SYSTEM, APPARATUS AND METHOD FOR MATERIAL PREPARATION AND/OR HANDLING

• US 20100178697A1
• Filed: 03/25/2010
• Published: 07/15/2010
• Est. Priority Date: 01/09/2008
• Status: Abandoned Application

• Current Assignee: Keck Graduate Institute
• Original Assignee: Keck Graduate Institute
• Inventors: Talbot, Ryan P., Woyski, Denice, Sterling, James D., Erwin, Barbara, Hickerson, Anna, Irvine, Bruce, Nadim, Ali, Doebler, Robert
• Application Number:
  US12/732,070
• Publication Number:
  US 20100178697A1
• Time in Patent Office: Days
• US Class Current: 435/325
• CPC Class Codes: C12M 23/28 disposable or single use
• CPC Class Codes: C12M 27/00 Means for mixing, agitating or circulating fluids in the vessel by introduction of gas C12M29/06, C12M29/14, mixing in general or mixers per se B01F; mixing in apparatus for chemical or physical processes B01J
• CPC Class Codes: C12M 47/06 Hydrolysis; Cell lysis; Extraction of intracellular or cell wall material lysis of microorganisms C12N1/06; extracting or separating nucleic acids from biological samples C12N15/1003
• CPC Class Codes: C12N 1/066 by physical methods
• CPC Class Codes: G01N 1/286 involving mechanical work, e.g. chopping, disintegrating, compacting, homogenising microtomes G01N1/06; pulverising in general B02C; mixing in general B01F
• CPC Class Codes: G01N 1/4077 by other techniques involving separation of suspended solids
• CPC Class Codes: G01N 2001/4083 sedimentation
• CPC Class Codes: G01N 2001/4088 filtration
• CPC Class Codes: G01N 2001/4094 using ultrasound

Abstract

Oscillating angularly rotating a container containing a material may cause the material to be separate. Denser or heavier material may unexpectedly tend to collected relatively close to the axis of rotation, while less dense or light material may tend to collect relatively away from the axis of rotation. Oscillation along an arcuate path provides high lysing efficiency. Alternatively, a micromotor may drive an impeller removably received in a container. Lysing may be implemented in batch mode, flow-through stop or semi-batch mode, or flow-through continuous mode. Lysing particulate material may exceed material to be lysed or lysed material and/or air may be essentially eliminated from a chamber to increase lysing efficiency.

Claims

1. A system to perform lysis on material to be lysed, the system comprising:

an arm having an attachment location to at least temporarily attach a container that at least temporarily holds a material to be lysed and a particulate lysing material;

a motor operable to provide a drive force; and

a drive mechanism coupled to transfer the drive force of the motor into oscillation of the attachment location of the arm along an arcuate path.

2. The system of claim 1 wherein the arm is a rigid arm that does not flex under a load in response to the oscillation of the attachment location of the arm along the arcuate path.

3. The system of claim 1 wherein the arm is a flexible arm that does flex under a load in response to the oscillation of the attachment location of the arm along the arcuate path.

4. The system of claim 1, further comprising:

a holder at the attachment location, the holder configured to removably hold the container.

5. The system of claim 4, further comprising:

the container and the particulate material.

6. The system of claim 1, further comprising:

the container, wherein the container is non-removably fixed to the arm at least proximate the attachment location.

7. The system of claim 1, further comprising:

the container, the container having at least one chamber with a first opening and at least a second opening spaced from the first opening, the first and the second openings to provide fluid communication into the chamber from an exterior thereof.

8. The system of claim 7 wherein the container includes a first filter positioned in the chamber and a second filter positioned in the chamber spaced from the first filter to form a particulate retainment area therebetween, the particulate retainment area positioned between the first and the second openings, the first and the second filters each having a plurality of apertures sized to substantially pass the material to be lysed and to block the particulate material.

9. The system of claim 8 wherein the first filter, the second filter and the particulate material form a cartridge that is selectively replaceable in the chamber.

10. The system of claim 9 wherein the plurality of beads includes at least one of ceramic beads, glass beads, zirconium beads, metal beads, plastic beads, and sand and wherein the plurality of beads have diameters in the range of approximately 10 microns to approximately 600 microns.

11. The system of claim 10 wherein when in use a volume of the particulate material is greater than a volume of material to be lysed.

12. The system of claim 11 wherein when in use there is essentially no air in the chamber.

13. The system of claim 8, further comprising:

a pump to pump the material to be lysed through the chamber.

14. The system of claim 13 wherein the pump is configured to intermittently pump the material to be lysed through the chamber.

15. The system of claim 14 wherein the material to be lysed has a residence time in the chamber that is sufficient to achieve a defined level of lysing.

16. The system of claim 13 wherein the pump continuously pumps the material to be lysed through the chamber.

17. The system of claim 16 wherein given a length and a volume of the chamber, a flow rate of the pump is such that the material to be lysed spends sufficient time in traversing the chamber from the first opening to the second opening to achieve a defined level of lysing.

18. The system of claim 8, further comprising:

a first tube coupled to provide fluid communication to the first opening for the material to be lysed to the first opening; and

a second tube coupled to provide fluid communication from the second opening for a material that has been lysed.

19. The system of claim 18 wherein ends of at least one of the first and the second tubes are reinforced.

20. The system of claim 18 wherein ends of at least one of the first and the second tubes are reinforced with additional tubes that are concentric about the ends of the tube.

21. The system of claim 18 wherein a length of at least one of the first and the second tubes does not restrict the oscillation of the attachment location.

22. The system of claim 21 wherein the length and means of attachment of at least one of the first and the second tubes is such that the at least one of the first and the second tubes does not resonate in response to the oscillation of the attachment location of the arm along an arcuate path.

23. The system of claim 18 wherein a respective lengths of each of the first and the second tubes is sufficiently long so as to not restrict the oscillation of the attachment location and are sufficiently short such that the first and the second tubes do not resonant during use.

24. The system of claim 18 wherein the drive mechanism comprises a four-bar linkage that includes a first member, a second member, a third member and a fourth member, the second member coupled to the first member, the first member rotationally driven by a motor to eccentrically drive a first end of the second member in a circular motion, the third bar member pivotally coupled to a second end of the second member, the third member connected to the fourth member at a pivot point;

where an amplitude of motion of the second member and a length of the third member define a angle of motion of the third and the fourth members and a length of the fourth member defines a distance of arcuate motion.

25. A method of lysing a material to be lysed, the method comprising:

receiving a material to be lysed in a chamber that contains a particulate lysing material;

oscillating the chamber containing the material to be lysed and a particulate lysing material along an arcuate path to produce a lysed material; and

removing the lysed material from the chamber.

26. The method of claim 25, further comprising:

pumping the material to be lysed into the chamber.

27. The method of claim 25, further comprising:

intermittently pumping the material to be lysed into the chamber while oscillating the chamber.

28. The method of claim 27 wherein intermittently pumping the material to be lysed into the chamber while oscillating the chamber includes intermittently pumping the material to be lysed into the chamber such that the material to be lysed spends sufficient time in the chamber to achieve a desired level of lysing.

29. The method of claim 27 wherein intermittently pumping the material to be lysed into the chamber while oscillating the chamber includes intermittently pumping the material to be lysed into the chamber such that the chamber is completely evacuated of the lysed material during each cycle of the intermittent pumping.

30. The method of claim 29 wherein the chamber is completely evacuated of the lysed material during each cycle of the intermittent pumping by the pumping into the chamber of more material to be lysed.

31. The method of claim 25, further comprising:

continuously pumping the material to be lysed into the chamber while oscillating the chamber.

32. The method of claim 31, further comprising:

adjusting a flow rate of the pumping of the material to be lysed into the chamber based on a length and a volume of the chamber, a flow rate of the pump is such that the material to be lysed spends sufficient time in the chamber to achieve a desired level of lysing.

33. The method of claim 25, further comprising:

directing the lysed material removed from the chamber to at least one analysis device.

34. The method of claim 25, further comprising:

evacuating the chamber with an inert fluid.

35. A method of lysing a material to be lysed, the method comprising:

receiving a first cartridge having a chamber that contains a particulate lysing material and a material to be lysed; and

oscillating the first cartridge having the chamber that contains the material to be lysed and the particulate lysing material along an arcuate path to produce a lysed material.

36. The method of lysing of claim 35, the method further comprising:

receiving a second cartridge in place of the first cartridge, the second cartridge having a chamber that contains a particulate lysing material and a material to be lysed; and

oscillating the second cartridge having the chamber that contains the material to be lysed and the particulate lysing material along an arcuate path to produce a lysed material.

37. The method of lysing of claim 35 wherein receiving a first cartridge includes receiving the first cartridge in a mounting bracket at an attachment point of an arm.

38. The method of lysing of claim 35 wherein oscillating the first cartridge includes oscillating a rigid arm on which the first cartridge is mounted.

39. The method of lysing of claim 35 wherein oscillating the first cartridge includes oscillating a flexible arm on which the first cartridge is mounted.

40. An article to perform flow-through lysis on material to be lysed, the article comprising:

at least one wall forming at least one chamber having a first opening and at least a second opening spaced from the first opening, the first and the second openings to provide fluid communication into the chamber from an exterior thereof;

a particulate lysing material received in the chamber, the particulate material including a plurality of particles sized to lyse a material to be lysed;

a first filter received in the chamber between the first opening and the particulate material, the first filter having a plurality of apertures sized to substantially pass the material to be lysed and to retain the particulate material; and

a second filter received in the chamber between the second opening and the particulate material, the second filter having a plurality of apertures sized to pass the material to be lysed and to retain the particulate material, wherein the first filter and the second filter form a particulate retainment area therebetween.

41. The article of claim 40, further comprising:

an attachment structure proximate the first opening.

42. The article of claim 40, further comprising:

a first attachment structure to attach a first tube to the first opening; and

a second attachment structure to attach a second tube to the second opening.

43. The article of claim 40, further comprising:

a nipple about the first opening.

44. The article of claim 40, further comprising:

a first nipple to attach a first tube about the first opening; and

a second nipple to attach a second tube about the second opening.

45. The article of claim 40 wherein the at least one wall is elongated and has a first end and a second end opposed to the first end.

46. The article of claim 45 wherein the first opening is at the first end and the second opening is at the second end.

47. The article of claim 45 wherein the at least one wall is cylindrically tubular.

48. The article of claim 40 wherein the particulate material is a plurality of beads.

49. The article of claim 40 wherein the plurality of beads includes at least one of ceramic beads, glass beads, zirconium beads, metal beads, plastic beads, and sand.

50. The article of claim 40 wherein the plurality of beads have diameters in the range of approximately 100 microns.

51. The article of claim 40 wherein the plurality of beads have diameters in the range of 50 microns to 150 microns.

52. The article of claim 40 wherein when in use a volume of the particulate material is greater than a volume of material to be lysed.

53. The article of claim 52 wherein when in use there is essentially no air in the chamber.

54. The article of claim 52 wherein the chamber has a volume that holds less than 60 μ

l of the material to be lysed.

55. The article of claim 52 wherein the chamber has a volume that holds approximately 10 μ

l to approximately 40 μ

l of the material to be lysed.

56. The article of claim 40 wherein the first and the second filters are fixed to the wall.

57. A system to perform lysis, the system comprising:

a container having at least one chamber to hold a material to be lysed and a lysing particulate material, the chamber having a first opening and at least a second opening to provide fluid communication into the chamber from an exterior thereof;

an impeller having a number of blades received in the chamber of the container; and

a micromotor coupled to turn the impeller.

58. The system of claim 57 wherein the first opening provides an entrance for material to be lysed and the second opening provides an exit for material that has been lysed.

59. The system of claim 58 wherein the chamber has a third opening, at least a portion of the micromotor is received by the third opening and seals the third opening.

60. The system of claim 59 wherein the micromotor is removably received in the first third opening.

61. The system of claim 60 wherein the micromotor is disposable.

62. The system of claim 57 wherein the container further includes at least a first filter positioned before the exit in a flow path, the first filter having a plurality of apertures sized to substantially pass material that has been lysed and to substantially block lysing material.

63. The system of claim 62 wherein the container further includes at least a second filter positioned following the entrance in the flow path, the second filter having a plurality of apertures sized to substantially pass material to be lysed and to substantially block lysing material.

64. The system of claim 57 wherein the micromotor pulsates.

65. The system of claim 57 wherein the micromotor drives the impeller at a rate of greater than 10,000 RPM in the presence of the lysing particulate material which includes a liquid and a plurality of beads.

66. The system of claim 57 wherein the micromotor drives the impeller at a rate of approximately 50,000 RPM, when not in the presence of the lysing particulate material which includes a liquid and a plurality of beads.

67. A method of system to perform lysis, the method comprising:

receiving a material to be lysed via an entrance in at least one chamber of a container that holds a lysing particulate material;

driving an impeller having a number of blades received in the chamber of the container via a micromotor; and

expelling a material that has been lysed via an exit from the chamber of the container.

68. The method of claim 67 wherein expelling a material that has been lysed via an exit includes expelling the material that has been lysed via a first filter positioned before the exit in a flow path, the first filter having a plurality of apertures sized to substantially pass the material that has been lysed and to substantially block the lysing particulate material.

69. The method of claim 68 wherein receiving a material to be lysed via an entrance includes receiving the material to be lysed via a second filter positioned following the entrance in the flow path, the second filter having a plurality of apertures sized to substantially pass the material to be lysed and to substantially block lysing particulate material.

70. The method of claim 68, further comprising:

intermittently pumping the material to be lysed into the at least one chamber via the entrance.

71. The method of claim 68, further comprising:

continuously pumping the material to be lysed into the at least one chamber via the entrance.

72. The method of claim 67 wherein driving an impeller includes pulsating the impeller.

73. The method of claim 67 wherein driving an impeller includes driving the impeller at a rate of greater than 10,000 RPM in the presence of the lysing particulate material that includes a plurality of beads and a liquid.

74. The method of claim 67, further comprising:

replacing the micromotor with a new micromotor.

75. The system of claim 74, further comprising:

disposing the micromotor.

76. A system to perform lysis, the system comprising:

a first container having at least one chamber to hold a material to be lysed and a lysing particulate material, the chamber having a single opening to provide fluid communication into the chamber from an exterior thereof;

an impeller having a number of blades received in the chamber of the first container; and

a micromotor coupled to turn the impeller, at least a portion of the micromotor removably received in the single opening of the first container to seal the single opening in use.

77. The system of claim 76 wherein the micromotor is disposable.

78. The system of claim 76 wherein the micromotor is removably received by a single opening of a second container after removal from the single opening of the first container.

79. The system of claim 76 wherein the micromotor pulsates.

80. The system of claim 76 wherein the micromotor drives the impeller at a rate of greater than 10,000 RPM in the presence of the lysing particulate material that includes a plurality of beads and a liquid.

81. A method of operating a system to perform lysis, the method comprising:

receiving a material to be lysed via an entrance in at least one chamber of a first container that holds a lysing particulate material;

locating an impeller in the chamber of the first container via the entrance;

closing the entrance of the first container with a micromotor that is coupled to drive the impeller; and

driving the impeller to circulate the material to be lysed and the lysing particulate material in the chamber of the first container.

82. The method of claim 81, further comprising:

removing the micromotor from the entrance of the first container; and

removing a material that has been lysed via the entrance of the first container.

83. The method of claim 81 wherein removing a material that has been lysed via the entrance of the first container includes withdrawing the material that has been lysed using a pipette.

84. The method of claim 81 wherein driving the impeller includes pulsating the impeller.

85. The method of claim 81, further comprising:

reusing the micromotor with a second container.

86. The method of claim 85, further comprising:

disposing of the micromotor.

87. A system to separate materials, the system comprising:

a base;

an actuator coupled to the base and selectively operable to provide a drive force; and

a drive mechanism coupled to the base and coupled to transfer the drive force of the motor into an oscillatory angular rotation of a container about an axis of rotation at a sufficiently high frequency to cause a relatively denser material to collected relatively closer to the axis of rotation than a relatively less dense material.

88. The system of claim 87 wherein the actuator is an electric motor.

89. The system of claim 87, further comprising:

a holder coupled to the drive mechanism for movement thereby, the holder configured to removably hold the container.

90. The system of claim 89, further comprising:

the container, wherein the container has an interior to hold the materials to be separated.

91. The system of claim 87, further comprising:

the container, wherein the container has an interior to hold the materials to be separated and the container is non-removably fixed to the drive mechanism.

92. The system of claim 87, further comprising:

the container, wherein the container has an interior to hold the materials to be separated and at least one inner port to provide fluid communication between the interior of the container and an exterior thereof, the at least one inner port positioned relatively proximate the axis of rotation with respect to an arc defined by an oscillatory movement of an outer most portion of the container from the axis of rotation.

93. The system of claim 87, further comprising:

the container, wherein the container has an interior to hold the materials to be separated and at least one inner port to provide fluid communication between the interior of the container and an exterior thereof, the at least one inner port positioned at an inner periphery of the container.

94. The system of claim 87, further comprising:

the container, wherein the container has an interior to hold the materials to be separated and at least one outer port to provide fluid communication between the interior of the container and an exterior thereof, the at least one outer port positioned relatively distal from the axis of rotation.

95. The system of claim 87, further comprising:

the container, wherein the container has an interior to hold the materials to be separated and at least one outer port to provide fluid communication between the interior of the container and an exterior thereof, the at least one outer port positioned at an outer periphery of the container.

96. The system of claim 87, further comprising:

the container, wherein the container has an interior to hold the materials to be separated, at least one inner port to provide fluid communication between the interior of the container and an exterior thereof and at least one outer port to provide fluid communication between the interior of the container and the exterior thereof, the at least one inner port spaced relatively closer to the axis of rotation with respect to the at least one outer port.

97. The system of claim 96 wherein the container includes at least one filter proximate one of the inner or the outer ports.

98. The system of claim 97 wherein the at least one filter is selectively replaceable in the container.

99. The system of claim 96, further comprising:

a pump to pump the material to be separated through the container.

100. The system of claim 99 wherein the pump is configured to intermittently pump the material through the container.

101. The system of claim 87 wherein the axis of rotation passes through the container.

102. The system of claim 87 wherein the container is spaced from the axis of rotation.

103. The system of claim 87 wherein the drive mechanism comprises a four-bar linkage that includes a first member, a second member, a third member and a fourth member, the second member coupled to the first member, the first member rotationally driven by a motor to eccentrically drive a first end of the second member in a circular motion, the third bar member pivotally coupled to a second end of the second member, the third member connected to the fourth member at a pivot point;

where an amplitude of motion of the second member and a length of the third member define a angle of motion of the third and the fourth members and a length of the fourth member defines a distance of arcuate motion.

104. The system of claim 87, further comprising:

a controller coupled to control a frequency of the oscillatory angular rotation of the container and selectively operable to set the frequency to a sufficiently low frequency as to cause the relatively denser material to collect relatively farther from the axis of rotation than the relatively less dense material.

105. A method of separating material, the method comprising:

receiving a material to be separated in a container;

oscillating angularly rotating the container at a high frequency; and

removing at least some of the separated material from the container.

106. The method of claim 105, further comprising:

pumping the material to be separated into the container.

107. The method of claim 105, further comprising:

intermittently pumping the material to be separated into the container while oscillating the container.

108. The method of claim 105, further comprising:

directing at least some of the separated material removed from the container to at least one analysis device.

109. The method of claim 105, further comprising:

evacuating the container with an inert fluid.

110. The method of claim 105, further comprising:

varying a speed of the oscillating angular rotating to change a direction in which particles in the material move during separation.