Optical vs. Electrochemical Assays as Point-Of-Care Diagnostic Tools
Author: Sean Lightheart
Both infectious and non-communicable diseases continue to be a significant cause for global mortality, particularly in rural areas of developing countries where access to medical resources may be limited.
In the fight against these diseases, a rapid and accurate diagnosis is crucial in offering a timely diagnosis to allow clinicians to deliver suitable medical treatment and see an improved patient prognosis. Early and accurate diagnostic testing stands to be a significant tool in overcoming this issue but, these tools are typically time and resource-intensive and require specialised personnel to be carried out accurately. This is why, it is of paramount importance that world-leading scientists come together to deliver effective and commercially cost-effective point-of-care (POC) diagnostic tools that are easy-to-use, portable, quick to diagnose, sensitive and specific.
As the requirement for these types of diagnostic technologies is showing no sign of abatement, we are seeing the emergence of a range of diagnostic modalities being further developed to enhance overall diagnotics’ effectiveness. With relation to POC infectious disease detection, there are four main modalities: optical, electrochemical, magnetic and colourimetric. It is important to note that the mere availability of rapid or simple tests does not automatically ensure their adoption or scale-up. A range of barriers prevent the successful use of POC testing, and the World Health Organisation (WHO) has developed a set of criteria for evaluating these tests. The criteria are summarised by the acronym ASSURED (Affordable, Sensitive, Specific, User-friendly, Robust and rapid, Equipment-free, Deliverable), which represents the characteristics needed for an ideal POC platform.
In this article, we are looking more closely at optical and electrochemical detection and weighing up their value to suitably present them as solutions to enabling effective diagnostic testing at the point of need. The objective of providing a rapid and accurate diagnosis that will allow clinicians to prescribe the proper medical treatment will be a critical factor in this evaluation.
What are the requirements for a market-ready POC test?
Nearly 5 million people die from the most prolific respiratory infections such as pneumonia, influenza and tuberculosis – which is twice as many HIV/AIDS-related deaths. Overall, infectious diseases caused by bacteria, viruses, parasites and fungi result in 15 million deaths each year, and approximately 95% of these deaths occur in lower-income countries. Noncommunicable diseases, including cardiovascular diseases, cancers, chronic respiratory diseases and diabetes, kill 41 million people each year. This is equivalent to 71% of all deaths globally and, of those, 77% are in low- and middle-income countries. Detection and screening of these diseases are key components in the global response to their control.
Thankfully the advancement of medical technology has delivered a host of effective methods for the detection of pathogenic agents such as culturing, microscopy, genomic amplification (such as PCR) and immunoassays (e.g. ELISA). Immunoassays can be successfully utilised to detect infectious diseases if the correct antibody-antigen interaction is determined but are difficult to develop and use for the detection of pathogens with high rates of epitope mutation. All of these approaches have allowed us to begin to combat the spread of infectious diseases however, the accessibility of some of these are restrictive in their appropriateness in resource-limited settings, typically the areas that require them the most.
In recent times, there have been several diagnostic platforms have been developed to detect infectious and pathogenesis biomarkers (DNA/RNA, glycoproteins, enzymes, antibodies, etc.) to deliver enhanced speed, simplicity and cost-effectiveness. These biosensors are often based on nano- or micro-technology platforms and they commonly rely on the production of optical, electrical, magnetic or visually detectable signals.
Optical Detection Biosensors
Optical-based detection of disease has been utilised in several attempts to design ideal POC platforms. Optical-based diagnostics rely on the sensitive detection of photon emission from dyes and molecules that are excitable by light. Often, fluorescent probes are designed that will only emit photons after interacting with targeted biomarkers, such as antibodies, antigens, or genomic material. Compared to other visualisation techniques, such as microscopy or colorimetry, fluorescence emission allows increased sensitivity, adding to the reliability of this modality.
However, intrinsic fluorescence properties of non-target molecules may also cause background noise and false positives, therefore this method usually requires somewhat clear sample solutions to prevent interference from other molecules. Because of their use of filter fluorometers or spectrofluorometers, these are often not found in resource-scarce settings due to cost and complexity. This can be overcome by combining the use of optical technologies with smartphones, making them more universally accessible.
Furthermore, their requirement for utilising fluorescence molecules which are utilised as probes can interfere with the binding of antibodies to the antigen, which would prohibit their use in the detection of certain diseases. The goal of POC diagnostic tools is to use raw samples such as blood, serum or urine with minimal to no preparation, so florescence-based platforms are often not ideal in this aspect.
In examples such as the commonly used fluorescence assay, fluorescence polarisation (FP), low-cost tests can be achieved for as little as $1 per test and achieve the rapid and low-cost design. However, in certain cases, these assays require the detection of intracellular components, requiring additional sample preparation steps, such as DNA extraction, adding further cost, preparation and time to the overall process.
Electrochemical Detection Biosensors
Electrochemical detection is one of the more commonly developed biosensing methods due to the potential for miniaturisation, portability, and cost reductions, with the glucosimeter being the most common example that utilises this modality. Electrochemical detection modalities utilise biosensors that are capable of binding to a target molecule associated with the disease. When these probes bind to the target molecule, they undergo a conformational change and create a small electrical current that can be detected. Unlike fluorescence-based detection, electrochemical biosensors are particularly well suited when utilised with non-clear samples such as blood. Additionally, electrochemical-based detection doesn’t require complex instrumentation that is used in many fluorescence-based detections.
Electrochemical-based biosensors quantify the antibody concentration by measuring the current or the impedance through various electrochemical analytical methods. Electrochemical POC diagnostic technology development has significant potential for miniaturisation and portability. Critical to the requirement for developing an effective electrochemical biosensor-based POC solution is the selectivity and sensitivity which determine the reliability and simplicity of the test. Using existing and future biorecognition elements, electrochemical biosensors can be developed for any specific analyte and offer highly sensitive, quantitative results.
While these methods can be initially costly and complicated to utilize, the technology can evolve into more miniaturised and easier to use platforms as the development progresses.
The Solution
The global requirement for adequate testing to support effective medical care is clear and electrochemical and optical biosensing strategies both show great potential for the development of infectious disease detection platform technologies. Both electrochemical and optical detection platforms are attractive for future infectious disease detection due to factors such as rapid readout, cost-effectiveness, sensitivity, selectivity, and portability. They are perfect candidates to meet the WHO requirements for an ASSURED POC solution for low-income countries if they can overcome the deliverability issues currently associated with routine laboratory testing.
There is thought that, in order to achieve the desired accessibility and affordability of electrochemical biosensor POC solutions, that further research on the integration of sensing elements, recognition elements and transduction elements into a preservable biosensor product is required.
3D Graphene Foam, Gii, is that sensing element. With its ability to transduce multiple signals, low limits of detection, high purity of carbon content, highly specific target responsive and low cost – Gii can facilitate the requirements to achieve a POC system that is widely applicable globally. With Gii-Sens we able to create the next-generation biosensing platforms to become a widespread standard for clinical POC screening and detection systems.
Help pave the way to personalised medicine in non-hospital settings and reduce overall costs of health management by bringing your assay directly to the point of need. Contact us today to find out how we can support your next POC assay.