The Backbone of Diagnostics

Analytical chemistry plays a pivotal role in clinical research by enabling precise and sensitive detection of biomarkers, facilitating early disease diagnosis, monitoring treatment efficacy, and ultimately improving patient outcomes. For many years, we’ve been working with electronic devices, particularly bioelectric transistors, to enable ultra-high-performance levels – not only in terms of low detection limits, but also in high reliability.

Advances in biosensors have also provided another avenue for analytical chemistry to positively affect clinical research – particularly in enabling early diagnosis. However, this progress must coincide with the discovery of new and specific biomarkers. With this in mind, we must take a comprehensive approach, encompassing both nucleic acid and antigen (protein) biomarkers. Improvement in performance levels of sensing devices is particularly notable in immunoassays as their performance is lower in comparison to molecular assays.

Today, we’re seeing a plethora of proposed assay technologies for improved diagnostic and clinical research. One of which I’ve worked closely with: the “Single-Molecule with a Large Transistor” (SiMoT) technology that’s being developed at technology readiness level 6 (TRL6). SiMoT can uniquely detect both antigens and oligonucleotides at extremely low concentrations with an accuracy of 96 percent. It’s particularly suitable for point-of-care testing, especially for screening asymptomatic individuals, providing fast, reliable, and cost-effective identification of illness. SiMoT can be used for various diseases – we proved its effectiveness in detecting SARS-CoV-2 in saliva (1) and diagnosing pancreatic cancer from a blood test (2, 3). 

SiMoT devices consist of a reusable reader and a compact disposable cartridge tailored for early disease diagnosis, offering ultra-portability and handheld convenience. The affordable cartridges work alongside smartphones or tablets, so they can be used anywhere, and the simple nature of the technology makes it suitable for untrained users – even in home settings or in resource-constrained environments. Array technology, on the other hand, is better suited to trained personnel in clinical facilities or smaller laboratories.

Another analytical technology stepping into the clinical spotlight is CRISPR/Cas biosensing, which employs precision gene editing to identify specific oligonucleotide sequences within a sample. This technique harnesses CRISPR's inherent capacity to pinpoint and target genetic sequences within an organism genome or biomarker. It’s also been tailored for diverse diagnostic and detection applications. CRISPR systems hold great promise for accurately and sensitively detecting pathogen-specific nucleic acids, which could potentially transform on-site diagnostic and genotypic applications. 

One notable advancement is the use of CRISPR-based paper biosensing platforms, which offer an innovative approach to pathogen detection evidence in recent work to detect mycoplasma pneumoniae (4). This newly developed test firstly amplifies the target gene with specific primers before using the CRISPR/Cas9 system for precision recognition, which reduces false negative results. This method is highly sensitive, detecting as few as three DNA copies, thanks to the efficient amplification and ability of the CRISPR/Cas9 system to work at a relatively low temperature of 39 °C.

Of course, these highly performing sensing devices would not be possible without multidisciplinary collaboration. When a project is tackled solely by specialists in one area, it can lead to imbalances in development. For example, focusing only on device performance level may result in a device with limited reliability. The SiMoT project in particular shows the importance of collaboration with other fields. 

Looking into the future of diagnostic and clinical research, it’s crucial that we stay resilient in the face of challenges and setbacks in our push for innovation. To my colleagues and fellow researchers, both experienced and new to the field, I propose that we advocate for ourselves and others across the scientific community. Without collaboration, we are destined for failure. But together, we can contribute clinical and diagnostic research that paves the way for future generations.