# US 5,705,059 A · Magnetic separation apparatus > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,705,059 A - Document ID: US5705059A - Status: Granted - Kind: A - Application number: 08/394,834 - Filed: 1995-02-27 - Granted: 1998-01-06 - Earliest claimed: 1995-02-27 - Inventors: Stefan Miltenyi - Web page: https://patentgrep.com/patent/US5705059A ## CPC - B03C 1/002: {High gradient magnetic separation (acting directly on the substance being separated B03C1/025; acting on the medium containing the substance being separated B03C1/32)} - A61M 1/3603: {in the same direction} - A61M 1/3604: {in opposite directions} - A61M 1/3618: {Magnetic separation} - A61M 1/362: {changing physical properties of target cells by binding them to added particles to facilitate their subsequent separation from other cells, e.g. immunoaffinity} - A61M 1/3647: {with recirculation of the priming solution} - B01D 35/06: Filters making use of electricity or magnetism (ultrafiltration, microfiltration B01D61/14; electrodialysis, electro-osmosis B01D61/42; devices comprising filters and magnetic separators B03C1/30) - B03C 1/01: by addition of magnetic adjuvants - B03C 1/025: High gradient magnetic separators - B03C 1/027: with reciprocating canisters - B03C 1/0332: {using permanent magnets} - B03C 1/0335: {using coils} - B03C 1/034: characterised by the matrix elements - G01N 33/54326: {Magnetic particles} - A61M 1/36: Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation {; Extra-corporeal blood circuits} - B03C 2201/18: Magnetic separation whereby the particles are suspended in a liquid - B03C 2201/26: for use in medical or biological applications - G01N 1/34: Purifying; Cleaning {(processes or apparatus for extracting or separating nucleic acids from biological samples C12N15/1003)} - Y10S 436/806: Electrical property or magnetic property - B03C: MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS (separating isotopes B01D59/00; combinations of magnetic or electrostatic separation with separation of solids by other means B03B, B07B) - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} - B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS ## Abstract Improved magnetic separators, devices and methods for magnetic separation procedures are provided. The improved separation devices contain matrices which provide uniform pores or channels that reduce the entrapment of air or non-target substances, and decrease the loss of target substances due to mechanical disruption. Target cells, from various systems and organs, or other target biological substances are labeled in conjunction with a suitable specific binding member, and isolated using the devices and methods of the present invention. In its simplest form, the cell separation system of the present invention has two main components: a magnetic separator and a cell separation reagent. A more complex separation device includes fluid passages, collection and storage containers and the separation column. The fluid circuitry can be constructed with integrated valves, or the valves may be applied externally to the fluid pathways. ## Claims ### Claim 1 A magnetic separator device for use in separating magnetic or magnetically labeled target substances from a sample, the device comprising: (a) a separation column including (i) a nonmagnetic housing having an inlet port, an outlet port, and defining a separation chamber having a diameter to length ratio of least 0.2 to 1, said separation chamber being fluidically disposed between said inlet port and said outlet port, and (ii) a fluid permeable matrix of ferromagnetic spheres disposed within said chamber, wherein said spheres have an average diameter of about 0.2 to about 0.5 millimeters and are stacked in a lattice configuration; (b) a prefiltration column that is substantially identical to said separation column; and (c) a first fluid pathway connecting the outlet port of said prefiltration column to the inlet port of said separation column. ### Claim 2 (depends on 1) The magnetic separator in accordance with claim 1, further comprising a second fluid pathway interconnecting said inlet port and said outlet port of said separation column, and pump means disposed in said second fluid pathway for recirculating fluid through said second fluid pathway and said separation column. ### Claim 3 (depends on 1) A magnetic separation instrument for use in separating magnetic or magnetically labeled target substances from a sample comprising the separator device of claim 1, and a magnetic means whereby said sample first passes through said prefiltration column in the absence of a magnetic field, and subsequently passes through said separation column in the presence of a magnetic field generated by said magnetic means. ### Claim 4 (depends on 3) The magnetic separation instrument in accordance with claim 3, wherein said magnetic means is a permanent magnet and said separation column is retained on a retractable arm by which said separation column is moved into or out of the magnetic field of said permanent magnet. ### Claim 5 (depends on 3) The magnetic separation instrument in accordance with claim 3, further comprising a second fluid pathway interconnecting said inlet port and said outlet port of said separation column, and pump means disposed in the second fluid pathway by which fluid can be recirculated through said second fluid pathway and said separation column at variable speeds and in varying directions. ### Claim 6 (depends on 3) The magnetic separation instrument in accordance with claim 3, wherein said magnetic means is a permanent magnet and is retained on a retractable arm for moving said magnet. ### Claim 7 A magnetic separator device for use in separating magnetic or magnetically labeled target substances from a sample, the device comprising: (a) a separation column including (i) a nonmagnetic housing having an inlet port, an outlet port, and defining a separation chamber having a diameter to length ratio of least 0.2 to 1, said separation chamber being fluidically disposed between said inlet port and said outlet port, and (ii) a fluid permeable matrix of ferromagnetic spheres disposed within said chamber, wherein said spheres have an average diameter of about 0.2 to about 0.5 millimeters and are stacked in a lattice configuration, wherein said matrix is coated with a substantially fluid impermeable coating and is deformation resistant; (b) a prefiltration column that is substantially identical to said separation column; and (c) a first fluid pathway connecting the outlet port of said prefiltration column to the inlet port of said separation column. ### Claim 8 (depends on 7) The magnetic separator in accordance with claim 7, further comprising a second fluid pathway interconnecting said inlet port and said outlet port of said separation column, and pump means disposed in said second fluid pathway for recirculating fluid through said second fluid pathway and said separation column. ### Claim 9 (depends on 7) A magnetic separation instrument for use in separating magnetic or magnetically labeled target substances from a sample, comprising the separator device of claim 7, and a magnetic means, whereby said sample first passes through said prefiltration column in the absence of a magnetic field, and subsequently passes through said separation column in the presence of a magnetic field generated by said magnetic means. ### Claim 10 (depends on 9) The magnetic separation instrument in accordance with claim 9, wherein said magnetic means is a permanent magnet and said separation column is retained on a retractable arm by which said separation column is moved into or out of the magnetic field of said permanent magnet. ### Claim 11 (depends on 9) The magnetic separation instrument in accordance with claim 9, further comprising a second fluid pathway interconnecting said inlet port and said outlet port of said separation column, and pump means disposed in the second fluid pathway by which fluid can be recirculated through said second fluid pathway and said separation column at variable speeds and in varying directions. ### Claim 12 (depends on 9) The magnetic separation instrument in accordance with claim 9, wherein said magnetic means is a permanent magnet and is retained on a retractable arm for moving said magnet.