The Best Things Come In Small Packages
The story behind the miniature molecular diagnostic device that will offer simple, affordable pathology in low-resource settings
Jonathan O’Halloran |
Molecular diagnostics are often key to unlocking the mysteries of disease – but the techniques required are often complex and time-consuming, and the equipment can be bulky and expensive. Those issues can be frustrating even in the most well-resourced laboratories, and the difficulties are significantly magnified when pathologists face resource limitations. So I decided to do something about it.
I began by defining what I thought were the ideal specifications for a point-of-care (POC) molecular diagnostic device – something that could remove the frustration I felt when processing samples. Once I had decided exactly how such a device should look, I set to work creating it – building, changing, building again, changing again. That early work, all done at home in my garage, is the foundation on which QuantuMDx’s technology is now built.
A sample’s journey
Once entered into Q-POC, the portable, simple-to-use testing platform, a patient sample is lysed and purified in a three-minute step that uses a novel filter to capture cellular components, such as carbohydrates and proteins, leaving the DNA in solution. It takes a further seven to nine minutes to amplify the DNA – a task accomplished by microfluidic PCR. How can your device do PCR? Q-POC uses static heat blocks at two or three distinct temperatures, moving the reaction mix back and forth between them to create the necessary thermal cycling. We then employ a world first: a two-method integrated detection system. The first method takes advantage of sensitive in-line optics to observe the generation of fluorescence as the target region is amplified, providing a six-channel quantitative PCR (qPCR) read-out in just over 10 minutes from sample input. The second method – hybridization to a microarray – adds another five minutes to the overall process, but enables us not only to quantitate up to six markers with the qPCR, but also allows us to genotype alleles or mutations within the amplicons – an important consideration for drug resistance testing.
The foundation of Q-POC’s development – and our end goal – was to create a platform that was quicker and more portable than current gold-standard tests. We also wanted to ensure that the devices were suitable for the economies and environments where they can be of greatest use. As a result, we have had to reinvent each stage of the molecular testing workflow. For example, when we were in the early stages of development, we reviewed the molecular diagnostic process and found that it wasn’t suited to microfluidic platforms. Our team has innovated each step in the process to overcome these issues and find a solution. For instance, the standard BOOM method of DNA extraction involves binding the nucleic acid to a silica surface, washing away the cellular constituents, and then eluting the DNA – but to do that, you need a number of wash and elution buffers, all of which cost money and take up space. Q-POC, in contrast, requires one buffer and no valving or waste management. Thermal cycling is another example of our innovation; rather than heat and cool a reaction mix, we move the mix itself back and forth between different temperature zones to create the necessary cycling. Not only does that save significant time in ramping, but it also preserves battery life to let the device run for much longer.
Surviving a rocky road
Clearly, any novel approach to improve complex technologies is going to be fraught with difficulties. Given that we had to reinvent nearly every aspect of the molecular testing process – not to mention miniaturize it without losing speed or effectiveness – we knew we had set ourselves a near-impossible task. Then we added the challenge of keeping the cost extremely low and things really got interesting. Despite all of that, I think the biggest challenge was integrating everything. Why? Each process of the molecular diagnostic workflow uses totally different chemistries and buffers to the others, so linking them together is a huge headache. Then add in a significant change to the reaction environments and dynamics, and different device materials, and you can see that the task seems impossible!
While we were in early development, experts in the field of molecular diagnostics thought we were crazy to take on a project like this. And many thought it was simply impossible...
But we have already demonstrated our first Q-POC test, a warfarin genotyping assay, and we are currently working on a number of infectious disease tests. These include tuberculosis, HPV and CT/NG/TV – although we’re still in the early stages with those tests. We have the Bill and Melinda Gates Foundation to thank for a grant that will support the further development of our tuberculosis assay and the preclinical data gathering required to support the optimization of our device ahead of clinical trials. We will then go through a process validation phase and then onto clinical trials, which we anticipate beginning in 2018. After the clinical trials are complete, we hope to apply for regulatory approval for each of the countries we wish to market in.
In the future, our challenges will be more familiar. We’ll need to scale up to manufacture Q-POC in large quantities, and we’ll have to predict sales volumes as accurately as possible. We have worked hard to ensure that we avoid the potential pitfalls in that part of the process, and that’s why we have brought on strong partners who have either the finances, knowledge or both to ensure the device reaches commercialization successfully. I’d recommend the same to anyone else looking to bring a novel device to market – find allies whose strengths complement yours, because it makes the entire journey easier and less risky.
Defeating HPV: A Partnership for Global Good
A collaborative project between the Global Good charity and QuantuMDx.
A sample (swab or cervical brush transfer buffer) that can be run on a disposable microarray on the Q-POC platform. The assay amplifies several regions of the human papillomavirus (HPV) genome to first confirm the presence of HPV, and second identify whether the virus is one of the 13 oncotypes. Almost all cervical cancer is caused by HPV infection, so the assay gives health workers the ability to screen and treat for the virus in a single visit.
It is estimated that more than 80 percent of cervical cancer deaths occur in low-resource settings (1). Current methods for screening in those settings are limited or nonexistent because they require considerable training and diagnostic quality is hard to maintain. In contrast, the assay is cost-efficient, easy to use, and accurate. It’s an especially timely intervention because recent changes in the FDA have dramatically decreased the number of new diagnostics for HPV. We felt a responsibility to act, and our new assay is a result of that feeling.
The assay will be trialed in low- and middle-income countries like Uganda and Kenya.
We’ve already begun transferring the assay, and we’re aiming to begin field trials in the first half of 2018.
The Internet of Life
Q-POC aims to speed up, simplify and automate the day-to-day workflow of molecular pathologists and laboratory professionals. Without laborious sample preparation, we’ll be able to just load the sample and press go! And we’ve designed the device to function in most situations and environments, so that it will work in countries with few other options. Those regions tend to have a high burden of diseases such as tuberculosis, malaria and STIs. Our ideal scenario is that Q-POC reaches the individuals whose countries lack a strong healthcare system – or even those who cannot access healthcare at all.
One really exciting feature is that all Q-POC devices will be connected to the cloud. Globally distributed devices will then be able to anonymize and geotag the data they collect so that it can be used for real-time disease and drug resistance monitoring. We hope that we can use this data to create a real-time map of disease prevalence, transforming the way non-governmental organizations, health ministries and even the World Health Organization monitor and control outbreaks. Of course, that’s still in the future – but we’re looking forward to distributing as many devices as possible so that we can begin to create this “Internet of Life.” That’s the first step – so any pathologists interested in adopting Q-POC are welcome to contact us. We’d be happy to help facilitate!
Now that we’ve achieved our initial goals, we know that all our early struggles and growing pains were worth it – after all, they brought us several steps closer to bringing quality pathology to the people who need it most.
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- DM Parkin, F Bray, “Chapter 2: The burden of HPV-related cancers”, Vaccine, 24 Suppl 3, 11–25 (2006). PMID: 16949997.