In recent times, we have all experienced the value of diagnostics used in the comfort and ease of our own homes. Imagine if we could look for other infectious diseases just as easily, with less invasive, self-administered, highly accurate, and reliable tests. Such tests would be highly valuable for patients where privacy is a concern, for patients in rural regions, and for rapidly screening large groups at venues and events. With the convergence of advances in telehealth and biotechnology, this is the direction that the diagnostics industry is heading towards.
Infectious disease diagnostics use nucleic acid (DNA or RNA) amplification techniques (NAAT) which look for target DNA and amplify this to gain an excellent limit of detection. The gold standard NAAT used is the polymerase chain reaction (PCR), a technique that has top-class accuracy. However, conventional PCR takes several steps to prepare and uses large, professional equipment, confining it to the laboratory. Players in the industry have been striving for decades to develop NAAT-based devices for point-of-care that has accuracy comparable with PCR. Some players have recently succeeded in commercializing their devices for at-home use. The recent report by IDTechEx, "Biosensors for Point-of-Care Diagnostics 2022-2032: Technology, Opportunities, Players and Forecasts", investigates the technologies that are opening NAATs to at-home use. Here are three key technologies bringing DNA diagnostics to the home.
Magnetic sample preparation
By far the most challenging issue for diagnostics developers is the issue of sample preparation. For NAATs to run, nucleic acids must be isolated from the sample's debris of cell material. In blood samples, there is extra debris from red blood cells and platelets. Lab-based PCR fractions off the nucleic acids from debris using large centrifuge machinery. However, at-home diagnostic devices cannot afford to be so generous with equipment. One popular approach several diagnostic players have turned to is the use of magnetic beads to isolate the nucleic acid. These magnetic beads are biofunctionalized with antibodies on their surfaces that will bind to all nucleic acids. The isolated nucleic acid can then be immobilized temporarily by a magnet, and the remaining debris in the sample can be washed away. Magnetic beads are very effective for small devices designed for the home, but they are expensive. Alternative sample preparation solutions exist, such as sonication methods but these trade off with other limitations, such as a need for a power source.
Amplification without the heat
Conventional PCR relies on a heating system that rapidly cycles through high and low temperatures to denature nucleic acids, opening them up for the amplification reaction to take place. In recent decades, players have turned to using isothermal NAATs, techniques that only use one temperature, to eliminate this constraint. There are many types of isothermal techniques, with the most used being loop-mediated isothermal amplification (LAMP), yet many industry players will use their own patented amplification chemistries. What these isothermal techniques have in common is the use of a polymerase with strand-displacement properties to replace the role of temperature in opening the nucleic acids. LAMP and other isothermal techniques are fast to amplify and eliminate the design issues of high temperatures. These technologies still have some challenges to solve, like issues with non-specific amplification (the amplification of unwanted DNA), which increases the risk of false positives in the test. These isothermal techniques also still require a small heating element (LAMP, for instance, runs at 60 degrees Celsius). Nevertheless, players are already optimizing their chemistries for room temperature.
Detection: Simple but effective LFAs
After amplification, diagnostic devices commonly use fluorescence as a readout. Amplified products (amplicons) are tagged with a fluorescent probe which can then be detected with a reader device. For professional point-of-care settings, such as in the clinic, the use of a benchtop reader device and single-use test cartridges employing the razorblade business model is standard. But at home, users do not want to have an expensive tabletop device that is only used occasionally. Instead, players are looking back to the oldest commercialized point-of-care diagnostic format to disrupt the detection space today: the lateral flow assay (LFA). The LFA is a cheap, compact, and single-use test that has been employed in pregnancy tests for decades and, more recently, COVID-19 immunoassays. These detect using a sandwich assay with gold nanoparticles coated in antibodies sensitive to proteins. When the antibodies bind their target, the gold is captured and gives a visible red color readout. For NAAT readouts, these antibodies can be designed to target specific nucleic acid amplicons instead of proteins.
These three technologies are examples of innovations enabling infectious disease diagnostics to become more rapid, automated, portable, and easy to use, making them more suitable for testing directly in the home. There is a wider range of technologies being developed by the industry, including techniques to automate sample preparation with microfluidics design; amplification techniques that look to miniaturize the PCR instead of using isothermal; and electrochemical detection methods that look for the electrical current generated by amplicons. The IDTechEx report "Biosensors for Point-of-Care Diagnostics 2022-2032: Technology, Opportunities, Players and Forecasts" explores this large array of technologies through the lens of their modular biosensor components, as well as by their diagnostic formats.
For more information, please visit www.IDTechEx.com/Biosensors, or for the full portfolio of healthcare research available from IDTechEx please visit www.IDTechEx.com/Research/Healthcare.
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