Apparatus for integrated process of magnetic particles and method of controlling the same

• US 6,805,840 B1
• Filed: 09/18/2000
• Issued: 10/19/2004
• Est. Priority Date: 03/19/1998
• Status: Expired due to Fees

• Current Assignee: Mortarless Technologies LLC
• Original Assignee: Mortarless Technologies LLC
• Inventors: Tajima, Hideji
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Handy, Dwayne K
• Application Number:
  US09/646,653
• Time in Patent Office: 1,492 Days
• Field of Search: 422/99, 422/100, 422/101, 422/102, 422/186.01, 436/174, 436/177, 436/180, 436/525, 436/526, 210/222, 210/223, 210/695
• US Class Current: 422/501
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/0029 with pistons or plungers
• CPC Class Codes: B01J 2219/00292 in the shape of pipette tips
• CPC Class Codes: B01J 2219/00308 interchangeably mounted in racks or blocks
• CPC Class Codes: B01J 2219/0031 the racks or blocks being mounted in stacked arrangements
• CPC Class Codes: B01J 2219/00313 the reactor vessels being formed by arrays of wells in blocks
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00319 the blocks being mounted in stacked arrangements
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00459 Beads
• CPC Class Codes: B01J 2219/00466 in a slurry
• CPC Class Codes: B01J 2219/00468 by manipulation of individual beads
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00686 Automatic
• CPC Class Codes: B01J 2219/0072 Organic compounds
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/0074 : Biological products
• CPC Class Codes: B01L 2300/0829 : Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 3/0231 : having several coaxial pistons
• CPC Class Codes: B01L 3/5025 : for parallel transport of multiple samples
• CPC Class Codes: B01L 3/50853 : with covers or lids
• CPC Class Codes: B03C 1/025 : High gradient magnetic separators
• CPC Class Codes: B03C 1/033 : characterised by the magnetic circuit
• CPC Class Codes: B03C 1/035 : Open gradient magnetic separators, i.e. separators in which the gap is unobstructed, characterised by the configuration of the gap
• CPC Class Codes: B03C 1/284 : with associated cleaning means, e.g. retractable non-magnetic sleeve
• CPC Class Codes: B03C 1/288 : disposed at the outer circumference of a recipient
• CPC Class Codes: B03C 2201/18 : Magnetic separation whereby the particles are suspended in a liquid
• CPC Class Codes: B03C 2201/26 : for use in medical or biological applications
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 35/0098 : involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: G01N 35/028 : having reaction cells in the form of microtitration plates
• CPC Class Codes: G01N 35/1065 : Multiple transfer devices
• CPC Class Codes: G01N 35/1074 : arranged in a two-dimensional array
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/25375 : Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

The present invention relates to an apparatus for an integrated process of magnetic particles and a method of controlling the same, for executing a process for magnetic particles incorporated in a fluid in an integrated state. The present invention aims to provide an apparatus for an integrated process of magnetic particles and a method of controlling the same, that can promptly and efficiently process all together in high precision, with the process of magnetic particles integrated.

The apparatus for an integrated process of magnetic particles comprises a reservoir body provided with plural pit-like reservoirs for storing a drawn liquid arranged in a matrix, a sliding body with jutting plural sliding projections sliding through the reservoirs and capable of moving vertically to and from the reservoir body, plural nozzles attached to the lower parts of the reservoirs and capable of passing the liquid therethrough, a magnetic force device capable of magnetization and demagnetization having plural through sections in which is inserted each nozzle and having a wall part in contact with or near the outer side surface of the nozzle, with the nozzles inserted thereinto, wherein each wall part has two divided wall parts being apart from one another in such a manner that the divided wall parts have opposite polarities by magnetization, respectively.

Claims

1. An apparatus for an integrated process of magnetic particles comprising:

a drawing/discharging device for drawing and discharging a fluid;

plural nozzles arranged in a plane-like state and passing the fluid therethrough while drawing and discharging; and

a magnetic force device for applying and removing a magnetic field to and from the nozzles respectively in a manner that the neighborhood of each nozzle exterior remains stationary;

wherein said magnetic force device can apply and remove the magnetic force to and from said nozzles respectively by enabling magnetization and demagnetization in a nozzle outer member brought in contact with or being near the outer surface of said nozzle or at least a part of said nozzle, in a manner that the neighborhood of each nozzle exterior remains stationary;

wherein said magnetic force device comprises a magnetic member made of a magnetic material and provided with a plurality of through sections arranged in a plane-like state and capable of taking insertion of nozzles;

wherein said nozzle outer member is a wall of said through sections; and

wherein each through section of said magnetic force device comprises a separate hole in which the nozzle is inserted in a way that the outer surface of the nozzle can come in contact with or approach to the nozzle outer member, and an insert-withdraw hole mounted adjacent to the separate hole and having an opening larger than that of the separate hole so that the nozzle can horizontally move to and from the separate hole and can be withdrawn and inserted at the insert-withdraw hole.

2. An apparatus for an integrated process of magnetic particles according to claim 1, wherein said nozzle comprises a small diameter section and a larger diameter section, said separate hole has an opening that only the small diameter section can be inserted in, and said insert-withdraw hole has an opening that the larger diameter section can be inserted in.

3. An apparatus for an integrated process of magnetic particles according to claim 1, wherein said nozzle outer member of the magnetic force device or a part of said nozzle comprises first and second parts that are spaced from one another in a manner so that the first and second parts have mutually opposite magnetic polarities.

4. An apparatus for an integrated process of magnetic particles according to claim 3, wherein said magnetic force device comprises a magnetic source having an electromagnet or a permanent magnet, the magnetic member comprising two magnetic plates made of magnetic material and connecting with the electromagnet or capable of connecting with the permanent magnet and capable of being magnetized and demagnetized, and mounted in face-to-face relationship in spaced positions, the plural through sections being arranged in a plane-like state, penetrating the two magnetic plates and being capable of taking insertion of the nozzles, and each nozzle outer member comprising a pair of projections mounted in each through section, projecting toward the opposite surface of each magnetic plate and made of magnetic materials, each projection corresponding to one of the first and second parts and the projections of each pair being spaced from one another in such a manner that they have mutually opposite polarities by magnetization.

5. An apparatus for an integrated process of magnetic particles according to claim 4, wherein said through sections comprise through holes penetrating through the magnetic plates and capable of taking insertion therethrough by the nozzles, and each wall part of the mutually separated through holes has opposite polarity respectively.

6. An apparatus for an integrated process of magnetic particles according to claim 4, wherein said magnetic force device comprises one or more of the magnetic sources, each magnetic source comprises a coil and a magnetic element provided with the coil, and one end of said magnetic element is connected with one of the two magnetic plates and the other end thereof is connected with the other of the two magnetic plates.

7. An apparatus for an integrated process of magnetic particles according to claim 6, wherein said magnetic elements are mounted outside of the space which is formed by the magnetic plates.

8. An apparatus for an integrated process of magnetic particles according to claim 7, wherein said magnetic elements comprise a third part and a fourth part which are separately mounted, wherein one end of the third part connects with one of the two magnetic plates, the other end of the fourth part connects with the other magnetic plate, wherein the third part and the fourth part are overlapped and are wound by wire of a coil, or the other end of the third part and one part of the fourth part are connected with each end of a fifth part and wound by wire of the coil and made of magnetic material.

9. An apparatus for an integrated process of magnetic particles according to claim 3, wherein the first and second parts are tapered toward a gap.

10. An apparatus for an integrated process of magnetic particles according to claim 4, wherein said pair of projections each project from the opening edge of the through section of one of the magnetic plates toward the other magnetic plate in a direction of insertion of the nozzle in respective directions opposite to one another, and each tip of the projections is spaced from the opposite surface by a first interval, and the tips of the projections are spaced from one another by a second interval shorter than the first interval, in such a manner that the tips have opposite polarities, respectively.

11. An apparatus for an integrated process of magnetic particles according to claim 1, wherein said magnetic force device comprises plural magnetic sources, and plural segments defined so as to include the area spatially near each magnetic source, respectively.

12. An apparatus for an integrated process of magnetic particles according to claim 1, wherein said magnetic force device comprises a magnetic source having a permanent magnet or an electromagnet, and a member made of magnetic material and magnetically connected to the electromagnet or capable of magnetically connecting to the permanent magnet, wherein the through sections are provided in the member and are capable of taking insertion of the nozzles.

13. An apparatus for an integrated process of magnetic particles according to claim 12, wherein the through holes of the magnetic force device comprise divided wall parts divided in the direction of the insertion of the nozzle in such a manner that divided wall parts are apart from one another and have opposite polarities by magnetization.

14. An apparatus for an integrated process of magnetic particles according to claim 13, wherein the nozzles comprise a larger diameter section and a small diameter section, and the member of the magnetic force device comprises plural column members arranged apart from each other at intervals capable of taking insertion of the larger diameter section of the nozzle, and plural protrusions made of magnetic material that are projected oppositely from each column member, magnetized in a manner that has opposite polarity to each other and arranged apart from each other at intervals capable of taking insertion of the smaller diameter section of the nozzle, and are arranged along the column member at intervals capable of taking insertion of the larger diameter section of the nozzle, wherein opposite pointed ends of the protrusions correspond with the divided wall parts.

15. An apparatus for an integrated process of magnetic particles according to claim 1, wherein said nozzles comprise small diameter pipes communicating with the through sections of the magnetic member and capable of being inserted into a vessel.

16. An apparatus for an integrated process of magnetic particles according to claim 1, wherein said drawing/discharging device comprises a reservoir body comprising plural reservoirs arranged in a plane-like state for storing a drawn fluid and communicating with the nozzles, and an increasing/decreasing device for increasing and decreasing pressure within the reservoirs and the nozzles in a manner that draws or discharges the fluid.

17. An apparatus for an integrated process of magnetic particles according to claim 16, wherein said increasing/decreasing device comprises a sliding body capable of moving vertically to and from the reservoir body, and sliding projections arranged in a plane-like state, projecting downward from the sliding body and capable of sliding through the nozzles in such a manner that the pressure within the reservoirs or nozzles increases or decreases.

18. An apparatus for an integrated process of magnetic particles according to claim 17, wherein said sliding projections are formed to have a two-step structure comprising a larger diameter section capable of sliding through the reservoir, and a smaller diameter section capable of extending along the axes of the larger diameter section and sliding through the nozzle communicating with the reservoir.

19. An apparatus for an integrated process of magnetic particles according to claim 16, wherein said nozzles comprise a tip capable of being mounted to and dismounted from the drawing/discharging device.

20. An apparatus for an integrated process of magnetic particles according to claim 19, comprising a pushing body having pushing pipes inserted from the upper side of the reservoirs into the reservoirs and capable of pushing the nozzles out of the reservoirs, wherein the nozzles are detachably mounted to the reservoirs while being inserted from the lower side of the reservoirs, and the increasing/decreasing device comprises a sliding body having plural sliding projections projecting downward, capable of sliding through the pushing pipes and capable of moving vertically to and from the reservoirs respectively, in a manner that the pressure within the reservoirs or nozzles can be increased or decreased.

21. An apparatus for an integrated process of magnetic particles according to claim 19, wherein said nozzles are detachably mounted to the lower part of the reservoirs and are inserted to a predetermined depth in the reservoirs, sliding projections can slide to a depth of the installation depth of the nozzles in the reservoirs, and a projecting lip part is projected from the outer side of the nozzles exposed under the magnetic force device for mounting and dismounting, and a stroke-down plate provided with plural small hole parts with respective diameters larger than that of the nozzles and smaller than that of the lip parts is mounted between the magnetic force device and the lip parts in a way that the hole parts take insertion of the nozzles and the nozzles can be detached by moving the stroke-down plate down.

22. An apparatus for an integrated process of magnetic particles according to claim 17, wherein an inner wall of the upper part of said reservoir is formed to be cylindrical, and that of the lower part of said reservoir is formed to be funnel-shaped and is connected with said nozzles.

23. An apparatus for an integrated process of magnetic particles according to claim 16, wherein a cleaning liquid can be poured into each reservoir from a passage mounted in the top or side of the reservoir body.

24. An apparatus for an integrated process of magnetic particles according to claim 1, comprising a light measuring device for receiving light from all the vessels or plural liquid containing parts arranged in a plane-like state, simultaneously or all together and measuring the strength of the light or processing it as an image in order to measure a state of light emission.

25. An apparatus for an integrated process of magnetic particles according to claim 24, wherein the light measuring device comprises plural receiving components arranged in a plane-like state, mounted at places corresponding to the liquid containing parts and having the same number as that of the liquid containing part, and shading fences mounted between neighboring receiving components for preventing light entering to other than the corresponding liquid containing part.

26. An apparatus for an integrated process of magnetic particles, comprising:

a drawing/discharging device for drawing and discharging a fluid;

plural nozzles arranged in a plane-like state and passing the fluid there through while drawing and discharging;

a magnetic force device for applying and removing a magnetic field to and from the nozzles respectively in a manner that the neighborhood of each nozzle exterior remains stationary, wherein said magnetic force device comprises an insulating device for preventing heat generated by magnetization or generation of a magnetic field from being transmitted toward the nozzle; and

a ventilator for sending air to the magnetic force device or the neighborhood thereof.

27. An apparatus comprising:

a plurality of nozzles for passing fluid; and

a magnetic field generator which can generate a magnetic field that is effective within the nozzles, the magnetic field generator comprising a part which has;

a plurality of first openings for receiving the nozzles; and

a plurality of second openings which are larger than and are each disposed adjacent to and communicate with a respective one of the first openings, so that the nozzles can each be inserted into and withdrawn from a respective one of the second openings, and can each be moved between one of the first openings and the second opening which communicates therewith.

28. An apparatus according to claim 27, further comprising a fluid flow portion cooperable with the nozzles for effecting fluid flow through the nozzles.

29. An apparatus according to claim 28, wherein each of the nozzles has therethrough a fluid flow opening, and the fluid flow portion has a plurality of movable projections which are each slidable within the fluid flow opening of a respective nozzle.

30. An apparatus according to claim 27, wherein the magnetic field generator has one of a permanent magnet and an electromagnetic, which is coupled to the part of the magnetic field generator.

31. An apparatus according to claim 30, wherein the part of the magnetic field generator has two spaced plates which are each coupled to the one of the permanent magnet and the electromagnetic in a manner so that the plates have opposite magnetic polarities when the magnetic field generator is generating a magnetic field, each of the two plates having the first and second openings extending therethrough.

32. An apparatus according to claim 27, wherein the part of the magnetic field generator member has, adjacent each of the first openings therein, a pair of portions which are spaced, and which have opposite magnetic polarities when the magnetic field generator is generating a magnetic field.

33. An apparatus according to claim 32, wherein the part of the magnetic field generator has two spaced plates which have opposite magnetic polarities when the magnetic field generator is generating a magnetic field, which each have the first and second openings extending therethrough, and which each have a plurality of projections extending toward the other thereof, the portions of each pair being two of the projections that are each provided on a respective plate.

34. An apparatus according to claim 33, wherein the projections on each plate have an end which is spaced from the other plate by a first distance, and wherein the ends of the projections of each pair are spaced from each other by a second distance less than the first distance.

35. An apparatus according to claim 27, wherein the part of the magnetic field generator has a plurality of spaced and approximately parallel column portions, and each column portion has along each side thereof a plurality of spaced protrusions which each project toward one of the protrusions on an adjacent column portion, each of the first openings being a region between ends of a respective pair of the protrusions, each of the second openings being a region between two column portions which is offset from the protrusions on the column portions, and the protrusions of each pair having opposite magnetic polarities when the magnetic field generator is generating a magnetic field.

36. An apparatus according to claim 27, further comprising a vessel having therein a plurality of holes into which the nozzles can be inserted.

37. An apparatus according to claim 36, further comprising a light measuring portion for receiving light from the vessel in order to measure a state of light emission which is a function of substances in the respective holes of the vessel.