WO2020264545A1

WO2020264545A1 - Methods and apparatus for rotary mixing of laboratory samples

Info

Publication number: WO2020264545A1
Application number: PCT/US2020/070014
Authority: WO
Inventors: Dan Harris; Eric Yeaton; Jeff ARAUJO
Original assignee: Siemens Healthcare Diagnostics Inc
Current assignee: Siemens Healthcare Diagnostics Inc
Priority date: 2019-06-24
Filing date: 2020-05-01
Publication date: 2020-12-30
Anticipated expiration: 2021-12-24

Abstract

Rotary sample mixing within a sample tube through fluid shear provides for efficient and inexpensive cell lysis. Angled vanes of a mixing head transfer spindle shaft rotary motion into rotary and vertical motion of the fluid. Disposing vanes at an offset angle achieves greater mixing efficiency, while the provision of openings within each vane at differing distances from an axis of rotation results in the creation of fluid shear. Providing over-sized vanes relative to the inner diameter of the sample tube allows the vanes to deform and wipe against the tube inner surface, churning up the sample fluid. Holes provided in each vane at differing radii relative to the axis of rotation also generate fluid shear. A unitary, disposable structure may be formed of a spindle shaft, a gear at an upper end of the spindle, and a mixing head at a distal end of the spindle.

Description

METHODS AND APPARATUS FOR

ROTARY MIXING OF UABORATORY SAMPUES

N/A

FIEUD OF THE DISCUOSURE

[0001] The disclosure herein relates generally to the field of lysis of cells within a fluid sample. More particularly, the present disclosure relates to rotary mixing of a sample within a sample tube to impart fluid shear for more effective and complete sample cell lysis.

BACKGROUND

[0002] Sample cell lysis is used in laboratories to break open cells to purify and/or further study their contents. Lysis as currently practiced is typically achieved through the use of enzymes, detergents, or other chaotropic agents. Mechanical disruption of cell membranes is achieved through techniques including repeated freezing and thawing, sonication, and filtration. Other known techniques include mixing glass, ceramic, or steel beads into a sample prior to agitation introduced by shaking or stirring. The resulting collisions between cells and beads results in membrane disruption.

[0003] Still other techniques include the use of high pressure to force cells through a narrow orifice, causing the cells to lyse due to the shear forces experienced across the resulting pressure differential. Systems for imparting alternating cycles of hydrostatic pressure, between ambient and ultra-high levels, achieve satisfactory results but are complex and expensive. Similarly, microfluidizers, which expose cells to elevated temperatures for very brief periods of time while cells are forced through microchannels, are capital intensive.

[0004] Innovations directed at simplifying highly efficient cell lysis through the use of inexpensive techniques would be highly desirable.

SUMMARY

[0005] In order to overcome the complexity and expense of the prior art techniques for cell lysis, the present disclosure provides for rotary mixing of a sample while it is held within a sample tube. Fluid shear introduced into the sample provides for efficient and inexpensive cell lysis. The presently disclosed device configurations and methods achieve improved cell or DNA fragment dispersion in the presence of lysis chemicals, thus improving the effectiveness of chemical lysis. [0006] One presently disclosed configuration provides multiple impellers, each disposed at a distal end of a spindle. Angled vanes or fins projecting from the respective impeller transfer spindle shaft rotary motion into rotary and vertical motion of the fluid. The rotational direction can be oscillated to alternately push fluid down, creating pressure on the bottom of the vial, thus forcing fluid up the walls of the vial or tube. Gravity then feeds the fluid back down to the impeller. Alternatively, the impeller may pull the fluid upwards, where it is then pulled back down due to gravity and again into the impeller.

[0007] Another presently disclosed configuration includes the use of four vanes that are offset with respect to an axis of symmetry of a spindle and an axis of rotation of a mixing head body to which the vanes are attached. By disposing the vanes at such an offset angle, greater mixing is achieved. In addition, openings are preferably formed within each vane. Two opposing vanes each have an opening proximate an outer edge thereof, while the other two opposing vanes each have an opening proximate the junction of the vane and the mixing head body. The openings are thus provided at different radii relative to the axis of rotation. Fluid flow through the short radius openings has a different velocity compared to fluid flow through the long radius openings. Fluid shear, and cell lysis, thus results.

[0008] A further configuration includes a mixing head comprised of three pliant vanes extending outwardly from a mixing head body affixed to the end of a spindle. The vanes are over-sized relative to the inner diameter of the sample tube. In other words, upon rotation of the spindle and the mixing head body about the axis of symmetry and rotation, the ends of the vanes engage the tube inner wall and the vanes deform, wiping the tube inner surface and churning up the sample fluid. Holes provided in each vane near the junction with the mixing head body and notches on the outer extent of the vanes proximate the tube inner surface allow some fluid to pass through, thus producing fluid flows of contrasting speed and thereby generating fluid shear.

[0009] In certain embodiments, a stator is disposed within the sample tube and remains stationary relative thereto through an interference fit between the stator and the sample tube inner wall surface. Such a stator is provided with a bore having a diameter sufficient to receive a mixing head and at least a portion of a spindle therein. The stator thus enables high speed rotation of the mixing head and spindle while inhibiting any tendency to travel of flex off-axis.

[0010] To simplify the use of the presently disclosed apparatus, a unitary, disposable structure may be formed of a spindle shaft, a gear at an upper end of the spindle, and a mix impeller structure at a distal end of the spindle. The structure may be automatically engaged by a permanent, cooperatively geared instrument, used for cell lysis, then disposed of. Robotic disposable structure placement and removal facilities may enhance processing speed. Rapid, efficient, high shear mixing is thus achieved with a low cost disposable.

BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Illustrative embodiments of the disclosed technology are described in detail below with reference to the attached drawing figures, which are incorporated by reference herein and wherein:

[0012] Fig. 1 is a perspective, partly sectional view of a first embodiment of a laboratory sample rotary mixing apparatus within a sample tube according to the present disclosure;

[0013] Fig. 2 is a perspective view of a rotary mixing head for use with a second embodiment of a laboratory sample rotary mixing apparatus according to the present disclosure;

[0014] Fig. 3A is a perspective, partly sectional view of a third embodiment of a laboratory sample rotary mixing apparatus within a sample tube according to the present disclosure;

[0015] Fig. 3B is a perspective view of a rotary mixing head of the third embodiment of Fig. 3A;

[0016] Fig. 4A is a perspective view of a fourth embodiment of a laboratory sample rotary mixing apparatus within a sample tube according to the present disclosure;

[0017] Fig. 4B is a perspective view of a rotary mixing head of the fourth embodiment of Fig. 4A;

[0018] Fig. 5A is a perspective view of a fifth embodiment of a laboratory sample rotary mixing apparatus within a sample tube according to the present disclosure;

[0019] Fig. 5B is an overhead sectional view of a rotary mixing head of the fifth embodiment of Fig. 5A;

[0020] Fig. 6A is a perspective view of a sixth embodiment of a laboratory sample rotary mixing apparatus within a sample tube according to the present disclosure;

[0021] Fig. 6B is a perspective view of a stator and rotary mixing head of the sixth embodiment of Fig. 6A;

[0022] Fig. 7A is a perspective view of a seventh embodiment of a laboratory sample rotary mixing apparatus within a sample tube according to the present disclosure; [0023] Fig. 7B is a perspective view of a stator and rotary mixing head of the seventh embodiment of Fig. 7A;

[0024] Fig. 8A is a perspective view of a portion of an eighth embodiment of a laboratory sample rotary mixing apparatus within a sample tube according to the present disclosure;

[0025] Fig. 8B is a perspective view of a stator of the eighth embodiment of Fig. 8A;

[0026] Fig. 9A is a perspective view of a first rotary mixing head, for use in the sixth, seventh or eighth embodiments of Figs. 6A, 6B, 7A, 7B, 8A, and 8B, mounted on a spindle;

[0027] Fig. 9B is a perspective view of the first rotary mixing head of Fig. 9A;

[0028] Fig. 10A is a perspective view of a second rotary mixing head, for use in the sixth, seventh or eighth embodiments of Figs. 6A, 6B, 7A, 7B, 8A, and 8B, mounted on a spindle; and

[0029] Fig. 10B is a perspective view of the second rotary mixing head of Fig. 10A.

DETAILED DESCRIPTION

[0030] Disclosed herein is a laboratory fluid mixing apparatus and method of use. Use of the presently disclosed apparatus enables the ability to cost-effectively and quickly lyse cells and purify samples for amplicon detection.

[0031] Rotary mixing of a sample within a sample tube is carried out using one of a variety of mixing head geometries. Rotary mixing as disclosed herein causes fluid shear within the sample, providing disruption of cells for lysing beyond that which results from currently practiced rotational mixing. The presently disclosed methods and techniques can be practiced with or without collisional beads, which are small spheres of durable material introduced into the sample before or during mixing. The methods and techniques can also be used in conjunction with chemical lysis techniques; rotary mixing ensures that each cell of DNA fragment gets dispersed while exposed to lysis chemicals which help make the chemical lysis more effective.

[0032] Fig. 1 provides a perspective view of a first embodiment of a laboratory sample rotary mixing apparatus 100 within a sectional view of a sample tube 102 The sample tube may be for example a Thermo Scientific Screw Cap Micro Tube, Part No. 346911 , having a complimentary screw cap 104 and O-ring and a conical bottom for efficient sample removal. The cap is provided with a bore 106 which is dimensioned to accommodate a substantially cylindrical spindle 110 therethrough. Other tubes are employable, though as will be seen, care must be taken in choosing tube inner diameters which are complimentary with the mixing apparatus outer diameter. The substantially cylindrical spindle defines an axis of symmetry within its length.

[0033] The mixing apparatus 100 of Fig. 1 is illustrated as also comprising a driven gear 108 on an upper or proximal end of the spindle 110 and a rotary mixing head 112 mechanically affixed at a distal end of the spindle. All of the embodiments of the present disclosure may include such a driven gear, though such is not shown and described with respect to every embodiment. This gear may be affixed to the spindle or may be formed integral thereto during a manufacturing process. The mixing head has an axis of rotation that is coaxial with the axis of symmetry of the spindle.

[0034] In operation, the mixing apparatus 100 comprised of the spindle 110, mixing head 112, and driven gear 108 may be robotically or manually assembled, and the mixing apparatus and respective sample tube 102 with sample may be robotically or manually inserted into a drive system (not shown) including an offset drive gear that engages the driven gear. A motor interfacing to the drive gear may be, for example, a stepper motor. The drive system may further comprise a heater to enhance cell lysis within the sample.

[0035] In each of the embodiments described herein, the spindle 110, driven gear 108, and mixing head 112 may be discrete components that are partially assembled prior to insertion within a cap 104, prior to being disposed with a tube 102 containing a respective sample. The mixing head may be, for example, stereography (SLA) printed.

[0036] The rotary mixing head 112 of the embodiment of Fig. 1 is comprised of a mixing head body 114 and plural mixing vanes 120. The mixing head body comprises an interface portion 116 that enables mechanical engagement with the distal end of the spindle 110. For example, the interface may include a socket dimensioned to frictionally engage the spindle distal end therein. Such a socket and the distal end of the spindle may have complimentary threads for secure engagement. Alternatively, the mixing head interface may include a projection (not shown) that is received with a complimentary socket within the distal end of the spindle.

[0037] The mixing head 112 of Fig. 1 also comprises a distal portion 118 mechanically engaged with or integral to the interface 116. The distal portion projects away from and is coaxial with the interface portion 116. [0038] The vanes 120 in the embodiment of Fig. 1 interface with the distal portion 118 of the mixing head body 114. The vanes are integrally formed with the mixing head body in one embodiment. Each vane interfaces with the distal portion along a straight line segment, though in other embodiments, this interface could be non-linear and, for example, curved. The linear interface between vanes and distal portion is offset or at an angle with respect to the axis of rotation of the mixing head 112. The vanes of Fig. 1 are also illustrated as being non-planar for the purpose of more efficient sample agitation. However, the vanes may also be provided in planar form as shown in other illustrated embodiments, such as for ease of manufacturability.

[0039] In Fig. 2, elements of a second rotary mixing apparatus 200 are illustrated. A rotary mixing head 212 is disposed on a respective spindle 210. This mixing head is comprised of a mixing head body 214 and four vanes 220, though other embodiments may have more or less than four vanes. The mixing head body is comprised of an interface 216 enabling secure, coaxial engagement with the spindle and a distal portion 218 extending away from the spindle. The vanes interface with the mixing head body across both the interface and the distal portion. This interface is substantially linear and the illustrated vanes are planar.

[0040] To produce fluid shear, the mixing head 212 of Fig. 2 includes offset vane apertures. In a first opposing pair of vanes 220, a lengthwise aperture 224 is formed in each vane proximate the mixing head body 214. In a second opposing pair of vanes, an aperture 222 is formed in each vane proximate an outer or distal edge. Thus, sample fluid flowing through the inner apertures 224 is at a first, smaller radius relative to the axis of rotation. Sample fluid flowing through the outer apertures 222 is at a second larger radius relative to the axis of rotation. Sample fluid thus flows at dissimilar speeds, imparting fluid shear upon the sample fluid. The outer or distal edge of each vane is selected to make the overall width of the mixing head slightly smaller than the inner diameter of the respective sample tube (not shown in Fig. 2).

[0041] A third embodiment of a rotary mixing apparatus 300 is shown in Figs. 3A and 3B with respect to a sample tube 302 in which is to be deposited a quantity of sample fluid. At a lower or distal end of a spindle 310, a mixing head 312 is comprised of a mixing head body 314 and two, coplanar vanes 320 on opposing sides of the mixing head body 314. Each vane includes a stem 322 that interfaces to the mixing head body. At an outer or distal end of each stem are a pair of opposing, coplanar blades 324 that interface with, or are integral with, the respective stem.

[0042] With respect to Fig. 3B, it is seen that the mixing head 312 includes an interface 316 that projects up from the mixing head body 314 to be received within a complimentary aperture within the lower extent of the spindle 310. The mixing head may be affixed to the spindle by conventional means, such as by gluing or ultrasonic welding.

[0043] Each opposing blade 324 of each vane 322 is shown in Fig. 3B to have a respective outer edge 330. The outer edges of the opposing blades in each pair are substantially coplanar. Preferably, the mixing head 312 is dimensioned such that when installed within a sample tube 302 there is minimal space between the outer edges and the tube inner wall. The opposing blades may have a notch 334 formed therebetween to enable a portion of the sample to flow therethrough to enhance shear force.

[0044] As shown in Fig. 3B, a planar tab 326 extends downwardly or distally from the mixing head body 314. The tab is symmetrical about, or coaxial with, the axis of rotation of the mixing head 312. The tab is also orthogonal to the plane of the opposing vanes 324. The tab is intended to contribute to the agitation of the sample fluid during selective rotation of the mixing head.

[0045] A fourth embodiment of a rotary mixing apparatus 400 is shown in Figs. 4A and 4B with respect to a sample tube 402 in which is to be deposited a quantity of sample fluid. At a lower or distal end of a spindle 410, a mixing head 412 is comprised of a mixing head body 414 and two, coplanar vanes 420 on opposing sides of the mixing head body 414. Each vane includes a stem 422 that interfaces to the mixing head body. At an outer or distal end of each stem are a pair of opposing, coplanar blades 424 that interface with, or are integral with, the respective stem.

[0046] With respect to Fig. 4B, it is seen that the mixing head 412 includes an interface 416 that projects up from the mixing head body 414 to be received within a complimentary aperture within the lower extent of the spindle 410. The mixing head may be affixed to the spindle by conventional means, such as by gluing or ultrasonic welding.

[0047] Each opposing blade 424 of each vane 422 is shown in Fig. 4B to have a respective outer edge 430. The outer edges of the opposing blades in each pair are substantially coplanar. Preferably, the mixing head 412 is dimensioned such that when installed within a sample tube 402 there is minimal space between the outer edges and the tube inner wall. The opposing blades may have a notch 434 formed therebetween to enable a portion of the sample to flow therethrough to enhance shear force.

[0048] As shown in Fig. 4B, a planar tab 426 extends downwardly or distally from the mixing head body 414. The tab is symmetrical about, or coaxial with, the axis of rotation of the mixing head 412. The tab is also orthogonal to the plane of the opposing vanes 424. The tab is intended to contribute to the agitation of the sample fluid during selective rotation of the mixing head. In this embodiment, a lateral member 428 is disposed intermediate one face of the tab and a lower one of the pair of blades 424 of each vane 420. The lateral member also contributes to additional fluid sample agitation.

[0049] The dimensions of the elements of the mixing heads 312, 412 of Figs. 3A, 3B, 4A, and 4B may be varied according to factors such as the viscosity of the sample fluid, the degree of fluid shear desired to be imparted upon the sample fluid, etc. For example, the width and/or length of the blades 324, 424 may be adjusted as needed.

[0050] A fifth embodiment of a rotary mixing apparatus 500 is shown in Figs. 5A and 5B with respect to a sample tube 502 in which is to be deposited a quantity of sample fluid. At a lower or distal end of a spindle 510, a mixing head 512 is comprised of a mixing head body 514 and plural vanes 520 distributed equally about the mixing head body 514. The plane of each vane intersects the axis of rotation of the mixing head. Each vane includes a stem 522 that interfaces to the mixing head body. At an outer or distal end of each stem are a pair of opposing, coplanar blades 524 that interface with, or are integral with, the respective stem.

[0051] While not illustrated in Figs. 5A and 5B, this mixing head embodiment 512 may also be provided with an interface that projects up from the mixing head body 514 to be received within a complimentary aperture within the lower extent of the spindle 510, such as shown in Figs. 3B and 4B. The mixing head may be affixed to the spindle by conventional means, such as by gluing or ultrasonic welding.

[0052] Each vane 520 shown in Figs. 5A and 5B is pliant and comprises a stem 522 with distally disposed and opposing blades 524. As the overall width of the mixing head 512 of this embodiment is wider than the inner diameter of the sample tube 502, the vanes are seen to bend as the mixing head is rotated about the axis of rotation. Thus, the outer or distal ends of the vane blades are configured to wipe along the inner surface of the tube during rotation. The opposing blades may have a notch 534 formed therebetween to enable a portion of the sample to flow therethrough to enhance shear force. As illustrated, each stem may also be provided with an aperture 538, also to enable a portion of the sample to flow therethrough, but at a velocity that differs from that of the fluid flowing through the notch.

[0053] Figs. 6A and 6B illustrate another embodiment of a rotary mixing apparatus 600 according to the present disclosure. The apparatus includes a rotary mixing head 620 in mechanical communication with a substantially cylindrical spindle 610. The mixing head has an axis of rotation that is coaxial with an axis of symmetry of the spindle. The mixing head includes an agitating member 622 at a distal end of the mixing head, relative to the spindle. As is visible in Fig. 6B, the agitating member in this embodiment is a planar, substantially rectangular tab.

[0054] The rotary mixing apparatus 600 of Figs. 6A and 6B also includes a stator 640. The stator is configured to be statically received within the fluid container, as described below. The stator is provided with a bore 644 therethrough and dimensioned and aligned to receive a portion of the spindle 610 and the agitating member 620 therein. Preferably, the gap between the bore inner diameter and spindle and agitating member outer diameter is minimized to inhibit vibration of the spindle and agitating member within the bore as the former are rotated about the axis of symmetry and rotation.

[0055] A distal end of the stator 640, relative to the spindle 610, is provided with plural linear discontinuities 642, each parallel with the axis of rotation and each for exposing a portion of the agitating member 622 within the stator to fluid within the fluid container 602. In the embodiment shown in Fig. 6B, the agitating member is configured as a planar tab dimensioned for rotation as part of the agitating member 620 within the stator.

[0056] The stator 640 of Figs. 6A and 6B includes a first set 650 of plural offset projections 654 and a second set 652 of offset projections 656. The projections of each set are coplanar and lie within a plane that is substantially orthogonal to the axis of rotation of the mixing head 620. Each projection within a set has substantially the same radial distance about the axis of rotation from the two neighboring offset projections within the respective set. In other words, the projections are substantially equally distributed about the axis of rotation. Each set of offset projections has a respective distance along the length of the stator with respect to the axis of rotation.

[0057] The stator 640 may be disposed into the sample tube 602 prior to introduction of mixing head and spindle. As noted above, such a mixing apparatus can also include a cap (not shown) such a shown in Fig. 1 for the tube, such a cap having an aperture to accommodate a rotatable spindle 610 therein. The spindle may also have a driven gear (not shown) such as also shown in Fig. 1.

[0058] The number of linear discontinuities and projections may be selected according to various factors such as sample viscosity, sample temperature, sample type, presence or absence of beads, diameter of beads if employed, etc.

[0059] Another embodiment of a rotary mixing apparatus 700 is illustrated with respect to Figs. 7A and 7B. This embodiment is substantially similar to that of Figs. 6A and 6B, described in the foregoing. As such, corresponding parts in Figs. 7A and 7B have the same reference number as shown in Figs. 6A and 6B, with the addition of 100. Thus, while the stator in Fig. 6A is 640, the stator in Fig. 7A is 740. The description of each part with respect to Figs. 6A and 6B also applies to the corresponding part with respect to Figs. 7A and 7B.

[0060] A point of distinction between the mixing apparatus 600 of Figs. 6A and 6B and the mixing apparatus 700 of Figs. 7A and 7B is the geometry of the agitating member 722. In the latter figures, the agitating member is comprised of two orthogonal, intersecting planar tabs, as best seen in Fig. 7B.

[0061] Another embodiment of a mixing apparatus 800 is shown with respect to Figs. 8A and 8B. A mixing head is not shown in these figures, though the agitating members 620, 720 of Figs. 6A and 6B or 7A and 7B could be used with the stator 840 of Figs. 8A, 8B. In fact, other non-illustrated mixing heads could also be employed with the stator 640, 740 of Figs. 6A, 6B, 7A, and 7B, as well as with the stator of Figs. 8A and 8B.

[0062] In the stator 840 of Figs. 8A and 8B, a first set 850 of plural offset projections 854 is provided at a position proximate an upper end of the stator 840. However, the second set of plural offset projections shown in Figs. 6A, 6B, 7A, and 7B is replaced with first and second subsets 860, 862 of offset projections 865, 867, each formed from a respective disk 861, 863 that is orthogonal to the axis of symmetry of the spindle 810. Peripheral discontinuities 864 in the disk of the first subset form the respective first offset projections and peripheral discontinuities 866 in the disk of the second subset form the respective second offset projections. The increased number of projections in this embodiment and the wider projections provide for greater surface contact between the stator and the inner surface of the sample tube, thereby enhancing the stability of the stator as the spindle 810 and an associated mixing head rotate within the bore 844 of this stator.

[0063] To increase fluid flows of varying velocities, one or both of the disks 861, 863 may be provided with apertures 871, such as those shown in the first disk in Figs. 8 A and 8B. Further, a plurality of equally spaced apertures 870 may be formed within an inner, peripheral surface of the stator, thereby exposing at least a part of a mixing head within the stator 840 to fluid within the sample tube 802.

[0064] A particular embodiment of a rotary mixing head 912 is illustrated with respect to Figs. 9A and 9B. Attached to a distal or lower end of a spindle 910 is the mixing head. In one embodiment, the mixing head is provided with a cylindrical projection 916 that may be received within a complimentarily shaped receptacle in the distal or lower end of the spindle. Conventional joining techniques may be employed, such as gluing or ultrasonic welding, to adhere the mixing head to the spindle. [0065] The mixing head 912 comprises a substantially cylindrical central core 918 and a plurality of planar vanes 920 that extend outwardly from and extend along substantially all of the length of the mixing head 912. Each of the plural vanes is coplanar with the axis of rotation of the mixing head and with the axis of symmetry of the spindle 910. An outer extent 922 of each vane along the majority of the length of the mixing head is substantially linear in the embodiment of Figs. 9A and 9B. Proximate a distal or lower end of the mixing head, however, the outer extent may be trimmed, cut or shaped such that the distal or lower end of the mixing head has a narrower outer diameter, thereby enabling the distal end of the mixing head to extend deeper into a sample tube having a concave lower extent, such as seen in Fig. 1

[0066] In addition, as seen in Figs. 10A and 10B, the outer extent 922 of the mixing head 912 vanes 920 may include at least one discontinuity 930. In the illustrated embodiment, each vane has four such discontinuities. While the discontinuities may take a variety of shapes, the illustrated discontinuities are semicircular. Preferably, a discontinuity in one vane aligns along the length of the mixing head with all other vane discontinuities thereby forming a band of vane discontinuities at substantially the same distance or linear position along the length of the central core 918. Four such bands are shown in the embodiment of Figs. 10A and 10B, though other numbers are employable.

[0067] A method of mixing fluid within a fluid container includes mechanically engaging a rotary mixing head having an axis of rotation with a substantially cylindrical spindle having an axis of symmetry coaxial with the axis of rotation. It is understood that while the spindle and the mixing head may be provided as discrete elements that are joined together through mechanical fastening means such as complimentarily threaded fasteners, interference fit, welding, bonding or gluing, the phrase mechanically engaging may also encompass a manufacturing process by which the spindle and mixing head are fabricated as a single piece article.

[0068] The mixing head and at least a portion of the spindle are then disposed into fluid within the fluid container, following which the spindle is selectively rotated about the axis of symmetry, whereby the mixing head is also selectively rotated about its axis of rotation (which may also be a respective axis of symmetry). Rotation may be in one direction or alternating in both directions. The step of rotating may also be intermittent, with periods of rest or slower rotation interposed between periods of active rotation. The mixing head may be any of the described in the foregoing. [0069] Another method of mixing fluid within a fluid container also includes mechanically engaging a rotary mixing head with a substantially cylindrical spindle, as described above. However, this method includes disposing a stator having a respective bore therethrough within the fluid container. The stator is configured to be statically received within the fluid container and configured to receive the mixing head within the bore, the bore being coaxial with the axis of rotation. Once the mixing head and at least a portion of the spindle are disposed into the fluid within the fluid container, the spindle is selectively rotated about the axis of symmetry, whereby the mixing head is rotated about the axis of rotation. The mixing head in this embodiment comprises a mixing head body and an agitating member distal from the spindle, such as disclosed and described in the foregoing.

[0070] The stator may have plural linear discontinuities and plural offset projections such as shown and described with respect to Figs. 6A, 6B, 7A, and 7B.

[0071] The foregoing description has been directed to particular embodiments. However, other variations and modifications may be made to the described embodiments, with the attainment of some or all of their advantages. It will be further appreciated by those of ordinary skill in the art that modifications to the above-described systems and methods may be made without departing from the concepts disclosed herein. Accordingly, the invention should not be viewed as limited by the disclosed embodiments. Furthermore, various features of the described embodiments may be used without the corresponding use of other features. Thus, this description should be read as merely illustrative of various principles, and not in limitation of the invention.

[0072] Many changes in the details, materials, and arrangement of parts and steps, herein described and illustrated, can be made by those skilled in the art in light of teachings contained hereinabove. It will be understood that certain features and sub-combinations are of utility and may be employed without reference to other features and sub combinations and are contemplated within the scope of the claims. Accordingly, it will be understood that the following claims are not to be limited to the embodiments disclosed herein and can include practices other than those specifically described, and are to be interpreted as broadly as allowed under the law.

Claims

CLAIMS I claim:

1. A laboratory fluid rotary mixing apparatus configured for being disposed within a fluid within a fluid container, the mixing apparatus comprising:

a substantially cylindrical spindle having an axis of symmetry; and

a rotary mixing head in mechanical communication with the spindle, the mixing head having an axis of rotation coaxial with the axis of symmetry of the spindle, the mixing head comprising a mixing head body and plural vanes projecting outwardly from the mixing head body for enabling fluid agitation upon selective rotation of the spindle about the axis of symmetry and the mixing head about the axis of rotation.

2. The mixing apparatus of claim 1, wherein the mixing head body comprises an interface for mechanically engaging with a distal end of the spindle.

3. The mixing apparatus of claim 2, wherein the mixing head further comprises a distal portion projecting away from and coaxial with the mixing head body.

4. The mixing apparatus of claim 3, wherein each of the vanes interfaces with the mixing head body and the distal portion of the mixing head.

5. The mixing apparatus of claim 1, wherein each of the vanes interfaces with the mixing head body in a line that is offset with respect to the axis of rotation.

6. The mixing apparatus of claim 5, wherein each of the vanes is non-planar.

7. The mixing apparatus of claim 5, wherein each of the vanes is planar.

8. The mixing apparatus of claim 7, wherein at least one of the vanes comprises a slot proximate an edge distal from the mixing head body.

9. The mixing apparatus of claim 7, wherein at least one of the vanes comprises a slot proximate the respective interface with the mixing head body.

10. The mixing apparatus of claim 1, wherein the mixing head comprises an interface for mechanically engaging with a distal end of the spindle and the plural vanes are two coplanar, opposing vanes projecting from the mixing head body.

11. The mixing apparatus of claim 10, wherein each vane comprises a stem interfacing with and extending outwardly from the mixing head body and a pair of opposing blades interfacing with and extending in opposite directions from the stem and parallel to the axis of rotation.

12. The mixing apparatus of claim 11, wherein the blades each have an outer edge, distal from the mixing head body, and wherein the outer edges of each pair of blades are substantially coplanar.

13. The mixing apparatus of claim 10, wherein the mixing head further comprises a planar tab extending distally from and coaxial with the mixing head body, the planar tab lying in a plane that is orthogonal to a plane in which the opposing vanes he.

14. The mixing apparatus of claim 13, wherein each vane further comprises a lateral member for connecting an end of one respective blade to the planar tab, the lateral member being substantially orthogonal to the axis of rotation.

15. The mixing apparatus of claim 1, wherein the mixing head comprises an interface for mechanically engaging the spindle and the plural vanes are plural pliant vanes projecting from the mixing head body, each pliant vane being coplanar with the axis of rotation.

16. The mixing apparatus of claim 15, wherein each pliant vane comprises at least two coplanar, opposing blades, each blade having an outer edge, distal from the mixing head body, and wherein the outer edges of the blades of each pliant vane are substantially coplanar.

17. The mixing apparatus of claim 1, wherein the mixing head comprises a substantially cylindrical central core and wherein each of the plural vanes is coplanar with the axis of rotation and projects outwardly from the central core.

18. The mixing apparatus of claim 17, wherein the central core comprises an interface for mechanically engaging with a distal end of the spindle.

19. The mixing apparatus of claim 17, wherein an outer extent of each of the plural vanes, distal from the central core, comprises at least one discontinuity formed therein and wherein each discontinuity in one vane is aligned along the length of the mixing head with discontinuities formed in each of the other vanes thereby forming at least one band of vane discontinuities at substantially the same distance along the central core.

20. The mixing apparatus of claim 19, wherein the discontinuities are semicircular.

21. A laboratory fluid mixing apparatus configured for being disposed within a fluid container, the mixing apparatus comprising:

a substantially cylindrical spindle having an axis of symmetry;

a rotary mixing head in mechanical communication with the spindle, the mixing head having an axis of rotation coaxial with the axis of symmetry of the spindle, the mixing head comprising an agitating member distal from the spindle; and

a stator having a bore therethrough, the stator configured to be statically received within the fluid container and configured to receive the mixing head within the bore, the bore being co-axial with the axis of rotation.

22. The mixing apparatus of claim 21, wherein a distal end of the stator comprises plural linear discontinuities, each parallel with the axis of rotation and each for exposing a portion of the agitating member within the stator to the fluid within the fluid container.

23. The mixing apparatus of claim 21, wherein the agitating member is configured as a planar tab or two orthogonally intersecting planar tabs.

24. The mixing apparatus of claim 21, wherein the stator comprises a first set of plural offset projections and a second set of plural offset projections, each set being coplanar and substantially orthogonal to the axis of rotation, each offset projection within a set having the same radial distance about the axis of rotation from the two neighboring offset projections within the respective set, and each set having a unique distance along the length of the stator.

25. The mixing apparatus of claim 24, wherein one set of offset projections comprises first and second subsets of offset projections each formed from a respective disk, orthogonal to the axis of rotation, having peripheral discontinuities therein, thereby forming the offset projections therebetween.

26. The mixing apparatus of claim 25, wherein the stator comprises a plurality of equally spaced apertures formed within an inner, peripheral surface thereof, between the first and second subsets of offset projections, for exposing at least a portion of the mixing head within the stator to the fluid within the fluid container.

27. A method of mixing fluid within a fluid container, comprising:

mechanically engaging a rotary mixing head, having an axis of rotation, with a substantially cylindrical spindle, having an axis of symmetry coaxial with the axis of rotation; disposing the mixing head and at least a portion of the spindle into the fluid within the fluid container; and

selectively rotating the spindle about the axis of symmetry and the mixing head about the axis of rotation,

wherein the mixing head comprises a mixing head body and plural vanes projecting outwardly from the mixing head body for enabling fluid agitation upon the selective rotation.

28. The method of claim 27 wherein each of the plural vanes interfaces with the mixing head body in a line that is offset with respect to the axis of rotation.

29. The method of claim 27 wherein each of the plural vanes is planar.

30. The method of claim 27 wherein at least one of the vanes comprises one or both of a slot proximate a vane edge distal from the mixing head body and a slot proximate the respective interface with the mixing head body.

31. The method of claim 27, wherein the plural vanes are two coplanar, opposing vanes extending from opposite sides of the mixing head body, each comprising a stem interfacing with and extending outwardly from the mixing head body and a pair of opposing blades interfacing with and extending in opposite directions from the stem and parallel to the axis of rotation.

32. The method of claim 31, wherein the mixing head further comprises a planar tab extending distally from and coaxially with the mixing head body, the planar tab lying in a plane that is orthogonal to a plane in which the opposing planes lie, and

wherein each vane further comprises a lateral member for connecting an end of one respective blade to the planar tab, the lateral member being substantially orthogonal to the axis of rotation.

33. The method of claim 27, wherein the plural vanes are plural pliant vanes projecting from the mixing head body, each pliant vane being coplanar with the axis of rotation and comprising at least two coplanar, opposing blades, each blade having an outer edge, distal from the mixing head body, and wherein the outer edges of the blades of each pliant vane are substantially coplanar.

34. The method of claim 27, wherein the mixing head body is substantially cylindrical and wherein each of the plural vanes is coplanar with the axis of rotation and projects outwardly from the central core.

35. The method of claim 34, wherein an outer extent of each of the plural vanes, distal from the mixing head body, comprises at least one discontinuity formed therein and wherein each discontinuity in one vane is aligned along the length of the mixing head with discontinuities formed in each of the other vanes thereby forming at least one band of vane discontinuities at substantially the same distance along the mixing head body.

36. A method of mixing fluid within a fluid container, comprising:

mechanically engaging a rotary mixing head, having an axis of rotation, with a substantially cylindrical spindle, having an axis of symmetry coaxial with the axis of rotation;

disposing a stator having a bore therethrough within the fluid container, the stator configured to be statically received within the fluid container and configured to receive the mixing head within the bore, the bore being coaxial with the axis of rotation;

disposing the mixing head and at least a portion of the spindle into the fluid within the fluid container; and

wherein the mixing head comprises a mixing head body and an agitating member distal from the spindle.

37. The method of claim 36, wherein a distal end of the stator comprises plural linear discontinuities, each parallel with the axis of rotation and each for exposing a portion of the agitating member within the stator to the fluid within the fluid container.

38. The method of claim 36, wherein the stator comprises a first set of plural offset projections and a second set of plural offset projections, each set being coplanar and substantially orthogonal to the axis of rotation, each offset projection within a set having the same radial distance about the axis of rotation from the two neighboring offset projections within the respective set, and each set having a unique distance along the length of the stator.

39. The method of claim 38, wherein one set of offset projections comprises first and second subsets of offset projections each formed from a respective disc, orthogonal to axis of rotation, having peripheral discontinuities therein, thereby forming the offset projections therebetween.

40. The method of claim 39, wherein the stator comprises a plurality of equally spaced apertures formed within an inner, peripheral surface thereof, between the first and second subsets of offset projections, for exposing at least a portion of the mixing head within the stator to the fluid within the fluid container.