Development of a rare cell fractionation device: application for cancer detection

Isolating rare cells from biological fluids including whole blood or bone marrow is an interesting biological problem. Characterization of a few metastatic cells from cancer patients for further study is desirable for prognosis/diagnosis. Traditional methods have not proven adequate, due to the compositional complexity of blood, with its large numbers of cell types. To separate individual cells based on their mechanical characteristics, we have developed a series of massively parallel microfabricated sieving device. These devices were constructed with four successively narrower regions of channels numbering /spl sim/1800 per region. As cells traversed the device, they encountered each region and stopped at a gap width that prohibited passage due to their size. Cultured neuroblastoma cells, when mixed with whole blood and applied to the device, were retained in the 10-/spl mu/m-wide by 20-/spl mu/m-deep channels. All other cells migrated to the output. A derivative of the same device was utilized to characterize migration of whole blood. Adult white blood cells were retained at the 2.5-/spl mu/m-wide by 5-/spl mu/m-deep channels, while red blood cells passed through these channels. Devices designed to capture rare cells in peripheral circulation for downstream analysis will provide an important tool for diagnosis and treatment.

[1]  Lori A. Lepak,et al.  Direct Casting of Polymer Membranes into Microfluidic Devices , 2004 .

[2]  F. Speleman,et al.  Application of laser capture microdissection in genetic analysis of neuroblastoma and neuroblastoma precursor cells. , 2003, Cancer Letters.

[3]  F. Speleman,et al.  Quality assessment of genetic markers used for therapy stratification. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  Robert Langer,et al.  Reactive polymer coatings: a first step toward surface engineering of microfluidic devices. , 2003, Analytical chemistry.

[5]  G. Brodeur.  Neuroblastoma: biological insights into a clinical enigma , 2003, Nature Reviews Cancer.

[6]  R. Bashir,et al.  Dielectrophoretic separation and manipulation of live and heat-treated cells of Listeria on microfabricated devices with interdigitated electrodes , 2002 .

[7]  Dorian Liepmann,et al.  A biomimetic method for extracting leukocytes from blood in microfluidic devices , 2002, 2nd Annual International IEEE-EMBS Special Topic Conference on Microtechnologies in Medicine and Biology. Proceedings (Cat. No.02EX578).

[8]  K. Klinger,et al.  Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data , 2002, Prenatal diagnosis.

[9]  B. Kushner,et al.  Quantitation of GD2 synthase mRNA by real‐time reverse transcription‐polymerase chain reaction , 2002, Cancer.

[10]  Yousef Haik,et al.  Development of magnetic device for cell separation , 1999 .

[11]  Maciej Zborowski,et al.  Continuous cell separation using novel magnetic quadrupole flow sorter , 1999 .

[12]  Giovanni De Gasperis,et al.  Microfluidic Cell Separation by 2-dimensional Dielectrophoresis , 1999 .

[13]  M. Heller,et al.  Isolation of cultured cervical carcinoma cells mixed with peripheral blood cells on a bioelectronic chip. , 1998, Analytical chemistry.

[14]  R. Austin,et al.  Activation and Sorting of Human White Blood Cells , 1998 .

[15]  H. Carlson,et al.  Sorting of White Blood Cells in a Lattice , 1997 .

[16]  Y. Kan,et al.  Prenatal diagnosis of sickle cell anaemia and thalassaemia by analysis of fetal cells in maternal blood , 1996, Nature Genetics.

[17]  C. van Rijn,et al.  A microsieve for leukocyte depletion of erythrocyte concentrates , 1996, Proceedings of 18th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[18]  S. Wachtel,et al.  Fetal cells in maternal blood: recovery by charge flow separation , 1996, Human Genetics.

[19]  F. Bischoff,et al.  Rare event selection of fetal nucleated erythrocytes in maternal blood by flow cytometry. , 1996, Cytometry.

[20]  Y. Huang,et al.  Dielectrophoretic separation of cancer cells from blood , 1995, IAS '95. Conference Record of the 1995 IEEE Industry Applications Conference Thirtieth IAS Annual Meeting.

[21]  Andreas Radbruch,et al.  Detection and isolation of rare cells. , 1995, Current opinion in immunology.

[22]  S Miltenyi,et al.  Enrichment of fetal cells from maternal blood by high gradient magnetic cell sorting (double MACS) for PCR‐based genetic analysis , 1994, Prenatal diagnosis.

[23]  G Kvalheim,et al.  Isolation and characterization of human hematopoietic progenitor cells: an effective method for positive selection of CD34+ cells. , 1992, Leukemia.

[24]  W. Holzgreve,et al.  Magnetic cell sorting and the transferrin receptor as potential means of prenatal diagnosis from maternal blood. , 1992, American journal of obstetrics and gynecology.

[25]  S. Latt,et al.  Isolation of fetal DNA from nucleated erythrocytes in maternal blood. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[26]  P. Pizzo,et al.  Principles and Practice of Pediatric Oncology , 1989 .

[27]  M. Nishi,et al.  Effects of the mass screening of neuroblastoma in sapporo city , 1987, Cancer.

[28]  F. Berthold,et al.  Neuroblastoma: diagnostic advances and therapeutic results in 370 patients , 1986 .

[29]  T. Matsumura,et al.  Neuroblastoma. Mass screening for early detection and its prognosis , 1984, Cancer.

[30]  B. Bloom,et al.  In vitro methods in cell mediated and tumor immunity , 1976 .

[31]  A. Bøyum,et al.  Separation of blood leucocytes, granulocytes and lymphocytes. , 2008, Tissue antigens.

[32]  Illiam,et al.  SCREENING OF INFANTS AND MORTALITY DUE TO NEUROBLASTOMA , 2022 .