Understanding how cells communicate is crucial for advancing our knowledge of various biological processes, particularly in diagnosing and treating medical conditions such as arrhythmia and Alzheimer’s disease. Traditional devices that monitor electrical signals in cell cultures typically rely on a multitude of wired connections, which can significantly limit the number of data collection points and the depth of information gleaned from cellular interactions.
Innovations from MIT researchers have led to the development of a revolutionary biosensing technique that eliminates these restrictive wires. Instead, this novel approach utilizes miniature, wireless antennas that harness light to detect minute electrical signals from biological cells.
These cutting-edge antennas, each just a hundredth the width of a human hair, leverage small electrical changes in their liquid environment to alter how they scatter light. By deploying an array of these tiny antennas, researchers can capture the electrical signals exchanged between cells with impressive spatial resolution.
The result is a device capable of continuously recording data for over 10 hours. This advancement offers biologists enhanced insights into cellular communication, particularly in relation to environmental changes. Ultimately, understanding these intricate processes could lead to groundbreaking advancements in diagnostic techniques and the development of targeted treatment options, fostering precise evaluations of new therapies.
“High-throughput and high-resolution recording of electrical activity in cells remains a significant challenge. Exploring innovative solutions is essential,” explains Benoît Desbiolles, lead author and former postdoc at the MIT Media Lab.
The team behind this research includes Jad Hanna, a visiting student; former visiting student Raphael Ausilio; postdoc Marta J. I. Airaghi Leccardi; Yang Yu from Raith America, Inc.; and Deblina Sarkar, senior author and AT&T Career Development Assistant Professor at the Media Lab and MIT Center for Neurobiological Engineering. Their groundbreaking study appears in the journal Science Advances.
“Electrical signals, or bioelectricity, are fundamental to cellular processes. Yet, achieving precise recordings of these signals has posed a challenge,” states Sarkar. “Our organic electro-scattering antennas (OCEANs) make it possible to wirelessly record electrical signals with micrometer resolution from thousands of points simultaneously, opening new avenues for understanding biology and altered signaling in disease states, as well as screening therapeutic effects for innovative treatments.”
Biosensing through Light
The team aimed to create a user-friendly biosensing device that required no wires or amplifiers, streamlining the use for biologists unfamiliar with complex electronic devices.
“We asked ourselves if it was feasible to convert electrical signals into light, allowing us to use common optical microscopes found in biological labs,” Desbiolles shares.
Initially, they explored a specialized polymer, PEDOT:PSS, to develop nanoscale transducers with small gold filament components designed to scatter light. However, their experimental results diverged from expected outcomes.
In a surprising twist, removing the gold components led to more consistent results aligning with their theoretical models. “We discovered that our measurements were primarily from the polymer, not the gold. This unexpected finding allowed us to advance our organic electro-scattering antennas,” Desbiolles explains.
The OCEANs consist of PEDOT:PSS, which interacts with positive ions in the liquid surrounding it upon the presence of electrical activity. This interaction modifies its chemical structure, affecting its refractive index, and thus alters its light scattering properties.
By shinning light onto these antennas, the intensity of the light variation corresponds directly to the electrical signals present in the surrounding liquid.
The researchers can now use an array of thousands to millions of these 1-micrometer-wide antennas to capture and analyze scattered light with an optical microscope, elevating the measurement of electrical signals to an unprecedented resolution. Since each antenna operates as an independent sensor, it allows for precise monitoring of electrical signals without the need to consolidate data from multiple sensors, leading to the superior micrometer-level resolution.
Specifically designed for in vitro studies, OCEAN arrays facilitate cell cultures growing directly atop them, making them easier to analyze under an optical microscope.
“Growing” Antennas on a Chip
The fabrication precision of these devices is paramount, achieved within MIT.nano facilities. The process begins with a glass substrate topped with alternating layers of conductive and insulating, optically transparent materials. The researchers then employ a focused ion beam to create intricate nanoscale holes in the upper layers, allowing for high-throughput nanofabrication.
“This specialized instrument operates much like a pen, etching patterns with incredible 10-nanometer precision,” Desbiolles notes.
Next, they immerse the chip in a solution containing polymer precursor materials. By applying an electric current, these precursors are drawn into the tiny holes, allowing mushroom-shaped antennas to grow from the bottom up.
This rapid fabrication technique permits the production of chips embedded with millions of antennas efficiently. “This method can be easily scaled up, with the only limitation being the number of antennas we can image simultaneously,” he adds.
The researchers meticulously optimized the dimensions of the antennas to achieve high sensitivity, successfully monitoring signals as low as 2.5 millivolts during simulated tests—much lower than the 100 millivolts typically used in neuronal communications.
“By thoroughly investigating the theoretical basis for this process, we have maximized sensitivity,” he states.
OCEANs can also quickly respond to fluctuating signals, capturing electrical activity with rapid kinetics. Future endeavors will test these devices with actual cell cultures, alongside efforts to redesign antennas for better membrane penetration, enhancing signal detection accuracy.
Moreover, the team aims to explore how OCEAN technology can be integrated into nanophotonic devices for future sensor and optical innovation.
This research receives funding from the U.S. National Institutes of Health and the Swiss National Science Foundation. The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health also supported some findings, with no endorsement from the NIH implied.
Photo credit & article inspired by: Massachusetts Institute of Technology
