The future of health care is in our cells
With a groundbreaking technology called nano-optoelectrodes, Virginia Tech associate professor Wei Zhou is working on a new way to make health care more personalized.
![Wei Zhou - Multi-Modal-Lab - Ben Murphy Associate Professor Wei Zhou holds up biochips in part of his Multi-Modal Lab in Whittemore Hall.](/content/news_vt_edu/en/articles/2024/05/eng-ece-personalized-healthcare-future-wei-zhou/_jcr_content/article-image.transform/m-medium/image.jpg)
In 1994, Ms. Frizzle took her fourth-grade elementary students aboard the Magic School Bus to investigate the inner workings of a classmate’s body while he fought off a cold. After they magically shrunk down the bus, they drove through the classmate's bloodstream, observed red and white blood cells working together, and endured almost being eaten by a blood cell when the bus was mistaken for bacteria.
Thirty years later, Wei Zhou is channeling his own inner Ms. Frizzle to make her cartoon adventure a reality with nano-antennas — incredibly tiny electrodes that go inside cells.
“We want to get information from within the cells,” said Zhou, associate professor in the Bradley Department of Electrical and Computer Engineering, “whether metabolite molecules, protein biomarkers, or even genetic information. But getting that information from within the cell without killing it is actually a very difficult challenge.”
Today’s standard technique of getting cellular information is called endpoint analysis, where cells are extracted for discovery, like when doctors perform a biopsy to diagnose a disease or infection. Using a needle or a scalpel, doctors remove fluid or tissue that is then analyzed for health issues. However, once the cells are extracted in a biopsy, the information they provide is finite — the cells are no longer connected to a living biological system.
Enter the Swiss army knife of small, bio-interfacing tools: nano-optoelectrodes.
![Chuan Xiao in the Multi-Modal Lab ECE graduate student Chuan Xiao works with biochips in the multi-modal lab.](/content/news_vt_edu/en/articles/2024/05/eng-ece-personalized-healthcare-future-wei-zhou/_jcr_content/content/adaptiveimage_copy.transform/m-medium/image.jpg)
Starting small, really small
As hybrid electrical-optical devices and sensors, nano-optoelectrodes are capable of reading both biochemical fingerprints and electrical activities of a cell’s molecules in a continuous, real-time stream. The multifunctional nature of the optoelectrodes sets it apart from other bio-interfacing tools because it fuses a nano-antenna — a microscopic version of the large-scale antennas we interact with every day, such as radio towers — and nano-electrodes, which are devices that deliver or take out electricity, like welding tools or batteries.
The optoelectrode design even mimics its full-sized counterparts, built into shape called a nanopillar. At the microscopic level it can look like the Eiffel Tower, with a solid base and a pointy top.
“Due to the structure of the nano-optoelectrodes, it can trick the cell into engulfing it,” Zhou said. “We use a short-pulsed laser to induce vapor nano-bubble generation, so the device can penetrate through the cell membrane and send out electrical signals.”
That nano-bubble generation is called optoporation, a pinpoint bit of heat that temporarily vaporizes a tiny hole in the cell membrane; it’s an ultra-precise, minimally invasive nano-surgery that Zhou is helping to pioneer. Unlike in endpoint analysis, where cells are removed from the body and permanently destroyed in the process of extracting data, the optoelectrodes go inside the cells and stay there, no damage necessary.
Once inside the cell, the nano-optoelectrodes will employ artificial intelligence (AI) capable of machine learning to process and send out the intracellular data. It’s like having a team of tiny doctors inside your cells, constantly studying, testing, and reevaluating results that get shared with an “outside” team.
While Zhou is starting with a single cell and antenna, the future of his research is to create and deploy large-scale nano-optoelectrode arrays in wearable or implantable devices that go beyond today’s fitness trackers, smartwatches, and blood pressure monitors. Zhou is specifically interested in how cancer and neuron cells interact with each other, antibodies, and immunotherapies.
“The living system, the human system, is probably the most complicated system,” Zhou said. “We currently lack the tools to pick up information from all the domains within the body or to de-mystify what’s really going on.”
![Yuming Zhao in the Multi-Modal Lab ECE graduate student Yuming Zhao prepares to measure biological samples.](/content/news_vt_edu/en/articles/2024/05/eng-ece-personalized-healthcare-future-wei-zhou/_jcr_content/content/adaptiveimage.transform/m-medium/image.jpg)
The future of personalized medicine
The most well-known personalized medicine right now is targeted therapy – a type of cancer treatment specifically designed to target the proteins that control how cancer cells grow, divide, and spread. Due to cancer’s ability to potentially develop resistance, these therapies are often used in combination with others, like chemotherapy and radiation, that cause the death of cancerous and healthy cells.
But Zhou’s nano-optoelectrodes don’t harm cells to help solve medical concerns. The data gathered by the electrode’s AI can be utilized by doctors to truly understand – at the cellular level – a patient’s disease and develop treatment plans.
“Our nano-optoelectrodes provide higher quality intracellular information and can use machine learning to recognize and understand the detailed patterns between biochemical and bioelectrical activities inside cells,” Zhou said. “We can really understand, at the cellular network level, the patient, the cancer, and drug therapies. It can be very helpful to find the best therapeutic plan for personalized treatment.”
With the ever-evolving nature of cancer treatments and patient-to-patient variations of the disease, individualized tools like nano-optoelectrodes can provide groundbreaking control through AI’s ability to analyze data and continuously stream information from inside the body. It also reduces the patient impact, with less need for tissue samples.
For Zhou, one of the most fundamental contributions of these nano-optoelectrodes would be to brain science. Building the devices into a soft, flexible, porous mesh structure, this bio-interfacing tool could be implanted within the brain, picking up bioelectrical and biochemical neural activity. The technology could be used to determine when a patient's onset of a negative health condition, like Parkinson’s, or mental illness, like depression.
Much like the boundless imagination of Ms. Frizzle, the applications of nano-optoelectrode arrays are endless.
“It’s ultimately a scalable, real-time information conversion interface between cyber-physical and biological-biochemical domains – it can be for the human brain, or it can be for a wastewater system,” Zhou said. “We’re pursuing collaborations in biology, food science, virus and bacteria detection, and even chronic wound monitoring. So, what we’re building isn’t really the end product – it’s the platform technology. When we have the hardware infrastructure, it can lead to many, many different applications.”