancements in diagnosis, spur the development of targeted treatments, and enable more precision in the evaluation of new therapies.
"Being able to record the electrical activity of cells with high throughput and high resolution remains a real problem. We need to try some innovative ideas and alternate approaches," says Benoît Desbiolles, a former postdoc in the MIT Media Lab and lead author of a paper on the devices.
He is joined on the paper by Jad Hanna, a visiting student in the Media Lab; former visiting student Raphael Ausilio; former postdoc Marta J. I. Airaghi Leccardi; Yang Yu, a scientist at Raith America, Inc.; and senior author Deblina Sarkar, the AT&T Career Development Assistant Professor in the Media Lab and MIT Center for Neurobiological Engineering and head of the Nano-Cybernetic Biotrek Lab. The research appears today in Science Advances.
"Bioelectricity is fundamental to the functioning of cells and different life processes. However, recording such electrical signals precisely has been challenging," says Sarkar. "The organic electro-scattering antennas (OCEANs) we developed enable recording of electrical signals wirelessly with micrometer spatial resolution from thousands of recording sites simultaneously. This can create unprecedented opportunities for understanding fundamental biology and altered signaling in diseased states as well as for screening the effect of different therapeutics to enable novel treatments."
Biosensing with light
The researchers set out to design a biosensing device that didn't need wires or amplifiers. Such a device would be easier to use for biologists who may not be familiar with electronic instruments.
"We wondered if we could make a device that converts the electrical signals to light and then use an optical microscope, the kind that is available in every biology lab, to probe these signals," Desbiolles says.
Initially, they used a special polymer called PEDOT:PSS to design nanoscale transducers that incorporated tiny pieces of gold filament. Gold nanoparticles were supposed to scatter the light -- a process that would be induced and modulated by the polymer. But the results weren't matching up with their theoretical model.
The researchers tried removing the gold and, surprisingly, the results matched the model much more closely.
"It turns out we weren't measuring signals from the gold, but from the polymer itself. This was a very surprising but exciting result. We built on that finding to develop organic electro-scattering antennas," he says.
The organic electro-scattering antennas, or OCEANs, are composed of PEDOT:PSS. This polymer attracts or repulses positive ions from the surrounding liquid environment when there is electrical activity nearby. This modifies its chemical configuration and electronic structure, altering an optical property known as its refractive index, which changes how it scatters light.
When researchers shine light onto the antenna, the intensity of the light it scatters back changes in proportion to the electrical signal present in the liquid.
With thousands or even millions of tiny antennas in an array, each only 1 micrometer wide, the researchers can capture the scattered light with an optical microscope and measure electrical signals from cells with high resolution. Because each antenna is an independent sensor, the researchers do not need to pool the contribution of multiple antennas to monitor electrical signals, which is why OCEANs can detect signals with micrometer resolution.
Intended for in vitrostudies, OCEAN arrays are designed to have cells cultured directly on top of them and put under an optical microscope for analysis.
"Growing" antennas on a chip
Key to the devices is the precision with which the researchers can fabricate arrays in the MIT.nano facilities.
They start with a glass substrate and deposit layers of conductive then insulating material on top, each of which is optically transparent. Then they use a focused ion beam to cut hundreds of nanoscale holes into the top layers of the device. This special type of focused ion beam enables high-throughput nanofabrication.
"This instrument is basically like a pen where you can etch anything with a 10-nanometer resolution," he says.
They submerge the chip in a solution that contains the precursor building blocks for the polymer. By applying an electric current to the solution, that precursor material is attracted into the tiny holes on the chip, and mushroom-shaped antennas "grow" from the bottom up.
The entire fabrication process is relatively fast, and the researchers could use this technique to make a chip with millions of antennas.
"This technique could be easily adapted so it is fully scalable. The limiting factor is how many antennas we can image at the same time," he says.
The researchers optimized the dimensions of the antennas and adjusted parameters, which enabled them to achieve high enough sensitivity to monitor signals with voltages as low as 2.5 millivolts in simulated experiments. Signals sent by neurons for communication are usually around 100 millivolts.
"Because we took the time to really dig in and understand the theoretical model behind this process, we can maximize the sensitivity of the antennas," he says.
OCEANs also responded to changing signals in only a few milliseconds, enabling them to record electrical signals with fast kinetics. Moving forward, the researchers want to test the devices with real cell cultures. They also want to reshape the antennas so they can penetrate cell membranes, enabling more precise signal detection.
In addition, they want to study how OCEANs could be integrated into nanophotonic devices, which manipulate light at the nanoscale for next-generation sensors and optical devices.
This research is funded, in part, by the U.S. National Institutes of Health and the Swiss National Science Foundation.