Synthetic Biology Meets Wearable Technology in a COVID-19 Detecting Face Mask

Researchers at Harvard and MIT have developed a face mask that uses wearable biological sensors to accurately detect COVID-19 in 90 minutes.

Wearable technology is rapidly changing the landscape of personal health and wellness. Wearable fitness trackers help people monitor their daily physical activity, heart rate, step count and more, while wearable medical devices are improving the lives of diabetics and epileptics. Currently, most wearable devices rely on flexible electrical components to deliver real-time data. However, with new advances in synthetic biology, cell-free technology allows researchers to incorporate complex diagnostic tools into wearables.

Recently, researchers at the Massachusetts Institute of Technology (MIT) and Harvard University created a face mask that uses cell-free biological sensors to detect the virus that causes COVID-19, SARS-CoV-2, in real-time. With the touch of a button, the wearer of the face mask can activate a biosensor to detect the virus in 90 minutes without the need for expensive machinery or a nasal swab. Their findings were recently published in Nature Biotechnology, and support an exciting new application for wearable technology in medical diagnostics.

A face mask incorporating the cell-free biosensor technology that detects SARS-CoV-2. (Image courtesy of the Wyss Institute at Harvard University.)

How Do We Detect SARS-CoV-2?

You’ve likely heard of several different types of testing when it comes to SARS-CoV-2 detection. In general, there are two main types of tests used to detect the virus globally: a PCR test and an antigen test.

The PCR test is the gold standard for SARS-CoV-2 detection and uses a process known as polymerase chain reaction (PCR) to detect anywhere from one to three of the genes found in the viral genome. Usually, a healthcare provider will collect a nasal swab and send the sample to a hospital or lab facility for testing. At the testing site, a technician will extract SARS-CoV-2 genetic material. Humans and other living organisms store their genetic material in DNA, but some viruses, like coronaviruses, store their genetic material in RNA. Because PCR is optimized to amplify DNA, a technician needs to first extract the viral RNA, turn it into DNA, and then amplify the DNA for detection in a PCR reaction. This process usually takes anywhere from one to three days.

A popular alternative to the PCR test widely available in most pharmacies is the rapid antigen test. Unlike the PCR test, samples can be collected and analyzed in under 20 minutes, delivering the fastest turnaround time available for test results. Instead of detecting the virus’s genetic material, the rapid antigen test detects proteins found on the surface of the virus. This process is called an immunoassay and involves the nasal swab being placed in an extraction buffer and then applied to a test strip that contains antibodies to detect viral protein. However, the benefit of speed comes at the cost of accuracy, and rapid antigen tests are usually used for screening purposes. Depending on why you need to get tested for SARS-CoV-2 infection, you will likely be sent for a PCR test to confirm your positive or negative result.

Serology tests are used to detect circulating antibodies in the blood to determine if a patient has been infected with SARS-CoV-2 or received a vaccine against the virus. This test cannot determine if a patient has an active infection, and uses known SARS-CoV-2 antigens to detect antibodies in a sample of blood.

An overview of the PCR test to detect active SARS-CoV-2 infection and the serology test to detect previous infection with the virus. (Image courtesy of the American Society for Microbiology.)

Despite the ongoing success of global vaccination campaigns, the COVID-19 pandemic is not over, and testing will be essential to help countries overcome the virus. A new face mask may help improve the testing process by using cell-free technology to rapidly detect SARS-CoV-2 infection with the accuracy of a PCR test.

The sensor uses wearable freeze-dried cell-free (wFDCF) technology and microfluidic chambers to extract, amplify, and ultimately detect SARS-CoV-2 genetic material. The mask is activated with the press of a button, allowing the wearer to release a sample of water that rehydrates the biological sensor and delivers a test result in 90 minutes. The test results are displayed inside the mask for privacy, and use a color-changing strip. One strip darkens if the wearer is positive for SARS-CoV-2 infection; a second strip also darkens if the wearer is negative.

The wFDCF technology takes the existing molecular machinery in cells that can read DNA and produce RNA and proteins. It then extracts and freeze-dries the material for stable, long-term storage. Just like the freeze-dried food you may have tried on a camping trip, these molecular tools can be re-activated by simply adding water.

The researchers first began developing this technology in response to the Zika outbreak that emerged in 2015. The team developed a paper-based diagnostic tool to rapidly detect the viruses that cause Zika and Ebola. They embedded a biosensor into paper to create an inexpensive and accurate tool for detecting the genetic material of both viruses. Since then, the scientists have been focused on incorporating this technology into wearables.

The detection process involves three sequential steps:

1. The sample and water flow into the “lysis zone,” where the virus’s membrane is cut open to release its genetic material.
2. Following a time delay, the sample and water enter the “amplification zone,” where an alternative to PCR, Recombinase Polymerase Amplification (RPA), makes many copies of the gene encoding the viral Spike protein.
3. Ultra-sensitive SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) CRISPR-based technology detects the amplified copies of the gene and then cuts a reporter molecule that is read out via the result strip in the mask.

An overview of the three stages of SARS-CoV-2 detection in the wearable diagnostic face mask. (Image courtesy of Nguyen et al., 2021, Nature Biotechnology.)

With the wFCDF face mask, the researchers have created a rapid, highly accurate detection system that operates at room temperature. Their wearable device allows individuals to receive a test result efficiently, without the need for expensive equipment, lab technicians, or invasive sampling techniques.

“We have essentially shrunk an entire diagnostic laboratory down into a small, synthetic biology-based sensor that works with any face mask, and combines the high accuracy of PCR tests with the speed and low cost of antigen tests,” said Peter Nguyen, study author and scientist at Harvard University’s Wyss Institute for Biologically Inspired Engineering.

However, the face mask still has some hurdles to overcome before it is available for consumer use. The researchers are working on a scalable manufacturing process and optimizing the test’s sensitivity to improve accuracy. Once their final prototype is optimized and ready for production, the researchers will need to conduct clinical trials and seek regulatory approval.

The researchers behind the SARS-CoV-2 detecting mask are already looking beyond the virus at the widespread applications of wFDCF technology for pathogen and toxin detection.

“This technology could be incorporated into lab coats for scientists working with hazardous materials or pathogens, scrubs for doctors and nurses or the uniforms of first responders and military personnel who could be exposed to dangerous pathogens or toxins, such as nerve gas,” said Nin Donghia, staff scientist at the Wyss Institute and co-author of the study.

With financial support from Johnson and Johnson’s “Lab Coat of the Future” challenge and the Defense Threat Reduction Agency, the team is poised to continue their research and develop new wearables for the detection of biologics.