Scientists at MIT have created a noninvasive healthcare monitoring apparatus potent enough to identify individual cells within blood vessels, yet compact enough to be worn like a wristwatch. A significant feature of this wearable gadget is its ability to allow ongoing observation of circulating cells within the human body.
This innovation was unveiled online on March 3 by the journal npj Biosensing and will soon appear in the journal’s print edition.
The device — called CircTrek — was developed by members of the Nano-Cybernetic Biotrek research collective, headed by Deblina Sarkar, an assistant professor at MIT and the AT&T Career Development Chair at the MIT Media Lab. This technology has the potential to significantly enhance early disease diagnosis, identify disease recurrence, evaluate infection risks, and ascertain the effectiveness of disease treatments, among various medical applications.
While conventional blood tests resemble a snapshot of a patient’s state, CircTrek was engineered for real-time evaluation, which the npj Biosensing paper describes as having been “an unmet goal until now.” Another technology that provides some level of continuous monitoring of cells in the bloodstream, known as in vivo flow cytometry, “demands a microscope the size of a room, and patients must stay there for extended periods,” explains Kyuho Jang, a doctoral student in Sarkar’s laboratory.
CircTrek, however, equipped with an integrated Wi-Fi module, has the capability to monitor a patient’s circulating cells from home, relaying that data to the patient’s physician or care team.
The apparatus functions by directing a focused laser beam to activate cells under the skin that have been fluorescently marked. This labeling can be achieved through various techniques, including applying antibody-based fluorescent dyes to the target cells or genetically altering those cells to express fluorescent proteins.
For instance, a patient undergoing CAR T cell therapy, wherein immune cells are gathered and modified in a laboratory to combat cancer (or, on an experimental basis, to treat HIV or Covid-19), could have those cells fluorescently labeled simultaneously using dyes or genetic modification for fluorescence. Notably, cells of interest may also be marked using in vivo labeling techniques approved for human use. Once the cells are labeled and circulating within the bloodstream, CircTrek is designed to administer laser pulses to amplify and detect the fluorescent signals from the cells, while a system of filters reduces low-frequency interference such as that produced by heartbeats.
“We fine-tuned the optomechanical components to significantly minimize noise, capturing only the signal from the fluorescent cells,” states Jang.
By detecting the labeled CAR T cells, CircTrek could evaluate the effectiveness of the cell therapy. For example, the persistence of CAR T cells in the bloodstream post-treatment is linked to better patient outcomes in those with B-cell lymphoma.
In order to maintain CircTrek’s compact and wearable design, the research team successfully miniaturized the components, such as the circuit that powers the high-intensity laser source and stabilizes the laser’s power level to prevent erroneous readings.
The sensor responsible for capturing the fluorescent signals of the labeled cells is also tiny but is capable of detecting light at the level of a single photon, according to Jang.
The subcircuits of the device, including the laser driver and noise suppression filters, were custom-designed to fit onto a circuit board measuring just 42 mm by 35 mm, allowing CircTrek to be roughly the same size as a smartwatch.
CircTrek underwent testing in an in vitro setup designed to emulate blood flow beneath human skin, and its single-cell detection capabilities were validated through manual counting utilizing a high-resolution confocal microscope. For the in vitro experiments, a fluorescent dye known as Cyanine5.5 was used. This particular dye was chosen for its peak activation at wavelengths within the optical window of skin tissue, enabling penetration through the skin with minimal scattering.
The device’s safety, especially concerning the temperature rise in experimental skin tissue from the laser, was also assessed. A rise of 1.51 degrees Celsius at the skin surface was determined to be well within safe limits, far below levels that would harm tissue, providing enough leeway to safely expand the device’s area of detection and power for observing at least one blood vessel.
Although further steps will be necessary for the clinical application of CircTrek, Jang believes that its parameters can be adjusted to expand its capabilities, ensuring that physicians can obtain crucial information on nearly any patient.