MSACL 2016 EU Abstract

Novel Devices for Blood Microsampling

Shinobu Kudoh (Presenter)
Shimadzu Techno-Research, Inc.

Bio: I'm a corporate officer of Shimadzu Techno-Research, Inc and the director, Pharmaceutical and Lifescience division. My divisionfs mission is to contribute to the drug/biomarker R&D to deliver safer & more efficacious drugs, new medications and diagnosis to patients and medical practices swiftly by providing superior expertise in analytical technology and sound sciences. LC, LC-MS/MS, LC-HRMS, GC-MS, MS-Imaging and LBA are our main analytical technologies. Bioanalysis for Pre-clinical and clinical PK & PK/PD evaluations, quantitative proteomics & metabolomics, and spec/stability analyses for drug materials and candidates products irrespective of molecular size are our main business fields. The microsampling devices and liver tissue derived from mouse ES cells and human iPS cells to be utilized for drug metabolic screening tests are our focusing topics to contribute to 3Rs initiative.

Authorship: Shinobu Kudoh and Ippei Takeuchi
(1) Shimadzu Techno-Research, Inc. (2)Shimadzu corp.

Short Abstract A new device set that enables an easy blood microsampling for an accurate quantitative analysis of drug compounds and endogenous compounds in body is presented. They are for contributing to two scientific and medical aspects. The one is to facilitate 4Rs initiative, namely Replacement, Reduction and Refinement in animal studies on drug R&D by fulfilling our Responsibility for it. The other one is to promote an easy blood sampling from seriously sick patients and neonates/infants where stress and sense of fear upon the sampling can be reduced as well as the sampling size.

Long Abstract

A newly developing device set that enables an easy microsampling of blood for an accurate quantitative analysis of drug compounds and endogenous compounds in body is presented. They are primary for contributing to two scientific and medical aspects. The one is to facilitate 4Rs (3Rs +1) initiative, namely Replacement, Reduction and Refinement in animal studies particularly on drug R&D by fulfilling our responsibility for it. The other one is to promote an easy blood sampling especially from seriously sick patients and neonates/infants where stress and sense of fear associated with the sampling can be reduced as well as the sampling size. The sampling can easily be done from capillary blood with a minimal sized puncture made on a finger, palm, heel, earlobe and etc. of patients in clinical studies and medical practices. The device set comprises of two components: a chip-type sampling device to collect blood and a carousel like disc designed to hold 14 of the sampling device to centrifuge them for plasma/serum separation. The sampling device has a suction capability of ca.20 or 40-µL of blood by a capillary phenomenon. Its narrow tubing structure is pre-coated with an anticoagulant reagent (EDTA) for plasma. After centrifugation for plasma or serum separation, the sampling devices set on the carousel-like disc can be stored in a deep freezer as they are until the day of analysis. The sampling device has compartments that can be snapped off with fingertips to give a chip holding 10µL or 5µL aliquots of the resultant plasma/serum. The chip can further be divided into two for a duplicate analysis or ISR requirement when needed. The chip can be processed for quantification with no volumetric re-measuring for further sample preparation procedures like a deproteination either with methanol or acetonitle for a quantitative analysis. So microsampling can be less complex with the present device set and hence productivities of a quantitative assay either for bioanalysis or metabolomics can be increased. As more sampling time-points from a single small animal are possibly set, their sacrificed numbers can be reduced and their determination data consistency can be improved in preclinical studies. The sampling device has been evaluated over variety of drug compounds in a wide range of hydrophobicity, acidity and molecular weights including humanized antibody. The evaluation tests have proved that the sampling accuracy and precision of blood and plasma by the device are comparable to those with typical micropipettes or even better. The present devices, therefore, can be the practical tools capable of an accurate quantitative microsampling for bioanalysis and metabolomics assays in a simple manipulation with no volumetric re-measuring nor transferring into a volumetric apparatus. Blood sampling even from neonates/infants and serious patients likely becomes less difficulty. Furthermore, the device set is considered to be applicable to the sampling of body fluids other than blood such as tears and saliva. So they can be handy devices for many cohort studies, epidemiological surveys and diagnoses where a quantitative determination provides scientifically relevant and accurate information beyond the developmental objectives contributing to preclinical and clinical studies where only a minute volume of specimen is collected.

References & Acknowledgements:

We are deeply grateful to Mr. M. Kakehi and his colleagues at Takeda Shonan Research Center and Mr. T. Karibe and his colleagues at Daiichi-Sankyo Shinagawa R&D Center for their cooperation. Special thanks to Misses. K. Ishibe and E. Matsubara for their technical contributions.

Financial Disclosure

IP Royalty: no

Planning to mention or discuss specific products or technology of the company(ies) listed above:

yes