Professor Discusses His Work in Microfluidics, SARS-CoV-2 Sequencing
Dr. Steven A. Soper is a Foundation Distinguished Professor in the Departments of Chemistry and Mechanical Engineering at the University of Kansas. He is an innovator who helped foster single-molecule detection and grow microfluidics. Soper is now pioneering new and unique nanofluidics applications for precision medicine, including molecular analysis of liquid biopsy markers. In November 2021, Rachel Muenz, G2 interim managing editor and senior editor at G2 sister publication Lab Manager, connected with Soper via phone to discuss his recent work in microfluidics and reconnected with him for a quick update via email in January 2022. Soper recently won the 2022 Ralph N. Adams Award in Bioanalytical Chemistry, which you can learn more about in the January/February 2022 issue of Lab Manager. ______________________________________________________________________________________________________________________________________ Q: How long have you worked in microfluidics? A: I fostered and kind of grew microfluidics from its infancy. This is an area that I’ve been working on since 1995. What’s really unique [with] our work is using plastic as the material of choice to build the microfluidics and even nanofluidics. Plastics are becoming extremely important, because people are transitioning microfluidic devices into the diagnostics regime. And we are doing that too, very heartily, and we’re developing […]
Q: How long have you worked in microfluidics?A: I fostered and kind of grew microfluidics from its infancy. This is an area that I've been working on since 1995. What's really unique [with] our work is using plastic as the material of choice to build the microfluidics and even nanofluidics. Plastics are becoming extremely important, because people are transitioning microfluidic devices into the diagnostics regime. And we are doing that too, very heartily, and we're developing disposable devices that can be mass produced at a small cost to facilitate their transition into the diagnostic or clinical market when using plastic as the substrate material.
Q: What are some of your recent projects?A: We have two big projects that I'm very, very excited about. One of them is developing an at-home test for infectious diseases, including COVID-19. So, we teamed up with a company (BioFluidica, Inc.) and we have an at-home test that we're now clinically testing that basically consists of taking a saliva sample, isolating the SARS-CoV-2 virus out of the saliva, and then counting them using a label-free strategy. And this can all be done in a small instrument that's about the size of an iPhone and uses a microfluidic chip that fits into the handheld instrument. So, the patient—the person—can basically get to the instrument and generate a result of ‘are they infectious.’ This is something that no other tests can currently do. And we're extremely excited about that. Within 15 minutes, they'll know whether they’re infected or not. So, right now, I'm just getting over a cold. I wasn't sure if it was COVID. I had to go in and get tested, and 48 hours later get my results and, in the interim, sit at home, when I really didn't have COVID at all. It was just a cold. So, this is going to change that entire paradigm. The second thing that we're working on is a single-molecule DNA/RNA sequencing platform. And this is quite revolutionary.
Q: What COVID-19-related applications does that sequencing platform have?A: We have another company that we teamed up with that will take a single DNA or RNA molecule, for example, the genome of SARS-CoV-2, and sequence through the entire RNA molecule and look for sequence variations with high accuracy, that can determine the variants that person may infected with, such as Delta and Omicron. So, this will actually enhance the sequencing capacity in the US and allow this to be done, fully automated back at the point of care. So, we will be taking sequencing out of the central laboratory and moving it into sites, for example, looking at infectious outbreaks, [where] we're then also screening...people coming across into the US to see if they're carrying any new infections. [We’re], basically, taking the sequencing out of the central laboratory and putting it into remote sites at the point of care.
Q: What new key developments have happened with these two projects since I spoke with you last in November 2021?A: The COVID-19 test has now been prototyped and we are engaged in running clinical samples (>500 saliva samples that have been collected over a two-year period), which will serve as documentation for FDA approval. Because the prototype is in a functional state, we are now engaging our production partners for both the instrument and the microfluidic cartridge. The microfluidic cartridge is very unique in that it is comprised of two chips interconnected using a fluidic motherboard, all of which are made from a plastic via injection molding. The motherboard also contains membrane valves for controlling the fluidics. There is also in place miniature electronics for the nano-Coulter counter for label-free counting of the affinity-selected virions from the clinical sample. With respect to the single-molecule DNA/RNA sequencing system, we have successfully injection molded the plastic chip. The plastic chip for sequencing contains structures that range in size from 5 nm to 50 um and in a single step, we can mold these structures. This will allow us to support high-scale production of the sequencing chip and at low cost (<$10 per chip). This will facilitate commercialization of the sequencing platform. We have also demonstrated that the sequencing chip can be interfaced to other chips using a fluidic motherboard similar to the one used for the COVID-19 test, meaning that the entire process of sequencing clinical samples (blood-to-sequencing) can be done using a single chip with full automation.
Q: With Omicron emerging since we last spoke, how does that change things with your work? Is there more urgency?A: The rise and fall of new variants associated with COVID-19 rapidly occurs, as they do with any virus. Our assay is based on the affinity selection of SARS-CoV-2 with the affinity agent (aptamer) designed for the original strain of SARS-CoV-2. Our affinity agent was designed to bind to the receptor binding domain of the spike protein and this is changing during the evolution of the variants. For example, the Omicron variant has 36 mutations in its spike protein while the delta variant only had nine mutations. Our test has the ability to show positive results for the beta, alpha, delta, and gamma variants and we are currently performing clinical tests for the Omicron variant. We should point out that the limit-of-detection for the variants was lower compared to the original strain due to a lower binding affinity of the aptamer to the spike protein of the variants. However, our test can be tailored for a particular variant with high sensitivity by simply changing the sequence composition of the aptamer affinity agent.
Q: I know these two projects are still in the works, but do you know when we might see them on the market?A: For the COVID-19 test, we have the chips in production and are building the handheld instrument as we speak. We have a commercial partner (BioFluidica, Inc.) for the handheld COVID-19 test and we are hoping to get that on the market by the third quarter of 2022. I would like to say that our COVID-19 test can be reprogrammed for other applications as well, such as large-scale screening for different cancers, a diagnostic for stroke, or a biodosimeter for triaging those exposed to radiation. In terms of the single-molecule sequencing platform, we have a new commercial partner and have launched a three-year program to get this technology to market. We are hoping to have this in an alpha prototype stage in less than two years and out in the research market in less than three years.
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