Bioanalysis Zone

COVID-19 and microsampling: from patient-centric testing to drug development and beyond

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Recently the National Institutes of Health (MD, USA) announced a study to quantify undetected cases of COVID-19 using antibody tests on blood samples collected in microsampling devices [1]. We asked microsampling expert Hua Li (Boehringer Ingelheim Pharmaceuticals, CT, USA) for her perspectives on the potential benefits and applications of patient-centric microsampling strategies amidst the coronavirus pandemic.

You can read more about Hua’s research using the Mitra® microsampling platform for pharmacokinetic bioanalysis in her Bioanalysis publication.


Hua Li photo“I majored in Biotechnology in college back in China and then earned a Master’s degree in Molecular, Cellular and Developmental Biology from the University of Kansas (KS, USA). After graduation, I started my career as a research associate and laboratory manager at the Stem Cell Center of Yale University (CT, USA). My main roles included investigating the essential proteins that play a critical role in the division and differentiation of mouse testes stem cells, as well as administrative responsibilities for a laboratory of around 12 people including graduate students, post-docs and laboratory technicians. Since 2008, my career has been focusing on the quantitation of pharmacokinetics (PK) and pharmacodynamics (PD) study of protein therapeutics. Currently I am a bioanalytical research scientist in the NBE PK Group in the Biotherapeutics Discovery department at Boehringer Ingelheim Pharmaceuticals (CT, USA).”

QWhat is the importance of the NIH study aiming to quantify undetected cases of COVID-19 and how do the antibody detection tests work?

This new antibody detection study is critical to understand the extent of the coronavirus spread in the general population. Until recently, the reporting of US cases of COVID-19 has been determined by the presence of the SARS-CoV-2 virus in a person’s airways. Unfortunately, this test does not tell whether a person was previously infected with the novel virus and recovered, thereby missing many cases in the reporting of infections. The new antibody detection test uses an ELISA protein binding assay to determine if there are anti-SARS-CoV-2 IgG and IgM antibodies in the blood, which is an indication of a prior infection. As Dr Anthony Fauci (Director, National Institute of Allergy and Infectious Diseases, NIH) said, “This study will give us a clearer picture of the true magnitude of the COVID-19 pandemic in the United States by telling us how many people in different communities have been infected without knowing it. These crucial data will help us measure the impact of our public health efforts now and guide our COVID-19 response moving forward [1].”

QWhat characteristics make microsampling techniques the collection method of choice in this scenario?

With the sensitivity and precision of today’s ELISAs , typically only a small amount of human whole blood (~10 µL) is needed to perform an antibody detection test.  In addition, when using microsampling techniques like Mitra®, blood samples can be collected non-invasively by the volunteers themselves rather than having to go to a medical office to have blood drawn.  Use of the Mitra® microsampling device also has the advantage of being able to ship blood samples by regular mail as opposed to the biohazard designation and temperature requirements typically in place for traditional blood sampling techniques.

QIn the midst of the global coronavirus pandemic, how important are patient-centric sampling strategies? Can you outline why microsampling strategies lend themselves to the idea of patient-centricity?

Patient-centric sampling strategies are always very important, especially in the current global coronavirus pandemic. With millions of people infected, including many who are asymptomatic, there is a critical need to rapidly enable testing on a wide scale.  Obviously, for people under strict stay at home orders, it’s not feasible to require people to travel to medical centers for blood sampling.  Also, by giving people the ability to conduct their own testing and to receive test results either electronically or by mail, the patient then becomes less dependent on medical professionals to get information regarding their health status.  Finally, as more and more molecular signaling pathways and biomarkers are discovered, those new evaluations can be integrated into blood screenings without requiring additional blood sampling.  Certainly, in less economically developed places, a sampling strategy that can still work well regardless of location and socioeconomic status is essential.  Mitra® microsamplers are a promising tool to help us get closer to the type of patient-centricity required in a global pandemic.

QNo technique is perfect, in this kind of large population study what do you think could be the potential limitations or bottlenecks?

The sheer number of samples to test in this kind of large population study could be challenging in many ways.  First, distribution of microsamplers to the population, and then to receive and handle the blood samples shipped back would require extensive coordination between the testing centers, practitioners and people being tested. Next, for scientists to recover antibodies from the microsamplers and to perform assays could take quite some time with such a large pool of samples. Data processing and interpretation could also be challenging since results are often not a black and white answer, but a cut-off point carefully considered and implemented in order to accurately separate the scientifically positive result from assay background signals. Although automated systems could help greatly in the bioanalytical processes, there is currently still a tremendous amount of human work involved in the assay design, calibration and validation before the real runs can occur. Ensuring that every component of this process will work smoothly even when scaled up will be a challenge.

The timing of bioanalysis after microsampling is another challenge.  For example, do we need to run the sample bioanalysis within a few days after microsampling, or could the samples be stored and for how long? That requires us to know ahead of time how stable the anti-SARS-CoV-2 antibodies would be on the dried microsamplers. We have very promising data (as yet unpublished) demonstrating that antibodies may be quite stable on dried Mitra® microsamplers, even at room temperature, for many days and perhaps even weeks.  This is encouraging since it means that microsampling could potentially be used for population-wide testing, even in locations without refrigeration and where getting samples to a processing facility may take much longer.

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QThe far-reaching impact of the coronavirus pandemic can be seen in every phase of drug development, from discovery research to clinical trials. How could microsampling strategies help to address some of these challenges?

The impact of the coronavirus pandemic will persist far into the future for the pharmaceutical industry, especially for protein therapeutics discovery and development.  As research scientists in the field of protein therapeutic PK/PD, we routinely test many different drug candidates in preclinical species.  This involves administering the drug candidates and then sampling whole blood or serum for protein quantification. Protein therapeutics sampling is very different from that of small molecule drugs in that we typically require a much longer time course to accurately characterize PK/PD properties.  Because the volume and frequency of blood sampling are strictly regulated in preclinical species, in the past we were often required to use additional animals and staggered sampling to get a complete time course. Microsampling, coupled with today’s more sensitive assays, allows us to minimize the use of animals while simultaneously increasing the amount of data we can get from each sample.

QWhat do you think the future holds for patient-centric microsampling – do you think the current trend in the use of microsampling could trigger technological breakthroughs and permanent changes in the field?

People started to realize the importance of microsampling a few decades ago, and we have already witnessed an incredible burst of new technologies and devices for microsampling on the market. Over the past decade, volumetric absorptive microsampling techniques such as dried blood spot and Mitra® microsamplers have been contributing to improvements in the three Rs: replacement, reduction and refinement of animal usage. We will absolutely continue to see more and better microsampling innovations in the future.

I have no doubt that the current trend in the application of microsampling will trigger more dramatic scientific and technological breakthroughs and permanent changes, especially in the clinical areas where it will help to connect patients with their sampling, diagnosis, monitoring and screening in a more efficient and practical fashion.

Looking into the future, I imagine it will not be long before we can implement a seamless automation system that will take barcoded microsamples, process them for the desired data and then output those results in a final electronic report with diagnosis and comments for review by physician and patient.


Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

The opinions expressed in this feature are those of the author and do not necessarily reflect the views of Bioanalysis Zone or Future Science Group.

References

[1] www.nih.gov/news-events/news-releases/nih-begins-study-quantify-undetected-cases-coronavirus-infection

COVID-19 hub

 

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