Instrument for cassette for sample preparation

A parallel processing system for processing samples is described. In one embodiment, the parallel processing system includes an instrument interface parallel controller to control a tray motor driving system, a close-loop heater control and detection system, a magnetic particle transfer system, a reagent release system, a reagent pre-mix pumping system and a wash buffer pumping system.

FIELD

The present invention relates to the field of biotechnology devices and, in particular, to devices and methods for preparing samples.

BACKGROUND

DNA can be used to develop new drugs or to link someone to a crime. However, before this can be done, the DNA must be isolated from a sample. These samples include, for example, blood, urine, human cells, hair, bacteria, yeast and tissue. Each of these samples include cells, which include nucleic acid. Nucleic acid is a nucleotide chain, which conveys genetic information. The most common forms of nucleic acid are DNA and RNA.

In order to isolate the nucleic acid from the samples, prior art devices use a tray having several exposed cavities. The sample is placed into one of the cavities and conventional processing steps are used to isolate the DNA from the sample.

This prior art system has several disadvantages, including contamination, and inability to perform parallel processing or asynchronous processing. Since the cavities are exposed, contaminants can easily affect the DNA. In addition, the prior art system requires the preparation of several samples at one time. In addition, these prior art systems require a significant amount of time to process multiple samples.

SUMMARY

In one embodiment, the present invention relates to an instrument for preparing samples. The instrument includes, for example, a parallel tray motor driving system; a close-loop heater control and detection system; a parallel magnetic particle transfer system; a parallel reagent release system; a reagent parallel pre-mix pumping system; a parallel wash buffer pumping system; and an instrument interface controller to control the biological sample processing instrument that includes the parallel tray motor driving system, the close-loop heater control and detection system, the parallel magnetic particle transfer system, the parallel reagent release system, the parallel reagent pre-mix pumping system, and the parallel wash buffer pumping system.

In another embodiment, the present invention relates to a system for preparing samples. The system includes, for example, an enclosure; a parallel tray motor driving system in the enclosure to insert one or more magazines which contain one or more cassettes into the enclosure, the cassette having a sample therein; a close-loop heater control and detection system in the enclosure; a parallel magnetic particle transfer system in the enclosure; a parallel reagent release system in the enclosure; a parallel reagent pre-mix pumping system in the enclosure; and a parallel wash buffer pumping system in the enclosure.

DETAILED DESCRIPTION

FIG. 1illustrates an instrument100in accordance with one embodiment of the invention. In one embodiment, the instrument100is a parallel processing system.

The illustrated instrument100includes a display104and openings108. The openings108are configured to receive magazines120. The magazines120each contain a series of cassettes124. Each cassette includes a sample of cells to be prepared. A protocol may be selected by a user at the display104for preparing the sample in the cassette124within the instrument100. The instrument100then automatically prepares the sample within the instrument according to the selected protocol.

In the embodiment illustrated inFIG. 1, the instrument can process four magazines120, each magazine120having twelve cassettes124, each cassette having a sample of cells therein at the same time according to the selected protocol. It will be appreciated, however, that fewer than forty-eight or greater than forty-eight samples can be processed at a time.

FIG. 2illustrates a magazine200in further detail. In one embodiment, the magazine200is the magazine120ofFIG. 1. In one embodiment, the magazine200is a rack. Several cassettes224(e.g., cassettes124fromFIG. 1) are placed into the magazine200.

FIG. 3illustrates a cassette300in further detail. In one embodiment, the cassette300is the cassettes124inFIG. 1and/or cassettes224inFIG. 2. The cassette300can be used to prepare cell samples.

FIG. 4is a detailed view of the cassette ofFIG. 3. The cassette400includes a housing412, a mixing chamber414, first, second, third and fourth holding chambers416,418,420and422, first, second, third and fourth plungers424,426,428and430, first, second and third valves432,434and436, first and second washing chambers438and440, an elution chamber442, first, second, third and fourth pumps444,446,448and450, first and second lids452and454, first and second heating elements456and458and a magnetic460. Each of the chambers414,416,418,420,422,438,440and442, plungers424,426,428and430, valves432,434,436, pumps444,446,448and450, and heating elements456and458are enclosed within the housing412. The lids452and454are movably attached to the housing412. The magnet460is removably positionable in the first valve432, second valve434and third valve436.

The mixing chamber414has a top surface462, a bottom surface464and opposing side surfaces466,468. The top surface462of the mixing chamber414includes an opening470therein.

The first lid452is configured to provide access to the opening470in the top surface460of the mixing chamber414. The first lid452and the opening470are coaxial. The first lid452is shown being movably attached to the housing412, such that when the lid452is open or off, the opening470is accessible and if the lid452is closed or on, the opening470is not accessible.

A thin film474forms one wall of the mixing chamber414. The thin chamber474is breakable, such that the mixing chamber414is accessible when the thin film474has been broken or ruptured.

The first holding chamber416, second holding chamber418, third holding chamber420and fourth holding chamber422are shown located next to the mixing chamber414and aligned vertically with one another. Each of the holding chambers416,418,420,422has an opening476next to the thin film474of the mixing chamber414.

The cassette400further includes magnetic iron particles in the form of magnetic beads in the first holding chamber416. The cassette400further includes a binding solution in the second holding chamber418. The cassette400further includes a lysis solution in the third holding chamber420. The cassette400further includes a proteinase K (PK) solution in the fourth holding chamber422. The magnetic iron particles (in the form of magnetic beads), lysis solution, binding solution, and proteinase K (PK) can also be provided in any chamber of the cassette400based on desired protocol.

The first, second, third and fourth plungers424,426,428and430are located in the first, second, third and fourth holding chambers416,418,420and422, respectively.

Each of the plungers416,418,420,422includes a base478, a shaft480and a piercing element482. The shaft480extends from the base478. The piercing element482is at the end of the shaft480opposing the base478and is pointed. The piercing element482is configured to break or rupture the thin film474of the mixing chamber414.

The first pump444is a bellows pump having a pumping portion and a nozzle portion. The nozzle portion of the first pump444is located inside the mixing chamber414. The pumping portion of the first pump444is located outside the mixing chamber, such that the pumping portion is actuatable.

A heating element456is provided at the bottom surface464of the mixing chamber414for heating the contents of the mixing chamber414. The heating element456may be a variable heating element.

The opposing side surface468of the mixing chamber414also includes an opening484. A first valve432is provided between the opening484in the side468of the mixing chamber414and the first washing chamber438.

The first valve432has a first stationary piece486and a second moveable piece488, the second piece488being moveable relative to the first piece486. The first stationary piece486includes a first opening490and a second opening492and has a surface494. The second piece488has an opening495therein for receiving the magnet460. The second piece488has a surface496with a cavity498therein. The magnet460is shaped to correspond to the opening495in the second piece488. The magnet460is moveable in the opening495of the second piece488, and is removable from the second piece488.

The cassette400includes a washing solution in the first washing chamber438. The second pump446is also a bellows pump, and the nozzle portion of the second pump446is located in the first washing chamber438.

The second valve434is provided between the first washing chamber438and the second washing chamber440. The second valve434is structurally and functionally the same as the first valve432, and also includes a first stationary piece486and a second moveable piece488. The first stationary piece486includes a first opening490and a second opening492and has a surface494. The second moveable piece has a surface496with a cavity498therein.

The cassette400includes a washing solution in the second washing chamber440. The third pump448is also a bellows pump, and the nozzle portion of the third pump448is located in the second washing chamber440.

The third valve436is provided between the second washing chamber440and the elution chamber442. The third valve436is structurally and functionally the same as the first valve432, and also includes a first stationary piece486and a second moveable piece488. The first stationary piece486includes a first opening490and a second opening492and has a surface494. The second moveable piece has a surface496with a cavity498therein.

The cassette400includes a washing solution in the elution chamber442. The fourth pump450is also a bellows pump, and the nozzle portion of the fourth pump450is located in the elution chamber442.

A heating element458is provided at the bottom surface of the elution chamber442for heating the contents of the elution chamber442. The heating element458may be a variable heating element.

The elution chamber442includes an opening499at its top surface for accessing the contents of the elution chamber442.

The second lid442is configured to provide access to the opening499in the top surface of the elution chamber442. The second lid454is coaxial with the opening499. The second lid454is shown being movably attached to the housing412, such that when the lid454is open or off, the opening499is accessible and if the lid454is closed or on, the opening499is not accessible.

In use, the first lid452is removed to provide access to the opening470of the mixing chamber414. A sample of cells is placed into the cassette400and, in particular, into the mixing chamber414. The cells in the sample include nucleic acid.

The PK solution is then added to the sample. The PK solution is added by moving the plunger430in the fourth holding chamber422. A force is applied to the base478of the plunger430to move the plunger430. As the piercing element482of the plunger430advances toward the mixing chamber414, the piercing element482punctures and ruptures the thin film474. The break in the thin film474provides access to the mixing chamber414. Continued motion of the plunger430transfers the contents (e.g., PK solution) of the first holding chamber422into the mixing chamber414.

The PK solution is mixed with the sample by pumping the mixture with, for example, the first pump444. The PK solution breaks up/destroys the walls of the cells of the sample, creating bulk material and nucleic acid in the bulk material.

The lysis solution is then added to the sample in a manner similar to the PK solution. The lysis solution is typically a salt or detergent. The lysis solution is used to solulibize the bulk material. The lysis solution typically does not solulibize proteins.

The heating element456may be used to heat the lysis solution and sample. As described hereinabove, the temperature of the heating element456may be variable, and is selected to optimize the effectiveness of the lysis solution.

The binding solution is then added to the sample, PK solution and lysis buffer solution. The binding solution is typically hydrophobic and increases salt in the solution. The binding solution causes the nucleic acid to be magnetically charged.

The magnetic beads are then added to the solution and pumped. The magnetic beads bind to the magnetically charged nucleic acid.

The magnetic beads, together with the nucleic acid, are bound to the first valve432. The removable positionable magnet460is placed in the first valve432and slid to a position in the first valve432to attract the magnetic beads, which are bound to the nucleic acid, from the mixing chamber414to the first valve432.

The magnetic beads, together with the nucleic acid, are then moved from the mixing chamber414and received in the first washing chamber438.

The magnet460is inserted into the opening494of the second piece488. The magnet460is inserted to a position corresponding to the openings490and492of the first piece486. The magnet460attracts the magnetic beads from the mixing chamber414through the opening490in the first piece486and into the cavity498in the second piece488. The second piece488is rotated such that the magnetic beads are sealed in the cavity498of the second piece488, between surfaces of the second piece488and the first piece486. The second piece488is rotated past the surface494of the first piece486, such that the cavity498is accessible in the opening492of the first piece486. The magnet460is then removed from the opening494in the second piece488to release the magnetic beads from the cavity498in the second piece488.

The magnetic beads and nucleic acid are then washed with the washing solution by pumping the solution with the second pump446. The magnetic beads, together with the nucleic acid, are then bound to the second valve434by inserting the magnet460into the second valve434.

The magnetic beads, together with the nucleic acid, are then moved from the first washing chamber438to the second washing chamber440using the second valve434. The second valve434transfers the magnetic beads and nucleic acid from the first washing chamber438to the second washing chamber440.

The magnetic beads and nucleic acid are then washed with the washing solution a second time by pumping the solution with the third pump448. The magnetic beads, together with the nucleic acid, are then bound to the third valve436by positioning the magnet460in the third valve436.

The magnetic beads and nucleic acid are then moved from the second washing chamber440to the elution chamber442. The magnetic beads and nucleic acid are transferred from the second washing chamber440to the elution chamber442.

An elution buffer solution is then mixed with the magnetic beads and nucleic acid by pumping the solution with the fourth pump450. The heating element458may be used to heat the elution buffer, magnetic beads and nucleic acid. The temperature may be variable and may be selected to optimize release of the nucleic acid from the magnetic beads.

The magnetic beads alone are then bound again to the third valve436by positioning the magnet460in the third valve436.

The magnetic beads alone are then moved from the elution chamber442back into the second washing chamber440, leaving the nucleic acid in the elution chamber442. The magnetic beads are transferred from the elution chamber442to the second washing chamber440.

The prepared sample of nucleic acid may be accessed from the opening499in the elution chamber442. The second lid54is removed to provide access to the opening499in the elution chamber42.

In one embodiment, a pipette or a multi-channel pipette may be used to place the sample in the cassette and/or access the sample or a plurality of samples in the cassette(s).

It will be appreciated that the cassette may vary from that illustrated and described above. For example, seals may be provided in the cassette as need. In another example, although the cassette400has been described as having a mixing chamber414, two washing chambers438and440and an elution chamber442, it is envisioned that only one washing chamber or no washing chamber may alternatively be provided.

In another example, the valves may have a different arrangement than that described above. In another example, although the cassette has been described as using a single removable magnet460, it is envisioned that each valve may include a positionable magnet, such that the magnet does not need to be removed. The magnet460may be rotatable, and used to rotate the second piece of the valves. Alternatively, the magnet may only slide inside of each of the valves, and the second piece is rotated independent of the magnet. It is envisioned that a cassette400that does not use valves as described herein may be used to transfer the magnetic particles from the mixing chamber to the elution chamber. In such an embodiment, a slideable magnet may be provided to transfer the magnetic particles from one chamber to the next.

It is envisioned that the housing412may be transparent, such that the procedure can be viewed. In one embodiment the thin film474is a lamination. In one embodiment, the lids452and454may be screw-top lids. In one embodiment, the lids452,454include a hydrophobic membrane, which allows gasses to vent through the lid, but does not allow the liquids to escape the cassette400. In one embodiment, pump450is insertable into opening499. In one embodiment, pump450can also be used as a pipette to remove the sample from the cassette400. It is also envisioned that the mixing chamber414may be provided without a puncturable thin film474. In such an embodiment, the plungers424,426,428and430would not need a piercing element482. Instead, the plungers424,426,428and430would have a sealing element to prevent leakage of the contents of the holding chamber416,418,420and422, associated with each plunger424,426,428and430, respectively, until the plunger was moved.

In one embodiment, a total of about 200 μL sample is placed into the cassette. The sample is mixed with a total of about 50 μL of the PK solution by pumping the mixture of the sample and PK solution for about one minute. A total of about 200 μL of the lysis solution is added to the sample and PK solution, and the solutions are pumped for about one minute to mix the solutions. The mixture is then heated at about 60° C. for about ten minutes, and the mixture is allowed to cool for about 5 minutes. The mixture is further pumped while it cools. A total of about 500 μL of binding solution is added to the mixture. The solutions are pumped for about one minute. The magnetic beads are added to the solution and pumped for about two minutes. The magnetic beads are transferred and washed as described above. A total of about 700 μL of washing solution is provided in each of the washing chambers. A total of about 200 μL of elution solution is provided in the elution chamber. The magnetic beads are mixed with the elution solution by pumping the mixture for about one minute. The mixture is then heated at about 90° C. for about two minutes. The process continues as previously described. It will be appreciated that the amounts, times and temperatures described above may vary from that described above.

Although the cassette400has been described as using a PK solution, lysis solution, binding solution and magnetic beads to release the nucleic acid and magnetic beads, it is envisioned that it may be possible to practice the invention without using each of the above solutions. In addition, although the solution was described as using a PK solution to break up the cells, it is envisioned that any enzyme which causes cells to break up to release nucleic acid may be used with the invention. Furthermore, it will be appreciated that additional solutions may be provided, as needed, to prepare the sample. One of skill in the art will also understand that the cassette400may be modified to have fewer holding chambers if fewer solutions are used or additional holding chambers if additional solutions are used.

FIG. 5illustrates another embodiment of an instrument500in accordance with one embodiment of the invention. It will be appreciated that the magazine and cassettes described herein with reference toFIGS. 2-4can be used with the instrument500. The instrument500allows for parallel processing of one or more samples within a closed, sterile environment.

Instrument500includes an enclosure502, an instrument handle504, stackable holders506, an instrument module508, a computer module510, a touch panel display512, an instrument run time indicator514, first and second automatic eject/load trays516,518, first and second tray doors520,522, and first and second tray safety guards524,526.

The instrument module508is within the enclosure502and is configured to perform the protocol selected to prepare the sample. The protocol is selected by the user using the touch screen display512. In one embodiment, the display512is a touch screen display. For example, the display512may be, for example, a 7″ to 12″ touch screen LCD display. The user's selection at the display512is communicated to the computer module510which communicates with the instrument module508via a controller area network bus (CAN-BUS) to coordinate processing within the instrument500.

The stackable holders506enable multiple instruments500to be stacked on top of one another such that even more samples can be processed at any given time. In one embodiment, one computer module510and display512may be provided to control processing within multiple stacked instruments.

The first and second automatic eject/load trays516,518are configured to receive a magazine (e.g., magazine200) having one or more cassettes therein (e.g., cassette400). The magazines are automatically loaded into the instrument500by the automatic eject/load trays516,518. The first and second cassette doors520,522are closed and engage with the first and second tray safety guards524,526to secure the magazine and cassettes within the enclosure502of the instrument500for preparation of the sample. It will be appreciated that in alternative embodiments the trays516,518and/or doors520,522may be manually opened and closed.

In one embodiment, the instrument run time indicator514is an LED or other exemplary light source. The instrument run time indicator514is illuminated to indicate to a user about the instrument ID and run status. In one embodiment, the computer module510provides an indication to the instrument run time indicator514to illuminate the communication status between the controller and the instrument.

FIG. 6Ais a block diagram of the system components600of the instrument500. The system components600include, a main computer602, a display panel604, a sub-system computer606, an instrument interface parallel controller608, an instrument real time microcontroller unit (MCU)610, a cooling system612, a tray motor driving system614, a heater control and detection system616, a magnetic particle transfer system618, a reagent release system620, a reagent pre-mix pumping system622and a wash buffer pumping system624.

Each of the cooling system612, tray motor driving system614, heater control and detection system616, magnetic particle transfer system618, reagent release system620, reagent pre-mix pumping system622and wash buffer pumping system624communicate with the instrument interface parallel controller608. In one embodiment, the instrument interface parallel controller is configured to control the subsystems612-624such that up to twenty-four samples can be prepared at a given time. It will be appreciated, however, that the instrument can be configured to prepare fewer than or greater than twenty-four samples. It will be appreciated that the system components600communicate with one another to enable parallel processing of the sample(s) within the instrument500.

The instrument interface parallel controller608also communicates with the instrument real time MCU610, the cooling system612and the sub-system computer606. The sub-system computer606communicates with the main computer602. The main computer602communicates with the touch screen display panel604.

In one embodiment, the main computer602, sub-system computer606, and/or the instrument interface parallel controller608are a digital processing system. The digital processing system may include a microprocessor, an ASIC (application specific integrated circuit), FPGA (field-programmable gate array), DSP (digital signal processor), or the like. In one embodiment, the display panel604is a 7″ high definition (HD) liquid crystal display (LCD) with a touch panel. The display panel604is on an external surface of the instrument500such that the user can interact with the display panel604. The main computer602may be a stand alone system that includes the computer module510and display512. The sub-system computer606and instrument interface parallel controller608are within the enclosure502of the instrument500. As described above with reference toFIG. 5, the user can select a protocol for processing the sample(s) with the display panel604. The display panel604communicates the user selection to the main computer602, sub-system computer606and/or parallel controller608to perform the protocol using the tray motor driving system614, heater control and detection system616, magnetic particle transfer system618, reagent release system620, reagent pre-mix pumping system622and wash buffer pumping system624.

In one embodiment, the tray motor driving system614is configured to control the automatic load/eject trays516,518(fromFIG. 5) and cassette doors520,522to automatically load the cassettes (e.g., cassette400) for processing and eject the cassettes when processing of the sample is completed.

In one embodiment, the heater control and detection system616is configured to control and detect the temperature of the cassette or cassettes. The heater control and detection system may also control the heaters within the cassette to perform a close loop temperature ramping and detection. Alternatively or in addition to controlling the heaters within the cassette, the heater control and detection system614may include heaters that are configured as a programmable temperature controller to heat the contents of the cassette to a predefined temperature, as needed, according to the selected protocol.

In one embodiment, the magnetic particle transfer system618is configured to transfer magnetic particles within the cassette (e.g., cassette400) according to the selected protocol. In one embodiment, the magnetic particle transfer system618manipulates the valves432,434,436to transfer the magnetic particles as described above with reference toFIG. 4.

In one embodiment, the reagent release system620is configured to release the reagents within the cassette. For example, the reagent release system is configured to release the PK solution, lysis solution, binding solution and magnetic beads from their respective holding chambers416,418,420and422and into the mixing chamber414, as described above with reference toFIG. 4.

In one embodiment, the reagent pre-mix pumping system622is configured to mix the reagents in the mixing chamber414as described above with reference toFIG. 4.

In one embodiment, the wash buffer pumping system624is configured to pump the washing solution in the cassette, as described above with reference toFIG. 4. For example, the wash buffer pumping system624may be configured to actuate the pumps446,448,450in the wash chambers438,440and elution chamber442.

FIG. 6Billustrates a block diagram of a digital system630in accordance with one embodiment of the invention. The illustrated digital system630includes a system controller module (SCM)632, a first instrument module (IM)1634, a second instrument module (IM)2636and a nth instrument module (IM) N638. The SCM632controls each of the IM1634, IM2636and up to an nth IM N638. it will be appreciated that the SCM632may control any number of IMs as represented by N. Thus, N may be any number from 0 up to 100 or even more.

FIG. 6Cis a block diagram illustrating the system controller module632ofFIG. 6Bin further detail. The system controller module632includes a main processor unit640, a Complex Programmable Logic Device (CPLD)642, a Liquid Crystal Display (LCD)644, a Synchronous Dynamic Random Access Memory (SDRAM)646, a NOR flash648, a NAND flash650, a Storage Device (SD) card652, a Universal Asynchronous Receiver-Transmitter (UART)654, a CANBUS656, a Universal Serial Bus (USB)658, an Ethernet660and a system bus662to couple each of the components640-662.

The bus662or other internal communication means is for communicating information, and the main processor unit640is coupled to the bus662for processing information. SDRAM646, NOR flash648, NAND flash650, and SD card652(referred to as memory) are for storing information and instructions to be executed by the main processor unit640, for storing temporary variables or other intermediate information during execution of instructions by main processor unit640, for storing static information and instructions for main processor unit640, and the like.

The system may further be coupled to a display device, such as a cathode ray tube (CRT) or a liquid crystal display (LCD)644, coupled to bus662through bus662for displaying information to a computer user. An alphanumeric input device675, including alphanumeric and other keys, may also be coupled to bus662through bus662for communicating information and command selections to the main processor unit640. An additional user input device is cursor control device, such as a mouse, a trackball, stylus, or cursor direction keys coupled to bus662through bus662for communicating direction information and command selections to main processor unit640, and for controlling cursor movement on display device644.

Another device, which may optionally be coupled to computer system, is a communication device, such as UART654, CANBUS656, USB658, and Ethernet660, for accessing other nodes of a distributed system via a network. The communication device may include any of a number of commercially available networking peripheral devices such as those used for coupling to an Ethernet, token ring, Internet, control area network (CAN), wide area network (WAN), and wireless network (WIFI). The communication device may further be a null-modem connection via UART, or any other mechanism that provides connectivity between the computer system and the outside world, or any other mechanism that provides connectivity between the controller computer system and instrument modules. Note that any or all of the components of this system illustrated inFIG. 6Cand associated hardware may be used in various embodiments of the present invention.

It will be appreciated by those of ordinary skill in the art that any configuration of the system may be used for various purposes according to the particular implementation. The control logic or software implementing the present invention can be stored in SDRAM646, NOR Flash648, NAND flash650, SD card652, FPGA, CPLD or other storage medium locally or remotely accessible to main processor unit640.

It will be apparent to those of ordinary skill in the art that the system, method, and process described herein can be implemented as software stored in memory and executed by main processor unit640. This control logic or software may also be resident on an article of manufacture comprising a computer readable medium having computer readable program code embodied therein and being readable by the storage device and for causing the main processor unit640to operate in accordance with the methods and teachings herein.

The present invention may also be embodied in a handheld or portable device containing a subset of the computer hardware components described above. For example, the handheld device may be configured to contain only the bus662, the main processor unit640, and SDRAM646. The handheld device may also be configured to include a set of buttons or input signaling components with which a user may select from a set of available options. The handheld device may also be configured to include an output apparatus such as a liquid crystal display (LCD) or display element matrix for displaying information to a user of the handheld device. Conventional methods may be used to implement such a handheld device. The implementation of the present invention for such a device would be apparent to one of ordinary skill in the art given the disclosure of the present invention as provided herein.

The present invention may also be embodied in a special purpose appliance including a subset of the computer hardware components described above. For example, the appliance may include a main processor unit640, SDRAM646and bus662, and only rudimentary communications mechanisms, such as a small touch-screen that permits the user to communicate in a basic manner with the device. In general, the more special-purpose the device is, the fewer of the elements need to be presented for the device to function. In some devices, communications with the user may be through a touch-based screen, USB devices, or similar mechanism.

It will be appreciated by those of ordinary skill in the art that any configuration of the system may be used for various purposes according to the particular implementation. The control logic or software implementing the present invention can be stored on any machine-readable medium locally or remotely accessible to processor. A machine-readable medium includes any mechanism for storing or transmitting information in a form readable by a machine (e.g. a computer). For example, a machine readable medium includes read-only memory (ROM), random access memory (RAM), magnetic disk storage media, optical storage media, flash memory devices, electrical, optical, acoustical or other forms of propagated signals (e.g. carrier waves, infrared signals, digital signals, etc.).

FIG. 6Dis a block diagram illustrating the instrument modules634,636,638ofFIG. 6Bin further detail. The instrument modules634,636,638include a databus664, a stepper motor controller666, initial data667, a main stepper controller668, an ADC reader670, an input data device672and an output data device674. The stepper motor controller666, initial data666, main stepper controller668, Analog-to-Digital Converter (ADC) reader670, input data device672and output data device674are each coupled to the databus664.

In the embodiment illustrated inFIG. 6D, the instrument module is shown for the tray motor driving module ofFIG. 6A. It will be appreciated that the instrument modules for the other modules ofFIG. 6Awill have similar components as the illustrated instrument module; however, the inputs and outputs coupled with the instrument modules may vary.

The illustrated databus664is also coupled with a MCU676. The stepper motor controller666is also coupled with the motor sensor678, motor driver2680and motor driver3682. The main stepper controller668is also coupled with the motor driver1684and protect sensor686. The ADC reader670is also coupled with the ADC688. The input data device672is also coupled with the door sensor690, main motor home sensor692, and cassette sensor694. The output data device674is also coupled with the fan696and the heater698.

FIG. 7illustrates a tray driving motor assembly module700. In one embodiment, the tray driving motor assembly module700is part of the tray motor driving system614ofFIG. 6. In one embodiment, the tray driving motor assembly module700is within the instrument module508of the instrument500as described above with reference toFIG. 5.

The tray driving motor assembly module700includes an alignment plate702, a first drive shaft retention block704, a second drive shaft retention block706, a load driving shaft708, a main driving motor710, a first parallel shaft712, a second parallel shaft714, a first parallel linear drive716, a second parallel linear drive718, a first load resistance tray720, a first door722, a second load resistance tray724and a second door726.

The main drive motor710is coupled with the load driving shaft708via the retention blocks704,706to automatically load and eject the rack trays720,724into the instrument. The trays720,724also slide along the parallel shafts712,714with the main drive motor710and the drives716,718to load and eject the racks720,724. The motor710and/or drivers712,714can also be used to open and close the doors722,726.

FIG. 8illustrates a reagent release and pre-mix assembly module800. In one embodiment, the reagent release and pre-mix assembly module800is part of the reagent release system620and reagent pre-mix pumping system622. In one embodiment, the reagent release and pre-mix assembly module800is within the instrument module508of the instrument500as described above with reference toFIG. 5.

The reagent release and pre-mix assembly module800includes a precision vertical engagement driving motor802, a vertical drive shaft803, a stand804, a first plunger assembly806, a second plunger assembly808, a first parallel horizontal pump activation motor810, a second parallel horizontal pump activation motor812, first, second, third and fourth horizontal parallel linear driving shafts and bearings814,816,818and820, and first, second, third and fourth vertical parallel linear bearings822,824,826and828.

In one particular embodiment, each of the plunger assemblies806,808includes twelve plungers (e.g., one plunger for each cassette in the magazine). It will be appreciated that the plunger assemblies806,808may have fewer than or greater than twelve plungers.

FIG. 9is a side view of reagent release and pre-mix assembly module800ofFIG. 8. As shown inFIG. 9, the reagent release and pre-mix assembly module800ofFIG. 8also includes a vertical position sensor830.

With reference toFIGS. 8 and 9, the stand804is coupled with the vertical drive shaft803, which is coupled with the vertical engagement driving motor802to vertically position the stand804. The plunger assemblies806,808are coupled with the stand804and are, thus, also vertically positioned with the stand804when the motor802is actuated. The vertical position sensor830is coupled with the stand804to sense the position of the stand804and/or plunger assemblies806,808. The vertical position sensor830communicates with a controller to control actuation of the motor802. The plunger assemblies806,808are also actuatable horizontally via the horizontal drive shafts and bearings814-820, which are coupled with the horizontal motors810,812.

The plunger assemblies806,808are actuated in a vertical direction to align the plungers806,808with one of the holding chambers of the cassette400. The plunger assemblies806,808are also actuated horizontally to force the contents of the holding chambers into the mixing chamber of the cassette400. The plunger assemblies806,808are then repositioned vertically to align with another holding chamber and are similarly actuated horizontally to force the contents of the holding chamber into the mixing chamber according to the selected protocol. In one embodiment, the plunger assemblies806,808are also actuated to actuate the pump444that mixes the contents of the mixing chamber of the cassette400.

FIGS. 10 and 11illustrate a heater and temperature sensor assembly module1000. In one embodiment, the heater and temperature sensor assembly module1000is part of the heater control and detection system616. In one embodiment, the heater and temperature sensor assembly module1000is within the instrument module508of the instrument500as described above with reference toFIG. 5.

The heater and temperature sensor assembly module1000includes a precision vertical engagement driving motor1002, a vertical position sensor1004, a rack1006, a first vertical linear bearing1008, a second vertical linear bearing1010, a plurality of heater and thermal sensor connectors1012and a plurality of individually controlled parallel heaters and thermal sensors1014. In one embodiment, the plurality of individually controlled parallel heaters and thermal sensors1014are self-aligned with the plurality of heater and thermal sensor connectors1012.

In one particular embodiment, the heater and temperature sensor assembly module1000includes twenty-four heater and thermal sensor connectors1012and twenty-four individually controlled parallel heaters and thermal sensors1014. It will be appreciated that the heater and temperature sensor assembly module1000may include fewer than or greater than twenty-four connectors1012and/or heaters/sensors1014.

The vertical linear bearings1008,1010are coupled with the vertical engagement driving motor1002to vertically position the rack1006. The plurality of heater and thermal sensor connectors1012and plurality of individually controlled parallel heaters and thermal sensors1014are coupled with respective sides of the rack1006. The plurality of heater and thermal sensor connectors1012and plurality of individually controlled parallel heaters and thermal sensors1014are vertically positionable by vertically positioning the rack1006. The vertical precision position sensor1004, coupled with the rack1006, can be used to accurately position the plurality of heater and thermal sensor connectors1012and plurality of individually controlled parallel heaters and thermal sensors1014.

FIGS. 12 and 13illustrate a wash buffer pumping assembly module1200. In one embodiment, the wash buffer pumping assembly module1200is part of the wash buffer pumping system624. In one embodiment, the wash buffer pumping assembly module1200is within the instrument module508of the instrument500as described above with reference toFIG. 5.

The wash buffer pumping assembly module1200includes a rack1202, a plurality of parallel vertical pump engagement plungers1204, a first parallel vertical pump activation motor1206, a second parallel vertical pump activation motor1208, and first, second, third and fourth vertical parallel linear driving shafts and bearings1210,1212,1214and1216. As shown inFIG. 13, the wash buffer pumping assembly module1200also includes first and second vertical precision position sensors1218and1220.

The first vertical pump activation motor1206is coupled with the first and second vertical parallel linear driving shafts and bearings1210,1212to vertically position a first set of parallel vertical pump engagement plungers1204a. Similarly, the second vertical pump activation motor1206is coupled with the third and fourth vertical parallel linear driving shafts and bearings1214,1216to vertically position a second set of parallel vertical pump engagement plungers1204b.

The plungers from the vertical pump engagement plungers1204engage with the cassette (e.g., cassette400) to actuate the pumps446,448,450in the wash chambers438,440and elution chamber442according to the selected protocol.

FIGS. 14 and 15illustrate a magnetic particles transfer assembly module1400. In one embodiment, the magnetic particles transfer assembly module1400is part of the magnetic particle transfer system618. In one embodiment, the magnetic particles transfer assembly module1400is within the instrument module508of the instrument500as described above with reference toFIG. 5.

The magnetic particles transfer assembly module1400includes a rack1402, a precision vertical engagement driving motor1402, a first particle transfer linear motor1404, a second particle transfer linear motor1406, first, second, third and fourth gear rack retention roller bearings1408,1410,1412and1416, first and second vertical linear bearings1418and1420, first and second driving gear racks1422,1423, a plurality of parallel precision gears1424and a plurality of parallel magnets and valve key shafts1426. As shown inFIG. 15, the magnetic particles transfer assembly module1400also includes first and second linear driving shafts1428and1430, first, second, third and fourth shaft and gear rack link blocks1432,1434,1436and1438, first, second, third and fourth horizontal precision position sensors1440,1442,1444and1446, and a vertical precision position sensor1448.

In one particular embodiment, the magnetic particles transfer assembly module1400includes twenty-four parallel precision gears1424and twenty-four parallel magnets and valve key shafts1426. It will be appreciated that the magnetic particles transfer assembly module1400may have fewer than or greater than twenty-four gears1424and magnets and key shafts1426.

The precision vertical engagement driving motor1402is coupled with vertical bearings1418,1420and the rack1403to vertically position the rack1403. The plurality of parallel magnets and valve key shafts1426are positioned on the rack1403and are vertically positioned when the rack1403is vertically positioned. The vertical precision position sensor1448is coupled with the rack1403and motor1402to accurately position the plurality of parallel magnets and valve key shafts1426in the cassette (e.g., cassette400).

The particle transfer linear motors1404,1405are positioned on either end of the rack1403and are coupled with the linear driving shafts1428,1430, shaft and gear rack link blocks1432-1438, driving gear racks1422, gears1424, to horizontally position and rotate the plurality of parallel magnets and valve key shafts1426via the gears1424to transfer magnetic particles as described above with reference toFIG. 4. It will be appreciated that the gears1424and magnets and shafts1426can be repositioned to transfer the particles with each valve of the cassette.

The foregoing description with attached drawings is only illustrative of possible embodiments of the described method and should only be construed as such. Other persons of ordinary skill in the art will realize that many other specific embodiments are possible that fall within the scope and spirit of the present idea. The scope of the invention is indicated by the following claims rather than by the foregoing description. Any and all modifications which come within the meaning and range of equivalency of the following claims are to be considered within their scope.