Hematologics Inc.

Innovations and Inventions

  1. The first calibration of fluorescence activated cell sorters using immunofluorescence demonstrated that the instruments could detect 3,000 molecules of fluorescein but that autofluorescence of the cells was the limit of detection.

    Loken MR, Herzenberg LA: Analysis of cell populations with a fluorescence-activated cell sorter. Ann. N.Y. Acad. of Sci. 254:163-171, 1975.

  2. Invented fluorescence compensation to be able to perform the first two color immunofluorescence with a single laser. This was extended to the first use of 3 and 4 colors of analysis of cell populations by using 2 excitation lasers.

    Loken MR, Parks DR, Herzenberg LA: Two color immunofluorescence using a Fluorescence Activated Cell Sorter. J. Histochem. Cytochem. 25:899. 1977.
    -see pdf file.

    Loken MR, Lanier LL: Three color immunofluorescence of Leu antigens on human peripheral blood using two lasers on a fluorescence activated cell sorter. Cytometry. 5:151-158 (1984).
    -see pdf file.

    Lanier LL, Loken MR: Human lymphocyte subpopulations identified using three-color immunofluorescence and flow cytometry analysis: Correlation of leu 2, leu 3, leu 7, leu 8 and Leu 11 cell surface antigen expression. J. Immunol. 131:151-156 (1984).

    Loken, MR, Parks, DR, Hardy RR: Method and apparatus for distinguishing multiple subpopulations of cells in a sample. European Patent 0121262B1

  3. The first review of immunofluorescence using a flow cytometer.

    Loken MR, Stout RD, Herzenberg LA: Lymphoid cell analysis and sorting. In: "Flow Cytometry and Sorting". Melamed MR, Mullaney PF, Mendelsohn ML, eds. John Wiley and Sons, New York, pp 505- 528, 1979.

  4. Produced the first commercial antibodies conjugated with phycoerythrin.

    Loken MR. Lanier LL, Recktenwald R, Warner NL. Flow Cytometry Monitoring of Leukocyte Sets and Subsets in Flow Cytometry and Monoclonal Antibodies for Therapy Monitoring: Quo Vadis? Jausell FK, Poucelet P, Roncucci R. eds . Group SANOFI, Montpellier pp. 1(107-120 ( 1984) .

  5. Developed techniques to optimize cellular discrimination using forward light scatter.

    Loken MR, Sweet RH, Herzenberg LA: Cell discrimination by multi-angle light scattering. J. Histochem. and Cytochem. 24:284-291, 1976.
    -see pdf file.

    Loken MR, Houck DW: Light scattered at two wavelengths can discriminate viable lymphoid cells on a Fluorescence Activated Cell Sorter. J. Histochem. Cytochem.. 29 609-615. 1981.
    -see pdf file.

    Horan PK, Loken MR: A practical guide for the use of flow systems in flow cytometry. In "Instrumentation and Data Analysis". MA Van Dilla, ed. Academic Press, San Diego. pp. 260-280 (1985) .

  6. The first description of using CD45 to discriminate cell lineages in bone marrow and blood has led to the technique of "CD45 gating".

    Shah VO, Civin CI, Loken MR: Flow cytometric analysis of human bone marrow: IV. Differential quantitative expression of T200 common leukocyte antigen during normal hematopoiesis. J. Immunol 140:1861-1867, 1988
    -see pdf file.

    Loken MR, Brosnan J, Bach BA, Ault KA: Establishing Optimal Lymphocyte Gates for Immunophenotyping. Cytometry 11:453-459, 1990.
    -see pdf file.

    Stelzer GT, Shults KE, Loken MR: CD45 Gating for routine flow cytometric analysis of human bone marrow specimens. Ann. NY Acad Sci 677:265-280, 1993.
    -see pdf file.

  7. First flow cytometric characterization of CD34 cell in normal bone marrow.

    Civin CI, Banquerigo, ML, Straus, LC. Loken MR, Antigenic Analysis of Hematopoiesis VI. Flow cytometric characterization of My-10-positive progenitor cells. Experimental Hematology, 15:10- 17, 1987
    -see pdf file.

  8. First description of normal antigen expression of adult and fetal bone marrow on the erythroid, B lymphoid and myeloid cells.

    Loken MR, Shah VO, Dattilio KA, Civin CI: Flow cytometric characterization of human bone marrow: 1. Normal Erythroid Development. Blood. 69:255-263, 1987
    -see pdf file.

    Loken MR, Civin CI, Bigbee WL, Langlois RG, Jensen RH: Coordinate glycosylation and cell surface expression of glycophorin A during normal human erythropoiesis. Blood 70:1959-1961. 1987
    -see pdf file.

    Loken MR, Shah VO, Dattilio KL, Civin CI: Flow cytometric analysis of human bone marrow: II. Normal B Iymphoid development. Blood 70:1316, 1987
    -see pdf file.

    Hollander Z, Shah VO, Civin CI. Loken MR: Assessment of proliferation during maturation of the B lymphoid lineage in normal human bone marrow. Blood 71:528-531, 1988
    -see pdf file.

    LeBien TW, Wormann B, Villablanca JG, Law CL, Shah VO, Loken MR: Multiparameter flow cytometric analysis of human fetal bone marrow B cells, Leukemia 4:354-358, 1990
    -see pdf file.

    Terstappen LWMM, Safford M, Loken MR: Flow cytometric analysis of human bone marrow III. Neutrophil Maturation. Leukemia 4:657-663, 1990.

  9. First characterization of normal human plasma cells

    Terstappen LWMM, Johnsen S, Segers-Nolten I, Loken MR: Identification and characterization of plasma cells in normal human bone marrow by high resolution flow cytometry. Blood, 76:1739-1747, 1990.
    -see pdf file.

  10. First characterization and purification of human hematopoietic stem cells identified by CD34+/CD38-.

    Terstappen LWMM, Huang S, Safford M, Lansdorp PM, Loken MR: Sequential generations of hematopoietic cononies derived from single nonlineage-committed CD34+CD38- progenitor cells. Blood 77:1218-1227, 1991.
    -see pdf file.

    Terstappen, LWMM, Loken MR, Huang, S, Olweus, J, Lund-Johansen, F: Phenotypic characterization of the hematopoietic stem cell. US Patent #5,840,580

  11. First comparison of phenotypes of acute lymphoblastic and acute myeloblastic leukemia with normal patterns of antigen expression demonstrated that leukemia is not a frozen state of normal development but that neoplastic cells express antigens in an aberrant pattern.

    Hurwitz, CA, Loken MR, Graham ML, Karp JE, Borowitz MJ, Pullen DJ, Civin CI: Asynchronous antigen expression in B lineage Acute Lymphoblastic Leukemia, Blood, 72:299-307, 1988.
    -see pdf file.

    Terstappen LWMM, Loken MR: Myeloid cell differentiation in normal bone marrow and acute myeloid leukemia assessed by multi-dimensional flow cytometry. Anal Cell. Path 2:229-240 (1990).
    -see pdf file.

    Terstappen LWMM, Loken MR: Multi-dimensional flow cytometric characterization of myeloid maturation in normal bone marrow and acute myeloid leukemia. in Advances in Analyitical Cellular Pathology, Burger G, Oberholzer M, Vooijs, GP (eds) Excerpta Medica, Amsterdam, 1990, pp209-210.
    -see pdf file.

    Terstappen LWMM, Konemann S, Safford M, Loken MR, Zurlutter K, Buchner Th, Hiddemann W, Wormann B: Flow cytometric characterization of Acute Myeloid Leukemia. Part II. Phenotypic heterogeneity at diagnosis. Leukemia, 6: 70-80, 1991
    -see pdf file.

  12. First to use "difference from normal" as a tumor specific marker to detect residual disease in patients treated for AML
    -see pdf file.
    -see pdf file.
    -see pdf file.

  13. First to use standardized panels in flow cytometry to detect residual disease in ALL and AML
    -see pdf file.

  14. First to demonstrate that occult B lymphoid neoplasms can be misdiagnosed as MDS.

    Wells DA, Hall MC, Shulman HE, Loken MR Occult B cell malignancies can be detected by three-color flow cytometry in patients with cytopenias. Leukemia 12:2015-2023, 1998.
    -see pdf file.

  15. First to quantify and correlate difference from normal in MDS patients with diagnosis and outcome post treatment.

    Denise A. Wells, Martin Benesch, Michael R. Loken, Carlos Vallejo, David Myerson, Wendy M. Leisenring, and H. Joachim Deeg Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation Blood 102: 394-403; (2003)
    -see pdf file.