COVID-19 DIAGNOSIS

Lab-on-a-chip biosensors

by Mohammad Al Mamun | Published: 00:00, Nov 27,2020

 
 

Healthcare workers are at a walk-up COVID-19 testing site in San Fernando, California on November 24. — Agence France-Presse/Robyn Beck

IMPROVED molecular and serological diagnostic testing is key to advancing patient outcomes and preventing spread of infection. The rapid spread of COVID-19 and morbidity statistics have put forth an unprecedented need for rapid diagnostics and quick and sensitive detection followed by contact tracing and containment strategies, especially when no vaccine or therapeutics are known. Although a significant number of methods such as qRT-PCR, enzyme-linked immune-sorbent assay and CT scans, are available for detecting virus particles, there are several difficulties that restrict the practical use of these methods.

These limitations include lower accuracy and sensitivity, tedious sample preparation and purification steps, time-consuming assays, expensive instrument and higher maintenance cost, complex operation and a requirement for highly qualified technical personnel, which are not suitable for rapid and on-site analysis. To date, almost all diagnostic testing for the virus occurs in centralised laboratories. The COVID-19 outbreak has emphasised the need for moving from traditional lab-centred diagnostics such as RT-PCR test to decentralised point-of-care clinical settings such as bedside diagnosis, remote setting or resource-limited settings.

Biosensors are analytical devices that convert a biological response into an electrical signal. In these devices, biological recognition molecules such as enzymes, antibodies, or nucleic acids are coupled with a transducer and a detector that detects the interacted analyte and gives a digital output. For example, in glucose biosensors or glucometers available in pharmacy or at diabetic people’s home for instant monitoring of glucose level in blood, glucose selective enzyme is used as biological recognition layer or sensing element.

In such devices, it is possible to quickly diagnose and potentially treat diseases. Biosensors can be used for medical diagnosis, environmental monitoring, food, water, and agricultural product processing. Viral biosensors offer exciting alternatives to traditional diagnostic assays and can provide inexpensive, sensitive, rapid, miniaturised and portable platforms compared with conventional laboratory-based methods. In the past few decades, the biosensor innovation has witnessed an exceptional and exponential surge in the development and performance because of the advancements in transduction systems, nanotechnology and genetic engineering that offer various strategies to improve the detection performance of biosensors.

Lab-on-a-chip biosensor platforms facilitate the translation to point-of-care settings via miniaturisation, portability, integration and automation of multiple assay functions onto a single chip. As a result, significant efforts are now directed towards the development of point-of-care tests, which can be operated at the patient site by non-trained personnel. The ideal vision for such a test would be an independent and self-sustainable operation that allows a non-trained operator to load a sample of extracted body fluid such as blood, urine, saliva and sweat into the instrument and obtain informative results with minimal user intervention. Labs on a chip can handle extremely small fluid volumes down to less than a picolitre. Lab-on-a-chip devices are a subset of micro-electromechanical system devices and are sometimes called ‘micro total analysis systems’.

The systems decrease the sample amount and reagent consumption, shorten the time of experiments and reduce the overall costs of applications. Furthermore, the integration of biosensors with different devices would help to reduce the risk of the potential future waves of COVID-19. For instance, linking an appropriate biosensor to smartphones has the potential to increase the speed and reliability of the contract tracing technique. A number of advantages of lab-on-a-chip devices are particularly relevant to COVID-19. Specifically, lab-on-a-chip devices are robust, rapid, sensitive and low-cost and they can provide results at the point-of-care. In the context of COVID-19, these advantages would help to support crucial efforts to increase access to testing.

The high availability of smartphones worldwide and their sophisticated technological features have increasingly led to their integration into a wide range of analytical sensing systems. Newly developed biosensor devices linked to smartphones could help medical practitioners to dramatically cut down the real-time detection rates in the battle against COVID-19 and other future viral outbreaks. For example, a custom-built smartphone application was used to quantitate a point-of-care lateral flow assay for the detection of ebola virus-specific antibodies in clinical human serum samples. This low-cost platform requires only the test strip and a smartphone and results are obtained in 15 minutes. Colorimetric-based detection using a multichannel smartphone spectrometer as an optical biosensor was recently used to detect protein content and cancer biomarker within human serum. A smartphone-based diagnostic platform for the rapid detection of zika, chikungunya, and dengue viruses has been reported in Scientific Reports in 2017.

Very recently, a group of scientists and engineers from the University of Manchester have created a novel computational fluid dynamics platform to aid biosensor devices to detect biological species and help to control the spread of virus outbreaks. The approach could help to track and trace people with infection while a vaccine could still be many months away. This breakthrough would allow the integration of biosensors to existing smartphones with the potential ability to improve the speed and reliability of the existing contact tracing system. It could also help to contain any other virus-related disasters and pandemics in the future through the same method.

While developing an effective vaccine can take months up to years, the detection of infected individuals is at the forefront of controlling the situation and a crucial tool in the contract tracing strategy, currently in use in the United Kingdom and most other countries. Time is a key parameter in containing highly pathogenic diseases and defeating a pandemic. Significant research efforts have already been directed towards the development of simple and low-cost devices for lab-on-a-chip medical diagnostics at point-of-care. Nevertheless, the commercialisation of such technologies remains limited. The lab-on-a-chip devices are suitable for daily tests and are user-friendly as no laboratory facilities are needed. These features make them a favourable real-time detection system. However, designing a reliable device is still very challenging and time-consuming.

For the chips to be used in areas with limited resources, many challenges must be overcome. In developed nations, the most highly valued traits for diagnostic tools include speed, sensitivity and specificity; but in countries where the healthcare infrastructure is less developed, attributes such as the ease of use and shelf life must also be considered. The micro-manufacturing process required to make them is complex and labour-intensive, requiring both expensive equipment and specialised personnel. It can be overcome with the recent technological advancement on low-cost 3D printing and laser engraving. Smartphone technology has expanded the analytical power and increased the accessibility of many platforms. But hygiene considerations — both contamination and disposal issues — must be carefully considered if smartphones are to be deployed.

A big motivation for the development of lab-on-a-chip biosensors for COVID-19 diagnosis is that they can potentially be manufactured at a very low cost. The reagents that come with the chip, for example, must be designed so that they remain effective for months even if the chip is not kept in a climate-controlled environment. Chip designers must also keep cost, scalability and recyclability in mind as they choose what materials and fabrication techniques to use. Finally, the social impact of this emerging technology as well as corresponding regulatory policies and concerns should be considered in designing an assay to facilitate, or at least preserve, its commercialisation potential.

 

Mohammad Al Mamun is a PhD student at the University of Malaya and an associate professor of chemistry at Jagannath University.

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