title: High-throughput lens-free blood analysis on a chip.
abstract: We present a detailed investigation of the performance of lens-free holographic microscopy toward high-throughput on-chip blood analysis. Using a spatially incoherent source that is emanating from a large aperture, automated counting of red blood cells with minimal sample preparation steps at densities reaching up to approximately 0.4 x 10(6) cells/muL is presented. Using the same lens-free holographic microscopy platform, we also characterize the volume of the red blood cells at the single-cell level through recovery of the optical phase information of each cell. We further demonstrate the measurement of the hemoglobin concentration of whole blood samples as well as automated counting of white blood cells, also yielding spatial resolution at the subcellular level sufficient to differentiate granulocytes, monocytes, and lymphocytes from each other. These results uncover the prospects of lens-free holographic on-chip imaging to provide a useful tool for global health problems, especially by facilitating whole blood analysis in resource-poor environments.
authors.affiliation: Electrical Engineering Department, University of California, Los Angeles, California 90095, USA.
authors.forename: Sungkyu
authors.initials: S
authors.lastname: Seo
authors.forename: Serhan O
authors.initials: SO
authors.lastname: Isikman
authors.forename: Ikbal
authors.initials: I
authors.lastname: Sencan
authors.forename: Onur
authors.initials: O
authors.lastname: Mudanyali
authors.forename: Ting-Wei
authors.initials: TW
authors.lastname: Su
authors.forename: Waheb
authors.initials: W
authors.lastname: Bishara
authors.forename: Anthony
authors.initials: A
authors.lastname: Erlinger
authors.forename: Aydogan
authors.initials: A
authors.lastname: Ozcan
mesh_terms: D001772:Blood Cell Count / Q000295:instrumentation* / Q000379:methods; D004906:Erythrocyte Count; D006696:Holography; D006801:Humans; D056656:Lab-On-A-Chip Devices; D007909:Lenses; D007958:Leukocyte Count; D008853:Microscopy; D013997:Time Factors
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11301-5
references.pmid: 11572982
references.citation: J Opt Soc Am. 1967 Apr;57(4):546-7
references.pmid: 6027838
references.citation: Lab Chip. 2009 Mar 21;9(6):777-87
references.pmid: 19255659
references.citation: J Biomed Opt. 2006 Nov-Dec;11(6):064004
references.pmid: 17212527
references.citation: Lab Chip. 2006 Oct;6(10):1274-6
references.pmid: 17102839
references.citation: Lab Chip. 2010 May 7;10(9):1109-12
references.pmid: 20390127
references.citation: Opt Express. 2005 Jun 13;13(12):4492-506
references.pmid: 19495364
references.citation: Nature. 2006 Jul 27;442(7101):368-73
references.pmid: 16871203
references.citation: Appl Opt. 2002 Aug 1;41(22):4489-96
references.pmid: 12153076
references.citation: Opt Lett. 2004 May 15;29(10):1132-4
references.pmid: 15182009
references.citation: Opt Lett. 2006 May 1;31(9):1211-3
references.pmid: 16642062
references.citation: Appl Opt. 1992 Aug 20;31(24):4973-8
references.pmid: 20733659
references.citation: Opt Express. 2010 Mar 1;18(5):4717-26
references.pmid: 20389485
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10670-5
references.pmid: 18663227
references.citation: Lab Chip. 2010 Jun 7;10(11):1417-28
references.pmid: 20401422
references.citation: Opt Lett. 2007 Dec 15;32(24):3492-4
references.pmid: 18087519