By measuring electrical signals in biological systems, researchers can understand how cells communicate, opening avenues for the diagnosis and treatment of disorders in general, such as arrhythmia and Alzheimer’s.
Existing devices for taking electrical signals from living cell cultures and other liquid media generally use wires to connect each electrode with its amplifier. Since only a limited number of wires can be connected to the device, this limits the number of recording sites possible. Hence, there are inherent limits to the amount of data gleaned from the cells.
Now, MIT scientists have developed a biosensing technique that does not involve wires. Instead, tiny, wireless antennas use light to detect tiny electrical signals.
The little electrical variations in the liquid environment changed how the antennas scattered the light. An array of small antennas, each one-hundredth the width of a human hair, was used to measure the electrical signals exchanged among cells with extreme spatial resolution.
The devices, capable of recording for over 10 hours, may one day help biologists gain insight into how cells communicate their responses to environmental change. Such scientific insights could lead to better diagnosis, targeted treatments, and more accurate assessments of new therapies.
Benoît Desbiolles, a former postdoc in the MIT Media Lab and lead author of a paper on the devices, said, “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.”
Senior author Deblina Sarkar said, “Bioelectricity is fundamental to the functioning of cells and different life processes. However, recording such electrical signals precisely has been challenging. The organic electro-scattering antennas (OCEANs) we developed enable the simultaneous recording of electrical signals wirelessly with micrometer spatial resolution from thousands of recording sites.”
“This can create unprecedented opportunities for understanding fundamental biology and altered signaling in diseased states and for screening the effect of different therapeutics to enable novel treatments.”
The researchers aimed, therefore, to design a biosensor that would not require wires or amplifiers. It could promote a hands-on approach to the world of biologists with minimal cross-linkages with electronic instruments.
“We were wondering whether we could make a device so that electrical signals would go into the light and then probe these signals with an optical microscope. The kind present in every biology lab,” says Desbiolles.
Initially, they were using a special polymer called PEDOT:PSS to create nanoscale transducers with tiny bits of gold filaments. The light was supposed to be blown around due to the gold nanoparticles — a process induced and controlled by the polymer. But those results didn’t conform to the theories.
Then, the researchers removed the gold, and surprisingly, the results were far more closely aligned with the model.
Desbiolles said, “We weren’t measuring signals from the gold but from the polymer itself. This was an astonishing but exciting result. We built on that finding to develop organic electro-scattering antennas.”
The organic electro-scattering antennas, or OCEANs, are comprised of PEDOT:PSS. This polymer attracts or repels positive ions from the surrounding fluid medium while there is electrical activity close to it. This causes a change in the chemical configuration and electronic structure of the OCEAN, which modifies its optical property and the refractive index, hence determining how the antenna scatters light.
When the researchers shine light through the antenna, the amount of light that scatters is directly proportional to the magnitude of a nearby electrical signal in the liquid.
With thousands or millions of tiny antennas in an array, each only 1 micrometer wide, the researchers can capture the scattered light with the optical microscope and measure electrical signals from the cells with very high resolution. Since each antenna works as a standalone sensor, OCEANs do not need to integrate the seldom-numbered channels to study or monitor small electrical signals.
The OCEAN arrays are intended for in vitro studies, enabling cells to grow over their surface while under optical examination.
Central to that device is the accuracy with which the researchers can fabricate these arrays in MIT.nano facilities.
Glass substrates and transparent conductive and insulating material layers placed on each other are coated to form a multilayered chip. A focused ion beam cuts the very top layers of the device, punching hundreds of nanoscale holes. This unique concentrated ion beam enables high-throughput nanofabrication.
This instrument functions on the same principle as a pen since anything can be etched in 10-nanometer resolution.
The fabrication process is relatively fast, and the researchers could use this technique to make a chip with millions of antennas.
Desbiolles said, “This technique could be easily adapted so it is fully scalable. The limiting factor is how many antennas we can image simultaneously.”
Optimized dimensions and fine-tuning parameters gave the researchers an excellent sensitivity to read voltage signals as low as 2.5 mV in simulated experiments. Signals sent by neurons to communicate are generally around 100 millivolts.
“We took the time to understand the theoretical model behind this process so that we can maximize the sensitivity of the antennas,” he says.
OCEANs also were rapidly responsive to changing signals, on the order of a few milliseconds, enabling them to record electrical signals with fast kinetics. In the future, the researchers hope to test the devices with real cell cultures and reform the antennas so that they can penetrate cell membranes for further improved signal sensing.
Integration of OCEANs together with nanophotonic devices would include exploiting how such substances, under the nanoscale framework, would in the long run motivate the development of next-generation sensors and optical devices.
Journal Reference:
- Benoit Desbiolles, Jad Hanna et al. Organic electro-scattering antenna: Wireless and multisite probing of electrical potentials with high spatial resolution. Science Advances. DOI: 10.1126/sciadv.adr8380
