Then. . .
It used to be that microsampling was not a major focus, and there was not a lot of visible activity in the industry. Scientists routinely reduced samples to generate bioanalytical data, and the impetus to change sampling on either toxicological or clinical studies was relatively minimal. The advantage of the sensitivity was used to drive down the amount of sample being extracted and to reduce the impact of matrix on analysis. The bioanalytical community became aware of the impact of matrix effects when using electrospray ionization, and one of the easiest ways to deal with this was to reduce the amount of matrix included in the final extract. So, scientists used the enhanced sensitivity they had gained to reduce the limit of quantification in assays, while also using significantly less matrix.
During the 1990s, there were some real advances in microsampling. The team at GSK (UK) had started to use dried blood spots (DBS) for samples in both preclinical and clinical studies. While we are acutely aware of the problems that have since come to light related to DBS, the cause for microsampling was significantly accelerated by the work that GSK undertook. At a similar time, the team at AstraZeneca (Södertälje, Sweden) was also investigating microsampling and developed an approach that was initially targeted at blood microsampling but adapted to generate extremely small volumes of plasma. Many researchers were keen on these new techniques. Since then, the scientific community, including Charles River, have done significant amounts of research and studies with both approaches supporting preclinical development.
Now. . .
The trend is starting to shift as more companies begin to embed microsampling into their nonclinical workflows. In the past couple of years, we have seen a greater commitment to microsampling from several large companies as well as from our regulators. In January 2016, the International Conference for Harmonization released a Q&A document on microsampling, which discusses the idea of taking safety data measurements from main study animals and generating the toxicokinetic and exposure data in the same animals. There has also been a lot of discussion within the industry about the need to ensure that safety and toxicokinetic data is generated from the same animals. Microsampling has not only facilitated these discussions but is also making it possible to achieve these objectives. The removal of toxicokinetic subgroups from studies is having, and will continue to have, a significant impact on reducing the number of animals used in research.
More popular in the early years of clinical microsampling, the use of DBS has lost traction over the past couple of years. Development continues, however, with excellent work in the pediatric space; Hitesh Pandya (University of Leicester, UK) has shown the advantages of DBS and is now working on a new volumetric absorptive microsampling (VAMS) device. VAMS is a unique approach to a solid matrix, which overcomes some of the concerns and issues that have been identified with DBS.
Future. . .
As an industry, we have moved into an exciting time in bioanalytical research as we take advantage of our wide variety of analytical platforms and gains in sensitivity to change the way we conduct our in vivo research. These advancements will be further supported by innovative developments in sample collection and handling.
We are certain that there will be continued advancements in the specificity of microsampling techniques as new technologies are introduced. Microsampling devices containing antibodies for highly specific assays are a reality within the future. Evolution of microsampling with biosensors has the potential to allow rapid patient assessment in underdeveloped countries that do not have access to advanced laboratory techniques.
Learn more about microsampling and the techniques mentioned in this article on the NC3Rs microsampling website.