PCR-like Lab-On-a-Chip Infection Test
Source: Imperial College London

Researchers at Imperial College London say they have developed a novel lab-on-a-chip infection test that could provide less expensive and faster portable diagnostics. The chip, known as TriSilix, is a micro laboratory which performs a miniature version of the polymerase chain reaction (PCR) on bodily fluids, feces, or environmental samples, according to the scientists who published a paper “Disposable silicon-based all-in-one micro-qPCR for rapid on-site detection of pathogens” in Nature Communications.

“Rapid screening and low-cost diagnosis play a crucial role in choosing the correct course of intervention when dealing with highly infectious pathogens. This is especially important if the disease-causing agent has no effective treatment, such as the novel coronavirus SARS-CoV-2, and shows no or similar symptoms to other common infections. Here, we report a disposable silicon-based integrated Point-of-Need transducer (TriSilix) for real-time quantitative detection of pathogen-specific sequences of nucleic acids,” write the investigators.

“TriSilix can be produced at wafer-scale in a standard laboratory (37 chips of 10 x 10 x 0.65mm in size can be produced in 7h, costing ~0.35 USD per device). We are able to quantitatively detect a 563bp fragment of genomic DNA of Mycobacterium avium subspecies paratuberculosis through real-time PCR with a limit-of-detection of 20fg, equivalent to a single bacterium, at the 35th cycle. Using TriSilix, we also detect the cDNA from SARS-CoV-2 (1pg) with high specificity against SARS-CoV (2003).”

To make the silicon chip, the scientists developed a series of methods to produce the chips in a standard laboratory, cutting the costs and time they take to fabricate, potentially allowing them to be produced anywhere in the world.

“Rather than sending swabs to the lab or going to a clinic, the lab could come to you on a fingernail-sized chip,” explains Firat Güder, PhD, lead researcher in the department of bioengineering. “You would use the test much like how people with diabetes use blood sugar tests, by providing a sample and waiting for results—except this time it’s for infectious diseases.”

The team has so far used TriSilix to diagnose a bacterial infection mainly present in animals as well as a synthetic version of the genetic material from SARS-CoV-2, the virus behind COVID-19. The researchers say the system could in future be mounted onto handheld blood sugar test-style devices. This would let people test themselves and receive results at home for colds, flu, recurrent infections like those of the urinary tract (UTIs), and COVID-19.

Table-top devices for testing of infections like COVID-19 already exist, but these tests can be time-consuming and costly since the patient must go to a clinic, have a sample taken by a healthcare worker, and go home or stay in clinic to wait. People leaving their homes when not feeling well increases the risk of spread of a pathogen to others.

If validated on human samples, this new test could provide results outside a clinic, at home, or on-the-go within minutes.

The scientists also say a highly portable test could accelerate diagnosis of infections and reduce costs by eliminating transportation of samples. Such tests could be performed by individuals in the absence of highly trained medical professionals. So, if they need to self-isolate, they can start immediately without potentially infecting others.

Making testing more accessible and cheaper is especially important for people in rural areas of low-income countries, where clinics can be far away and expensive to travel to, notes Estefania Nunez-Bajo, PhD, also in the department of bioengineering and first author. If made available to patients, it could also be used to diagnose and monitor infections like UTIs, which often recur despite antibiotics.

“Monitoring infections at home could even help patients, with the help of their doctor, to personalize and tailor their antibiotic use to help reduce the growing problem of antibiotic resistance,” points out Nunez-Bajo.

Each lab-on-a-chip contains a DNA sensor, temperature detector, and heater to automate the testing process. A typical smartphone battery could power up to 35 tests on a single charge.

Next, the researchers plan to validate their chip with clinical samples, automate the preparation of samples and advance their handheld electronics. They are looking for partners and funders to help accelerate the translation of the technology deliver testing at resource limited settings at homes, farms, or remote locations in the developing world.

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