title: Monitoring of benzene-induced hematotoxicity in mice by serial leukocyte counting using a microcavity array.
abstract: Monitoring of hematotoxicity, which requires serial blood collection, is difficult to carry out in small animals due to a lack of non-invasive, individual animal-appropriate techniques that enable enumeration of leukocyte subsets from limited amounts of whole blood. In this study, a microfluidic device equipped with a microcavity array that enables highly efficient separation of leukocytes from submicroliters of whole blood was applied for hematotoxicity monitoring in mice. The microcavity array can specifically separate leukocytes from whole blood based on differences in the size and deformability between leukocytes and other blood cells. Mouse leukocytes recovered on aligned microcavities were continuously processed for image-based immunophenotypic analysis. Our device successfully recovered almost 100% of mouse leukocytes in 0.1 μL of whole blood without the effect of serial blood collection such as changes in body weight and total leukocyte count. We assessed benzene-associated hematotoxicity in mice using this system. Mice were administered with benzene once daily and the depression of leukocyte numbers induced in individual mice was successfully monitored from tail vein blood collected every other day for 2 weeks. Serial monitoring of the leukocyte number in individual mice will contribute to the understanding of hematotoxicity and reduction of the number of animal experiment trials.
authors: Division of Biotechnology and Life Science, Institute of Engineering, Tokyo University of Agriculture and Technology, 2-24-16, Koganei, Tokyo 184-8588, Japan.
authors: Masahito
authors: M
authors: Hosokawa
authors: Marie
authors: M
authors: Asami
authors: Tomoko
authors: T
authors: Yoshino
authors: Noriyuki
authors: N
authors: Tsujimura
authors: Masayuki
authors: M
authors: Takahashi
authors: Satoshi
authors: S
authors: Nakasono
authors: Tsuyoshi
authors: T
authors: Tanaka
authors: Tadashi
authors: T
authors: Matsunaga
mesh_terms: D000818:Animals; D001554:Benzene / Q000633:toxicity*; D001800:Blood Specimen Collection / Q000295:instrumentation*; D002469:Cell Separation / Q000295:instrumentation; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006402:Hematologic Diseases / Q000097:blood* / Q000139:chemically induced* / Q000473:pathology; D053878:Hemolytic Agents / Q000633:toxicity; D007958:Leukocyte Count / Q000295:instrumentation*; D007962:Leukocytes / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D046888:Tissue Array Analysis / Q000295:instrumentation
chemical_list: D053878:Hemolytic Agents; D001554:Benzene