Paper-Based Analytical Devices: A Simple yet Powerful Diagnostic Method

During the COVID-19 pandemic, have you ever woken up with a strange feeling in your throat and felt feverish? To determine if it was COVID-19, it used to take at least 24 hours to see a doctor and get the results of a sample sent to an external lab. However, in the later stages of the pandemic, antigen test kits made rapid, low-cost, and simple at-home diagnosis possible. What exactly are these antigen test kits? Most are narrow strips of paper on which the necessary reagents are pre-stored in a dried state. A dropped sample flows along with the reagents through capillary action, allowing the result to be read with the naked eye.

Beyond antigen test kits, there is a growing demand in clinical diagnostics for "Point-of-care testing" (POCT), which are tests performed near the patient. In 2003, to provide practical and effective diagnostic methods even in environments with limited resources and infrastructure, the WHO introduced the ASSURED criteria - A ffordable, S ensitive, S pecific, U ser-friendly, R apid, E quipment-free, and D eliverable to end-users.

Our laboratory focuses on developing paper-based analytical devices (PADs) that meet these criteria, and we have been creating highly sensitive and user-friendly devices. This involves adapting chemical and biochemical diagnostic methods, which are typically performed by skilled technicians with dedicated labware and instruments, onto a paper substrate. By doing so, we have been able to simplify complex, multi-step clinical tests to the level of POCT, making them accessible to the general public without requiring special equipment or reagents. One key to success is selecting the right reagents and stabilizing them in a dry state through chemical techniques. Sometimes, this even requires synthesizing new materials. A second key is the fabrication of microfluidic channels. By creating paper devices with microfluidic patterns that utilize capillary forces—designed not just in two dimensions but extended into three—it is possible to achieve time-sequential, multi-step reactions. Through such approaches, we have developed easy-to-use devices that omit most of the operational steps.

Furthermore, while antigen test kits often provide only a positive/negative result, more quantitative information is sometimes necessary. Displaying easy-to-understand test results without specialized equipment is challenging, and achieving this requires innovative analytical approaches. Some of these methods are introduced below.

・Distance-based PADs: Similar to reading a temperature on an analog thermometer, the concentration of a sample can be determined from the length of the color-changed channel (Fig. 1a).

・QR code-based PADs: By printing chemically responsive reagents in the shape of a QR code, the test result can be read with a smartphone and delivered to a remote healthcare professional (Fig. 1b).

・Traffic light-style PADs: By representing the test result in the form of a traffic light, the level of risk can be intuitively communicated to the user (Fig. 1c).

・Text-based PADs: By devising combinations and shapes of printed reagents, graded test results can be read directly as text, rather than just the presence or absence of a line (Fig. 1d).

While PADs allow for the simple and intuitive presentation of test results, significant effort is required to realize such systems and apply them to biological samples. Nevertheless, I believe that the development of PADs is a challenging yet highly rewarding field of research for scientists.