PMID- 32102446 OWN - NLM STAT- MEDLINE DCOM- 20210308 LR - 20240423 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 9 IP - 2 DP - 2020 Feb 24 TI - Microfluidic Device for On-Chip Immunophenotyping and Cytogenetic Analysis of Rare Biological Cells. LID - 10.3390/cells9020519 [doi] LID - 519 AB - The role of circulating plasma cells (CPCs) and circulating leukemic cells (CLCs) as biomarkers for several blood cancers, such as multiple myeloma and leukemia, respectively, have recently been reported. These markers can be attractive due to the minimally invasive nature of their acquisition through a blood draw (i.e., liquid biopsy), negating the need for painful bone marrow biopsies. CPCs or CLCs can be used for cellular/molecular analyses as well, such as immunophenotyping or fluorescence in situ hybridization (FISH). FISH, which is typically carried out on slides involving complex workflows, becomes problematic when operating on CLCs or CPCs due to their relatively modest numbers. Here, we present a microfluidic device for characterizing CPCs and CLCs using immunofluorescence or FISH that have been enriched from peripheral blood using a different microfluidic device. The microfluidic possessed an array of cross-channels (2-4 microm in depth and width) that interconnected a series of input and output fluidic channels. Placing a cover plate over the device formed microtraps, the size of which was defined by the width and depth of the cross-channels. This microfluidic chip allowed for automation of immunofluorescence and FISH, requiring the use of small volumes of reagents, such as antibodies and probes, as compared to slide-based immunophenotyping and FISH. In addition, the device could secure FISH results in <4 h compared to 2-3 days for conventional FISH. FAU - M Weerakoon-Ratnayake, Kumuditha AU - M Weerakoon-Ratnayake K AUID- ORCID: 0000-0002-6839-4515 AD - Department of Chemistry, The University of Kansas, Lawrence, KS 66047, USA. AD - Center of BioModular Multiscale Systems for Precision Medicine, Lawrence, KS 66045, USA. FAU - Vaidyanathan, Swarnagowri AU - Vaidyanathan S AUID- ORCID: 0000-0003-0397-5543 AD - Center of BioModular Multiscale Systems for Precision Medicine, Lawrence, KS 66045, USA. AD - Bioengineering, The University of Kansas, Lawrence, KS 66045, USA. FAU - Larky, Nicholas AU - Larky N AD - Center of BioModular Multiscale Systems for Precision Medicine, Lawrence, KS 66045, USA. AD - Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA. FAU - Dathathreya, Kavya AU - Dathathreya K AD - Department of Chemistry, The University of Kansas, Lawrence, KS 66047, USA. AD - Center of BioModular Multiscale Systems for Precision Medicine, Lawrence, KS 66045, USA. FAU - Hu, Mengjia AU - Hu M AD - Center of BioModular Multiscale Systems for Precision Medicine, Lawrence, KS 66045, USA. AD - Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA. FAU - Jose, Jilsha AU - Jose J AD - Center of BioModular Multiscale Systems for Precision Medicine, Lawrence, KS 66045, USA. FAU - Mog, Shalee AU - Mog S AD - Department of Chemistry, The University of Kansas, Lawrence, KS 66047, USA. AD - Center of BioModular Multiscale Systems for Precision Medicine, Lawrence, KS 66045, USA. FAU - August, Keith AU - August K AD - Children's Mercy Hospital, Kansas City, MO 64108, USA. FAU - K Godwin, Andrew AU - K Godwin A AUID- ORCID: 0000-0002-3987-9580 AD - Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA. FAU - L Hupert, Mateusz AU - L Hupert M AD - Biofluidica Inc., BioFluidica Research Laboratory, Lawrence, KS 66047, USA. FAU - A Witek, Malgorzata AU - A Witek M AD - Department of Chemistry, The University of Kansas, Lawrence, KS 66047, USA. AD - Center of BioModular Multiscale Systems for Precision Medicine, Lawrence, KS 66045, USA. FAU - A Soper, Steven AU - A Soper S AD - Department of Chemistry, The University of Kansas, Lawrence, KS 66047, USA. AD - Center of BioModular Multiscale Systems for Precision Medicine, Lawrence, KS 66045, USA. AD - Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA. AD - Biofluidica Inc., BioFluidica Research Laboratory, Lawrence, KS 66047, USA. AD - Department of Mechanical Engineering, The University of Kansas, Lawrence, KS 66045, USA. LA - eng GR - P30 CA168524/CA/NCI NIH HHS/United States GR - R33 CA235597/CA/NCI NIH HHS/United States GR - P20 GM130423/GM/NIGMS NIH HHS/United States GR - P41 EB020594/EB/NIBIB NIH HHS/United States GR - R44 CA224848/NH/NIH HHS/United States GR - R33 CA235597/NH/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200224 PL - Switzerland TA - Cells JT - Cells JID - 101600052 SB - IM MH - B-Lymphocytes/*immunology MH - Blood Donors MH - Cell Line MH - Cytogenetic Analysis/*instrumentation/methods MH - Humans MH - Immunophenotyping/*instrumentation/methods MH - In Situ Hybridization, Fluorescence/*instrumentation/methods MH - *Lab-On-A-Chip Devices MH - Liquid Biopsy MH - Microfluidics/*instrumentation/methods MH - Molecular Diagnostic Techniques/*instrumentation/methods MH - Neoplastic Cells, Circulating/*immunology MH - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology PMC - PMC7072755 OTO - NOTNLM OT - circulating leukemia cells OT - circulating plasma cells OT - fish OT - immunophenotyping OT - liquid biopsy OT - microfluidics COIS- S.A.S. and M.L.H. hold equity shares in BioFluidica, Inc., a company that holds commercialization rights to the cell isolation technology described herein. M.A.W declares COI as a spouse of a BioFluidica, Inc. employee. EDAT- 2020/02/28 06:00 MHDA- 2021/03/09 06:00 PMCR- 2020/02/01 CRDT- 2020/02/28 06:00 PHST- 2019/12/19 00:00 [received] PHST- 2020/02/10 00:00 [revised] PHST- 2020/02/18 00:00 [accepted] PHST- 2020/02/28 06:00 [entrez] PHST- 2020/02/28 06:00 [pubmed] PHST- 2021/03/09 06:00 [medline] PHST- 2020/02/01 00:00 [pmc-release] AID - cells9020519 [pii] AID - cells-09-00519 [pii] AID - 10.3390/cells9020519 [doi] PST - epublish SO - Cells. 2020 Feb 24;9(2):519. doi: 10.3390/cells9020519.