As discussed in the previous blog, “Electrochemical Biosensors for the Diagnostics of Infectious Diseases”, the global demand for effective electrochemical biosensors has risen. Specifically, the demand is for point of care test (POCT) devices due to their ability to produce rapid results with better sensitivity at low costs and their availability in resource-scarce settings, where many of the outbreaks occur.
Previously, POCT was limited for infectious diseases, namely doubts on their accuracy and the cost (1); as well as meeting the “ASSURED” guidelines for POC diagnostics designated by WHO (see Figure 1). Most commercially available POCT devices for infectious diseases are simplified convention testing that required large expensive equipment but don’t have the same accuracy (2).
Figure 1: The WHO "ASSURED" criteria for POC diagnostics development. https://pubs.rsc.org/en/content/articlelanding/2018/ra/c8ra06132g
Fortunately, recent advancements in technology have allowed POCT, like our innovative electrochemical biosensor Gii-Sens, to overcome such limitations (1). This article will discuss some of the challenges POCT have faced and how rapid advancements in technology have allowed science to overcome these issues.
The accuracy of POC devices for the detection of infectious diseases was a major issue. False negatives and false positives are common problems that POCT can exhibit:
- False positives usually occur due to non-specific binding which may relate to issues during manufacture, or the lack of specificity in the test as infectious disease may have similar structures that may induce a false positive for a different disease from the one that is being tested whereas,
- False negatives are mostly likely to occur when the amount of analyte present is below the limit of detection of a device so the device cannot detect the analyte and present a false negative result.
These issues would defeat the purpose of their implementation as priority treatment would be given to patients who didn’t need it; no treatment for those that did; or wrong diagnosis and treatment. With infectious diseases, if people were misdiagnosed as negative then there is a high risk imposed for further spread (3).
Recent developments of novel materials have allowed rapid improvement in the accuracy and sensitivity of electrochemical biosensors specifically as they have lower limits of detection i.e., the amount of viral load that is detectable for a positive result is now lower; specificity has also increased with the new developments, and POCT can be engineered to test for specific markers. This enables the primary goal of POCT implementation by accurately detecting individuals with an infectious disease before it becomes infectious (2).
One aspect of electrochemical biosensors that previously posed a problem for their widespread use was the cost of such devices. As the world has seen recently with the outbreak of the coronavirus, POC devices, such as the lateral flow assays, for the detection of such viruses were needed in great quantity. This ideally meant that both the device and its production had to come at a low cost. However, the accuracy and reliability of such devices can often come at a sacrifice to cost (2).
Recent, rapid advances in novel materials have allowed electrochemical biosensors to move away from the inclusion of precious metals, reducing the cost of modern biosensors. The cost of a POCT for infectious disease is a critical factor, more so than for other diseases. This is due to the magnitude of tests needed and the resource-limited settings that provide the largest demand for them.
Sample preparation is a challenge that often limited the availability of electrochemical biosensors, especially in low resource areas.
Previously, many POCT tests used whole blood as the sample however, the challenge with whole blood is that it could not be processed without sample preparation: this required skilled individuals and extra expensive equipment which reduced the availability of the tests while adding extra costs.
Now, however, many POCT incorporate microfluidics; opening the possibility to process whole sample through the integration of sample preparation, nucleic acid amplification and detection steps into a single device; thus eliminating the need for sample preparation and trained individuals (2).
Multiplexing and microfluidics
Multiplexing allows for the analysis of multiple target analytes at the same time. In infectious diseases this is important as at different stages of disease progression, different analytes can be present and in varying quantities. Co-infection is common with infectious diseases: this means additional analytes of different forms will also be present (4).
The ability to multiplex at the point of care allows for a fuller diagnosis of more than one common analyte related to specific infectious diseases to occur in a single test: this can result in greater patient outcomes, as patients can be tested against multiple infectious diseases and receive the most appropriate treatment at right time.
The ability to multiplex is possible due to recent developments in microfluidics (5). The result turnaround, throughput and physical size of the test devices are also benefits as a result of the advancement in technology to apply multiplex into POCT, which allow POCT to be more accessible. Although the advancement of microfluidics has attributed to many benefits for new POCT, there are still some challenges regarding the cost of the development process, scalability and smooth incorporation of all processes in a cartridge or device that can be addressed as microfluidic technology continues to develop (6).
How Gii-Sens has overcome the challenges
Integrated Graphene has developed a label-free 3D graphene (3DG) foam for use in electrochemical biosensors. This has removed the need for precious metals and enzymes that can often drive the costs of POCT up. Additionally, Gii-Sens is compatible with high volume manufacturing and is scalable for reel-to-reel manufacturing meaning that the cost of production is also kept down. Our
Gii-Sens technology operates via a three-electrode system that allows for a low assay volume. This enables tests to be conducted on a finger prick of blood for example, eliminating the need for complex blood sample extraction. Gii-Sens has the ability to be miniaturised and embedded inside microfluidic chips allowing for multiple diagnostic tests to be performed in one test.
Finally, Integrated Graphene addressed accuracy issues in POC devices with their novel technology. Gii-Sens offers greater performance than precious metals, at the price of carbon. Meanwhile, compared to other electrochemical biosensors, Gii-Sens can offer a higher assay performance under the same operating conditions. This is due to the large electrochemically active surface area provided by the 3DG foam and the greater than 98% carbon purity that we ensure our devices have. Contact us via the form below if you would like to learn more about our technology and how we can help you.
Rapid advancements in technology have allowed for the development of POCT for infectious disease to be more specific, sensitive and affordable.
Novel materials have allowed for a shift away from previously expensive components, whilst their ease of manufacturing has helped maintain a low production cost: increasing the accessibility for low income, resource-scarce areas that provide the greatest demand. They have allowed for highly accurate testing of whole samples at point of care. The incorporation of microfluidics to allow for multiplexing has enabled the now accurate biosensors to provide a more whole diagnosis to ultimately increase the patient outcome.
Despite challenges of sensitivity and accuracy of devices for infectious diseases are still challenges to be addressed; with the continuous advancement, there is huge potential for a novel technology to be exploited to develop the ideal POCT device: one that meets the “ASSURED” criteria and is portable, rapid, reproducible, low cost and highly sensitive for infectious diseases (2).
- Point-of-Care Testing for Infectious Diseases: Past, Present, and Future. Kozel, T R and Burnham-Marusich, A. 8, 2017, Vol. 55.
- Point-of-care diagnostics for infectious diseases: From methods to devices. Wang, C, Liu, M, Wang, Z, Li, S, Deng, Y and He, N . Nano Today. 2021 Apr;37:101092. doi: 10.1016/j.nantod.2021.101092. Epub 2021 Feb 6. PMID: 33584847; PMCID: PMC7864790.
- Point of Care Testing for Infectious Diseases. Chen, H, et al.l. : Clinicia Chimica Acta, 2019, Vol. 493.
- A new point-of-care test for the diagnosis of infectious diseases based on multiplex lateral flow immunoassays. Kim, H, Chung, D and Kang, M.l. : Analyst, 2019, Vol. 144.
- Electrochemical biosensors: perspective on functional nanomaterials for on-site analysis. Cho, IH., Kim, D.H. & Park, S. Biomater Res24, 6 (2020). https://doi.org/10.1186/s40824-019-0181-y
- Advancement in POCT Molecular Testing: The Multiplex PCR POCT Devices for Infectious Diseases. Alp A. EJIFCC. 2018 Nov 7;29(3):205-209. PMID: 30479605; PMCID: PMC6247132.