Abstract:
A system for at least one of homogenization and lysis of a sample includes one or more walls forming an enclosed chamber, a permanent magnet within the enclosed chamber, a magnet guide, and one or more magnets located outside the chamber. The enclosed chamber has an inlet and one or more fluidic connections configured to introduce at least the sample into the chamber. The permanent magnet has a positive pole and a negative pole. The magnet guide is configured to laterally guide the permanent magnet between a first position and a second position and maintain a substantially constant orientation of the permanent magnet during the movement. Movement of the magnets outside the chamber changes a magnetic field between the one or more magnets and the permanent magnet. The permanent magnet moves between the first and second positions in response to the changing magnetic field.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims the benefit under 35 U.S.C. §119(e), to provisional application No. 61/622,847 filed on Apr. 11, 2012, the disclosure of which is incorporated by reference herein in its entirety. 
     
    
     BACKGROUND 
       [0002]    1. Field 
         [0003]    Embodiments of the present invention relate to bead beaters. 
         [0004]    2. Background 
         [0005]    Given the complexity of the automation of molecular testing and immunoassay techniques, there is a lack of products that provide adequate performance to be clinically usable in near patient testing settings. Typical molecular testing includes various processes involving the correct dosage of reagents, sample introduction, sample homogenization, lysis of cells to extract DNA and/or RNA, purification steps, and amplification for its subsequent detection. Even though there are central laboratory robotic platforms that automate these processes, for many tests requiring a short turnaround time, the central laboratory cannot provide the results in the needed time requirements. 
         [0006]    The homogenization and/or lysis of a biological specimen is usually the initial step in a testing process such that a suitably purified analyte or analytes can be obtained for molecular testing. Generally speaking there are three main approaches to cell lysis: chemical, enzymatic and physical. These processes may be used alone or in combination, sequentially or in a single step, to achieve a more optimal process. The use of chemical and enzymatic processes can prove problematic as some chemicals used to rupture the cell wall can denature any enzymes present or generate problems in subsequent processes. 
         [0007]    Physical methods for cell rupture include sonication, heating (usually between 90° C.-100° C.), repeated freeze-thawing, creation of rapid and large changes in pressure and mechanical methods. Mechanical methods involve the physical rupture of the cell wall through physical forces such as high-shear forces, grinding, and bombardment of the cell with small particles, often consisting of beads. Mechanical methods of disruption have a number of advantages. They often employ a one-step process, are generally very rapid, are amenable to automation, and have the ability to disrupt solid specimens, such as bone, where the analyte(s) of interests may not be made obtainable without mechanical homogenization. 
       BRIEF SUMMARY 
       [0008]    Mechanical bead beater systems and methods that can be integrated with a near patient testing system are provided. 
         [0009]    In an embodiment, a system for at least one of homogenization and lysis of a sample includes one or more walls forming an enclosed chamber, a permanent magnet within the enclosed chamber, a magnet guide, and one or more magnets located outside the chamber. The enclosed chamber has an inlet and one or more fluidic connections configured to introduce at least the sample into the chamber. The permanent magnet has a positive pole and a negative pole. The magnet guide is configured to laterally guide the permanent magnet between a first position and a second position. The magnet guide is also configured to maintain a substantially constant orientation of the positive pole and the negative pole of the permanent magnet during the movement. Movement of the one or more magnets outside the chamber changes a magnetic field between the one or more magnets and the permanent magnet. The permanent magnet is configured to move between the first and second positions in response to the changing magnetic field. 
         [0010]    An example method of homogenizing a sample is described. The method includes introducing a sample into an enclosed chamber and actuating one or more magnets located outside the chamber. The magnetic field generated by the one or more magnets induces a force upon a permanent magnet disposed within the chamber, the permanent magnet having a positive pole and a negative pole. The induced force causes the permanent magnet to move. The method further includes laterally guiding the movement of the permanent magnet between a first position and a second position within the chamber. An orientation of the positive pole and the negative pole of the permanent magnet remains substantially constant during the movement. The method further includes homogenizing the sample within the chamber via the movement of the permanent magnet. 
         [0011]    Another example method of homogenizing a sample is described. The method includes introducing a sample into an enclosed chamber and actuating one or more magnets located outside the chamber. The magnetic field generated by the one or more magnets induces a force upon a permanent magnet disposed within the chamber, the permanent magnet having a positive pole and a negative pole. The induced force causes the permanent magnet to move. The method further includes laterally guiding the movement of the permanent magnet between a first position and a second position within the chamber. An orientation of the positive pole and the negative pole of the permanent magnet remains substantially constant during the movement. The movement of the permanent magnet excites a plurality of beads located within the chamber. The method further includes homogenizing the sample within the chamber via the movement of the permanent magnet and the plurality of beads. 
         [0012]    An example method of lysing a sample is described. The method includes introducing a sample into an enclosed chamber and actuating one or more magnets located outside the chamber. The magnetic field generated by the one or more magnets induces a force upon a permanent magnet disposed within the chamber, the permanent magnet having a positive pole and a negative pole. The induced force causes the permanent magnet to move. The method further includes laterally guiding the movement of the permanent magnet between a first position and a second position within the chamber. An orientation of the positive pole and the negative pole of the permanent magnet remains substantially constant during the movement. The method further includes lysing the sample within the chamber via the movement of the permanent magnet. 
         [0013]    Another example method of lysing a sample is described. The method includes introducing a sample into an enclosed chamber and actuating one or more magnets located outside the chamber. The magnetic field generated by the one or more magnets induces a force upon a permanent magnet disposed within the chamber, the permanent magnet having a positive pole and a negative pole. The induced force causes the permanent magnet to move. The method further includes laterally guiding the movement of the permanent magnet between a first position and a second position within the chamber. An orientation of the positive pole and the negative pole of the permanent magnet remains substantially constant during the movement. The movement of the permanent magnet excites a plurality of beads located within the chamber. The method further includes lysing the sample within the chamber via the movement of the permanent magnet and the plurality of beads. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS/FIGURES 
         [0014]    The accompanying drawings, which are incorporated herein and form a part of the specification, illustrate embodiments of the present invention and, together with the description, further serve to explain the principles of the invention and to enable a person skilled in the pertinent art to make and use the invention. 
           [0015]      FIG. 1  is a graphical representation of a test cartridge platform, according to an embodiment. 
           [0016]      FIGS. 2A-F  display various views of a bead beater system, according to an embodiment. 
           [0017]      FIGS. 3A-C  display various other views of the bead beater system, according to an embodiment. 
           [0018]      FIGS. 4A-B  display a permanent magnet and magnet covers, according to an embodiment. 
           [0019]      FIGS. 5-8  are diagrams illustrating methods performed by the bead beater system, according to an embodiment. 
           [0020]      FIG. 9  is a graph of Ct values from  Bacillus subtilis  spores. 
       
    
    
       [0021]    Embodiments of the present invention will be described with reference to the accompanying drawings. 
       DETAILED DESCRIPTION 
       [0022]    Although specific configurations and arrangements are discussed, it should be understood that this is done for illustrative purposes only. A person skilled in the pertinent art will recognize that other configurations and arrangements can be used without departing from the spirit and scope of the present invention. It will be apparent to a person skilled in the pertinent art that this invention can also be employed in a variety of other applications. 
         [0023]    It is noted that references in the specification to “one embodiment,” “an embodiment,” “an example embodiment,” etc., indicate that the embodiment described may include a particular feature, structure, or characteristic, but every embodiment may not necessarily include the particular feature, structure, or characteristic. Moreover, such phrases do not necessarily refer to the same embodiment. Further, when a particular feature, structure or characteristic is described in connection with an embodiment, it would be within the knowledge of one skilled in the art to effect such feature, structure or characteristic in connection with other embodiments whether or not explicitly described. 
         [0024]    Embodiments described herein relate to a bead beater system for homogenization and/or lysing of a sample. The sample may be a liquid, solid, semi-solid, or a combination thereof. In one embodiment, the bead beater system is integrated with a test cartridge platform. The test cartridge platform includes a network of fluidic channels, a portion of which may couple to the integrated bead beater. The fluidic channels may provide the sample to a bead beater chamber, extract the sample from the bead beater chamber, and/or be used to pressurize or depressurize the bead beater chamber. 
         [0025]    The bead-beater system is designed to use physical disruption of samples by the oscillation of, for example, a permanent magnet within the bead-beater chamber. This physical disruption may in turn be aided by the presence of beads (e.g., inert beads made of glass and/or other materials). In one example, the lysis and/or homogenization process is further optimized through the use of a lysis buffer within the bead beater chamber. In another example, enzymatic lysis is performed by applying heat to the sample. Heating the sample may be performed before the actual bead beating of the sample in some examples. In an embodiment, all the necessary reagents and components of the bead-beater are contained within the test cartridge platform. 
         [0026]    In some embodiments, both the test cartridge platform and the integrated bead beater are designed to be disposable after use. Once the reagents or the sample are placed within the integrated test cartridge, they do not again enter into contact with the external environment or with any part of an external measurement instrument. This feature is important for many laboratories and hospitals to safely dispose of the products after their use. 
         [0027]    The bead-beater chamber itself is designed to be able to process a wide variety of specimens and to disrupt a wide variety of cell types. This is, in part, achieved by the availability of different test cartridge platforms that are specific to each particular specimen/cell type combination. In another example, variable conditions that are controlled by the analyzer, such as the speed and duration of oscillation of the permanent magnet, allow for processing a wide variety of sample types. 
         [0028]    Further details relating to the components of the bead beater system are described herein with references made to the figures. It should be understood that the illustrations of each physical component are not meant to be limiting and that a person having skill in the relevant art(s) given the description herein would recognize ways to re-arrange or otherwise alter any of the components without deviating from the scope or spirit of the invention. 
         [0029]      FIG. 1  illustrates an example test cartridge system into which a bead beater may be integrated, according to an embodiment. Although reference will be made herein to the structure of the example test cartridge system, one of skill in the art will recognize that bead beater embodiments described herein may be used with any number of testing system types and configurations. 
         [0030]    The test cartridge system includes a cartridge housing  102 . Other components may be considered as well for inclusion it the test cartridge system, such as an analyzer module or various active components such as pumps or heaters. 
         [0031]    Cartridge housing  102  includes a variety of fluidic channels, chambers, and reservoirs. For example, cartridge housing  102  may include a plurality of storage chambers  116  which may contain various buffers or other reagents to be used during an assay or PCR protocol. Storage chambers  116  may be pre-filled with various liquids so that the end user will not need to fill storage chambers  116  before placing the test cartridge system into an analyzer. Cartridge housing  102  may further include one or more processing chambers  124   a - b  connected to fluidic channels along a side of cartridge housing  102 . Processing chambers  124   a - b  may be used for a variety of processing and/or waste applications. 
         [0032]    Samples are introduced into cartridge housing  102  via sample port  114 , according to an embodiment. A user may place a swab completely within sample port  114  and its corresponding chamber  124   b , and subsequently seal the port with a port lid  112 . In another example, sample port  114  receives solid, semi-solid, or liquid samples. In an embodiment, cartridge housing  102  includes more than one inlet to introduce samples. 
         [0033]    The various chambers and channels around cartridge housing  102  may be sealed via the use of covers  118 ,  126 , and  128 . The covers may be films capable of sealing the fluid within cartridge housing  102 . In another example, the covers may be plastic panels. In an example, one or more of the covers are transparent. Additionally, one or more of the covers may be thermally controlled for heating portions of housing  102 . 
         [0034]    The integrated test cartridge system allows a user to place a sample into, for example, sample port  114 , then place the test cartridge system into an analyzer. In embodiments, the reaction steps to be performed including, for example, purification, lysing, mixing, binding, labeling and/or detecting can all be performed within the test cartridge system via interaction with the analyzer without any need for the end user to intervene. Additionally, since all of the liquids remain sealed within the test cartridge system, after the test is completed, the test cartridge system may be removed from the analyzer and safely disposed of without contamination of the analyzer. 
         [0035]    The test cartridge system may further include fluidic channels which lead to an inner processing chamber having an opening  132 . In an embodiment, the inner processing chamber is an integrated bead beater chamber disposed within cartridge housing  102 . Although the chamber itself is hidden from view in  FIG. 1 , various other components of the system are shown in the exploded view. For example, the bead beater system includes a processing lid  134  that fits over opening  132 . Within the chamber itself, a permanent magnet  138  is disposed along with magnet covers  136   a - b , according to an embodiment. In another example, a single magnet cover may be used to surround permanent magnet  138 . The end of the bead beater chamber is closed using, for example, a panel cover  140 . Each of the components of the bead beater system will be explained in more detail herein. 
         [0036]      FIGS. 2A-F  illustrate various views of the bead beater system, according to embodiments. The description of each view is set forth to describe features that may be present on or within the bead beater system, but should not be limiting as to the placement or dimensional properties of the features. 
         [0037]      FIG. 2A  provides a perspective view of a bead beater  201  which can be integrated into a test cartridge system, such as example system  100 , according to an embodiment. The outer view of bead beater  201  displays panel cover  140  and processing inlet  132  as described previously. In one example, processing inlet  132  may be placed on a side of bead beater  201 . Processing inlet  132  is configured to accept any type of sample, including liquid, solid, semi-solid, or any combination thereof. Processing inlet  132  leads into an enclosed chamber where the bead beating process takes place. In another example, samples entering processing inlet  132  are lead to a first chamber, and then transferred from the first chamber into a second chamber where the bead beating process takes place. 
         [0038]    On one side of bead beater  201 , fluid inlets  203   a - b  are provided to couple with a fluidic system. For example, fluid inlets  203   a - b  may couple to channels connecting to any one of storage chambers  116  or processing chambers  124   a - b . In an embodiment, fluid inlets  203   a - b  lead into the chamber where the bead beading takes place. As such, fluid inlets  203   a - b  may be used for introducing any liquid into the bead beating chamber, extracting any liquid from the bead beating chamber, applying a pressure differential in the bead beating chamber, or any combination thereof. 
         [0039]    External to bead beater  201 , an actuator system  202  is attached to a beam  206 , according to an embodiment. In one example, actuator system  202  is a rotary actuator that applies a rotational force upon beam  206 . Actuator system  202  may receive various signals via coupling  204 . For example, the signals may include power or control signals. Coupling  204  may represent wires, RF signals, or optical signals. Actuator system  202  may rotate beam  206  at any speed within the capabilities of actuator system  202 . In one example, actuator system  202  rotates beam  206  at speeds ranging from 50 RPM to 8000 RPM. In another example, actuator system  202  rotates beam  206  at around 4000 RPM. 
         [0040]    Near either end of beam  206 , external magnets  208   a - b  are attached, according to an embodiment. External magnets  208   a - b  may have the same polarity or opposite polarities. As beam  206  rotates, external magnets  208   a - b  pass by an outside wall of bead beater  201  in an alternating manner. Thus, a changing magnetic field is generated between the rotating external magnets  208   a - b  and, for example, a permanent magnet (not shown) disposed within the chamber of bead beater  201 . 
         [0041]    In one embodiment, bead beater  201  may include a cavity through one of the walls of bead beater  201 . The cavity may be covered by a thermally conductive film, such as, for example, an aluminum foil. By heating the thermally conductive film, the contents within the inner processing chamber of bead beater  201  may be heated via the cavity. In another example, one of the walls of the inner processing chamber may be a thermally controlled surface to heat the contents of the inner processing chamber without requiring a cavity. Introducing heat into the inner processing chamber may allow for enzymatic lysis of a sample to occur. In one example, enzymatic lysis may be performed using an applied heat to a sample before the actual bead beating of the sample commences. 
         [0042]      FIG. 2B  provides a side cross-sectional view of bead beater  201  along with actuator system  202 , according to an embodiment. The view also illustrates a magnetic beater  214  disposed within an enclosed chamber  212  of bead beater  201 . Both processing inlet  132  and panel cover  140  are shown as well. 
         [0043]    In an embodiment, beam  206  is coupled to actuator system  202  by means of an axle  210  that attaches to the center of beam  206 . As previously described, the rotation of beam  206  alternates the passing of external magnets  208   a - b  outside of enclosed chamber  212 . Magnetic beater  214  is a permanent magnet having polarity. In an embodiment, magnetic beater  214  has a positive pole  215   a  and a negative pole  215   b . In an example, each pole of magnetic beater  214  faces either substantially towards or away from panel cover  140 . 
         [0044]    As beam  206  rotates, the magnetic force induced upon magnetic beater  214  either attracts or repels magnetic beater  214 . The attraction or repulsion of magnetic beater  214  causes magnetic beater  214  to move back and forth within enclosed chamber  212 . For example, external magnet  208   a  has a positive polarity and causes magnetic beater  214  to move away due to a magnetic repulsive force  216  between external magnet  208   a  and positive pole  215   a  of magnetic beater  214 . Magnetic beater  214  may be pushed against the back wall of enclosed chamber  212 . In another example, permanent magnet may be pushed to a stop position within enclosed chamber  212  before reaching the back wall. 
         [0045]    In one embodiment, one or more walls of enclosed chamber  212  are manufactured from metals having a high thermal conductivity such as aluminum, copper, etc., and can be thermally controlled. Introducing heat into the inner processing chamber may allow for enzymatic lysis of a sample to occur. In one example, enzymatic lysis may be performed using an applied heat to a sample before the actual bead beating of the sample commences. 
         [0046]      FIG. 2C  illustrates a situation where beam  206  has rotated to bring external magnet  208   b  outside of enclosed chamber  212 . Magnet  208   b  may have a negative polarity which induces a magnetic attractive force  218  upon magnetic beater  214  due to the attraction between external magnet  208   b  and positive pole  215   a  of magnetic beater  214 . Magnetic beater  214  may be pulled up against the inner wall of panel cover  140 . In another example, magnetic beater  214  may be pulled to a stop position within enclosed chamber  212  before reaching panel cover  140 . 
         [0047]    The lateral back and forth movement of magnetic beater  214  is guided by the geometry of enclosed chamber  212 , according to an embodiment. The geometry may be designed to prevent the face of positive pole  215   a  and negative pole  215   b  from flipping within enclosed chamber  212 . The movement frequency of magnetic beater  214  within enclosed chamber  212  is associated with the rotation speed of beam  206 . Samples placed within enclosed chamber  212  are lysed and/or homogenized by the movement of magnetic beater  214 . 
         [0048]      FIG. 2D  illustrates enclosed chamber  212  having a plurality of beads  220 , according to an embodiment. The beads may be included to aid in the homogenization and/or lysing process of a sample within enclosed chamber  212 . The back and forth lateral movement of magnetic beater  214  excites plurality of beads  220  into movement as well. Plurality of beads  220  may range in size from one micron in diameter up to 3000 microns in diameter. Additionally, plurality of beads  220  may be manufactured from various inert materials including plastics, glass, ceramics, and silica. 
         [0049]      FIG. 2E  illustrates another embodiment for actuating a set of external magnets  224   a - b . Horizontal beam  222  is connected to a linear actuator (not shown) and lateral back and forth movement of horizontal beam  222  passes external magnets  224   a - b  by an outside wall of bead beater  201  in an alternating manner, according to an embodiment. Similarly to the discussion above, each of external magnets  224   a - b  may have opposite polarities, causing magnetic beater  214  to move back and forth within enclosed chamber  212  of bead beater  201 . Other alternatives for external magnetic field actuation are also contemplated, such as using an electromagnet to produce an alternating electromagnetic field. 
         [0050]      FIG. 2F  illustrates another embodiment of bead beater  201  in which a sensor  226  has been included. Sensor  226  may be used to monitor the rate of movement of magnetic beater  214  within enclosed chamber  212 . The data collected from sensor  226  is helpful for determining whether magnetic beater  214  is in any way obstructed and/or not moving correctly within enclosed chamber  212 . Sensor  226  may be, for example, a magnetic sensor or an optical sensor that identifies movement of magnetic beater  214 . 
         [0051]      FIG. 3A  illustrates a view within enclosed chamber  212  of bead beater  201 , according to an embodiment. Magnetic beater  214  is shown surrounded by chamber walls. The geometry of the chamber walls includes lobes  302  and ridges  304  that act as magnet guides, according to an embodiment. Lobes  302  and ridges  304  may be utilized to provide a trefoil or quatrefoil cross-section to the chamber walls. Other arrangements are possible as well for the purpose of guiding the movement of magnetic beater  214 . In one example, a recess  301  is provided to accept panel cover  140 . 
         [0052]    Ridges  304  provide contact points for magnetic beater  214  and prevent magnetic beater  214  from flipping around within enclosed chamber  212 . Additionally, ridges  304  reduce wobbling of magnetic beater  214  as it moves laterally within enclosed chamber  212 . Ridges  304  may be made of the same material as the rest of chamber walls  302 , or may be a softer material, such as Teflon, to reduce mechanical stress on magnetic beater  214 . 
         [0053]    Lobes  302  provide adequate space around magnetic beater  214  for liquid and beads to move while magnetic beater  214  traverses enclosed chamber  212 . The geometry of the chamber walls may include any number of lobes  302 . The curvature and general size of lobes  302  may be chosen so as to reduce any dead volume within enclosed chamber  212  during the movement of magnetic beater  214 . In one example, the volume existing around magnetic beater  214  within enclosed chamber  212  is 1 ml, though other volumes may be considered as well. 
         [0054]      FIG. 3B  illustrates the interior of enclosed chamber  212  with magnetic beater  214  removed, according to an embodiment. A protruding element  306  may be included on a back wall of inner chamber  212  to act as a mechanical stop and minimize the contact area of magnetic beater  214  against the back wall. Protruding element  306  protects plurality of beads  220 , if included, from being crushed by magnetic beater  214 . Protruding element  306  may be any suitable shape and/or size to reduce the contact area as magnetic beater  214  is pushed against the back wall. A second protruding element may also be included on the inner wall of panel cover  140  (not shown). 
         [0055]      FIG. 3C  illustrates a perspective view of bead beater  201  along with processing lid  134  and panel cover  140 , according to an embodiment. Processing lid  134  may be dimensioned to seal processing inlet  132  so as to prevent any leakage through processing inlet  132 . Panel cover  140  fits into recess  301  to seal the enclosed chamber from the side. In an embodiment, panel cover  140  may be removed in order to remove any objects within the enclosed chamber, such as a permanent magnet. 
         [0056]      FIG. 4A  illustrates a side view of components of magnetic beater  214 , according to an embodiment. In an example, magnetic beater  214  includes permanent magnet  138  sandwiched between two magnet covers  136   a - b . Permanent magnet  138  may have a substantially cylindrical shape. Magnet covers  136   a - b  may be utilized to protect permanent magnet  138  from any damage due to collisions within the bead beater system. Magnet covers  136   a - b  may be made of a compliant material which can absorb the shock caused by magnetic beater  214  colliding with the inner walls or protruding elements  306  of enclosed chamber  212 . Magnet covers  136   a - b  may be coupled together via an adhesive or suitable locking mechanism. In another example, a single magnet cover is used or molded around permanent magnet  138 . 
         [0057]      FIG. 4B  illustrates another embodiment of magnetic beater  214 . Magnetic covers  136   a - b  may include cover protrusions  402   a - b . Cover protrusions  402   a - b  may provide the same mechanical stop benefits as described previously for protruding elements  306 . 
         [0058]      FIGS. 5-8  describe example methods to be employed for homogenizing or lysing a sample with or without beads, according to embodiments. It should be understood that methods  500 ,  600 ,  700 , and  800  describe example operation sequences that can be performed with bead beater  201 , and should not be considered limiting. Any of methods  800 ,  900 ,  1000 , and  1100  may also include a step of heating the contents within bead beater  201  to perform an enzymatic lysis. In one example, the enzymatic lysis is performed before the bead beating occurs. 
         [0059]      FIG. 5  displays a flowchart of an example method  500  for homogenizing a sample using bead beater  201 . 
         [0060]    At block  502 , at least the sample is introduced into an enclosed chamber. The sample may be introduced, for example, through processing inlet  132  or via fluid inlets  203   a - b . In an embodiment, a solid or semi-solid sample may be provided for homogenization. For example, samples with a high viscosity (e.g. sputum, tissue, bone) are well suited for homogenization to break down complex matrices that hold the cellular components of the sample together. 
         [0061]    At block  504 , one or more magnets disposed outside the enclosed chamber are actuated. The one or more magnets may be rotated by or linearly translated by an outer wall of the enclosed chamber. Additionally, the one or more magnets may have opposite polarities so as to alternate the direction of an induced magnetic field. Alternatively, an alternating electromagnet may be actuated outside of the enclosed chamber. 
         [0062]    At block  506 , a force is induced upon a permanent magnet disposed within the chamber. The force is generated due to either magnetic attraction or repulsion. 
         [0063]    At block  508 , the movement of the permanent magnet is laterally guided between a first position and a second position within the chamber due to the induced magnetic force. The force causes the permanent magnet to move within the chamber in a direction either towards or away from the magnet outside of the chamber walls. The first and second position may correspond to each end of the enclosed chamber. The geometry of the chamber facilitates the lateral movement of the permanent magnet, according to an embodiment. 
         [0064]    At block  510 , the sample is homogenized within the chamber via the movement of the permanent magnet. The homogenized sample may be lysed using bead beater  201  or transferred to another chamber for further processing. 
         [0065]      FIG. 6  displays a flowchart of an example method  600  for homogenizing a sample using bead beater  201  containing a plurality of beads. The included beads act to speed up the process of breaking down the sample. 
         [0066]    At block  602 , at least the sample is introduced into an enclosed chamber. The sample may be introduced, for example, through processing inlet  132  or via fluid inlets  203   a - b . In an embodiment, a solid or semi-solid sample may be provided for homogenization. For example, samples with a high viscosity (e.g. sputum, tissue, bone) are well suited for homogenization to break down complex matrices that hold the cellular components of the sample together. 
         [0067]    At block  604 , one or more magnets disposed outside the enclosed chamber are actuated. The one or more magnets may be rotated by or linearly translated by an outer wall of the enclosed chamber. Additionally, the one or more magnets may have opposite polarities so as to alternate the direction of an induced magnetic field. Alternatively, an alternating electromagnet may be actuated outside of the enclosed chamber. 
         [0068]    At block  606 , a force is induced upon a permanent magnet disposed within the chamber. The force is generated due to either magnetic attraction or repulsion. 
         [0069]    At block  608 , the movement of the permanent magnet is laterally guided between a first position and a second position within the chamber due to the induced magnetic force. The force causes the permanent magnet to move within the chamber in a direction either towards or away from the magnet outside of the chamber walls. The first and second position may correspond to each end of the enclosed chamber. The geometry of the chamber facilitates the lateral movement of the permanent magnet, according to an embodiment. 
         [0070]    At block  610 , a plurality of beads within the chamber are excited by the movement of the permanent magnet. The beads may vary in shape, size and/or material as described previously. The added movement of the beads within the chamber provide further beating of the sample and a more efficient homogenization process. 
         [0071]    At block  612 , the sample is homogenized within the chamber via the movement of the permanent magnet and the plurality of beads. The homogenized sample may be lysed using bead beater  201  or transferred to another chamber for further processing. 
         [0072]      FIG. 7  displays a flowchart of an example method  700  for lysing a sample using bead beater  201 . The objective of cell lysis is to release cellular contents which are required for analysis. Examples of cellular contents include, but are not limited to, DNA, RNA, polypeptides, enzymes, prions, proteins, antibodies, antigens, allergens, and virons. 
         [0073]    At block  702 , at least the sample is introduced into an enclosed chamber. The sample may be introduced, for example, through processing inlet  132  or via fluid inlets  203   a - b.    
         [0074]    At block  704 , one or more magnets disposed outside the enclosed chamber are actuated. The one or more magnets may be rotated by or linearly translated by an outer wall of the enclosed chamber. Additionally, the one or more magnets may have opposite polarities so as to alternate the direction of an induced magnetic field. Alternatively, an alternating electromagnet may be actuated outside of the enclosed chamber. 
         [0075]    At block  706 , a force is induced upon a permanent magnet disposed within the chamber. The force is generated due to either magnetic attraction or repulsion. 
         [0076]    At block  708 , the movement of the permanent magnet is laterally guided between a first position and a second position within the chamber due to the induced magnetic force. The force causes the permanent magnet to move within the chamber in a direction either towards or away from the magnet outside of the chamber walls. The first and second position may correspond to each end of the enclosed chamber. The geometry of the chamber facilitates the lateral movement of the permanent magnet, according to an embodiment. 
         [0077]    At block  710 , the sample is lysed within the chamber via the movement of the permanent magnet. The lysate may be transferred from the chamber to a second chamber via one of fluid inlets  203   a - b.    
         [0078]      FIG. 8  displays a flowchart of an example method  800  for lysing a sample using bead beater  201  containing a plurality of beads. The objective of cell lysis is to release cellular contents which are required for analysis. Examples of cellular contents include, but are not limited to, DNA, RNA, polypeptides, enzymes, prions, proteins, antibodies, antigens, allergens, and virons. The included beads act to speed up the process of tearing the cell walls to release the cellular contents. 
         [0079]    At block  802 , at least the sample is introduced into an enclosed chamber. The sample may be introduced, for example, through processing inlet  132  or via fluid inlets  203   a - b.    
         [0080]    At block  804 , one or more magnets disposed outside the enclosed chamber are actuated. The one or more magnets may be rotated by or linearly translated by an outer wall of the enclosed chamber. Additionally, the one or more magnets may have opposite polarities so as to alternate the direction of an induced magnetic field. Alternatively, an alternating electromagnet may be actuated outside of the enclosed chamber. 
         [0081]    At block  806 , a force is induced upon a permanent magnet disposed within the chamber. The force is generated due to either magnetic attraction or repulsion. 
         [0082]    At block  808 , the movement of the permanent magnet is laterally guided between a first position and a second position within the chamber due to the induced magnetic force. The force causes the permanent magnet to move within the chamber in a direction either towards or away from the magnet outside of the chamber walls. The first and second position may correspond to each end of the enclosed chamber. The geometry of the chamber facilitates the lateral movement of the permanent magnet, according to an embodiment. 
         [0083]    At block  810 , a plurality of beads within the chamber are excited by the movement of the permanent magnet. The beads may vary in shape, size and/or material as described previously. The added movement of the beads within the chamber provide further beating of the cells and lead to a more efficient lysing process. 
         [0084]    At block  812 , the sample is lysed within the chamber via the movement of the permanent magnet and the plurality of beads. The lysate may be transferred from the chamber to a second chamber via one of fluid inlets  203   a - b.    
       Example 
       [0085]    An Example protocol to be performed using embodiments of bead beater  201  is now discussed. The protocol is an example only and is not limiting on embodiments of the present invention. The lysing efficiency of the bead beater with different bead sizes is analyzed based on DNA detection. It should be understood that the steps recited here provide just one possible example for using the system. 
         [0086]      Bacillus subtilis , known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium. A member of the genus  Bacillus; B. subtilis  is rod-shaped, and has the ability to form a tough, protective endospore, allowing the organism to tolerate extreme environmental conditions. Endospores of various Bacillus species are formed in sporulation, a process that is generally induced by reduced levels of nutrients in the environment. Endospores contain an outer spore cortex that is extremely resistant to harsh physical and chemical treatments making it challenging to identify a spore lysis method that can be completed in a few minutes. 
         [0087]    An example protocol for lysing the cells of  Bacillus subtilis  is adapted from W. Nicholson and P. Setlow,  Molecular Biological Methods for Bacillus , New York, John Wiley, pp. 391-450, 1990. In this example protocol, a 100 mL culture of  Bacillus subtilis  subsp.  spizizenii  (ATCC 6633) grown in sporulation medium (SM) is vortexed, then separated in two volumes of 50 mL. After centrifugation at 3750 g for 15 minutes, the pellets are washed three to five times with 50 mL sterile cold distilled water, each wash being centrifuged at 3750 g for 15 minutes. The final pellets are re-suspended in 50 mL of sterile cold distilled water. Spore suspensions are treated with DNase to remove external residual DNA, quantified and diluted to a final concentration of 5×10 9  endospores/mL. Serial 10-fold-dilutions are prepared (1×10 4 , 1×10 3 , 1×10 2 , and 10 endospores/mL) in nucleases free water to be used as a starting material in the fluidically integrated magnetic bead beater. 
         [0088]    First, 400 mg of sterile, acid washed glass beads are introduced into the bead beater chamber. Second, a 400 μL endospores dilution is transferred to the bead beater chamber via the processing inlet. The magnets on the outside of the bead beater are rotated at around 4000 RPM for about 1 minute to perform lysis on the cells within the bead beater chamber. Bacterial nucleic acids are released when spores are disrupted by the mechanical action of the bead beater. Nucleic acid extractions remain stable for several months when stored frozen at −80° C. or −20° C. and may be frozen and thawed several times without any significant loss in PCR analytical sensitivity. 
         [0089]    Amplification and detection of DNA from  Bacillus subtilis  endospores at different starting concentrations is performed on the StepOnePlus™ Real-Time PCR System from Applied Biosystems with the TaqMan® Universal master mix II no UNG, with Taq Gold polymerase (from Applied Biosystems, ref 4440040), according to the manufacturer&#39;s instructions. 1.5 μL of prepared lysate is added directly to a qPCR reaction having 1× TaqMan® Universal master mix II no UNG with Taq Gold polymerase, 0.90 μM of each SpoA  Bacillus subtilis -specific primer, 0.25 μM of SpoOA TaqMan® probe, and 0.8 mg/mL BSA; in a final volume of 15 μL. In parallel, spores without processing are tested as untreated controls (at the same concentrations). 1.5 μL of distilled water is also added to a qPCR reaction as a negative control. The optimal cycling conditions for maximum sensitivity and specificity are 10 minutes at 95° C. for initial denaturation, then fifty cycles of two steps consisting of 15 seconds at 95° C. and 60 seconds at 60° C. Amplification is monitored during each elongation cycle by measuring the level of fluorescence. Table 1 below provides the SpoOA  Bacillus subtilis -specific primers and probe sequence used in the TaqMan® qPCR reaction. 
         [0000]    
       
         
               
               
               
               
             
           
               
                 TABLE 1 
               
               
                   
               
               
                   
                   
                   
                 Product 
               
               
                   
                   
                 Length 
                 size 
               
               
                 Primer 
                 Sequence (5′-&gt;3′) 
                 (bp) 
                 (bp) 
               
               
                   
               
             
             
               
                 SpoOA F 
                 ccatcatcgcaaagcagtatt 
                 21 
                 70 
               
               
                   
               
               
                 SpoOA R 
                 tgggacgccgatttcatg 
                 18 
                   
               
               
                   
               
               
                 SpoOA 
                 ctcgacgcgagcatcacaagcatt 
                 24 
                   
               
               
                 probe 
               
               
                   
               
             
          
         
       
     
         [0090]      FIG. 9  provides a graph of the Ct values (number of PCR cycles needed to produce a positive signal) for samples processed with various sizes beads, and untreated samples, at four different  B. subtilis  starting concentrations. Results are a mean of 10 replicates at each concentration. 
         [0091]    At low  Bacillus subtilis  concentrations (10 and 1×10 2  endospores/mL), Ct values were lower in the presence of 150-212 μm diameter beads (higher DNA concentration) compared to the &lt;106 μm diameter bead conditions, increasing the sensitivity of the process. At higher concentrations (1×10 3  and 1×10 4  endospores/mL) no difference was observed between the two bead sizes tested. The larger bead size (150-212 μm diameter) consistently produced lower Ct values than the untreated samples for each starting concentration of  Bacillus subtilis , while the smaller bead size (&lt;106 μm diameter) produced lower Ct values than the untreated samples only for the higher starting concentrations (1×10 3  and 1×10 4  endospores/mL.) Untreated samples were undetectable at the lowest  Bacillus subtilis  concentration (10 endospores/mL.) 
         [0092]    The best results in terms of sensitivity and lysis efficiency are observed with the fluidically integrated magnetic bead beater having 150-212 μm diameter silica beads, in this example. 
         [0093]    The foregoing description of the specific embodiments will so fully reveal the general nature of the invention that others can, by applying knowledge within the skill of the art, readily modify and/or adapt for various applications such specific embodiments, without undue experimentation, without departing from the general concept of the present invention. Therefore, such adaptations and modifications are intended to be within the meaning and range of equivalents of the disclosed embodiments, based on the teaching and guidance presented herein. It is to be understood that the phraseology or terminology herein is for the purpose of description and not of limitation, such that the terminology or phraseology of the present specification is to be interpreted by the skilled artisan in light of the teachings and guidance. 
         [0094]    Embodiments of the present invention have been described above with the aid of functional building blocks illustrating the implementation of specified functions and relationships thereof. The boundaries of these functional building blocks have been arbitrarily defined herein for the convenience of the description. Alternate boundaries can be defined so long as the specified functions and relationships thereof are appropriately performed. 
         [0095]    The Summary and Abstract sections may set forth one or more but not all exemplary embodiments of the present invention as contemplated by the inventor(s), and thus, are not intended to limit the present invention and the appended claims in any way. 
         [0096]    The breadth and scope of the present invention should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the following claims and their equivalents.