|website:||Multi-Scale Design Laboratory|
- Cell Sorting
- Cell Biomechanics
- Circulating Tumor Cells
- Malaria and Red Blood Cell Deformability
- Single Cell Technologies
- Cell Migration and Chemotaxis
- Deformability based cell sorting:The mechanical deformability of individual cells could often be used to distinguish different cell types from each other or diseased cells from healthy cells. Simple filtration methods have not been able to reliably sort or separate cells based deformability because of the inability to precisely control the filtration force applied to each cell. We are developing new deformability based cell sorting mechanisms, such as the microfluidic ratchet and the resettable cell trap, that ensure consistent forces are applied to each cell by actively preventing cell clogging and adhesion in the filter microstructure.
- Circulating tumor cell separation and analysis:Circulating tumor cells are malignant cells released from a primary tumor into the bloodstream where they have the potential to form metastases that are ultimately responsible for >90% of all cancer-related deaths. The number and molecular status of these cells are thought to be of significant utility in the diagnosis, treatment, and study of cancer because these tumor cells can be rapidly obtained from a simple blood test without the need for invasive biopsies, and represent a key subpopulation of tumor cells that are relevant to metastasis. Applying mechanisms we developed for biophysical cell separation and biochemical cell separation, our group is able to capture these cells from whole blood at high purity. Working with clinical collaborators at the Vancouver Prostate Centre, we are performing molecular analysis of these cells and correlating their status with clinical outcomes.
- Red blood cell deformability as a biological assay:Red blood cells (RBCs) perform the critical function of transporting oxygen and carbon dioxide between tissues in the body. This capability is enable in part by their extraordinary mechanical deformability where they must repeatedly squeeze through capillaries many times smaller than their diameter. The loss of RBC deformability is associated with many diseases, including malaria, sickle cell disease, thalassemia, and nutritional deficiencies. We have developed multiple microfluidic devices for measuring the deformability of RBC in a physiologically relevant manner with high sensitivity and throughput. Our focus now is to apply these technologies as a biological assay for challenges in malaria and transfusion medicine. In particular, we recently showed that all clinical antimalarials reduces deformability of RBCs infected with Plasmodium falciparum (the parasite that causes malaria), which potentially enabling this property to be used as an functional screen for antimalarial drugs, as well as a method to evaluate antimalarial drug efficacy. Additionally, we are using this method to investigate the degradation of RBC deformability during cold storage and how this approach could be used to reduce complications.
- Fabrication and instrumentation technologies for microfluidics:Advances in microfluidics are fundamentally enabled by advances in fabrication and instrumentation. We are continuously developing new microfabrication methods and electronic instrumentation technologies (including both hardware and software) to provide sensitive control and readout for microfluidics systems.
- Guo Q, Duffy SP, Matthews K, Islamzada E, Ma H. Deformability based Cell Sorting using Microfluidic Ratchets Enabling Phenotypic Separation of Leukocytes Directly from Whole Blood. Scientific reports. 2017 Jul 26;7(1):6627. [Link to Article]
- Matthews K, Duffy SP, Myrand-Lapierre ME, Ang RR, Li L, Scott MD, Ma H. Microfluidic analysis of red blood cell deformability as a means to assess hemin-induced oxidative stress resulting from Plasmodium falciparum intraerythrocytic parasitism. Integrative Biology. 2017 May 19;9(6):519-28. [Link to Article]
- Park ES, Duffy SP, Ma H. Microfluidic Separation of Circulating Tumor Cells Based on Size and Deformability. InCirculating Tumor Cells 2017 (pp. 21-32). Humana Press, New York, NY. [Link to Article]
- Lin H, Li Q, Hu Y, Zhu C, Ma H, Gao J, Wu J, Shen H, Jiang W, Zhao N, Yin Y. The prevalence of multiple non-communicable diseases among middle-aged and elderly people: the Shanghai Changfeng Study. European journal of epidemiology. 2017 Feb 1;32(2):159-63. [pdf]
- Guo Q, Duffy SP, Ma H. Microfluidic technologies for deformability-based cell sorting. In Microtechnology for Cell Manipulation and Sorting 2017 (pp. 225-254). Springer, Cham. [pdf]
- Guo Q, Duffy SP, Matthews K, Deng X, Santoso AT, Islamzada E, Ma H. Deformability based sorting of red blood cells improves diagnostic sensitivity for malaria caused by Plasmodium falciparum. Lab on a Chip. 2016;16(4):645-54. [pdf]
- Todenhöfer T, Park ES, Duffy S, Deng X, Jin C, Abdi H, Ma H, Black PC. Microfluidic enrichment of circulating tumor cells in patients with clinically localized prostate cancer. InUrologic Oncology: Seminars and Original Investigations 2016 Nov 1 (Vol. 34, No. 11, pp. 483-e9). Elsevier. [Link to Article]
- Park ES, Jin C, Guo Q, Ang RR, Duffy SP, Matthews K, Azad A, Abdi H, Todenhöfer T, Bazov J, Chi KN. Continuous flow deformability‐based separation of circulating tumor cells using microfluidic ratchets. Small. 2016 Apr;12(14):1909-19. [Link to Article]
- Santoso AT, Deng X, Lee JH, Matthews K, Duffy SP, Islamzada E, Myrand-Lapierre M, McFaul SM, Ma H, Microfluidic Cell-phoresis Enabling High-throughput Analysis of Red Blood Cell Deformability and Biophysical Screening of Antimalarial Drugs, Lab on a Chip, 2015, DOI: 10.1039/C5LC00945F.[Link to Article]
- Deng X, Duffy SP, Myrand-Lapierre M, Matthews K, Santoso AT, Du Y, Ryan KS, Ma H, Reduced Deformability of Parasitized Red Blood Cells as a Biomarker for Antimalarial Drug Efficacy, Malaria Journal, 2015. (Accepted)
- Matthews K, Myrand-Lapierre M, Ang RR, Duffy SP, Scott MD, Ma H, Microfluidic Deformability Analysis of the Red Cell Storage Lesion, Journal of Biomechanics, 2015. (Accepted)
- Qin X, Park S, Duffy SP, Matthews K, Ang RR, Todenhöfer T, Abdi H, Azad A, Bazov J, Chi KN, Black PC, Ma H, Size and Deformability based Separation of Circulating Tumor Cells from Castrate Resistant Prostate Cancer Patients using Resettable Cell Traps, Lab on a Chip, 15, 2278-2286, 2015. [pdf]
- Myrand-Lapierre M, Ang RR, Deng X, Matthews K, Santoso AT, Ma H, Multiplexed Fluidic Plunger Mechanism for High-Throughput Analysis of Red Blood Cell Deformability, Lab on a Chip, 15(1), 159-167, 2015.[pdf]
- Park S, Ang RR, Bazov J, Chi KN, Black PC, Ma H, Morphological Differences Between Circulating Tumour Cells from Prostate Cancer Patients and Cultured Prostate Cancer Cells, PLoS ONE, 9(1), e85264, 2014. DOI: 10.1371/journal.pone.0085264.[pdf]
- Guo Q, McFaul SM, Park S, Ma H, Microfluidic micropipette aspiration for measuring the deformability of single cells, Lab on a Chip, 12(15), 2687-95, 2012.[pdf]
- M. McFaul, B.K. Lin, H. Ma, Physical Cell Separation Using Microfluidic Funnel Ratchets, Lab on a Chip, DOI: 10.1039/C2LC21045B, 2012.[pdf]
- Guo, S.J. Reiling, P. Rohrbach, H. Ma, Microfluidic Biomechanical Assay for Red Blood Cells Parasitized by Plasmodium falciparum, Lab on a Chip, 12 (6), 1143-1150, 2012.[pdf]
- Guo, S.M. McFaul, H. Ma, Deterministic microfluidic ratchet based on the deformation of individual cells, Physical Review E, Vol. 83, 051910, 2011. [pdf]