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Am I Getting Sick?


A microfluidic chip for diagnosing diseases, which uses a minimal number of components and can be powered wirelessly by a smartphone.

Credit: Laboratory of Nanostructures and Biosensing, University of Minnesota

The future of "at-home" medical diagnostics went viral recently when the government started giving out free Covid tests.

People have been familiar with at-home medical testing for more than 50 years; the first patent for an in-home pregnancy test was filed in 1969.

Experts like Boston University professor Kenneth Burch say that what people really want from such in-home tests is not to just know what they already suspect (such as whether they are pregnant after missing a menstrual cycle), but to know the root cause of ambiguous symptoms. Are your sniffles just the result of a high pollen-count day and nothing worth worrying about, or are they an early sign of something more serious, ranging from a common cold to influenza to a weaponized laboratory-born virus?

For that reason, experts like Burch believe the future of over-the-counter at-home medical tests is trending toward multiple-malady detection—the first of which will likely be debuting as soon as next year (from Johnson and Johnson).

"I suspect a wider range of single-malady tests are unlikely. More likely are devices that are multiplexed—in other words, which can detect multiple targets—for example, the eight most common causes of your symptoms," said Burch.

Burch has been working in this field for many years, and has become a sought-after advisor on the capabilities of state-of-the-art medical electronics. According to Burch, the technology for eight simultaneous tests has just become the state of the art of what is possible for medical diagnostics whose goal is not to cure, but to aim people with very early symptoms to the correct medical specialist. Labs already prototyping multi-malady at-home tests range from government-funded bioweapon experts like the Biomedical Advanced Research and Development Authority (BARDA, a part of the U.S. Department of Health and Human Services) to giant consumer labs like Johnson and Johnson Innovation (JLABS), as well as independent at-home testing startups such as GRIP (Graphene Rapid Identification Platform) Molecular Technologies Inc.

The key to the technology underlying at-home simultaneous testing for multiple potential ailments is graphene—the pure crystalline lattice form of carbon, the building block of biology. Once thought to be a successor to silicon chips, graphene chips may have found a more suitable application in at-home medical testing, because graphene is the ultimate in bio-compatibility (since we are carbon-based life forms). Graphene also can function in field-effect transistors (FETs), which already are used in many type of medical devices.

In particular, G-FETs behave in the same manner as the silicon FETs that enable electronics with which we are already familiar, from mainframes to smartphones to pacemakers to defibrillators. They also smoothly interface with human "analytes"—the bodily fluids that can indicate the presence of a specific malady. A single atomic layer of graphene—used as the channel of a G-FET—can identify the presence of any known human analyte, thus detecting nearly any type of disease, according to the experts.

"G-FETs are appealing for developing diagnostics due to their ease of functionalization, electrical readout, robustness and ultrahigh sensitivity to numerous biological analytes," said Burch. "One simply stacks a 'linker' molecule on the graphene, then attaches any of a wide variety of biological molecules that bond with specific analytes."

The National Institute of Health (NIH) is developing such devices to identify rare diseases, blood disorders, and chronic obstructive pulmonary diseases. Independent labs have developed other devices for at-home medical testing, such as the Digital Dipstick for instantly identifying bacteria infections, and the Flow Cytometer for quickly pinpointing the severity of HIV infections.

The devices typically use atomically thin crystalline graphene lattices atop the "detection" channel of an FET. The linked analyte-detector molecules then are exposed to a human bodily fluid, such as saliva. If the malady analyte within the fluid attaches to the linked detector molecule, then the G-FET electrical output changes, indicating a "positive" result (and its severity). If there is no change in the G-FET's output, the test indicates a "negative" result for that malady.

The G-FET was developed for use in "at-home" malady detection by University of Minnesota professor Bruce Batten, who subsequently founded GRIP Molecular, where he now serves as Chief Science Officer (CSO). The development process at GRIP led to G-FET chips specialized to detect a specific pathogen. GRIP also has deals with Johnson and Johnson JLabs for commercialization of the chips, and with BARDA for bioweapon detection on the battlefield.

Batten explains in creating the G-FET chips, "We use CVD [chemical vapor deposition] to put a single atomic layer of graphene on a copper substrate. Then we chemically etch the copper away and transfer the atomically thin graphene layer to a silicon wafer." Standard photolithography is used to construct the source and drain electrodes at each end of the graphene-topped transistor channel, he said, adding, "We have achieved very high specificity when targeting specific molecules, the unique proteins that detect covid, influenza, and the four viruses causing the common cold."

8-Way Detection

GRIP initially was stymied when it came to multiplexing—that is, distributing a single bodily fluid sample among an array of G-FET chips, each specialized to detect a different malady. Attempting to keep the resulting devices cheap enough for "at home" use, GRIP first explored manual methods for distributing the fluid sample among the chips. One alternative explored was providing a syringe from which the test sample could be squeezed down a tube with an opening over each G-FET chip; air bubbles and fluid inconsistencies foiled any easy ways to equalize how much was received by each chip. Other methods using microelectromechanical systems (MEMS) were also considered, but required a battery-powered pump that would inflate the cost of materials out of the disposable test-kit range.

Finally, a colleague—Sang-Hyun Oh, Distinguished McKnight University Professor and Sanford P. Bordeau Chair in the Department of Electrical and Computer Engineering at the University of Minnesota—found a method that worked: radio-frequency (RF) open-channel pumping. Oh's lab perfected a method of using RF-stimulated electrodes to motivate biological test samples to move between G-FETs in an open-topped channel that releases air bubbles to produce a consistent even flow.

The key was carefully energizing closely spaced (10nm) electrodes that gently "push" the open-channel stream, then depending on capillary action to compel an even flow to the next G-FET, whereupon another gentle wireless RF push repeats the process until it reaches all eight G-FET chips.

"The ability to pump fluid along micron-sized open channels with wireless RF, without the need for complex MEMS structures, is elegant, practical, and paves the way for a new host of at-home testing applications," said Jaime Peraire, H. N. Slater Professor in Aeronautics and Astronautics at the Massachusetts Institute of Technology (who was not involved with the research).

"This technology has the potential to rapidly detect multiple targets in an easy-to-use, low-cost and low-power setup. The G-FETs can be made to work with a wide variety of detectors. The use of the RF reduces the needed time between delivering the sample and reading out results—both crucial for eventual at-home use," said Burch.

The RF signal can be delivered by an app of any smartphone capable of no-touch payments (using near-field communication). The reflected NFC signal also informs the app as to which G-FET detectors read-out results as positive, with the strength of the signal(s) indicating the seriousness of the malady. An app screen shows the results of all eight tests to the at-home user, and suggests the type of remedy required—from off-the-shelf pharmacy items to the kind of doctor that should be consulted. The results, of course, can also be directly sent to your doctor for professional evaluation.

All these details are being worked out, with the debut device from GRIP slated for next year, with the familiar Johnson and Johnson distribution and labeling the most likely consumer presentation.

 

R. Colin Johnson is a Kyoto Prize Fellow who has worked as a technology journalist for two decades.


 

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