Development of A Novel Noncapillary Plasma Microsampling Device for Ultra-Low Volume of Blood Collection

Abstract

The desire for serial microsampling in mice has led to extensive research in this field within the pharmaceutical industry. The ability to profile a compound’s in vivo properties with less material and fewer mice has obvious advantages. A new device and workflow was developed at the Takeda Oncology site to allow scientists to isolate plasma from very low volumes of mouse blood (as low as 20 μl) collected using standard microsampling techniques. A side-by-side in vitro comparison of plasma concentrations was performed using this new device and conventional sampling methods with commercial and in-house molecules. The plasma concentrations of the molecules tested were very consistent between the conventional sampling techniques and this new device/workflow. In addition, several in-life studies have also been conducted to validate this new technique as a primary PK screening tool at the Takeda Boston. The new device is simple to use and very cost effective with the added benefit that no additional training is needed for the animal technicians and the same centrifuge equipment can be employed. This device can be used for blood volumes ranging from 20 to 100 μl enabling studies not just in rat and dog but more importantly in mice.

Keywords::

• capillary microsampling (CMS)
• dried matrix spot (DMS)
• hematocrit
• mean percentage difference (MPD)
• serial tail vein bleed

Financial & competing interests disclosure

This study was supported by Takeda Oncology Company (MA, USA). The authors were all employees of Takeda at the time the study was performed and eligible for Takeda stock options and stock ownership. The authors have no other 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 apart from those disclosed.

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

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors acknowledge Mingxiang Liao, Bingli Ma, Bei-Ching Chuang for measuring hematocrit levels of mouse blood, and also Mark Qian and Steve Langston for reviewing the manuscript.

Additional information

Funding

This study was supported by Takeda Oncology Company (MA, USA). The authors were all employees of Takeda at the time the study was performed and eligible for Takeda stock options and stock ownership. The authors have no other 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 apart from those disclosed.