Our laboratory investigates novel methods of cell separation for medical applications including rapid screening for cancer cells in blood, and isolation of blood-forming stem cells. Magnetic flow sorting is studied in model cell systems of human peripheral lymphocytes, cultured cell lines, bone marrow, and peripheral blood primed for apheresis, in collaboration with the Cleveland Clinic Taussig Cancer Center. The cell sorting performance depends on the specificity of magnetic nanoparticles used for cell tagging. The mechanics of cell sorting in a flow, in the presence of a magnetic field, is poorly understood. We study cell motion using a unique system, Cell Tracking Velocimetry (CTV), developed in collaboration with The Ohio State University. The characteristic cell velocities are correlated with the biophysical cell properties, such as cell size and cell surface marker expression used for binding of the magnetic nanoparticles to the wanted cells. An interesting offshoot of the microscopic cell motion analysis in the magnetic field is the observation of natural cell mobility due to the presence of paramagnetic species inside the cell. In collaboration with the Center for Global Health and Diseases at CASE, we have demonstrated increased mobility of the malaria parasite-infected red blood cells, and its dependence on the parasite development stage. The method has been tested in the field in the malaria endemic region of Papua-New Guinea.
We have developed instrumentation to measure magnetic properties of a single, live cell by measuring its motion in physiologic electrolyte solutions in strong magnetic fields and gradients. A highly automated and rapid process of cell image track acquisition and computer-aided tracking velocimetry allows us to sample a large number of cells (up to tens of thousands in under an hour) and determine cell magnetophoretic mobility distribution in a cell population. The cell magnetophoretic mobility is directly proportional to its magnetic susceptibility (relative to that of the fluid medium) or its spin density. We have shown that the results of such quantitative magnetophoretic analysis agrees to within the experimental error with those calculated based on the low-spin to high-spin intracellular iron compound conversion in red blood cells (RBCs) and malaria parasite infected RBCs. Other applications include intracellular iron uptake by mammalian cells and paramagnetic metal incorporation by bacteria. Such information is inaccessible by the current, state of the art magnetic susceptometers limited to measuring the bulk magnetic properties of matter. Thus, the cell magnetophoretic mobility analysis offers unique opportunities to probe the magnetic properties at a single cell level and to develop more efficient magnetic cell separation devices for use in cancer research and infectious diseases research.
|US Patent||Patent Title||Issue Date||First-Named Inventor|
|6,557,430||System And Device For Determining Particle Characteristics||5/6/2003||Maciej Zborowski Ph.D|
|6,467,630||Continuous Particle And Molecule Separation With An Annular Flow Channel||10/22/2002||Maciej Zborowski Ph.D|
|6,412,359||System And Device For Determining Particle Characteristics||7/2/2002||Maciej Zborowski Ph.D|
|6,142,025||Method For Determining Particale Characteristics||11/7/2000||Maciej Zborowski Ph.D|
|6,120,735||Fractional cell sorter||9/19/2000||Maciej Zborowski Ph.D|
|6,082,205||System And Device For Determining Particle Characteristics||7/4/2000||Maciej Zborowski Ph.D|
|5,974,901||Method For Determining Particle Characteristics||11/2/1999||Maciej Zborowski Ph.D|
|5,968,820||Method For Magnetically Separating Cells Into Fractionated Flow Streams||10/19/1999||Maciej Zborowski Ph.D|
Jing Y, Mal N, PS Williams, Mayorga M, Penn MS, Chalmers JJ, Zborowski M., Quantitative intracellular magnetic nanoparticle uptake measured by live cell magnetophoresis. FASEB J 2008; 22: 4239-4247
Williams PS, Carpino F, Zborowski M., Characterization of magnetic nanoparticles using programmed quadrupole magnetic field-flow fractionation. Philosophical Transactions of the Royal Society A -Mathematical Physical and Engineering Sciences 2010: 368; 4419-4437
Zborowski M, Moore RL, Williams PS, Chalmers JJ., Magnetic pressure as a scalar representation of field effects in magnetic suspensions. American Institute of Physics Conference Proceedings 2010; 1311: 111-117
Hoyos M, Moore LR, Williams PS, Zborowski M., The use of a linear Halbach array combined with a step-SPLITT channel for continuous sorting of magnetic species. Journal of Magnetism and Magnetic Materials 2011; 323: 1384-1388