Enhanced blood test monitoring with new lab-on-chip technology

Stanford researchers have developed a new device that can continuously sense levels of virtually any protein or molecule in the blood. The researchers say it could be transformative for disease detection, patient monitoring and biomedical research.

The RT-ELISA (Enzyme-linked Immunosorbent Assay) prototype consists of three modules: in the first (bottom), blood from the subject is mixed with a solution containing beads of target protein-detecting probes and fluorescent detection antibodies. The second module (top-right) eliminates excess blood cells. And the third module (top-left), transfers the fluorescently labeled beads to a detection window for measurement by a high-speed camera. 

Stanford Professor Tom Soh  explained that a blood test is unable to tell, for example, whether insulin or glucose levels are increasing or decreasing in a patient.

Soh, in collaboration with Eric Appel, an assistant professor of materials science and engineering, and colleagues has developed a technology that can provide this crucial piece of missing information. Real-time ELISA  is able to perform many blood tests very quickly and then stitch the individual results together to enable continuous, real-time monitoring of a patient’s blood chemistry. Instead of a snapshot, the researchers end up with something more like a movie, the researchers said.

ELISA has been the “gold standard” of biomolecular detection since the early 1970s and can identify virtually any peptide, protein, antibody , or hormone in the blood. An ELISA assay is good at identifying allergies, for instance. It is also used to spot viruses like HIV, West Nile and the SARS-CoV-2 coronavirus that causes COVID-19.

The Real-time ELISA is essentially an entire lab within a chip with tiny pipes and valves no wider than a human hair. An intravenous needle directs blood from the patient into the device’s tiny circuits where ELISA is performed over and over.

Soh likens the process of making a protein sandwich in which two molecules, or antibodies, are attached to the protein of interest. One antibody can be custom-tailored to seek out and latch onto the specific biomarker. Once it is attached, the second antibody is activated. This antibody fluoresces or glows, which is monitored by a high-speed camera. Based on how brightly the blood sample glows, scientists can determine not only whether the target protein is present but also its concentration. The more target molecule exists in the blood, the brighter the sample will be.

Real-time, continuous blood monitors have been developed for a few blood markers like glucose, lactate, and oxygen, but extending the technology beyond those few examples has proven “exceedingly difficult,” Soh said. This is why the Real-time ELISA’s adaptability to myriad proteins is especially promising.

Category: Features, Technology & Devices