In mid-March, WHO Director General Dr Tedrous Adhanom Ghebreyesus said, “We have a simple message for all countries: test, test, test.” Testing is necessary to break the chains of transmission by isolating patients made more important because this virus spreads before symptoms become visible. Contact tracing and testing of SARS-CoV-2 in China, South Korea and Hong Kong has been largely successful. As exiting lockdown as soon as it is safely possible is every country’s priority. Contact tracing and testing will form the crux of the strategy to prevent a second wave of infection.
Testing involves extracting RNA from a patient’s cells, converting it to DNA and detecting viral DNA by Real Time PCR. In addition to these PCR tests, serological antibody and antigen tests are coming into use and some labs are sequencing the entire genome of SARS-CoV-2 isolates to track its mutation rate. Testing capacity of labs was initially boosted by donated PCR machines, automated liquid handling, and volunteers from universities and research institutes. Despite this, bottlenecks to increasing testing capacity have formed around supply chains of key reagents and consumables.
Bottlenecks and roadblocks
Shortage has been a theme throughout the previous few months. Shortages of toilet paper and pasta in supermarkets, shortages of PPE for healthcare and essential workers, and shortages of reagents and key consumables for research and testing. The UK Government issued a call for nose and throat swabs, transport media and vials, reagents, plates and pipette tips, all of which are essential for increasing testing capacity.
This represents a major cost challenge, especially for developing nations. Latin America and Africa are being outspent by the US and Europe in the hunt to secure supplies for testing. It’s been noted African countries, facing their own unique challenges in this crisis, have funds for purchasing reagents but cannot buy them. In India, a nation of 1.3 billion people, leading scientists recognize existing PCR kits and methods will not scale for the nation, leading them – like most nations short on reagents and testing capacity – to prioritize who gets tested.
Leading academics have weighed in on the supply shortages, in particular the need for reagents as recent shortages of guanidine thiocyanate for RNA isolation have highlighted, but also the enzymes for cDNA synthesis and testing by PCR. A similar shortage is occurring with other consumables as testing increases, for example the shortage of cotton swabs in March. In testing labs, pre-sterilized plastic pipette tips, plastic plates and tubes are required in massive quantities to process samples. Labs where automated solutions to increase capacity have been put in place are now facing the distinct possibility of running out of pipette tips for their machines as well as the global shortage of reagent.
With so many process bottlenecks and supply chain roadblocks in play, labs are seeking out and developing alternative solutions for themselves. How can they address all these challenges at once?
Miniaturization saves reagent and cost
A little goes a long way, as the old saying goes. That is certainly the case in our field of low-volume liquid handling. Miniaturization of the testing process using automated low-volume liquid handlers addresses the three key bottlenecks to increasing testing capacity: reliability, cost, and supply chain.
Automated liquid handling allows for precision science. Once a protocol is validated – a rapid and easy process with common protocols – the machine carries it out identically every time, eliminating human error and providing robust and reliable results. Automation also affords conducting an experiment on scales that hand pipetting simply cannot achieve when using low volumes. Protocols like the cDNA synthesis and PCR test for COVID-19 are extremely sensitive and amenable to scaling down to low volumes while giving reliable results. Miniaturizing too much, however, can compromise the results of your protocol. We provide expert training in low-volume liquid handling to help you rapidly miniaturize and validate your protocol to achieve reliable results.
The cost of testing is a major global issue. Countries want to ramp up testing but are prohibited by testing capacity and cost, especially in developing regions or those that simply cannot outbid the US and Europe for key supplies. Miniaturization of the test protocol can achieve huge cost reduction while maintaining throughput and reliability. A single PCR test is currently priced at $20 USD. By scaling this down 20-fold with our specialized low-volume liquid handlers, such as the dragonfly discovery and mosquito robots, the cost can be reduced to $2.50 per test. We are collaborating with existing customers and labs working on SARS-CoV-2 detection to validate these protocols so they may be implemented.
Miniaturization naturally tackles other supply chain challenges. By using less reagent per test, fewer materials need to be purchased and stored. Additionally, other consumables such as pipette tips generate more samples per use, resulting in less waste. With miniaturization, pipetting to homogenize a mixture after dispensing a reagent is unnecessary due to the low volume. The dragonfly discovery uses positive displacement technology to dispense precise volumes without contacting the well beneath, allowing the tips to be reused without contamination. We produce our own tips for both the mosquito and dragonfly machines, ensuring a secure supply chain for our users.
Automated liquid handling already provides researchers with a new layer of possibility that cannot be achieved by manual pipetting alone. Miniaturization adds additional dimensions to these research possibilities in what can be performed. Miniaturization is seen as a cornerstone of advancing biological research.
In the past 20 years, technology has trended towards miniaturization to increase throughput (microarray and DNA/protein on chip technology) and develop accurate assays to characterize cells and molecules in research and drug discovery.
The cost benefits to miniaturization of assays speak for themselves, however it is important to note that the approach to assay development itself changes dramatically with miniaturization. Automation allows for robust experimental design and data collection. Thorough design of experiments, testing multiple factors simultaneously, is finally gaining traction in life science. This lets researchers optimize their assays to achieve the most replicable and robust results. Molecular biology assays in both genomics and proteomics are both suited to miniaturization and automated liquid handling, saving time, cost and reagent with common laboratory protocols validated for single cell genomics, next generation sequencing and PCR.
In the emerging field of synthetic biology, which takes an engineering approach to biological design, miniaturization plays a doubly important role. The field focuses on bio-based, sustainable solutions to global problems. Using a miniaturized liquid handling platform, environmentally toxic reagents and their waste is minimized considerably, as is the waste from single-use plastics thanks to the reusability and throughput of our platform.
Unfortunately, many still view these technologies as inaccessible due to cost or skills requirements. The long-term savings in miniaturizing standard protocols are significant, and our technology is easy to use. It can be thoroughly taught to the user in a single day workshop and does not require knowledge of complex software coding.
As the COVID-19 outbreak develops, new tests, drug screens and vaccines will be developed in labs worldwide, in addition to widespread testing by RT-PCR. When lockdown restrictions ease and more laboratories come back to life across the globe, demand will again rise for the most common reagents and consumables. In the short term, miniaturization is a cost-effective strategy allowing labs to continue testing accurately while reagents and key consumables such as pipette tips remain less accessible than usual.
In the long term, automated low-volume liquid handling will save labs reagent, time, and money on their research while achieving robust data and having a lower environmental impact. The technology is effective across a wide range of biological applications. Perhaps most importantly of all, it provides valuable time for the scientist to spend doing what they do best: design cutting-edge experiments and make new discoveries.