Abstract:
The present invention is directed to a microcentrifuge apparatus adapted to simultaneously spin a plurality of samples contained within a plurality of rotors. The microcentrifuge comprises an upper plate that has a plurality of upper plate holes; and a lower plate that has a plurality of lower plate holes or recesses. The lower plate is adjacent and substantially parallel to the upper plate, and the plurality of lower plate holes or recesses are in axial alignment with the plurality of upper plate holes. The plurality of rotors are adapted for retaining and spinning the plurality of samples, and are positioned between the upper plate and the lower plate. Each of the plurality of rotors has at opposing ends an upper shaft and a lower shaft, wherein the upper shaft engages one of the upper plate holes and the lower shaft engages one of the lower plate holes or recesses such that the axes of rotation of each of the plurality rotors are substantially perpendicular to the upper and lower plates. In addition, each of the rotors has a central outer surface portion positioned between the upper and lower plates, wherein the central outer surface portion is outwardly bulged. The microcentrifuge further comprises a pulley and a drive belt that is operatively engaged with the pulley and the bulged central outer surface portion of each of the plurality of rotors.

Description:
This application claims the benefit of U. S. Provisional Application No. 60/118,013, filed Jan. 29, 1999. 
    
    
     STATEMENT OF GOVERNMENT INTEREST 
     This invention was made with government support under Grant Nos. HG02125-01 and HG02125-02 awarded by The National Human Genome Research Institute. The government may have certain rights in this invention. 
    
    
     TECHNICAL FIELD 
     This invention relates generally to microcentrifugation instruments and techniques, specifically to an improved arrayable microcentrifuge for simultaneous centrifugation of samples. 
     BACKGROUND OF THE INVENTION 
     Centrifugation as a means of accelerating sedimentation of precipitates and particulates has long been an integral part of biochemical protocols. A typical centrifuge consists of a rotor encased in a housing. The rotor is powered by a drive motor or some other force that allows it to complete a set number of rotations per minute (rpm). Attached to the rotor are holders in which to place sample containers, such as test tubes or well plates. These holders are placed symmetrically around the circumference of the rotor. The sample containers are balanced to insure a symmetric mass distribution around the rotor. The sample containers are placed in the holders and the samples can then be spun and separated. 
     Separation of the samples occurs because each component has a different density and thus a different sedimentation velocity. Sedimentation velocity is a measure of how fast a component will migrate through other more buoyant sample components as a result of the centrifugal field generated by the centrifuge. 
     Using centrifugation, a variety of samples can be separated. Specific types of cell organelles can be isolated, particles can be removed from a suspension, and different liquids in a solution can be separated. The amount of separation of a sample is determined by the rpm used and the length of time the sample is spun. Recently, the increasing demand for high-throughput assays in the field of biochemistry has created a need for parallel processing and automation of many such protocols. Standard centrifuges have proven to be incompatible with these needs. 
     The need for highly parallel sample processing has led the science community to usage of multiwell plates. Because of the plates&#39; insufficient mechanical strength, centrifugation of samples held in such plates is limited to accelerations below 3,500×g. Furthermore, multiwell plate centrifuges are large and cumbersome to automate. Though automation of centrifuge-based sample preparation has been performed (AutoGen 740, AutoGen, Framingham, Mass.), the resulting instruments have limits (&lt;96 samples/hr per instrument) as a result of these difficulties. 
     Filter-based separation protocols also have been automated by several companies (Qiagen, Chatsworth, Calif., and Beckman Coulter, Palo Alto, Calif) but also are limited in throughput (roughly 96 samples/hr per instrument) and are at least 10 times more expensive than centrifuge-based separations. 
     The main limitations of centrifuges are 1) the need for a large amount of manual labor to load and unload them, 2) the small number of samples that can be spun down at one time, and 3) the length of time it takes to spin down samples. In addition, the maximum acceleration used in current centrifuges is limited by the mechanical strength of the sample containers, particularly multi-well plates, which increases the amount of time needed to spin down samples. Although these problems could be overcome by the use of robotic arms and the purchase of more centrifuges, the cost and space requirements would be prohibitive for most laboratories. 
     PCT Application No. PCT/US98/18930 (published as International Publication No. WO 99/12651) addresses some of these problems by disclosing a high-throughput centrifugation system in which samples are spun directly in contact with individual, miniature rotors rather than a sample holder. However, this system does not disclose an efficient means for the simultaneous rotation and restraint of the rotors. Moreover, this application does not disclose an efficient means for containing samples and protecting the apparatus from spillage. What is needed is a reliable and efficient high-throughput automated centrifugation apparatus. 
     SUMMARY OF THE INVENTION 
     In one embodiment, a microcentrifuge apparatus has a plurality of rotors for simultaneously spinning a plurality of samples; a retainer for retaining each of the rotors on a bearing surface; and at least one source of motive power (i.e., a motor), coupled to the rotors by a coupling means, for causing each of the rotors to spin at substantially the same rate. The coupling means is preferably a drive belt such as a single continuous drive belt. 
     In another embodiment, the microcentrifuge apparatus has a plurality of rotors for spinning a plurality of samples; a retainer for retaining each of the rotors on a bearing surface; at least one source of motive power for spinning the rotors; and at least one drive belt, coupled between the power source and each of the rotors, for applying the motive power to each of the rotors. 
     In another embodiment, the microcentrifuge has a plurality of rotors, each having a longitudinal axis and each containing a sample, a plurality of retainers for retaining each rotor at its predetermined location; a bearing surface located at each predetermined location for supporting each rotor as it is spun; and a source of rotating power coupled to the rotors for spinning each rotor on its longitudinal axis. 
     In another embodiment, the micro-array centrifuge has the following: a. a lower plate with a plurality of recesses; b. an upper plate with a plurality of holes, each hole lined by a raised cuff; c. a plurality of rotors, each having a longitudinal axis, top, bottom, crown, side and upper shaft, the side and crown maintaining contact with a drive belt; d. a motor for moving the drive belt, which in turn spins the rotors about their longitudinal axes; e. a cap with an inner and an outer lip, the inner lip adhering to the upper shaft and the outer lip being outside of the raised cuff and in close proximity to the top surface of the top plate, whereby fluid is prevented from getting into the microarray centrifuge; and f. each rotor bottom contacting at least one bearing which contacts at least one recess in the lower plate. 
     In another embodiment, the microcentrifuge has a lower plate divided into strips, each of which is anchored at its end. 
     In another embodiment, the microcentrifuge has a plurality of disposable rotors for simultaneously spinning a plurality of samples, a retainer for retaining each of the rotors on a bearing surface; and a source of motive power, coupled to the rotors, for spinning each of the rotors at substantially the same rate. The disposable rotors fit into and are removable Prom a plurality of rotor encasements of the array centrifuge. The disposable rotors comprise one or more chambers for samples. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is an overview of a microcentrifuge. 
     FIG. 2 is an overview of the microcentrifuge after the cover has been removed. 
     FIG. 3 is an overview of the microcentrifuge of FIG. 2 with an exaggerated belt for purposes of illustration. 
     FIG. 4A is a cross-sectional view of a row of 12 centrifuge rotors. 
     FIG. 4B is an enlargement of area B of FIG.  4 A. 
     FIG. 5 is an overview of the top cover plate of the centrifuge that shows pins to align other tools. 
     FIG. 6A shows the bottom half of the rotor. 
     FIG. 6B shows the top half of the rotor. 
     FIG. 6C is a cross-sectional view of FIG. 6A showing the slight bulge or crown of the bottom half of the rotor. 
     FIG. 7 illustrates a second embodiment of the microcentrifuge that can accommodate two motors. 
     FIG. 8 illustrates the eight “strips” that comprise the lower plate of the second embodiment and can accommodate 12 rotors each. 
     FIG. 9 highlights the path of two belts in the second embodiment of the microcentrifuge. 
     FIG. 10 is a partial cross-sectional view of a disposable rotor embodiment. 
     FIG. 11A is a top view of the disposable rotor with spacers. 
     FIG. 11B is a cross-sectional view of the disposable rotors with spacers. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     One of the best ways to address the need for highly parallel sample processing in the field of biotechnology is a high-throughput centrifugation system in which samples are spun directly in contact with individual, miniature rotors rather than with a sample holder. One such system is disclosed in PCT Application No. PCT/US98/18930 (published as International Publication No. WO 99/12651). The application discloses the preferred embodiment of using a fluid stream to spin the rotors on their longitudinal axis, wherein the transferring momentum comprises a set of indentations in an exterior surface of each rotor. However, due to variable bearing friction, it is difficult to obtain uniformity of rotation rates from rotor to rotor especially over a wide range of velocities using a high velocity fluid stream as a means of driving the rotors. This difficulty arises due to the variation of the friction from bearing to bearing in the ball bearings used to retain the rotors and results in widely varying steady state rotational velocities of the rotors. 
     The present invention discloses an improved high-thoroughput, automated centrifuge. Similar to the invention disclosed above, it is a centrifuge in which samples are spun directly in contact with individual, miniature rotors rather than with a sample holder. However, instead of powering the rotors with a fluid stream, the present invention discloses a source of motive power, such as a motor, coupled to the rotors by various mechanical coupling means. This configuration provides for precise, uniform rotational velocity of the rotors across the entire array of rotors for a wide range of velocities and helps keep the rotors in place. The invention further discloses a means of restraining the rotors using lubricated bearings and a bearing surface. Another advantage is the addition of a resilient ring between the lubricated bearings and the bearing surface for providing consistent pre-load for the bearings as well as noise reduction. 
     In FIG. 1, an exemplary microcentrifuge  100  has an upper plate  102  and a lower plate  104 , both of which enclose a plurality of rotors (not shown). A preferred material for the upper and lower plates  102 ,  104  is aluminum. The lower plate  104  may have a solid bottom, or it may have holes (not shown) under any and all the rotors (not shown) and their respective bearings (not shown). The upper plate  102  has a plurality of holes  106  surrounded by raised cuffs  108 , which in turn surround the rotors (not shown). The upper plate  102  is connected to the lower plate  104  by a plurality of screws (not shown) located on the periphery of the upper plate  102  within a plurality of screw holes  110 . The upper plate  102  also has a plurality of instrument alignment holes  112  to accommodate alignment pins (not shown) associated with other instruments, such as for example a pipetter used for dispensing and aspirating samples into the rotors (not shown). An air inlet hole  114  lets in air for passive cooling; for more effective cooling or heating, a tube (not shown) may be attached to a fitting (not shown) at the air inlet hole  114  such that heated or cooled air may be delivered to the microcentrifuge  100 . An open slot  116  may be used for a speed sensor (not shown) that monitors the rotational rate of the rotors (not shown) and ensures that the rotors are moving at the correct rate. A plurality of drainage slots  118  are located on the upper plate  102  allow for drainage if there is spillage of the samples. FIG. 1 also illustrates a pulley cover plate  120  that covers a pulley (not shown) and protects it from outside elements. The pulley cover plate  120  is preferably made out of a machinable metal, such as anodized aluminum. 
     FIG. 2 shows the microcentrifuge  100  of FIG. 1, but with the upper and pulley cover plates  102 ,  120  removed thereby showing the placement of the plurality of rotors  220 . As shown, each of the plurality of rotors  220  has an upwardly protruding shaft portion  222 . Also shown is the pulley  224  that is driven by a DC motor (not shown). A controller (not shown) connects the motor and a remote computer (not shown), which determines when and how fast the rotors  220  will spin. 
     FIG. 3 shows the path that a belt  326  takes around the pulley  224  and rotors  220 . The belt  326  may be made from a variety of materials that tolerate temperature change and avoid stretching. Preferably the belt  326  is made of KAPTON polyimide tape (DuPont, Wilmington, Del.). In this configuration, the belt  326  is  61  inches in length, 0.250 inches wide and 0.003 inches thick. The belt  326  is held in place by a rotor “crown” (not shown) associated with the lower rotor (not shown), as discussed below. The belt  326  is further held in place by a pulley “crown” (not shown) associated with the pulley  224 , which crown is a slight concave bulge with a radius of curvature of approximately 4.5 inches around the circumference of the outer surface of the pulley  224 . 
     FIG. 4A is a cross section of twelve of the plurality of rotors  220 . Circle “B” of FIG. 4A has been exploded in FIG.  4 B. FIG. 4B shows the details of the assembly of each rotor  220 , including the cooperation between rotors  220  and upper plate  102  (wherein a secure seal is formed that protects the inside of the microcentrifuge from fluid contamination and corrosion). Each of the plurality of rotors  220  may be fabricated in two parts: an upper rotor half  428  and a lower rotor half  430 . The rotors  220  are further discussed below. The upper rotor half  428  includes the upwardly protruding shaft portion  222  (also shown in FIG.  2 ), wherein each shaft portion  222  is covered with a cap  432 . The cap  432  is preferably made of TEFLON (DuPont, Wilmington, Del.). The cap  432  has an inner lip  434  and an outer lip  436 . The inner lip  434  is flush with the upwardly protruding shaft portion  222  so as to form a tight seal. The outer lip  436  is positioned outside the raised cuff  108  of upper plate  102  and ends just above the upper plate  102 , leaving a narrow space  438  (surface tension associated with a spilled fluid prevents any fluid from entering around the outside of the rotor). 
     Between upper plate  102  and upwardly protruding shaft portion  222  is a bearing  440 , which presses on the shoulder  442  of upper rotor half  428  for controlled turning. Each bearing  440  is preferably lubricated and made of stainless steel, with a plastic retainer made of polyimide (DuPont, Wilmington, Del.). There may also be an optional O-ring  444  to absorb sound and to preload the bearings and decrease radial and axial movement. Each O-ring  444  is preferably made of silicone rubber. At location  446 , outside the cap  432 , an absorbent material (not shown) may also be placed to attenuate noise. Preferred is a sponge-like material or a fibrous mat with 96 holes or any other appropriate number cut out to accommodate the rotors  220 , which can be easily removed and replaced. 
     FIG. 5 illustrates a top cover plate  548  having a plurality of sample inlet holes  550  to match up with the array of rotors (not shown). The top cover plate  548  holds the caps (not shown) in place during centrifugation. The top cover plate  548  is preferably made of a machinable plastic, such as a polycarbonate or acrylic plastic. Also illustrated are three alignment pins  552  that help align other instruments, such as for example a pipetter, with the plurality of sample inlet holes  550 . 
     FIG. 6A, FIG. 6B, and FIG. 6C provide detail of the upper half  428  and the lower half  430  of each of the plurality of rotors, both outside and inside. Each rotor is preferably made from strong, non-reactive material such as titanium. On the lower half  430  and as best seen in FIGS. 6A and 6B, there is a “crown”  654 , which constitutes a slight concave bulge with a radius of curvature of approximately 7 inches around the circumference of the outer surface of the rotor. The belt (not shown) seeks the highest point of the crown  654  such that the belt stays centered on the rotor and keeps it from sliding off its track. 
     FIG. 7 shows a top view of a second embodiment of the micro-array centrifuge of the present invention. In this configuration, the array centrifuge  700  has two motors (not shown). It is modular and can easily be moved to various desired locations in a workspace. In this embodiment there is no upper plate; rather the array centrifuge  700  includes an enclosure, preferably comprised of one piece. This solid configuration provides stability and sound abatement. FIG. 7 also illustrates a shelf  702  for spillage of the samples. 
     FIG. 8 shows a bottom of the second embodiment, wherein the lower means for retaining the rotors (not shown) include 8 separate “strips”  804  that form a lower plate. Each strip  804  has a plurality of bottom holes  806  that hold 12 rotors (not shown) in place. Providing multiple strips significantly decreases the planar movement of the rotors that can occur in a solid lower plate that holds all 96 rotors. Each strip has end screw holes  808  for screws to securely anchor each strip. 
     FIG. 9 illustrates how each of the two motors (not shown) associated with the second embodiment combine with two pulleys  910 ,  912  and two belts  914 ,  916  (each belt drives one half of the array). Each motor is connected to a remote computer (not shown) by a controller (also not shown), which determines when and how fast the rotors  918  will spin. The two belts  914 ,  916  are each weaved around its respective pulley  910 ,  912  and around one half of the plurality of rotors  918 . The spinning of the pulleys  910 ,  912  moves the belts  914 ,  916  and in turn spins the array of rotors  918 . The use of two motors lowers the power requirements of each motor thereby increasing their lives and centrifuge reliability. Moreover, in this second embodiment of the invention, the two belts  914 ,  916  each wraps around more surface area of its respective pulley  910 ,  912  (such differences in configuration may be observed by comparing FIGS.  9  and  3 ). The larger surface area results in a lower likelihood for belt slippage. 
     It can be seen that a 96-channel pipetter will work with the 96-well micro-array centrifuge. The advantages of the microcentrifuge are many. Because the rotors are so small, there is less mass to overcome in acceleration and deceleration. Hence, the rotors can accelerate rapidly to a speed of 2,000 revolutions and stop very quickly. The microcentrifuge takes up very little room and uses very little energy. Due to the small size and mass of the rotors, very high centrifugation forces can be achieved, on the order of 14,000 times the force of gravity and therefore very short sedimentation times can be obtained. 
     In another embodiment, various coatings, such as TEFLON or polypropylene, of the rotor interior provide optimal pellet retention and easy cleaning of the rotors. 
     In another embodiment of the microcentrifuge apparatus, the rotors are coupled to the source of motive power by a drive belt, wherein the source of motive power may be a motor or engine. 
     In another embodiment, the rotors are controlled by electromagnetic means. Each rotor effectively becomes an individual motor. A shaft is attached and extends out from the rotor. The shaft is surrounded by electrically conductive wire windings. A circular magnet surrounds these windings and is held in place by a retaining plate. The ends of the wire windings are attached to commutators. The commutators are contacted by electrically conductive metal brushes. Electrical current from the motor control source is supplied through the brushes to the windings to produce alternating magnetic fields. The interaction of this alternating magnetic field with the stationary circular magnet produces torque on the shaft that drives the circular rotation of the rotor. The same control voltage can be applied to all motors allowing all rotors to rotate at the same speed. Additionally, each motor can be controlled individually allowing each rotor to achieve different rotational speeds. 
     In another embodiment of the array centrifuge, the rotors are disposable. The use of disposable rotors avoids the problem of the cross-contamination of samples. The rotors fit into an independent drive train comprised of a plurality of permanent rotor encasements and a motive means. Each sample is processed in its own unique disposable rotor and is replaced before a new sample is introduced. This avoids the need for washing out the rotors between samples and saves processing time. 
     FIG. 10 illustrates the preferred embodiment of the apparatus with disposable rotors. The disposable rotors are preferably made of a tough non-reactive material such as polypropylene. Each disposable rotor  400  fits snugly into a rotor encasement  402  of the array centrifuge. The encasement is preferably made from strong material such as titanium. The rotor encasement  402  has at least one opening  404  into which a disposable rotor  400  may be inserted. The lower portion of the rotor encasement has a shaft  406  that fits into one or more bearings  408  that accommodate the movement of the rotor encasement  402 . The bearings  408  are preferably lubricated and comprised of stainless steel, with a plastic retainer made of polyamide (DuPont, Wilmington, Del.). Each bearing  408  has at least one retaining plate  410  to hold the bearing  408  in place. There may also be an optional O-ring  412  between the lower portion of the rotor encasement  402  and the retaining plate  410  to absorb sound and preload the bearings  408  and decrease radial and axial movement. The O-rings  412  are preferably made of silicone rubber. 
     Directly below the first bearing  408 , a pulley  416  is wrapped around the shaft  406  of the rotor encasement  402 . A belt  418  may be woven around each pulley  416  in the array of rotor encasements  402  for motion. The belt  418  is actuated by a motive means, such as a motor (not shown) and an independent pulley (not shown). Beneath the pulley  416  is a second lubricated bearing  420  and at least one retaining plate  411  to keep the bearing  420  in place. Optionally, an O-ring  412  may be used to absorb sound and preload the bearings  420  and decrease radial and axial movement. 
     Figures  11 A and  11 B illustrates yet another embodiment of disposable rotors for an array centrifuge. The disposable rotor  400  includes spacers  422  on the outside of the rotor  400  as shown in FIG. 11 A. The spacers  422  maintain a pocket between the rotor  400  and the rotor encasement  402 . FIG. 11B illustrates that the rotor  400  is shorter in length than the rotor encasement  402  which creates a space between the bottom of the rotor  400  and the rotor encasement  402 . This design allows for spillage of the samples to drain down the sides of the rotor  400  and out the bottom of the shaft  406  to avoid sample contact with the mechanical parts of the apparatus. Sample contact with the mechanical parts of the apparatus, such as the belt  418  or pulley  416 , could corrode parts. 
     In another embodiment of disposable rotors, the rotors have one or more chambers for the retention of samples. This embodiment of the rotor decreases the likelihood of cross-contamination in sample preparations. The chambers are stacked on top of one another inside the disposable rotor. Each chamber, for example, can contain a sample, a precipitation agent, a buffer, and a mixing reagent or other liquid necessary for a particular protocol. An entire cell preparation can be accomplished without the sample ever leaving the rotor&#39;s chamber. 
     For example, a rotor with a first chamber containing plasmid DNA and its host  E. coli  cells suspended in a growth media and a second chamber containing a precipitation agent could be used to isolate DNA. The rotor is centrifuged and a cell pellet containing the DNA forms on wall of the rotor. At the end of centrifugation, supernatant is collected at the bottom of the rotor. The supernatant is aspirated from the first chamber. A re-suspension reagent, a lysis buffer and a neutralization buffer are each added individually, mixed with the DNA and its host  E. coli  cells and centrifuged. After this process is completed, a pellet made up of flocculants, such as a cell membrane, mitochondria, and other cell organelles, is formed on the wall of the first chamber and plasmid DNA is dissolved in the lysate at the bottom of the chamber. Typically, the next step in the isolation of DNA is removing the lysate containing the plasmid DNA and replacing or cleaning out the rotors before the DNA is further purified. In this embodiment of rotors, the lower half of the first chamber is punctured, and the lysate containing the DNA flows through into the second chamber leaving the pelletted flocculants behind. The precipitation agent in the second chamber is then mixed with the lysate containing the plasmid DNA. The centrifuge is actuated and spins the rotor, forming a DNA pellet on the wall of the rotor. When the centrifuge is brought to a standstill, there is a DNA pellet on the wall and alcohol at the bottom of the rotor. The alcohol is removed. 70% ethanol is added to wash the DNA. The mixture of 70% ethanol and DNA is centrifuged and the excess ethanol is removed. Water is added and the DNA is resuspended in it. This process results in purified DNA suspended in water with less likelihood of cross-contamination of the samples. 
     EXAMPLE 1 
     Plasmid DNA Isolation 
     The disclosed array centrifuge can be used in conjunction with a robotic workstation for the automated isolation of plasmid DNA (RevPrep™, GeneMachines, San Carlos, Calif.). The workstation includes, but is not limited to, a bulk reagent dispenser, a 96-channel pipetter, a server arm and the disclosed array centrifuge. All tools are available from GeneMachines, San Carlos, Calif. The workstation has a base, a deck, and a support column. In this configuration, the bulk reagent dispenser and 96-channel pipetter are connected to the support column, on which they move vertically. The disclosed array centrifuge and a wash station are bolted to the rotary deck, and at least one microwell plate sits on the deck, which moves the items thereon horizontally to interact with the tools on the column. LabVIEW™ Software (National Instruments™, Austin, Tex.) is programmed to run this configuration of the robotic workstation. 
     Plasmid DNA and its host  E. coli  cells suspended in a growth media are contained in a plurality of wells of a microwell plate. The microwell plate is placed on the deck of robotic workstation by a robotic server arm. The deck moves horizontally until the microwell plate is precisely aligned with the pipetter. The pipetter is vertically moved toward the deck, and it aspirates the samples of growth media and cloned plasmid DNA from the microwell plate. The pipetter is then moved to its original position. 
     The array centrifuge is located on the deck of the robotic workstation. The deck moves horizontally until the array centrifuge is precisely aligned with the pipetter. The pipetter is vertically moved toward the array centrifuge and deposits the samples into a plurality of rotors of the array centrifuge. The pipetter is then moved back to its original location. The array centrifuge is actuated, and the rotational rate of the rotors is increased from a standstill position to a maximum rotational rate of around 60,000 rpm in 20 seconds. This rotational rate is maintained for approximately 30 to 40 seconds. During this time, the cell pellet, forms on the interior wall of the rotor, and the supernatant with the plasmids collects towards the center of the rotor. The rotational rate is steadily decreased to a standstill over a period of two minutes and the supernatant is collected at the bottom of the rotor. This length of time limits turbulence and accidental re-suspension of the cells. The pipetter is then vertically moved towards the array centrifuge, the supernatant is aspirated, and the pipetter vertically moves back to its original position. 
     The deck then moves horizontally until the array centrifuge is precisely aligned with the bulk reagent dispenser. The dispenser moves vertically toward the array centrifuge and dispenses a resuspension reagent into the array of centrifuge rotors. The centrifuge rotors are rapidly accelerated and decelerated to resuspend the cells in the resuspension reagent. Twenty-five acceleration/deceleration cycles occur in as few as 20 seconds with the rotors approaching a top speed of about 20,000 rpm. Meanwhile, the bulk reagent dispenser has obtained and introduces Lysis buffer into the array of centrifuge rotors. The bulk reagent dispenser is then moved to its original position, while the rotors are then gently accelerated and decelerated to mix the re-suspended cells and the lysis buffer without disrupting the plasmid DNA, yet lysing cell membranes. The mixture is incubated for 3 to 5 minutes. 
     In the meantime, the bulk reagent dispenser has moved to the wash station where it rinses the pipette tips and aspirates neutralizing buffer. As the array centrifuge slows, it is moved to the pipetter, which dispenses neutralization buffer into the array of centrifuge rotors after it has come to a complete stop. The mixture is gently mixed by accelerating and decelerating the rotors and then incubated for 3 to 5 minutes. This brings the pH back to neutral before the plasmid DNA is denatured. The array centrifuge is actuated and the rotational rate of the rotors is increased from a standstill position to a maximum rotational rate of around 60,000 rpm in 20 seconds. This rotational rate is maintained for approximately 1 minute. The rotational rate is steadily decreased to a standstill over a period of two minutes. 
     A pellet forms on the interior wall of each centrifuge rotor and is made up of flocculants such as cell membranes, mitochondria, and other cellular organelles. Plasmid DNA dissolved in the lysate is located at the bottom of each rotor. Alcohol precipitation and centrifugation may further purify the plasmid DNA. 
     It is to be understood that the description above is intended to be illustrative and not restrictive. Many embodiments will be apparent to those of skill in the art upon reviewing the above description. The scope of the invention should be determined not with reference to the above description but should instead be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. 
     While the invention has been described in some detail by way of illustration, the invention is amenable to various modification and alternative forms, and is not restricted to the specific embodiments set forth. These specific embodiments are not intended to limit the invention but, on the contrary, the intention is intended to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention.