07-05-2020 | | By Liam Critchey
While the coronavirus halts the movement and economic activity of the world, medical professionals are trying to contain the spread of the virus by testing as many people as possible who have COVID-19 symptoms. Testing is currently the most effective way of containing the virus. It enables people who have the virus to either self-isolate or seek appropriate medical treatment – and offers a way of providing vital statistics into infection and mortality rates that can are used to plan the next government strategy for tackling the outbreak.
The coronavirus possesses a single stranded RNA genome that is around 30,000 nucleotides in length, and it is this RNA sequence that is often targeted by the different sensing and diagnostic platforms out there. In cases where the genome is not a target, the focus has been on the characteristic protein spike that lies on the outside of the virus and on the antibodies that are produced by the body to fight the virus. Understanding how the virus functions and where it resides within the body upon infection has helped researchers to build more effective diagnostic platforms.
This article focuses on some of the common coronavirus diagnostic approaches in use today. Still, it should be noted that while this is correct at the time of writing, the tests being developed are appearing at a rapid rate with more and more tests becoming available all the time. So, it may be the case that the standard testing methods are different in a few months.
Reverse transcription polymerase chain reaction (RT-PCR) testing, which is a type of nucleic acid testing, is the most common method to date and is used around the world as the standard laboratory test. Swabs from the patient are taken and are sent off to a laboratory for testing. It is a universal technique because the targets selected in each country are genetically similar. However, the method has come under some discussion because it has produced a lot of false positive and false negative results. But out of the laboratory-based tests, it is the quickest and the best available diagnostic test at the moment.
RT-PCR works by measuring the concentration of a specific type of RNA. Because the coronavirus has a long, distinct RNA strand, scientists have found a complementary DNA strand that binds to the RNA. This is the reverse transcriptase part of the technique. The polymerase chain reaction part involves amplifying the specific DNA targets so that they can be detected/sensed, and a confirmation can be given as to whether a patient has coronavirus or not.
The different steps can either be done simultaneously or one after the other. If done simultaneously, the result is obtained quicker, but the DNA is not amplified as much, leading to less accurate results. If done separately, the result is more accurate but not as quick. In some cases, especially when testing kits are not widely available or the tests have been producing a lot of false results, computed tomography (CT) has been used to confirm the test by taking non-invasive images of the patient’s chest cavity.
While laboratory tests are currently the gold standard at the moment, there are a number of biosensors and diagnostic platforms being developed that can be used directly on the front line, in real-time, without the samples being needed to be sent off to a separate laboratory for binding, amplification and analysis. Such point of care biosensors could offer a way of introducing rapid mass testing capabilities should they be developed further.
The need for small, yet highly sensitive, point of care systems has been realised by using different nanomaterials as the active sensing materials. The high active surface area of nanomaterials and inherent small size has made them an ideal choice in such biosensors. The two main nanomaterials being trialled are gold nanoparticles and graphene. This is because gold nanoparticles have surface plasmons that enhance the sensitivity of many sensors when biomolecules (such as the SARS-CoV-2 antibodies) interact with the sensing surface, and graphene has many active properties that enable it to be functionalised to accept the protein spikes of the virus (or other biomolecules) and transform this molecular attachment into a readable output.
As well as nanomaterials, there are a number of microfluidic-based devices out there which can be used as a point of care devices, including some with nanomaterial-based sensing elements within them. Many existing microfluidic platforms that have been used for other diseases can be easily adapted to identify the coronavirus and offer another promising way of bringing the point of care sensors to the front line.
As it stands, many of these sensors are made in academia, and while it’s true that some will not be commercially viable, some have attracted the attention of the industry and intermediary partners that can help to facilitate the transition from academia to real-world use. There are also some companies that have a point of care diagnostic sensors that are used to detect a number of viral strains, including the flu and these are currently being adapted for the specific surface proteins of the novel coronavirus, and there are companies already putting nanomaterial-based COVID-19 sensors out on to the market. So, there is much interest and work going on in this area and is a rapidly developing area to watch out for.
One area that is growing is the use of smartphone monitoring, as smartphones are becoming a more widely utilised tool as a sensor output medium, for transferring data, and for coordinating outbreak responses, particularly in remote and rural areas where technology infrastructure is not as widely accessible. This is because modern-day smartphones possess the connectivity, computational power, and hardware to facilitate electronic reporting, databasing, and point-of-care testing, mainly when more advanced options are not available.
There is also a growing use of smartphones tracking people who are known to have the coronavirus via specialist apps, meaning that smartphones can be used to inform anyone if they come in close contact with someone with a confirmed case of the coronavirus. This makes it easier to see if people need to be tested and to ensure that infected people remain at a safe distance from others. Therefore, smartphones are now being used as a tool to help the health service through better information and monitoring communication, which will hopefully offer a way of preventing the spread of the disease. Such contact tracing methods have been used in Asian countries and are now making the way to the UK.
The current consensus is that the RT-PCR is still the go-to technique, and there are other tests such as protein testing and other nucleic acid tests that are not mentioned here which also show promise but currently don’t offer high accuracy over RT-PCR, nor are they able to provide a point of care diagnostics like some biosensors being developed can.
While laboratory tests are the current standard, it is likely that nanomaterial and/or microfluidic point of care biosensors are going to be the way forward once more get made and adopted as they tend to offer higher accuracies and more rapid testing capabilities. There are also a number of antibody-based tests hitting the market, but their accuracies have been questionable to this point, and many have failed government testing. However, there are many new tests being developed and deployed, including ones which use gold nanoparticles as the sensing medium, so it’s possible that these tests will become important in the future for testing if a person has, and has had, the coronavirus.
Whether these different tests become the norm, or whether the laboratory-based status quo continues to be the dominant test, remains to be seen, but there’s much work going in across the electronics, biotechnology, healthcare and nanomaterial spaces to make more efficient COVID-19 tests.