**4. Outlook for the future POCT development**

Over the last decade, several POCTs have been introduced to the market, but these tests have not been widely accepted by clinicians [42]. Moreover, the 2009 National Institute for Clinical Excellence (NICE) guideline CG 86 recommended that self-tests and/or POCT for celiac disease should not be used as a substitute for laboratory-based tests [43]. Therefore, even though the current POCT devices can be used to detect celiac disease with a relatively high sensitivity, their specificity somewhat lags behind lab-based tests. However, one of the biggest drawbacks of the current available POCTs is their lack of usability by a non-trained person.

Most of the lab-based tests for celiac disease are performed by trained clinical technicians, but POCTs are generally aimed to be performed by a non-trained person. Multiple steps and components, such as blood drawn from a finger prick, accurate amount of blood requirement, addition of dilatants or other solutions and visual interpretation, would typically introduce user errors leading to a decrease in accuracy of the tests. The usability of POCTs has been assessed on the example of HIV self-testing kits [44]. In this particular study, authors found that almost 50%

of the untrained participants performing POCT HIV test had made multiple errors during testing. It is clear that for a successful adaptation of POCTs across the globe, ideal self-test kits must include easy-to-understand instructions, preferably onestep operation and easy-to-interpret results.

As discussed above, most of the POCT systems utilize whole blood or serum samples for celiac disease detection. Drawing blood from vein or from finger prick can be viewed by some people as invasive and painful leading to a withdrawal from voluntary testing. In addition, all the mentioned laboratory or POCTs target autoantibodies, such as antibody against tTG, DGP, or even EMA. It means that celiac disease can only be detected after antibodies are circulated in the human body. However, antibody-based tests generally fail at the latent or silent cases of celiac disease or people on voluntary gluten-free diet. Can we achieve celiac disease detection when there is a low amount or no antibodies found? Maybe it is another challenge that researchers have to face when devising the future screening methods and tools for celiac disease.

In other fields of analyte detection, including the detection of blood glucose, onsite alcohol and illicit drug tests, and confirmation of pregnancy, there are already various well-developed and commercialized products from different brands. These examples comprise of the use of nanotechnology, microfluidics, or the combination of these two methods together that provide some inspiration for future methods of POCT for celiac disease. In particular, highly accurate and sensitive fast test of HIV [45, 46], tuberculosis [47–49], and malaria [50–52] combine the utilization of lateral flow microfluidics with visual colorimetric observation detection. Indeed, these POCT diagnostic devices can probably provide the most effective and useful tool for mass diagnosis. Additionally, these tests have been proven to be cost-effective, simple, and portable, as well as with capacity for multiplexing.
