PMID- 33149998 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201106 IS - 2156-7085 (Print) IS - 2156-7085 (Electronic) IS - 2156-7085 (Linking) VI - 11 IP - 10 DP - 2020 Oct 1 TI - Nanometer precise red blood cell sizing using a cost-effective quantitative dark field imaging system. PG - 5950-5966 LID - 10.1364/BOE.405510 [doi] AB - Because of the bulk, complexity, calibration requirements, and need for operator training, most current flow-based blood counting devices are not appropriate for field use. Standard imaging methods could be much more compact, inexpensive, and with minimal calibration requirements. However, due to the diffraction limit, imaging lacks the nanometer precision required to measure red blood cell volumes. To address this challenge, we utilize Mie scattering, which can measure nanometer-scale morphological information from cells, in a dark-field imaging geometry. The approach consists of a custom-built dark-field scattering microscope with symmetrically oblique illumination at a precisely defined angle to record wide-field images of diluted and sphered blood samples. Scattering intensities of each cell under three wavelengths are obtained by segmenting images via digital image processing. These scattering intensities are then used to determine size and hemoglobin information via Mie theory and machine learning. Validation on 90 clinical blood samples confirmed the ability to obtain mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW) with high accuracy. Simulations based on historical data suggest that an instrument with the accuracy achieved in this study could be used for widespread anemia screening. CI - (c) 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement. FAU - Chen, Xiaoya AU - Chen X AD - Key Laboratory of Precision Scientific Instrumentation of Anhui Higher Education Institutes, Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, Hefei, Anhui, China. FAU - Luo, Peng AU - Luo P AD - Department of Clinical Laboratory, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China. FAU - Hu, Chuanzhen AU - Hu C AD - Key Laboratory of Precision Scientific Instrumentation of Anhui Higher Education Institutes, Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, Hefei, Anhui, China. FAU - Yan, Shaojie AU - Yan S AD - Key Laboratory of Precision Scientific Instrumentation of Anhui Higher Education Institutes, Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, Hefei, Anhui, China. FAU - Lu, Dapeng AU - Lu D AD - Department of Clinical Laboratory, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China. FAU - Li, Yaning AU - Li Y AD - Key Laboratory of Precision Scientific Instrumentation of Anhui Higher Education Institutes, Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, Hefei, Anhui, China. FAU - Chu, Kaiqin AU - Chu K AD - Key Laboratory of Precision Scientific Instrumentation of Anhui Higher Education Institutes, Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, Hefei, Anhui, China. AD - Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, China. FAU - Smith, Zachary J AU - Smith ZJ AUID- ORCID: 0000-0002-7946-7863 AD - Key Laboratory of Precision Scientific Instrumentation of Anhui Higher Education Institutes, Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, Hefei, Anhui, China. LA - eng PT - Journal Article DEP - 20200928 PL - United States TA - Biomed Opt Express JT - Biomedical optics express JID - 101540630 PMC - PMC7587267 COIS- ZJS in a named inventor on US patent 10024858B2. The other authors declare no conflicts of interest. EDAT- 2020/11/06 06:00 MHDA- 2020/11/06 06:01 PMCR- 2020/10/01 CRDT- 2020/11/05 06:08 PHST- 2020/08/14 00:00 [received] PHST- 2020/09/16 00:00 [revised] PHST- 2020/09/18 00:00 [accepted] PHST- 2020/11/05 06:08 [entrez] PHST- 2020/11/06 06:00 [pubmed] PHST- 2020/11/06 06:01 [medline] PHST- 2020/10/01 00:00 [pmc-release] AID - 405510 [pii] AID - 10.1364/BOE.405510 [doi] PST - epublish SO - Biomed Opt Express. 2020 Sep 28;11(10):5950-5966. doi: 10.1364/BOE.405510. eCollection 2020 Oct 1.