WO2022139822A1 - Reservoir actuating devices and methods - Google Patents

Reservoir actuating devices and methods Download PDF

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Publication number
WO2022139822A1
WO2022139822A1 PCT/US2020/066651 US2020066651W WO2022139822A1 WO 2022139822 A1 WO2022139822 A1 WO 2022139822A1 US 2020066651 W US2020066651 W US 2020066651W WO 2022139822 A1 WO2022139822 A1 WO 2022139822A1
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WO
WIPO (PCT)
Prior art keywords
carriage
actuator
sample preparation
reservoir
actuating
Prior art date
Application number
PCT/US2020/066651
Other languages
French (fr)
Inventor
Keith William Joseph JARIABKA
Justin Michael ROMAN
Original Assignee
Hp Health Solutions Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hp Health Solutions Inc. filed Critical Hp Health Solutions Inc.
Priority to PCT/US2020/066651 priority Critical patent/WO2022139822A1/en
Publication of WO2022139822A1 publication Critical patent/WO2022139822A1/en

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Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00Sampling; Preparing specimens for investigation
    • G01N1/28Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/38Diluting, dispersing or mixing samples
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/0098Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation

Definitions

  • Sample preparation cartridge modules may include reservoirs and/or pouches, for example for releasing chemicals into the sample preparation cartridge modules and/or for dispensing a sample from the sample preparation cartridge modules in a sample preparation process.
  • Figure 1 A is a perspective view of an example sample preparation device for actuating reservoirs of sample preparation cartridge modules held by a cassette.
  • Figure 1 B is a perspective view of the example sample preparation device of Figure 1 A showing the cassette at the example sample preparation device.
  • Figure 2 is a perspective view of a portion of the device of Figure 1 A showing details of one pair of mating devices.
  • Figure 3A and Figure 3B respectively show a perspective and side view of a first actuating device of the device of Figure 1 A, that actuates a row of reservoirs concurrently, with a carriage moved to align the mating devices, which further aligns reservoir actuating tips with the row of reservoirs.
  • Figure 4A and Figure 4B respectively show a perspective and side view of the first actuating device of the device of Figure 1 A with the mating devices mated to closer position the reservoir actuating tips with the row of reservoirs.
  • Figure 5A and Figure 5B respectively show a perspective and side view of the first actuating device of the device of Figure 1 A with the reservoir actuating tips moved to actuate the row of reservoirs.
  • Figure 6 depicts a portion of a biasing mechanism of the first actuating device of the device of Figure 1 A that better positions the reservoir actuating tips into a position for actuating a row of reservoirs.
  • Figure 7 A depicts a perspective view of a second actuator device that actuates a single reservoir in a row of reservoirs.
  • Figure 7B depicts a cross-section of the second actuator device relative to a reservoir through a line A-A in Figure 7A, in an unactuated position.
  • Figure 7C depicts a cross-section of the second actuator device relative to a reservoir through the line A-A in Figure 7A, in an actuated position and showing actuation of the reservoir.
  • Figure 8A is a perspective view of an example sample preparation device that incorporates the device of Figure 1A.
  • Figure 8B is a block diagram of the device of Figure 8A.
  • Figure 8C is a block diagram of the device of Figure 8A with a carriage in a sample dispensing position.
  • Figure 9 is a flow diagram of a method to actuate reservoirs implemented using the device of Figure 1 A and/or the device of Figure 8A.
  • a biological component can be intermixed with other components in a biological sample that can interfere with subsequent analysis.
  • biological component can refer to materials of various types, including proteins, cells, cell nuclei, nucleic acids, bacteria, viruses, or the like, that can be present in a biological sample.
  • a “biological sample” can refer to a fluid or a dried or lyophilized material obtained for analysis from a living or deceased organism. Isolating the biological component from other components of the biological sample can permit subsequent analysis without interference and can increase an accuracy of the subsequent analysis.
  • Isolation can also be referred to as “purification”, whereby biological component may be separated from the rest of the biological sample after introduction to a sample preparation cartridge module interchangeably referred to hereafter as a sample container, a sample dispensing container, a cartridge module, and the like. It will be understood that the isolated biological component may be output in association with (e.g., bound to) particulate substrate and a reagent solution, or the like.
  • isolation or purification refers to the separation of the biological component from other components of the biological sample with which it was originally introduced in the cartridge module, but it does not mean that the biological component is completely isolated when it is dispensed.
  • isolation refers to the fact that the biological component is sufficiently separated or “purified” from other components of the original biological sample to facilitate further processing such as detection and/or amplification.
  • isolation techniques can include repeatedly dispersing and reaggregating samples.
  • the repeated dispersing and re-aggregating can result in a loss of a quantity of the biological component.
  • isolating a biological component with some of these techniques can be complex, time consuming, and labor intensive and can result in less than maximum yields of the isolated biological component.
  • Such Isolation techniques are done using specific devices.
  • Obtaining precise biological sample preparation devices can be challenging due to many moving parts present in the devices, for example to move a carriage holding a cartridge of sample dispensing containers relative to sample receiving wells.
  • the cartridge may hold a plurality of the sample dispensing containers or sample preparation devices or sample preparation cartridge modules which contain different respective biological samples.
  • sample dispensing containers or sample preparation devices or sample preparation cartridge modules may heat the samples to perform for example, lysis on cells in the biological samples to release biological component of interest, coming from the biological sample, may be a nucleic acid (such as DNA or RNA).
  • Resulting sample fluid may be drawn through a fluid density gradient in the sample dispensing containers and dispensed into sample receiving wells, which may be transferred to further analytical assay such as, for example, a Polymerase Chain Reaction (PCR).
  • PCR Polymerase Chain Reaction
  • initial quantities of the biological component of interest present in the biological sample may be small, precise dispensing of the component of interest from the sample dispensing containers into the sample receiving wells should occur so as to not lose any content and/or to prevent cross-contamination between samples.
  • a precise determination of a position of a shuttle and/or well carriage, that holds the sample receiving wells, relative to the carriage is important, and vice versa.
  • the device of the present disclosure is a device that can be used to prepare sample to be used in a process of preparing samples for a PCR (polymerase chain reaction) assay.
  • PCR assays are processes that can rapidly copy millions to billions of copies of a very small DNA or RNA sample.
  • PCR can be used for many different application, included sequencing genes, diagnosing viruses, identifying cancers, and others.
  • sequencing genes included in the PCR process, a small sample of DNA or RNA is combined with reactants that can form copies of the DNA or RNA.
  • the biological sample comprises a biological component.
  • the biological component of interest coming from the biological sample, may be a nucleic acid (such as DNA or RNA).
  • a particulate substrate can be configured to be associated with the biological component, to isolate the biological component from the biological sample.
  • the particulate substrate comprises paramagnetic beads and/or any magnetizing particle and/or magnetizing microparticles.
  • the biological component comprises nucleic acids such as DNA and/or RNA that may be extracted from the biological sample by lysing, bound to magnetic particulate substrate, and separated from the lysate and dragged towards an output by an externally generated (para)magnetic force.
  • Lysate may refer to the fluid containing the material resulting from the lysis of a biological sample. Such lysis may release the biological component that is contained therein. Lysing itself may include mixing and/or heating the biological sample, chemically lysing the biological sample, and/or a combination of the foregoing.
  • sample preparation device that accepts a cassette that includes a plurality of sample preparation cartridge modules into which samples have been inserted, for example biological samples that may include a biological component of interest as described above.
  • the sample preparation cartridge modules include respective reservoirs and/or blisters and/or pouches into which chemicals have been provided, and which may be released into the sample preparation cartridge modules upon actuation of the reservoirs and/or pouches in a sample preparation process.
  • the sample preparation cartridge modules also include a respective reservoir and/or blister pouch that may include air, and the like, such that, when a respective reservoir and/or pouch that includes air is actuated, a sample (e.g.
  • reservoirs and/or blisters pouches will be referred to interchangeably as reservoirs, though it is understood that the term reservoir may be replaced with the term blister and/or pouch.
  • the sample preparation device generally includes a first actuator device which concurrently actuates a row of reservoirs that a release a given chemical on all the sample preparation cartridge modules held in the cassette to concurrently process samples therein.
  • the sample preparation device further includes a second actuator device which individually actuates respective reservoirs that dispense a respective sample (e.g. after processing to isolate and/or purify the biological component of interest) from a given sample preparation cartridge module, for example after the carriage holding the sample preparation cartridge modules is placed into a respective sample dispensing position for the given sample preparation cartridge module.
  • the sample preparation process may occur concurrently at the sample preparation cartridge modules, while sample dispensing may occur individually at the sample preparation cartridge modules.
  • a first aspect of the present specification provides a device comprising: a carriage comprising a first mating device; and an actuator device comprising: a second mating device that mates with the first mating device; a first actuator to move the second mating device to mate with the first mating device to position the actuator device at a given position relative to the carriage; reservoir actuating tips that are positioned, relative to the carriage, when the actuator device is positioned at the given position relative to the carriage; and a second actuator to move the reservoir actuating tips towards the carriage.
  • the device of the first aspect may further comprise a biasing mechanism to move the actuator device into the given position, relative to the carriage, when the second mating device mates with the first mating device.
  • the first mating device may comprise a pair of V-shaped grooves on opposite ends of the carriage, and the second mating device may comprise a corresponding pair of pins to move into the V- shaped grooves.
  • the second actuator may be further to actuate the reservoir actuating tips towards the carriage with a reservoir actuating force.
  • the device of the first aspect may further comprise a pair of arms, and wherein: the reservoir actuating tips may extend between the pair of arms, the first mating device may comprise a pair of V-shaped grooves on opposite ends of the carriage, the second mating device may comprise a pair of pins respectively located at the pair of arms, to move into the pair of V-shaped grooves, the first actuator may be to move the second mating device to mate with the first mating device by moving the pair of arms to move the pair of pins into the pair of V-shaped grooves, and the second actuator may be to actuate the reservoir actuating tips towards the carriage by pivoting the pair of arms around the pair of pins mated with the pair of V-shaped grooves, which further moves the reservoir actuating tips towards the carriage.
  • a second aspect of the present specification provides a device comprising: a carriage; and an actuator device, the carriage movable into a given position relative to the actuator device, the actuator device comprising: a single reservoir actuating tip; a first actuator to move the single reservoir actuating tip into respective given positions relative to the carriage; and a second actuator to actuate the single reservoir actuating tip towards the carriage.
  • the device of the second aspect may further comprise a motor to move the carriage along into the given position.
  • the first actuator may comprise a first motor to move the single reservoir actuating tip along a respective path perpendicular to a path of the carriage, into the respective given positions; and the second actuator may comprise a second motor to move the single reservoir actuating tip towards the carriage.
  • the second actuator may be to actuate the single reservoir actuating tip towards the carriage, perpendicular to a path of the single reservoir actuating tip along which the single reservoir actuating tip moves into the respective given positions relative to the carriage.
  • the single reservoir actuating tip may be mounted on a rail that extends along a respective path along which the single reservoir actuating tip moves into the respective given positions relative to the carriage, and the first actuator may be further to move the single reservoir actuating tip along the rail into the respective given positions.
  • a third aspect of the present specification provides a method comprising: controlling, at a sample preparation device, a carriage to move along a path, relative to an actuator device, into a first carriage position; controlling, at the sample preparation device, a first actuator of the actuator device to cause respective mating devices of the carriage and the actuator device to mate; when the respective mating devices are mated, controlling, at the sample preparation device, a second actuator of the actuator device to actuate reservoir actuating tips towards, and then away from, the carriage; controlling, at the sample preparation device, the first actuator to unmate the respective mating devices; controlling, at the sample preparation device, the carriage to move, along the path into a second carriage position; controlling, at the sample preparation device, a third actuator of the actuator device to move a single reservoir actuating tip, different from the reservoir actuating tips, into different positions perpendicular to the path of the carriage; and at the different positions, controlling a fourth actuator, of the actuator device, to actuate the single reservoir actuating tip towards, and then away
  • controlling the first actuator of the actuator device to cause the respective mating devices to mate may align the reservoir actuating tips with a row of reservoirs of a plurality of sample preparation cartridge modules held by the carriage such that, when the second actuator actuates the reservoir actuating tips towards the carriage, the reservoir actuating tips actuate the reservoirs in the row to release a chemical held by the reservoirs into the plurality of sample preparation cartridge modules.
  • controlling the third actuator of the actuator device to move the single reservoir actuating tip into the different positions may cause the single reservoir actuating tip to align with one respective reservoir at one respective sample preparation cartridge module, of a plurality of sample preparation cartridge modules, held by the carriage such that, when the fourth actuator actuates the single reservoir actuating tip towards the carriage, the single reservoir actuating tip actuates the one respective reservoir to dispense a sample from the one respective sample preparation cartridge module.
  • controlling the second actuator of the actuator device to actuate the reservoir actuating tips towards, and then away from, the carriage may occur by: partly actuating the reservoir actuating tips towards, and then away from, the carriage; and then fully actuating the reservoir actuating tips towards, and then away from, the carriage.
  • the single reservoir actuating tip may be located at a row of reservoirs of a plurality of sample preparation cartridge modules held by the carriage.
  • Figure 1 A and Figure 1 B show perspective views of an example device 100 into which a cassette 102 may be inserted.
  • Figure 1 A shows the device 100 without the cassette 102
  • Figure 1 B shows the device 100 with the cassette 102, for example after the cassette 102 has been inserted into the device 100.
  • the cassette 102 generally holds a sample preparation cartridge module 104 and/or sample preparation cartridge modules 104, for example in a frame, and the like.
  • the sample preparation cartridge modules 104 may alternatively be referred to as cartridge modules sample containers and/or sample dispensing containers, and the like. While as depicted the cassette 102 includes eight sample preparation cartridge modules 104, the cassette 102 may include as few as one sample preparation cartridge module 104 and/or a number of sample preparation cartridge modules 104 different from eight.
  • the sample preparation cartridge module 104 includes reservoirs 106 (e.g.
  • reservoirs 106 some of which contain chemicals, for example in a fluid form, used for processing a sample in the sample preparation cartridge module 104, and which may be released into a sample processing region of the sample preparation cartridge module 104 upon actuation though (some of the reservoirs 106 may be used in sample processing to mix chemicals and/or puncture foil in the reservoirs 106 prior to the chemicals being inserted into a sample preparation cartridge module 104).
  • the reservoirs 106 may contain air, and the like, and which, upon actuation, is used to dispense the sample (e.g. a biological component of interest) from the sample preparation cartridge module 104 after sample processing, as described in more detail below.
  • an “XYZ” coordinate system 107 is also depicted in Figure 1A and Figure 1 B and which will be used herein to show relative positions of components of the device 100 and/or the cassette 102.
  • a “Z” direction may be along a length of a sample preparation cartridge module 104 when held by the device 100
  • an “X” direction may be along the row of the sample preparation cartridge modules 104 in the cassette 102 when held by the device 100
  • a “Y” direction may be perpendicular to the “X” and “Y” directions.
  • each reservoir 106 in a row may perform a same function and/or hold a same chemical, and the like, such that when a row of reservoirs 106 is actuated concurrently, a same process occurs in the sample preparation cartridge modules 104.
  • components of the device 100 may be components of a larger sample preparation device used for preparation of samples.
  • the device 100 may be used in a larger sample preparation device to perform lysis of samples in sample preparation cartridge modules.
  • Such a sample preparation device is described below with respect to Figure 8A and Figure 8B.
  • the device 100 generally comprises a carriage 108 to receive the cassette 102, a first actuator device 110 that actuates some reservoirs 106 concurrently at the sample preparation cartridge modules 104, for example a row of reservoirs 106, and a second actuator device 112 that actuates other reservoirs 106 individually at the sample preparation cartridge modules 104.
  • the second actuator device 112 is between two components of the first actuator device 110.
  • the actuator devices 110, 112 are understood to be mounted together. However, in other examples, the actuator devices 110, 112 may be provided separately from each other.
  • the device 100 will hence be described hereafter with separate reference to the actuator devices 110, 112, with the first actuating device 110 described first with respect to Figure 1A, Figure 1 B, Figure 2, Figure 3A, Figure 3B, Figure 4A, Figure 4B, Figure 5A, Figure 5B and Figure 6.
  • the second actuator device 112 will be described with reference to Figure 7A, Figure 7B and Figure 7C.
  • the device 100 comprises the carriage 108, which includes a region 115 into which the cassette 102 is received and hence includes any suitable combination of grooves, constraining devices, and the like for holding and constraining the cassette 102 in the carriage 108.
  • the carriage 108 comprises a first mating device 116
  • the device 100 further comprises the first actuator device 110 which comprises: a second mating device 118 that mates with the first mating device 116.
  • the first mating device 116 comprises a pair of V-shaped grooves on opposite ends of the carriage 108 (e.g. in the “X” direction), and the second mating device 118 comprises a corresponding pair of pins to move into the V-shaped grooves. While, due to the angle of perspective in Figure 1A and Figure 1 B, only one pin of the second mating device 118 is visible, it understood that a second pin of the second mating device 118 is present, such that the carriage 108 may be moved (e.g. in the “Z” direction) to a position where the pins of the second mating device 118 are arranged to be near and/or adjacent respective V-shaped grooves of the first mating device 116.
  • the first mating device 116 comprises a plurality of pairs of V-shaped grooves, for example arranged along the “Z” direction, with which the pins of the second mating device 118 may be mated for example to position the first actuator device 110 relative to different rows of reservoirs 106 at the sample preparation cartridge modules 104.
  • the carriage 108 and the first actuator device 110 move relative to each other to about align the pins of the second mating device 118 with a given pair of V-shaped grooves to actuate a given row of reservoirs 106, as described in more detail below.
  • the carriage 108 is mounted to both rails 120 and a lead and/or drive screws 122 of a carriage guide (e.g. a vertical carriage guide described below with respect to Figure 8B) and the carriage 108 may be moved on the rails 120 to different predetermined positions relative to the first actuator device 110, for example, via a motor 124 and/or motors (e.g. a stepper motor) driving the drive screws 122.
  • a carriage guide e.g. a vertical carriage guide described below with respect to Figure 8B
  • the carriage 108 may be moved on the rails 120 to different predetermined positions relative to the first actuator device 110, for example, via a motor 124 and/or motors (e.g. a stepper motor) driving the drive screws 122.
  • the carriage 108 may be moved to different positions, for example along a path 125 in the “Z” direction.
  • the carriage 108 may be moved to as many positions as there are V-grooves of the first mating device 116 (e.g. as depicted, six positions) however, the carriage 108 may be moved to any number of positions along the path 125, which may also include a position for individually actuating a reservoir 106 for dispensing a respective sample from a sample preparation cartridge module 104, described in more detail below with respect to the second actuator device 112 in Figure 7 A, Figure 7B and Figure 7C.
  • the rails 120, drive screws 122 and motor(s) 124 may also be used to position the carriage 108 within the larger sample preparation device.
  • the actuator device 110 further comprises a first actuator 126 to move the second mating device 118 to mate with the first mating device 116 to position the first actuator device 110 at a given position relative to the carriage 108, for example assuming that the carriage 108 has been moved along the path 125 into a position along the rails 120 where a pair of V-grooves of the first mating device 116 is about aligned, and/or adjacent to, the pins of the second mating device 118.
  • the first actuator 126 may comprise any suitable combination of gears, motors, pulleys, and the like, to move the second mating device 118 to mate with the first mating device 116, a process which will be described in more detail below with respect to Figure 3A, Figure 3B, Figure 4A, Figure 4B, Figure 5A and Figure 5B.
  • the actuator device 110 further comprises reservoir actuating tips 128 that are positioned (e.g. at respective positions), for example arranged in a row, relative to the carriage 108, when the actuator device 110 is positioned at the given position relative to the carriage 108 defined at least in part by the mating of the mating devices 116, 118.
  • the given position of the actuator device 110 at which the actuator device 110 is positioned when the mating devices 116, 118 are mated, may be a position where the reservoir actuating tips 128 are about aligned with a row of reservoirs 106 to actuate the reservoirs 106 in the row, as described hereafter.
  • the reservoir actuating tips 128 are interchangeably referred to hereafter as the tips 128.
  • FIG. 1 A While the row of the tips 128 are not visible from the perspective shown in Figure 1 A and Figure 1 B, also depicted in Figure 1 A is a block diagram of a view 130 of the tips 128 from an angle 132, for example as viewed along the “Y” direction through the region 115. While in the view 130 other components of the actuator devices 110, 112 are not depicted, they are nonetheless understood to be present.
  • tips 128 there are eight tips 128 (e.g. mounted to a block 134, a rear side of which is visible in Figure 1 A and Figure 1 B), for example as many tips 128 as there are sample preparation cartridge modules 104 and/or reservoirs 106 in a row.
  • the row of tips 128, as depicted, comprise cylindrically shaped devices that are of a size, shape, position and spacing to actuate a respective reservoir 106, in a row of reservoirs 106 at the sample preparation cartridge modules 104.
  • actuating a reservoir 106 may be understood herein to include pressing and/or pushing on a reservoir 106, for example to crush the reservoir 106, to release a chemical (e.g. in fluid form) held by a reservoir 106 into a sample preparation cartridge module 104 and/or pressing and/or pushing on a reservoir 106 to dispense a sample (e.g. an isolated and/or purified biological component of interest) held by a sample preparation cartridge module 104.
  • a sample e.g. an isolated and/or purified biological component of interest
  • the view 130 further shows a single reservoir actuating tip 136 (e.g. the tip 136) of the second actuating device 112 which will be described in more detail below.
  • the first actuator device 110 further comprises a second actuator 138 to actuate and/or move the tips 128 towards the carriage 108, for example towards the region 115 and/or towards a row of reservoirs 106 when the cassette 102 is received in the carriage 108.
  • the tips 128 may be used to concurrently actuate a row of reservoirs 106 at the sample preparation cartridge modules 104 to concurrently release respective chemicals held by the reservoirs 106 in the row, to concurrently process samples in the sample preparation cartridge modules.
  • the second actuator 138 may comprise any suitable combination of gears, motors, pulleys, and the like, actuate and/or move the tips 128 towards the carriage 108 to actuate a row of reservoirs 106, a process which will be described in more detail below with respect to Figure 3A, Figure 3B, Figure 4A, Figure 4B, Figure 5A and Figure 5B.
  • a given reservoir 106 used for sample processing may include an outer foil shell, and the like (e.g. as seen in Figure 1 B) and an inner foil barrier which, together, hold a chemical, and the like, for example in fluid form, and the like (e.g. which may include, but is not limited to gel form, and the like) in the given reservoir 106.
  • the inner foil barrier may be adjacent a respective aperture in a sample preparation cartridge module 104 that acts as a passage between the given reservoir 106 and a portion of the sample preparation cartridge module 104 within which sample processing and/or sample dispensing occurs.
  • the reservoir actuating force applied to a row of reservoirs 106 by the tips 128 is understood to be sufficient to press on the outer plastic shell and break the inner foil barrier to release a respective chemical into the sample preparation cartridge module 104 and/or perform any other suitable process associated with actuating a reservoir 106.
  • the actuator device 110 and the carriage 108 may be operated to position the tips 128 at different rows of the reservoirs 106 (for example in a sequence), for example by mating the pins of the second mating device 118 with different pairs of V-grooves of the first mating device 116; when the pins of the second mating device 118 are mated with a given pairs of V- groove of the first mating device 116, the second actuator 138 may be operated to concurrently actuate a respective row of reservoirs 106.
  • the actuator device 110 may be positioned at a plurality of given positions, corresponding to the pins of the second mating device 118 being mated with different V-grooves of the first mating device 116, and the given positions of the actuator device 110 may be respective positions at which the tips 128 are about aligned with a respective row of reservoirs 106 to actuate respective row of reservoirs 106.
  • the device 100 further comprises a pair of arms 140 (only one of which is visible in Figure 1 A and Figure 1 B), and that the tips 128 extends between the pair of arms 140; for example, opposite ends of the block 134, to which the tips 128 are attached, may be rotationally attached to the arms 140 and/or the block 134 may extend between the arms 140.
  • the pair of pins of the second mating device 118 may be respectively located at the pair of arms 140, for example at positions that allow the pins to move into a pair of V-shaped grooves of the first mating device 116.
  • the first actuator 126 is to move the pins of the second mating device 118, to mate with respective V-shaped grooves of the first mating device 116, by moving the pair of arms 140 to move the pair of pins into the pair of V-shaped grooves.
  • the second actuator 138 is to actuate the reservoir actuating tips 128 towards the carriage 108 and/or a row of reservoirs 106, by pivoting and/or rotating the pair of arms 140 around the pair of pins mated with the pair of V-shaped grooves, which further moves the reservoir actuating tips towards the carriage and/or a row of reservoirs 106.
  • the device 100 further comprises a biasing mechanism and/or, as depicted, biasing mechanisms 142-1 , 142-2, which are interchangeably referred to hereafter as the biasing mechanisms 142 and/or a biasing mechanism 142.
  • the biasing mechanism 142 is to move the actuator device 110 into the given position (and/or one of the given positions), relative to the carriage 108, when the second mating device 118 mates with the first mating device 116.
  • first biasing mechanism 142-1 present at the carriage 108, is visible in Figure 1A and Figure 1 B, it is understood that a second biasing mechanism 142-2 is associated with the actuator device 110, and will be describe in more detail with respect to Figure 6, and further is visible in Figure 2, Figure 3A, Figure 3B, Figure 4A, Figure 4B, Figure 5A, and Figure 5B.
  • the first biasing mechanism 142-1 may comprise a pair of chamfered grooves in the carriage 108 (only one of which is visible in Figure 1A and Figure 1 B), into which respective complementary shaped chamfered arms (e.g. the second biasing mechanism 142-2) are inserted (e.g. mated) when the second actuator 138 moves the tips 128 towards the carriage 108.
  • the biasing mechanism 142 may shift and/or move the actuator device 110 into the given position in the “X” direction to more precisely position the tips 128 relative to a row of reservoirs 106.
  • the actuator device 110 may be biased (e.g.
  • the second biasing mechanism 142-2 exerts a stabilizing force on the first biasing mechanism 142-1 to assist with holding the actuator device 110 into the given position relative to the carriage 108.
  • the XYZ coordinate system 107 may alternatively be defined with respect to the device 100 without the carriage 108.
  • the “Z” direction may be understood to be along the path 125 of the carriage 108
  • the “X” direction may be understood to be along a row of the tips 128 which are about perpendicular to the path 125
  • the “Y” direction may be understood to be perpendicular to the path 125 and row of the tips 128 and/or in a direction of movement of the tips 128 towards and away from the carriage 108.
  • the XYZ coordinate system 107 is provided on further figures herein to show relative orientations of the device 100, and the like, between the figures.
  • Figure 2 depicts a portion of the device 100 showing details of one pair of the mating devices 116, 118 and, in particular, pins of the second mating device 118 as mated with one pair of V- shaped grooves 144-1 of the first mating device 116.
  • Figure 2 shows that the second mating device 118 includes six pairs of V-shaped grooves 144-1 , 144-2, 144-3, 144-4, 144-5, 144-6.
  • V-shaped grooves 144-1 , 144-2, 144-3, 144-4, 144-5, 144-6 are interchangeably referred to hereafter, collectively, as the V- shaped grooves 144 and/or a V-shaped groove 144.
  • FIG. 2 Also depicted in Figure 2 is a rear of the block 134, with two reservoir actuating tips 128 shown in outline to indicate the row of the tips 128 are on an opposite side of the block 134. Also depicted in Figure 2 are reservoirs 106 of two of the sample preparation cartridge modules 104 (e.g. the reservoirs 106 are depicted without the remainder of the sample preparation cartridge modules 104) to show that an example sample preparation cartridge module 104 may include six reservoirs 106-1 , 106-2, 106-3, 106-4, 106-5 (e.g. indicated as 106- 5A and 106-5B), 106-6.
  • the reservoir 106-5 is understood to include a larger volume of fluid and/or chemical therein, as compare to the other reservoirs 106, and hance includes two regions 106-5A and 106-5B which may be individually actuated to dispense such a larger volume.
  • the reservoirs 106 of a given sample preparation cartridge module 104 may be provided as a unit attachable to a remainder of the given sample preparation cartridge module 104 (e.g. using glue and the like).
  • one of the reservoirs 106 may be for dispensing a sample from a sample preparation cartridge module 104, but the remaining reservoirs 106-1 , 106-2, 106-3, 106-4, 106-5 may be to release chemicals into the sample preparation cartridge module 104 for sample processing, and the like, though some of the remaining reservoirs 106-1 , 106-2, 106-3, 106-4, 106-5 may be used to assist with puncturing an inner foil of an adjacent reservoir 106-1 , 106-2, 106-3, 106-4, 106-5, and/or mixing chemicals therein, and the like.
  • the reservoirs 106-1 , 106-2, 106-3, 106-4, 106-5 are to be actuated by the reservoir actuating tips 138, and the reservoir 106-6, for sample dispensing, is to be actuated by the tip 136 of the second actuator device 112, described in more detail below.
  • the pins of the second mating device 118 are mated with the first V-shaped grooves 114-1 , which aligns the tips 128 with a row of the first reservoirs 106-1 .
  • the pins of the second mating device 118 are mated with the second V-shaped grooves 114-2, the tips 128 are aligned with a row of the second reservoirs 106-2.
  • the pins of the second mating device 118 are mated with the third V-shaped grooves 114-3, the tips 128 are aligned with a row of the third reservoirs 106-3.
  • the tips 128 are aligned with a row of the fourth reservoirs 106-4.
  • the tips 128 are aligned with a row of the fifth reservoirs 106-5 corresponding to the portion labelled as “106-5A”.
  • the tips 128 are aligned with a row of the fifth reservoirs 106-5 corresponding to the portion labelled as “106-5B”.
  • dimensions of the arms 140, distances between the V-shaped grooves 144 and/or dimensions of other suitable components of the device 100 are selected such that, when the pins of the second mating device 118 are mated with a V-shaped groove 144 of the first mating device 116, the tips 128 are aligned with a respective row of reservoirs 106, which may then be concurrently actuated via the second actuator 138 moving the tips 128 towards the row of reservoirs 106.
  • Figure 2 also shows one arm of the second biasing mechanism 142-2, which is understood to be located at end of a row of the tips 128, with the other arm of the second biasing mechanism 142-2 located at an opposite end of the row of tips 128.
  • Figure 3A and Figure 3B Figure 4A and Figure 4B, and Figure 5A and Figure 5B which show the device 100 implementing a process for actuating the row of the tips 128 against a row of reservoirs 106.
  • Figure 3A, Figure 4A, and Figure 5A show a perspective view of different configurations the device 100 as the first actuator 126 mates the mating devices 116, 118 (e.g. in Figure 3A and Figure 4A and as the second actuator 138 moves the tips 128 to concurrently acuate a row of reservoirs 106 (e.g. in Figure 5A).
  • Figure 3B, Figure 4B, and Figure 5B show side views respectively corresponding to the configurations of Figure 3A, Figure 4A, and Figure 5A.
  • the carriage 108, cassette 102 and sample preparation cartridge modules 104 are removed, other than the reservoirs 106 (e.g. similar to Figure 2.
  • some other components of the device 100 are omitted, such as the first actuator 126, but are nonetheless understood to be present.
  • Figure 3A, Figure 4A, and Figure 5A further show details of the arms 140 (e.g. both of which are depicted in Figure 3A, Figure 4A, and Figure 5A) and components of the second actuator 138 that pivot the arms 140 around the pair of pins of the second mating device 118, when mated with a pair of V-shaped grooves 144 (e.g. as depicted, the V-shaped grooves 144-1) of the first mating device 116.
  • a pair of V-shaped grooves 144 e.g. as depicted, the V-shaped grooves 144-1
  • the second actuator 138 may comprise a frame 146, and the like, to which respective ends of the arms 140 are attached, for example ends opposite respective ends of the arms 140 at which the pins of the second mating device 116 are attached.
  • the frame 146 may slide on a guide rail 148 in a direction that is towards and/or away from the carriage 108, and (e.g. the “Y” direction) via a lead and/or drive screw 150 (or multiple drive screws) via a motor (not depicted).
  • the arms 140 may be pivotably attached to the frame 146 via respective hinges and/or pivot mechanisms 152 and the like.
  • the second actuator 138 may hence pivot the pair of arms 140 around the pair of pins of the second mating device 118, when mated with the pair of V-shaped grooves 144- 1 , which moves the tips 128 towards the carriage 108 and/or a row of reservoirs 106-1.
  • the first actuator 126 may comprise a frame 154, and the like, to which respective ends of the arms 140 are attached, for example ends at which the pins of the second mating device 116 are attached.
  • the frame 154 may slide on a guide rail 156 in a direction that is towards and/or away from the carriage 108, and (e.g. the “Y” direction) via a lead and/or drive screw 158 (or multiple drive screws) via a motor (not depicted).
  • the arms 140 may be pivotably attached to the frame 154 via respective hinges and/or pivot mechanisms which may be coincident with the pins of the second mating device 118.
  • the first actuator 126 may hence move the pair of pins of the second mating device 118, to mate with the pair of V-shaped grooves 144-1 by moving the arms 140 towards the carriage 108 via the guide rail 156 and the drive screws 158, which causes the arms 140 to pivot accordingly around the pivot mechanisms 152.
  • the V-shaped grooves 144 may be asymmetrically shaped to accommodate an approach angle and/or an approach path of the pins of the second mating device 118, for example to “catch” the pins of the second mating device 118 into the V-shaped grooves 144 as they approach the V-shaped grooves 144 and push them into a deepest portion of the V-shaped grooves 144.
  • the asymmetry of the V-shaped grooves 144 may be such that an “upper” portion of a V-shaped groove 144 is angled closer to 90° than a “lower” portion with the pins being biased towards the upper” portions of the V-shaped grooves 144 by a suitable biasing mechanism.
  • FIG. 3A, Figure 3B, Figure 4A, Figure 4B, Figure 5A and Figure 5B are also depicted in Figure 3A, Figure 3B, Figure 4A, Figure 4B, Figure 5A and Figure 5B.
  • the arms of the biasing mechanism 142-2 associated with the second actuator 138 which, as depicted, are attached to respective arms 140, for example at opposite ends of the row of tips 128.
  • the tips 128 and the reservoirs 106-1 are shown in outline “through” the biasing mechanism 142-2, to show relative positions thereof.
  • the first actuator 126 actuates the frame 154 along the guide rail 156 via the drive screw 158, and the like, to pivot the arms 140 and move the pins of the second mating device 118 into the V-shaped grooves 144-1 .
  • the first actuator 126 is understood to apply a suitable force to the pins of the second mating device 118 that “holds” the pins in the V-shaped grooves 144-1.
  • the first actuator 126 may actuate the frame 154 along the guide rail 156 via the drive screw 158 until motor thereof stalls, which may occur when the pins of the second mating device 118 mate with the V-shaped grooves 144-1 and/or are located at a deepest position within the V-shaped grooves 144-1 such that the pins of the second mating device 118 stop (e.g. thereby stalling the motor thereof).
  • the second actuator 138 actuates the frame 146 along the guide rail 148 via the drive screw 150, and the like, to pivot the arms 140 around the pins of the second mating device 118, as indicated by the arrow 164 in Figure 5B.
  • the arms 140 may also pivot around the pivot mechanisms 152.
  • the tips 128 concurrently press and/or push respective first reservoirs 106-1 to release a chemical therein into respective sample preparation cartridge modules 104.
  • the second actuator 138 may actuate the frame 146 along the guide rail 148 via the drive screw 150 in a feedback loop with a motor (not depicted) that applies a torque to the drive screw 150 corresponding to a linear force that is translated to the tips 128, such that the tips 128 apply a sufficient force to the reservoirs 106-1 of the sample preparation cartridge module 104 to push and/or crush the reservoirs 106-1 .
  • the second actuator 138 may partly actuate the reservoir actuating tips 128 towards, and then away from, the carriage 108 and/or the row of reservoirs 106-1 , and then fully actuating the reservoir actuating tips towards the carriage and/or the row of reservoirs 106-1 .
  • the reservoirs 106-1 may initially be partly actuated by the tips 128, and the tips 128 may be backed off the reservoirs 106-1 ; then the reservoirs 106-1 may fully actuated by the tips 128.
  • the reservoirs 106-1 may initially be partly actuated by the tips 128 a plurality of times, for example to different depths, which may cause the chemicals (e.g. in a fluid form) to cause turbulence, and the like, within a respective sample preparation cartridge module 104, which may assist with mixing of fluids therein.
  • the rows of reservoirs 106 may be actuated in any suitable order.
  • the process shown in Figure 3A, Figure 3B, Figure 4A, Figure 4B, Figure 5A and Figure 5B is described with respect to actuating the row of reservoirs 106-1
  • another row of reservoirs 106 may be first actuated and/or the rows of reservoirs 106 may be actuated in any suitable order consistent with sample processing at the sample preparation cartridge modules 104 (and hence which may depend on which chemicals are held in which row of reservoirs 106, and the like).
  • Figure 6 depicts a portion of one set of the biasing mechanisms 142, with a portion of the carriage 108 that includes a groove of a first biasing mechanism 142-1 in cross-section (e.g. through a plane perpendicular to the “Z” direction and/or parallel to the “X” and Y directions). While only one set of the biasing mechanisms 142 are shown, it is understood that the device 100 may include two sets of the biasing mechanisms 142, for example at positions corresponding to the positions of the arms of the second biasing mechanisms 142-2 depicted in Figure 3A, Figure 4A and Figure 5A.
  • the arm of the second biasing mechanism 142-2 has been inserted into the groove of the first biasing mechanism 142-1 which may move the arm of the second biasing mechanism 142-2, as well as the actuator device 110 and the tips 128 (e.g. not depicted in Figure 6, but nonetheless understood to be present) in a the “X” direction, as indicated by the arrow 166, to more precisely move the actuator device 110 into a given position where the tips 128 align with a reservoirs 106 of a given row thereof.
  • a force 168 is applied (e.g.
  • the arm of the second biasing mechanism 142-2 may move into a rest position (e.g. as depicted in Figure 3A and Figure 4A).
  • corners of the biasing mechanisms 142 may be chamfered and/or rounded to promote movement of the arm of the second biasing mechanism 142-2 into the groove of the first biasing mechanism 142-1.
  • the groove of the first biasing mechanism 142-1 may be shaped to promote movement of the arm of the second biasing mechanism 142-2 therein.
  • the pins and grooves of the mating devices 116, 118 may be replaced with any suitable structures, such hooks and pins in any suitable locations at the carriage 108 and/or at the first actuator device 110 and which hold and/or lock the carriage 108 in a position when a force is applied to the reservoirs 106 by the tips 128 (e.g. to prevent the carriage 108 from moving away from the tips 128).
  • the tips 128 are depicted as cylindrical, the tips 128 may be any suitable shape.
  • actuation of the tips 128 has been described with respect to the arms 140, as well as the frames 146, 154 etc., the tips 128 may be actuated with any suitable combination of mechanical devices.
  • Figure 7A depicts a perspective view of the second actuator device 112 relative to a row of the reservoirs 106-6.
  • Figure 7B and Figure 7C show a cross-section of the second actuator device 112 through a line A-A in Figure 7A.
  • the carriage 108 has been moved along the path 125 (e.g. by the motor 124, etc.) into a given position relative to the second actuator device 112 until a respective path 170 of the single reservoir actuating tip 136 aligns with the row of reservoirs 106-1 .
  • the second actuator device 112 comprises the single reservoir actuating tip 136, for example mounted to a rail and/or a drive screw 172 and the like.
  • the second actuator device 112 further comprises a first actuator 174 to move the single reservoir actuating tip 136 into respective given positions relative to the carriage 108, for example where the single reservoir actuating tip 136 aligns with one respective reservoir 106-1.
  • the first actuator 174 may be to move the single reservoir actuating tip 136 along the respective path 170, perpendicular to the path 125 of the carriage 108, into respective given positions relative to the carriage 108, for example where the single reservoir actuating tip 136 aligns with one respective reservoir 106-1 .
  • the first actuator 174 may comprise any suitable combination of gears, motors, pulleys, and the like.
  • the first actuator 174 may comprise a worm drive that turns the drive screw 172, via a motor 175.
  • the single reservoir actuating tip 136 may be moved along the path 170 to align with any of the reservoirs 106-1 and/or along any suitable path where the single reservoir actuating tip 136 aligns with any of the reservoirs 106-1 .
  • the single reservoir actuating tip 136 may be mounted on a rail and/or drive screw 172 that extends along the respective path 170, and the first actuator 174 may be further to move the single reservoir actuating tip 136 along the rail and/or drive screw 172 into respective given positions that align the tip 136 with individual reservoirs 106-1.
  • the second actuator device 112 further comprises a second actuator 176 to actuate and/or move the single reservoir actuating tip 136 towards the carriage 108 and/or a reservoir 106-1 , for example in a manner similar to that described above with respect to the tips 128.
  • the second actuator 176 may comprise a frame 178, to which the first actuator 174, the drive screw 172 and the single reservoir actuating tip 136 are attached, and the frame 178 may slide on a guide rail 180 (only partially visible in Figure 7A) in a direction that is towards and/or away from the carriage 108, and (e.g.
  • the second actuator 176 is to actuate the single reservoir actuating tip 136 towards the carriage 108, perpendicular to the respective path 170 of the single reservoir actuating tip 138, for example to actuate a reservoir 106-6.
  • the first actuator 174 comprises a first motor 175 to move the single reservoir actuating tip 136 along the respective path 172 into respective given positions (e.g. that align with respective reservoir tips 106-6), and that the second actuator 176 comprises a second motor 184 to move the single reservoir actuating tip 136 towards the carriage 108 and/or a reservoir tip 106-6.
  • Figure 7B and Figure 7C depict the second actuator device 112 in cross section through a plane perpendicular to the “X” direction (e.g. and that includes the “Y” and “Z” directions), and which is through the single reservoir actuating tip 136.
  • Figure 7B and Figure 7C show the second actuator device 112 from a side view that also shows the single reservoir actuating tip 136 moved to a given position by the first actuator 174 where the single reservoir actuating tip 136 is aligned with a reservoir 106-6.
  • Figure 7B and Figure 7C further show gears, and the like, of the second actuator 176, at a rear side of the second actuator device 112 (e.g. similar as depicted in Figure 1A and Figure 1 B).
  • Figure 7B the second actuator 176 has moved the single reservoir actuating tip 136 to a position away from the carriage 108 so that, for example, the carriage 108 may move without interference by the single reservoir actuating tip 136.
  • Figure 7B also shows a position of the single reservoir actuating tip 136 while repositioning along the path 170 to align with a reservoir 106-6.
  • the second actuator 176 has moved the single reservoir actuating tip 136 towards the carriage 108 to actuate a reservoir 106-6 which, in Figure 7C, is depicted as pressed and/or crushed, for example to push air therein into a respective sample preparation cartridge module 104 to dispense a sample therefrom (e.g. after sample processing to isolate and/or purify a biological component of interest).
  • the second actuator 176 may move the single reservoir actuating tip 136 to the position shown in Figure 7B such that the first actuator 174 may move the single reservoir actuating tip 136 to a next position along the path 170 (e.g. along rail and/or drive screw 172) to align with another reservoir 106-6 of another sample preparation cartridge module 104.
  • the second actuator device 112 may be used to actuate individual reservoirs 106-6 and/or any other of the reservoirs 106.
  • sample preparation cartridge modules 104 may be dispensed into sample wells in the sample preparation device (e.g. after sample processing to isolate and/or purify a biological component of interest), as described below with respect to Figure 8B, and that between dispensing events, a sample well may be aligned with a tip of a sample preparation cartridge module 104 that has a reservoir 106-6 that is next to be actuated by the second actuator device 112. Hence, actuating of individual reservoirs 106-6 may be coordinated with positioning of individual tips of the sample preparation cartridge modules 104 relative to the sample wells.
  • Figure 8A and Figure 8B respectively depict a perspective view and a block diagram of an example sample preparation device 800 that incorporates aspects of the device 100 and of Figure 1.
  • the sample preparation device 800 (interchangeably referred to hereafter as the device 800) includes a chassis 802 that includes a carriage access door 804 for loading the cassette 102 that includes the sample preparation cartridge module 104 and/or sample preparation cartridge modules 104 therein, the sample preparation cartridge module 104 holding a sample for testing as described hereafter. While the sample preparation cartridge modules 104 are depicted as being in an elongate shape and/or in the form of a column, similar to Figure 1 B, Figure 2 and Figure 3, the sample preparation cartridge modules 104 may be any suitable shape.
  • the chassis 802 further includes a well access door 810 for loading a well holder 812 containing a well 814 and/or wells for receiving processed samples (e.g.
  • sample preparation cartridge module 104 after sample processing to isolate and/or purify a biological component of interest dispensed from the sample preparation cartridge module 104 after processing by the device 800. While only one sample preparation cartridge module 104 is depicted, and eight wells 814, it is understood that the cassette 102 may hold a same number of sample preparation cartridge modules 108 as there are wells 814 at the well holder 812. For example, as depicted, similar to Figure 1 B, there may be eight sample preparation cartridge modules 104 and hence eight wells.
  • the components of the device 800 may cause the cassette 102 and the well holder 812 to be loaded into the device 800 in any suitable relative orientation including, but not limited to, about parallel to one another such that a line of the sample preparation cartridge module 104 is about aligned with a line of the wells 814.
  • the device 800 further comprises an input device 818, such as a touch screen display, and the like, which may be used to control the device 800 into a loading mode, which causes the carriage access door 804 and the well access door 810 to open such that the cassette 102 and the well holder 812, with the wells 814, may be manually loaded into the device 800.
  • a sample preparation cartridge module 104 is loaded with a sample 838 (e.g. such as a biological sample retrieved from a human by medical personnel), and the like, via the port 820.
  • the input device 818 may also be used to set given temperatures to which the sample preparation cartridge module 104 is to be heated and/or a heating cycle of the sample preparation cartridge module 104 and/or a heating/mixing cycle (e.g. setting mixing speeds of a actuator 844 of the device 800).
  • the carriage 108 of the device 800 which may alternatively be referred to as the cassette carriage 108, is raised along a vertical carriage guide 826 (e.g. which may include the rails 120 and drive screws 122) to at least partially emerge from an opening that is normally covered by the carriage access door 804.
  • the cassette 102 may then be manually loaded into the carriage 108.
  • the shuttle e.g. a well carriage
  • the planar surface e.g.
  • a horizontal carriage guide 830 is moved out of an opening that is normally covered by the well access door 810, for example by moving and/or rotating an end of planar surface 830 at which the shuttle 828 is located in the loading mode, out of the opening.
  • the well holder 812 is then manually loaded into a complementary shaped depression and/or holder 831 in the well carriage 108. While the terms vertical and horizontal are used herein with regards to a position of the device 800 in a normal use mode, such terms are meant for ease of description only and/or to indicate relative positions of components of the device 800 (e.g. the guide 826 and the planar surface 830 may be about perpendicular to each other as one is vertical and the other horizontal, but may be in any suitable orientation).
  • the cassette carriage 108 moves the cassette 102 into the device 800 (e.g. closing the door 804), and then into different positions in the device 800, for example along the vertical carriage guide 826 (e.g. via the rails 120, the drive screws 122 and the motor 124), to process the sample 838, for example at least by concurrently actuating rows of reservoirs 106 using the first actuating device 110, before dispensing the sample 838 from the sample preparation cartridge module 104 into a well 814, for example at least by actuating individual reservoirs 106 using the second actuating device 112.
  • the planar surface 830 moves inside the device 800 (e.g. closing the door 810) and the shuttle 828 is moved into a position to receive the sample 838 from the sample preparation cartridge module 104 into a corresponding well 814.
  • the shuttle 828 is moved into respective positions to receive respective samples 838 dispensed from respective sample preparation cartridge modules 104 into corresponding wells 814.
  • the shuttle 828 may be positioned at an angle relative to the cassette carriage 108 and/or the cassette 102 such that different sample preparation cartridge modules 104 align with different wells 814 at different positions of the shuttle 828.
  • the device 800 is further understood to include motors and/or a servomotors, and the like, to move the planar surface 830 into and out of the device 800, and to linearly move the shuttle 828 along the planar surface 830.
  • the device 800 may further include respective components for opening and closing the doors 804, 810.
  • a sample preparation cartridge module 104 may be divided into a first region 832 and a second region 834 (e.g. depicted in Figure 3), divided by a barrier 836.
  • a sample 838 is received into the sample preparation cartridge module 104 via the port 820, and may reside at a bottom of the first region 832, at the barrier 836.
  • the sample preparation cartridge module 104 may further comprise an agitator 840 in the first region 832 which may be actuated via a mixer actuator 842 and an actuator 844, and the like of the device 800 as described below.
  • the mixer actuator 842 may include a servomotor and/or servomotors, and the like, to move/rotate the actuator 844 to mix the sample 838 via the agitator 840, while the sample 838 is heated, as described below.
  • the cassette 102 may be moved, along the vertical carriage guide 826, via the cassette carriage 108, into a heating position for heating by one or both of two heaters 846 (e.g. heaters 846-1 , 846-2) attached to respective mechanical devices 848 (e.g. mechanical devices 848-1 , 848-2).
  • two heaters 846 e.g. heaters 846-1 , 846-2
  • respective mechanical devices 848 e.g. mechanical devices 848-1 , 848-2).
  • the device 800 is understood to include respective temperature sensors at the heaters 846 and/or the mechanical devices 848 so that, in a heating position of the cassette carriage 108, the heaters 846 may be positioned adjacent the first region 832 of the sample preparation cartridge module 104 to heat the sample 838, while the agitator 840 is actuated by the actuator 844, to agitate and/or mix the sample 838 while it is being heated, for example to promote lysis in cells of the sample 838.
  • the actuator 844 itself is understood to be further moved by the mixer actuator 842 into a position to agitate and/or mix the sample 838, while it is being heated, and actuated by the mixer actuator 842 which may comprise any suitable combination of motors for moving and turning the actuator 844.
  • the first region 832 may include magnetizing microparticles having surfaces to which a biological component of interest, expelled by cells of the sample 838 due to lysis, bond; hence, in some examples, the actuator 844 may comprise a magnetic agitating device which agitates the sample 838 during lysis by applying a changing magnetic field to the first region 832 to move the magnetizing microparticles; in such examples, the agitator 840 may be omitted from the sample preparation cartridge module 104.
  • the agitator 840 is generally configured to mate with the actuator 844; for example, as depicted, the agitator 840 may be attached to a pressure source 250, such as a plunger, and the like, an outer surface of which may be used to both mate with the actuator 844, to actuate the agitator 840, and move the sample 838 to the second region 834, for example by applying pressure to the pressure source 850 via the actuator 844 to break the barrier 836.
  • a pressure source 250 such as a plunger, and the like
  • the second region 834 may further include a wash buffer which may be mixed with the biological components of interest (e.g. bonded to the magnetizing microparticles) (e.g. when plunged into the second region 834), by concurrent actuation of a suitable row of reservoirs 106 that hold the wash buffer, for example by the first actuator device 110. Concurrent actuation of other rows of reservoirs 106 the first actuator device 110 by release a grease barrier into the second region 834, and chemicals to stabilize biological components of interest, another reservoir 106.
  • a wash buffer which may be mixed with the biological components of interest (e.g. bonded to the magnetizing microparticles) (e.g. when plunged into the second region 834), by concurrent actuation of a suitable row of reservoirs 106 that hold the wash buffer, for example by the first actuator device 110. Concurrent actuation of other rows of reservoirs 106 the first actuator device 110 by release a grease barrier into the second region 834, and chemicals to stabilize biological components of interest, another reservoir 106.
  • reservoirs 106 in another row may be individually actuated by the second actuator device 112 to dispense the biological components of interest bonded to the magnetizing microparticles into a well 814, for example via a needle and/or tip 854 of the sample preparation cartridge module 104.
  • the cassette 102 may hold a plurality of sample preparation cartridge modules 104 and hence the device 800 may have the device 100 incorporated therein to actuate a plurality of corresponding reservoirs 106 (e.g. concurrently) on a plurality of sample preparation cartridge modules 104 for sample processing, and to actuate individual reservoirs 106 (e.g. independent of each other) on the sample preparation cartridge modules 104 for sample dispensing.
  • the device 800 includes the first actuator device110 (e.g. a multiple reservoir actuator) including the row of reservoir tips 128 (though only one is depicted) which may be used to actuate a plurality of corresponding reservoirs 106 (e.g. concurrently) on a plurality of sample preparation cartridge modules 104, for example to concurrently introduce the wash buffer, or the stabilizing chemicals or the grease barrier into the second regions 834 of the plurality of sample preparation cartridge modules 104.
  • the device 800 includes the second actuator device 112 (e.g. a single reservoir actuators) with the single reservoir tip 136, for independently actuating respective reservoirs 106 at the plurality of sample preparation cartridge modules 104 to independently dispense samples 838 into respective wells 814 via respective tips 854.
  • cassette carriage 108 may be moved into various suitable positions along the vertical carriage guide 826 relative to other components of the device 800, to effect actuation of the pressure source 850 and/or actuation of respective reservoirs 106 by the reservoir actuator devices110, 112.
  • the device 800 and/or the sample preparation cartridge module 104 may include other suitable components.
  • the sample preparation cartridge module 104 may include magnetizing microparticles in the first region 832 which have surfaces treated to bond to a biological component of interest from the sample 838 when heated.
  • the second region 834 may include a wash buffer density gradient, when the wash buffer is introduced into the second region 834; in particular, the second region 834 may comprise a fluid density gradient isolates and/or purifies the biological components of interest bonded to magnetizing microparticles.
  • the second region 834 may alternatively be referred to as a fluid density gradient region.
  • the device 800 may include a magnet and/or magnets 864, which may be actuated via a magnetic actuator 866 to move the magnet(s) 864 adjacent the sample preparation cartridge module 104 to attract the magnetizing microparticles in the sample 838 to wash the magnetizing microparticles and move the sample 838 towards the tip 854 and/or through the wash buffer density gradient in the second region 834, for example in combination with moving the sample preparation cartridge modules 104 via the carriage 108.
  • a magnet and/or magnets 864 which may be actuated via a magnetic actuator 866 to move the magnet(s) 864 adjacent the sample preparation cartridge module 104 to attract the magnetizing microparticles in the sample 838 to wash the magnetizing microparticles and move the sample 838 towards the tip 854 and/or through the wash buffer density gradient in the second region 834, for example in combination with moving the sample preparation cartridge modules 104 via the carriage 108.
  • the device 800 further includes a cooler and/or air-intake port 868 and/or tube which may include a fan, and the like (not depicted) for drawing air into the device 800 via a filter 870, and an exhaust port 872 (which may also include a fan) for expelling air drawn into the device 800 via the cooler port 868 via a respective filter 874.
  • the ports 868, 872 may provide passive and/or active cooling at the device 800 to cool the sample 838 when heated.
  • the ports 868, 872 may be located in any respective suitable positions at the device 800.
  • the cassette carriage 108 may be moved into a sample dispensing position relative to the shuttle 828 and/or the wells 814 to dispense samples 838 into the wells 814 from the sample preparation cartridge modules 104; the shuttle 828 may be moved into sample receiving positions, relative to the carriage 108, to position the wells 814 relative to the sample preparation cartridge modules 104 to receive the samples 838 as dispensed via actuation of individual suitable reservoirs 106 by the second actuator device 112.
  • the device 800 further comprises a processor 890 and a memory 892.
  • the processor 890 may include a general-purpose processor and/or controller or special purpose logic, such as a microprocessor and/or microcontroller (e.g. a central processing unit (CPU) and/or a graphics processing unit (GPU) an integrated circuit or other circuitry), an application specific integrated circuit (ASIC), a Field Programmable Gate Array (FPGA), a programmable array logic (PAL), a programmable logic array (PLA), a programmable logic device (PLD), and the like.
  • a microprocessor and/or microcontroller e.g. a central processing unit (CPU) and/or a graphics processing unit (GPU) an integrated circuit or other circuitry
  • ASIC application specific integrated circuit
  • FPGA Field Programmable Gate Array
  • PAL programmable array logic
  • PLA programmable logic array
  • PLD programmable logic device
  • the processor 890 may be implemented as a hardware element with no software elements (e.g. such as an ASIC, an FPGA, a PAL, a PLA, a PLD etc.).
  • the memory 892 may comprise instructions 894 for controlling the processor 890 and/or a processor thereof to perform the various processes described herein and which may include the various positions at which the carriage 108 is to be located relative the actuator devices 110, 112 as described herein.
  • a memory 892 may include, but is not limited to, any suitable combination of a volatile computer-readable medium (e.g., volatile RAM, a processor cache, a processor register, etc.), a non-volatile computer-readable medium (e.g., a magnetic storage device, an optical storage device (e.g. a Digital Versatile Disc (DVD), a paper storage device, flash memory, read-only memory, non-volatile RAM, etc.), and/or the like.
  • a volatile computer-readable medium e.g., volatile RAM, a processor cache, a processor register, etc.
  • a non-volatile computer-readable medium e.g., a magnetic storage device, an optical storage device (e.g. a Digital Versatile
  • Figure 8C is substantially similar to Figure 8B with like components having like numbers.
  • the cassette 102 has been loaded into the cassette carriage 108, and the carriage access door 804 has been closed.
  • the sample 838 has undergone lysis via heating by the heaters 846, and moved to the second region 834 of the sample preparation cartridge module 104 via the pressure source 850 being actuated (e.g. by moving the cassette carriage 108 to move the sample preparation cartridge module 104 towards the actuator 844 so that the actuator 844 actuates the pressure source 850 to break the barrier 836, for example by pushing the agitator 840 towards the barrier 836 via the pressure source 850).
  • reservoirs 106 containing the wash buffer, the stabilizing chemicals and the grease barrier have been concurrently actuated by the first actuator device 110 and the tips 128.
  • the reservoirs 106 associated with sample processing are no longer seen at the sample preparation cartridge module 104, having been crushed by the tips 128.
  • the processed sample 838 has been drawn through the wash buffer density gradient/fluid density gradient to better isolate and/or purify a biological component of interest bonded to magnetizing microparticles attached thereto.
  • the carriage 108 has been moved to a sample dispensing position and the wells 814 have been loaded into the well holder 812 at the shuttle 828, and the planar surface 830, with the shuttle 828, has been moved/rotated into the device 800 from an external position to an internal position, with the well access door 810 closed.
  • the shuttle 828 has been moved into a sample receiving position (e.g. a first sample receiving position), relative to the sample dispensing position of the carriage 108, such that a well 814 is aligned with the sample preparation cartridge module 104, and specifically the tip 854 thereof.
  • the second actuator device 106 has been controlled to move the single reservoir actuating tip 136 to actuate a dispensing reservoir 106-6 (not depicted in Figure 8C, having been crushed by the single reservoir actuating tip 136).
  • the processed sample 838 at the tip 854 now processed to isolate and/or purify the biological component of interest bonded to the magnetizing microparticles is being dispensed into a corresponding well 814.
  • the wells 814 and/or regions around the tip 854 at the sample preparation cartridge module 104 may include splash guards, and the like, to assist with reducing cross-contamination between the wells 814.
  • the shuttle 828 While the shuttle 828 is depicted as being at one sample receiving position, the shuttle 828 may be moved to other sample receiving positions (e.g. up to eight sample receiving positions, one for each well 814 and corresponding sample preparation cartridge module 104 when there are eight of each; sample preparation cartridge modules 104, that do not contain a sample may be skipped in the dispensing process), and similarly the single reservoir actuating tip 136 may be moved to respective positions along the path 170 to actuate individual reservoirs 106-6 to dispense samples.
  • a flow diagram of an example method 900 to actuate reservoirs is depicted. In order to assist in the explanation of method 900, it will be assumed that method 900 may be performed with the device 800 (e.g. via the processor 890 implementing the instructions 894 stored at the memory 892). The method 900 may be one way in which the device 800 may be configured. Furthermore, the following discussion of method 900 may lead to a further understanding of the device 800, and their various components.
  • method 900 may not be performed in the exact sequence as shown, and various blocks may be performed in parallel rather than in sequence, or in a different sequence altogether. Furthermore, the method 900 may be performed by the device 100.
  • the actuators 126, 138, 174, 176 will be referred to, respectively, as the first actuator 126, the second actuator 138, the third actuator 174 and the fourth actuator 176.
  • the processor 890 and/or the device 800 controls the carriage 108 to move along the path 125, relative to the first actuator device 110, into a first carriage position (e.g. where the mating devices 116, 118 are aligned as depicted in Figure 3A and Figure 3B).
  • the processor 890 and/or the device 800 controls the first actuator 126 of the first actuator device 110 to cause respective mating devices 116, 118 of the carriage 108 and the first actuator device 110 to mate.
  • the processor 890 and/or the device 800 when the respective mating devices 116, 118 are mated, controls the second actuator 138 of the first actuator device 110 to actuate the reservoir actuating tips 128 towards, and then away from, the carriage 108 for example to actuate a respective row of reservoirs 106.
  • controlling the first actuator 126 of the first actuator device 110 to cause the respective mating devices 116, 118 to mate aligns the reservoir actuating tips 128 with a row of reservoirs 106 of a plurality of sample preparation cartridge modules 104 held by the carriage 108 such that, when the second actuator 138 actuates the reservoir actuating tips 128 towards the carriage 108, the reservoir actuating tips 128 actuate the reservoirs 106 in the row for example which may release a chemical held by the reservoirs 106 into the plurality of sample preparation cartridge modules 104.
  • the controlling the second actuator 138 of the first actuator device 110 to actuate the reservoir actuating tips 128 towards, and then away from, the carriage 108 may occur by: partly actuating the reservoir actuating tips 128 towards, and then away from, the carriage 108; and then fully actuating the reservoir actuating tips 128 towards, and then away from, the carriage 108, for example to partially dispense and then fully dispense a chemical, and the like, held by the reservoirs 106 being actuated by the tips 128.
  • the processor 890 and/or the device 800 controls the first actuator 126 to unmate the respective mating devices 116, 118.
  • the blocks 902, 904, 906, 908 may be implemented any suitable number of times to actuate different rows of the reservoirs 106 in any suitable order.
  • the processor 890 and/or the device 800 controls the carriage 108 to move, along the path 125 into a second carriage position for example, in the second carriage position, the single reservoir actuating tip 136 may located at the row of reservoirs 106-6 of a plurality of sample preparation cartridge modules 104 held by the carriage 108.
  • the processor 890 and/or the device 800 controls a third actuator 174 of the second actuator device 112 to move the single reservoir actuating tip 136, (e.g. different from the reservoir actuating tips 128), into different positions perpendicular to the path 125 of the carriage 108, for example in the “X” direction to align with one reservoir 106-6.
  • the processor 890 and/or the device 800 at the different positions controls a fourth actuator 176, of the second actuator device 112, to actuate the single reservoir actuating tip 136 towards, and then away from, the carriage 108, for example to actuate one reservoir 106-6, before the third actuator moves the single reservoir 106 actuating tip into a next position to actuate another reservoir 106-6.
  • controlling the third actuator 174 of the second actuator device 112 to move the single reservoir actuating tip 136 into the different positions causes the single reservoir actuating tipi 36 to align with one respective reservoir 106-6 at one respective sample preparation cartridge module 104, of a plurality of sample preparation cartridge modules 104, held by the carriage 108 such that, when the fourth actuator 176 actuates the single reservoir actuating tip 136 towards the carriage 108, the single reservoir actuating tip 136 actuates the respective single reservoir 106-6 for example to dispense a sample from the one respective sample preparation cartridge modules 104.

Abstract

An example device comprises: a carriage comprising a first mating device; and an actuator device comprising: a second mating device that mates with the first mating device; a first actuator to move the second mating device to mate with the first mating device to position the actuator device at a given position relative to the carriage; reservoir actuating tips that are positioned, relative to the carriage, when the actuator device is positioned at the given position relative to the carriage; and a second actuator to move the reservoir actuating tips towards the carriage.

Description

Reservoir Actuating Devices and Methods
BACKGROUND
[0001] Sample preparation cartridge modules may include reservoirs and/or pouches, for example for releasing chemicals into the sample preparation cartridge modules and/or for dispensing a sample from the sample preparation cartridge modules in a sample preparation process.
BRIEF DESCRIPTION OF THE DRAWINGS
[0002] Reference will now be made, by way of example only, to the accompanying drawings in which:
[0003] Figure 1 A is a perspective view of an example sample preparation device for actuating reservoirs of sample preparation cartridge modules held by a cassette.
[0004] Figure 1 B is a perspective view of the example sample preparation device of Figure 1 A showing the cassette at the example sample preparation device.
[0005] Figure 2 is a perspective view of a portion of the device of Figure 1 A showing details of one pair of mating devices.
[0006] Figure 3A and Figure 3B respectively show a perspective and side view of a first actuating device of the device of Figure 1 A, that actuates a row of reservoirs concurrently, with a carriage moved to align the mating devices, which further aligns reservoir actuating tips with the row of reservoirs.
[0007] Figure 4A and Figure 4B respectively show a perspective and side view of the first actuating device of the device of Figure 1 A with the mating devices mated to closer position the reservoir actuating tips with the row of reservoirs.
[0008] Figure 5A and Figure 5B respectively show a perspective and side view of the first actuating device of the device of Figure 1 A with the reservoir actuating tips moved to actuate the row of reservoirs.
[0009] Figure 6 depicts a portion of a biasing mechanism of the first actuating device of the device of Figure 1 A that better positions the reservoir actuating tips into a position for actuating a row of reservoirs.
[0010] Figure 7 A depicts a perspective view of a second actuator device that actuates a single reservoir in a row of reservoirs.
[0011] Figure 7B depicts a cross-section of the second actuator device relative to a reservoir through a line A-A in Figure 7A, in an unactuated position.
[0012] Figure 7C depicts a cross-section of the second actuator device relative to a reservoir through the line A-A in Figure 7A, in an actuated position and showing actuation of the reservoir.
[0013] Figure 8A is a perspective view of an example sample preparation device that incorporates the device of Figure 1A.
[0014] Figure 8B is a block diagram of the device of Figure 8A.
[0015] Figure 8C is a block diagram of the device of Figure 8A with a carriage in a sample dispensing position.
[0016] Figure 9 is a flow diagram of a method to actuate reservoirs implemented using the device of Figure 1 A and/or the device of Figure 8A.
DETAILED DESCRIPTION
[0017] In biological assays, a biological component can be intermixed with other components in a biological sample that can interfere with subsequent analysis. As used herein, the term “biological component” can refer to materials of various types, including proteins, cells, cell nuclei, nucleic acids, bacteria, viruses, or the like, that can be present in a biological sample. A “biological sample” can refer to a fluid or a dried or lyophilized material obtained for analysis from a living or deceased organism. Isolating the biological component from other components of the biological sample can permit subsequent analysis without interference and can increase an accuracy of the subsequent analysis. In addition, isolating a biological component from other components in a biological sample can permit analysis of the biological component that would not be possible if the biological component remained in the biological sample. In this context, “Isolation” can also be referred to as “purification”, whereby biological component may be separated from the rest of the biological sample after introduction to a sample preparation cartridge module interchangeably referred to hereafter as a sample container, a sample dispensing container, a cartridge module, and the like. It will be understood that the isolated biological component may be output in association with (e.g., bound to) particulate substrate and a reagent solution, or the like. The isolation or purification refers to the separation of the biological component from other components of the biological sample with which it was originally introduced in the cartridge module, but it does not mean that the biological component is completely isolated when it is dispensed. For example, isolation refers to the fact that the biological component is sufficiently separated or “purified” from other components of the original biological sample to facilitate further processing such as detection and/or amplification.
[0018] Many isolation techniques can include repeatedly dispersing and reaggregating samples. The repeated dispersing and re-aggregating can result in a loss of a quantity of the biological component. Furthermore, isolating a biological component with some of these techniques can be complex, time consuming, and labor intensive and can result in less than maximum yields of the isolated biological component. Such Isolation techniques are done using specific devices.
[0019] Obtaining precise biological sample preparation devices can be challenging due to many moving parts present in the devices, for example to move a carriage holding a cartridge of sample dispensing containers relative to sample receiving wells. The cartridge may hold a plurality of the sample dispensing containers or sample preparation devices or sample preparation cartridge modules which contain different respective biological samples.
[0020] During the isolation process, The sample dispensing containers or sample preparation devices or sample preparation cartridge modules may heat the samples to perform for example, lysis on cells in the biological samples to release biological component of interest, coming from the biological sample, may be a nucleic acid (such as DNA or RNA). Resulting sample fluid may be drawn through a fluid density gradient in the sample dispensing containers and dispensed into sample receiving wells, which may be transferred to further analytical assay such as, for example, a Polymerase Chain Reaction (PCR).
[0021] However, as initial quantities of the biological component of interest present in the biological sample, may be small, precise dispensing of the component of interest from the sample dispensing containers into the sample receiving wells should occur so as to not lose any content and/or to prevent cross-contamination between samples. As such a precise determination of a position of a shuttle and/or well carriage, that holds the sample receiving wells, relative to the carriage is important, and vice versa.
[0022] In some examples, the device of the present disclosure is a device that can be used to prepare sample to be used in a process of preparing samples for a PCR (polymerase chain reaction) assay. PCR assays are processes that can rapidly copy millions to billions of copies of a very small DNA or RNA sample. PCR can be used for many different application, included sequencing genes, diagnosing viruses, identifying cancers, and others. In the PCR process, a small sample of DNA or RNA is combined with reactants that can form copies of the DNA or RNA.
[0023] As described herein, the biological sample comprises a biological component. In some examples, the biological component of interest, coming from the biological sample, may be a nucleic acid (such as DNA or RNA). A particulate substrate can be configured to be associated with the biological component, to isolate the biological component from the biological sample. In one example, the particulate substrate comprises paramagnetic beads and/or any magnetizing particle and/or magnetizing microparticles. In one example, the biological component comprises nucleic acids such as DNA and/or RNA that may be extracted from the biological sample by lysing, bound to magnetic particulate substrate, and separated from the lysate and dragged towards an output by an externally generated (para)magnetic force. Lysate may refer to the fluid containing the material resulting from the lysis of a biological sample. Such lysis may release the biological component that is contained therein. Lysing itself may include mixing and/or heating the biological sample, chemically lysing the biological sample, and/or a combination of the foregoing.
[0024] Provided herein is a sample preparation device that accepts a cassette that includes a plurality of sample preparation cartridge modules into which samples have been inserted, for example biological samples that may include a biological component of interest as described above. The sample preparation cartridge modules include respective reservoirs and/or blisters and/or pouches into which chemicals have been provided, and which may be released into the sample preparation cartridge modules upon actuation of the reservoirs and/or pouches in a sample preparation process. The sample preparation cartridge modules also include a respective reservoir and/or blister pouch that may include air, and the like, such that, when a respective reservoir and/or pouch that includes air is actuated, a sample (e.g. after sample processing) from the sample preparation cartridge module is dispensed, for example via a tip of the sample preparation cartridge module. Hereafter the reservoirs and/or blisters pouches will be referred to interchangeably as reservoirs, though it is understood that the term reservoir may be replaced with the term blister and/or pouch.
[0025] For expediency in the sample preparation process, the sample preparation device provided herein generally includes a first actuator device which concurrently actuates a row of reservoirs that a release a given chemical on all the sample preparation cartridge modules held in the cassette to concurrently process samples therein. However, the sample preparation device further includes a second actuator device which individually actuates respective reservoirs that dispense a respective sample (e.g. after processing to isolate and/or purify the biological component of interest) from a given sample preparation cartridge module, for example after the carriage holding the sample preparation cartridge modules is placed into a respective sample dispensing position for the given sample preparation cartridge module. As such, the sample preparation process may occur concurrently at the sample preparation cartridge modules, while sample dispensing may occur individually at the sample preparation cartridge modules.
[0026] A first aspect of the present specification provides a device comprising: a carriage comprising a first mating device; and an actuator device comprising: a second mating device that mates with the first mating device; a first actuator to move the second mating device to mate with the first mating device to position the actuator device at a given position relative to the carriage; reservoir actuating tips that are positioned, relative to the carriage, when the actuator device is positioned at the given position relative to the carriage; and a second actuator to move the reservoir actuating tips towards the carriage.
[0027] The device of the first aspect may further comprise a biasing mechanism to move the actuator device into the given position, relative to the carriage, when the second mating device mates with the first mating device.
[0028] At the device of the first aspect, the first mating device may comprise a pair of V-shaped grooves on opposite ends of the carriage, and the second mating device may comprise a corresponding pair of pins to move into the V- shaped grooves.
[0029] At the device of the first aspect, the second actuator may be further to actuate the reservoir actuating tips towards the carriage with a reservoir actuating force.
[0030] The device of the first aspect may further comprise a pair of arms, and wherein: the reservoir actuating tips may extend between the pair of arms, the first mating device may comprise a pair of V-shaped grooves on opposite ends of the carriage, the second mating device may comprise a pair of pins respectively located at the pair of arms, to move into the pair of V-shaped grooves, the first actuator may be to move the second mating device to mate with the first mating device by moving the pair of arms to move the pair of pins into the pair of V-shaped grooves, and the second actuator may be to actuate the reservoir actuating tips towards the carriage by pivoting the pair of arms around the pair of pins mated with the pair of V-shaped grooves, which further moves the reservoir actuating tips towards the carriage.
[0031] A second aspect of the present specification provides a device comprising: a carriage; and an actuator device, the carriage movable into a given position relative to the actuator device, the actuator device comprising: a single reservoir actuating tip; a first actuator to move the single reservoir actuating tip into respective given positions relative to the carriage; and a second actuator to actuate the single reservoir actuating tip towards the carriage.
[0032] The device of the second aspect may further comprise a motor to move the carriage along into the given position.
[0033] At the device of the second aspect, the first actuator may comprise a first motor to move the single reservoir actuating tip along a respective path perpendicular to a path of the carriage, into the respective given positions; and the second actuator may comprise a second motor to move the single reservoir actuating tip towards the carriage.
[0034] At the device of the second aspect, the second actuator may be to actuate the single reservoir actuating tip towards the carriage, perpendicular to a path of the single reservoir actuating tip along which the single reservoir actuating tip moves into the respective given positions relative to the carriage.
[0035] At the device of the second aspect, the single reservoir actuating tip may be mounted on a rail that extends along a respective path along which the single reservoir actuating tip moves into the respective given positions relative to the carriage, and the first actuator may be further to move the single reservoir actuating tip along the rail into the respective given positions.
[0036] A third aspect of the present specification provides a method comprising: controlling, at a sample preparation device, a carriage to move along a path, relative to an actuator device, into a first carriage position; controlling, at the sample preparation device, a first actuator of the actuator device to cause respective mating devices of the carriage and the actuator device to mate; when the respective mating devices are mated, controlling, at the sample preparation device, a second actuator of the actuator device to actuate reservoir actuating tips towards, and then away from, the carriage; controlling, at the sample preparation device, the first actuator to unmate the respective mating devices; controlling, at the sample preparation device, the carriage to move, along the path into a second carriage position; controlling, at the sample preparation device, a third actuator of the actuator device to move a single reservoir actuating tip, different from the reservoir actuating tips, into different positions perpendicular to the path of the carriage; and at the different positions, controlling a fourth actuator, of the actuator device, to actuate the single reservoir actuating tip towards, and then away from, the carriage, before the third actuator moves the single reservoir actuating tip into a next position.
[0037] At the method of the third aspect, controlling the first actuator of the actuator device to cause the respective mating devices to mate may align the reservoir actuating tips with a row of reservoirs of a plurality of sample preparation cartridge modules held by the carriage such that, when the second actuator actuates the reservoir actuating tips towards the carriage, the reservoir actuating tips actuate the reservoirs in the row to release a chemical held by the reservoirs into the plurality of sample preparation cartridge modules.
[0038] At the method of the third aspect, controlling the third actuator of the actuator device to move the single reservoir actuating tip into the different positions may cause the single reservoir actuating tip to align with one respective reservoir at one respective sample preparation cartridge module, of a plurality of sample preparation cartridge modules, held by the carriage such that, when the fourth actuator actuates the single reservoir actuating tip towards the carriage, the single reservoir actuating tip actuates the one respective reservoir to dispense a sample from the one respective sample preparation cartridge module.
[0039] At the method of the third aspect, controlling the second actuator of the actuator device to actuate the reservoir actuating tips towards, and then away from, the carriage may occur by: partly actuating the reservoir actuating tips towards, and then away from, the carriage; and then fully actuating the reservoir actuating tips towards, and then away from, the carriage.
[0040] At the method of the third aspect, in the second carriage position, the single reservoir actuating tip may be located at a row of reservoirs of a plurality of sample preparation cartridge modules held by the carriage.
[0041] Figure 1 A and Figure 1 B show perspective views of an example device 100 into which a cassette 102 may be inserted. In particular, Figure 1 A shows the device 100 without the cassette 102 and Figure 1 B shows the device 100 with the cassette 102, for example after the cassette 102 has been inserted into the device 100.
[0042] With brief reference to Figure 1 B, the cassette 102 generally holds a sample preparation cartridge module 104 and/or sample preparation cartridge modules 104, for example in a frame, and the like. The sample preparation cartridge modules 104 may alternatively be referred to as cartridge modules sample containers and/or sample dispensing containers, and the like. While as depicted the cassette 102 includes eight sample preparation cartridge modules 104, the cassette 102 may include as few as one sample preparation cartridge module 104 and/or a number of sample preparation cartridge modules 104 different from eight. The sample preparation cartridge module 104 includes reservoirs 106 (e.g. as depicted six reservoirs 106), some of which contain chemicals, for example in a fluid form, used for processing a sample in the sample preparation cartridge module 104, and which may be released into a sample processing region of the sample preparation cartridge module 104 upon actuation though (some of the reservoirs 106 may be used in sample processing to mix chemicals and/or puncture foil in the reservoirs 106 prior to the chemicals being inserted into a sample preparation cartridge module 104). However, one of the reservoirs 106 may contain air, and the like, and which, upon actuation, is used to dispense the sample (e.g. a biological component of interest) from the sample preparation cartridge module 104 after sample processing, as described in more detail below.
[0043] For reference, an “XYZ” coordinate system 107 is also depicted in Figure 1A and Figure 1 B and which will be used herein to show relative positions of components of the device 100 and/or the cassette 102. For example, a “Z” direction may be along a length of a sample preparation cartridge module 104 when held by the device 100, an “X” direction may be along the row of the sample preparation cartridge modules 104 in the cassette 102 when held by the device 100, and a “Y” direction may be perpendicular to the “X” and “Y” directions.
[0044] In particular, as best seen in Figure 1 B, the reservoirs 106 of adjacent sample preparation cartridge modules 104 are arranged in rows across the cassette 102 in the “X” direction. It is understood that each reservoir 106 in a row may perform a same function and/or hold a same chemical, and the like, such that when a row of reservoirs 106 is actuated concurrently, a same process occurs in the sample preparation cartridge modules 104.
[0045] While described in more detail below, it is understood that components of the device 100 may be components of a larger sample preparation device used for preparation of samples. In particular, the device 100 may be used in a larger sample preparation device to perform lysis of samples in sample preparation cartridge modules. Such a sample preparation device is described below with respect to Figure 8A and Figure 8B.
[0046] With reference to Figure 1 A and/or Figure 1 B, the device 100 generally comprises a carriage 108 to receive the cassette 102, a first actuator device 110 that actuates some reservoirs 106 concurrently at the sample preparation cartridge modules 104, for example a row of reservoirs 106, and a second actuator device 112 that actuates other reservoirs 106 individually at the sample preparation cartridge modules 104. As depicted, the second actuator device 112 is between two components of the first actuator device 110. As such, the actuator devices 110, 112 are understood to be mounted together. However, in other examples, the actuator devices 110, 112 may be provided separately from each other.
[0047] The device 100 will hence be described hereafter with separate reference to the actuator devices 110, 112, with the first actuating device 110 described first with respect to Figure 1A, Figure 1 B, Figure 2, Figure 3A, Figure 3B, Figure 4A, Figure 4B, Figure 5A, Figure 5B and Figure 6. The second actuator device 112 will be described with reference to Figure 7A, Figure 7B and Figure 7C.
[0048] As depicted, the device 100 comprises the carriage 108, which includes a region 115 into which the cassette 102 is received and hence includes any suitable combination of grooves, constraining devices, and the like for holding and constraining the cassette 102 in the carriage 108.
[0049] As depicted, the carriage 108 comprises a first mating device 116, and the device 100 further comprises the first actuator device 110 which comprises: a second mating device 118 that mates with the first mating device 116.
[0050] In particular, as depicted, the first mating device 116 comprises a pair of V-shaped grooves on opposite ends of the carriage 108 (e.g. in the “X” direction), and the second mating device 118 comprises a corresponding pair of pins to move into the V-shaped grooves. While, due to the angle of perspective in Figure 1A and Figure 1 B, only one pin of the second mating device 118 is visible, it understood that a second pin of the second mating device 118 is present, such that the carriage 108 may be moved (e.g. in the “Z” direction) to a position where the pins of the second mating device 118 are arranged to be near and/or adjacent respective V-shaped grooves of the first mating device 116.
[0051] Furthermore, as depicted, the first mating device 116 comprises a plurality of pairs of V-shaped grooves, for example arranged along the “Z” direction, with which the pins of the second mating device 118 may be mated for example to position the first actuator device 110 relative to different rows of reservoirs 106 at the sample preparation cartridge modules 104. As such, it is understood that the carriage 108 and the first actuator device 110 move relative to each other to about align the pins of the second mating device 118 with a given pair of V-shaped grooves to actuate a given row of reservoirs 106, as described in more detail below.
[0052] In particular, as depicted, the carriage 108 is mounted to both rails 120 and a lead and/or drive screws 122 of a carriage guide (e.g. a vertical carriage guide described below with respect to Figure 8B) and the carriage 108 may be moved on the rails 120 to different predetermined positions relative to the first actuator device 110, for example, via a motor 124 and/or motors (e.g. a stepper motor) driving the drive screws 122. In particular, as best seen in Figure 1A, the carriage 108 may be moved to different positions, for example along a path 125 in the “Z” direction.
[0053] For example, the carriage 108 may be moved to as many positions as there are V-grooves of the first mating device 116 (e.g. as depicted, six positions) however, the carriage 108 may be moved to any number of positions along the path 125, which may also include a position for individually actuating a reservoir 106 for dispensing a respective sample from a sample preparation cartridge module 104, described in more detail below with respect to the second actuator device 112 in Figure 7 A, Figure 7B and Figure 7C. The rails 120, drive screws 122 and motor(s) 124 may also be used to position the carriage 108 within the larger sample preparation device.
[0054] The actuator device 110 further comprises a first actuator 126 to move the second mating device 118 to mate with the first mating device 116 to position the first actuator device 110 at a given position relative to the carriage 108, for example assuming that the carriage 108 has been moved along the path 125 into a position along the rails 120 where a pair of V-grooves of the first mating device 116 is about aligned, and/or adjacent to, the pins of the second mating device 118.
[0055] As depicted, the first actuator 126 may comprise any suitable combination of gears, motors, pulleys, and the like, to move the second mating device 118 to mate with the first mating device 116, a process which will be described in more detail below with respect to Figure 3A, Figure 3B, Figure 4A, Figure 4B, Figure 5A and Figure 5B.
[0056] The actuator device 110 further comprises reservoir actuating tips 128 that are positioned (e.g. at respective positions), for example arranged in a row, relative to the carriage 108, when the actuator device 110 is positioned at the given position relative to the carriage 108 defined at least in part by the mating of the mating devices 116, 118. For example, the given position of the actuator device 110, at which the actuator device 110 is positioned when the mating devices 116, 118 are mated, may be a position where the reservoir actuating tips 128 are about aligned with a row of reservoirs 106 to actuate the reservoirs 106 in the row, as described hereafter. The reservoir actuating tips 128 are interchangeably referred to hereafter as the tips 128.
[0057] While the row of the tips 128 are not visible from the perspective shown in Figure 1 A and Figure 1 B, also depicted in Figure 1 A is a block diagram of a view 130 of the tips 128 from an angle 132, for example as viewed along the “Y” direction through the region 115. While in the view 130 other components of the actuator devices 110, 112 are not depicted, they are nonetheless understood to be present.
[0058] As depicted, there are eight tips 128 (e.g. mounted to a block 134, a rear side of which is visible in Figure 1 A and Figure 1 B), for example as many tips 128 as there are sample preparation cartridge modules 104 and/or reservoirs 106 in a row. Hence, as there may be a number of sample preparation cartridge modules 104 different from eight, there may be a number of tips 128 that are different from eight. The row of tips 128, as depicted, comprise cylindrically shaped devices that are of a size, shape, position and spacing to actuate a respective reservoir 106, in a row of reservoirs 106 at the sample preparation cartridge modules 104. Hence, for example, when row of the tips 128 are aligned with a row of reservoirs 106, a particular tip 128 is positioned to actuate a respective reservoir 106 in a one-to-one relationship. In particular, “actuating” a reservoir 106 may be understood herein to include pressing and/or pushing on a reservoir 106, for example to crush the reservoir 106, to release a chemical (e.g. in fluid form) held by a reservoir 106 into a sample preparation cartridge module 104 and/or pressing and/or pushing on a reservoir 106 to dispense a sample (e.g. an isolated and/or purified biological component of interest) held by a sample preparation cartridge module 104.
[0059] The view 130 further shows a single reservoir actuating tip 136 (e.g. the tip 136) of the second actuating device 112 which will be described in more detail below.
[0060] The first actuator device 110 further comprises a second actuator 138 to actuate and/or move the tips 128 towards the carriage 108, for example towards the region 115 and/or towards a row of reservoirs 106 when the cassette 102 is received in the carriage 108. As such, the tips 128 may be used to concurrently actuate a row of reservoirs 106 at the sample preparation cartridge modules 104 to concurrently release respective chemicals held by the reservoirs 106 in the row, to concurrently process samples in the sample preparation cartridge modules.
[0061] As depicted, the second actuator 138 may comprise any suitable combination of gears, motors, pulleys, and the like, actuate and/or move the tips 128 towards the carriage 108 to actuate a row of reservoirs 106, a process which will be described in more detail below with respect to Figure 3A, Figure 3B, Figure 4A, Figure 4B, Figure 5A and Figure 5B.
[0062] In particular, however, the combination of gears, motors, pulleys, and the like of the second actuator 138 are selected such that the second actuator 138 is further to actuate the tips 128 towards the carriage 108 with a reservoir actuating force, for example a force sufficient to actuate a row of reservoirs 106 when the tips 128 press on the row of reservoirs 106. For example, a given reservoir 106 used for sample processing may include an outer foil shell, and the like (e.g. as seen in Figure 1 B) and an inner foil barrier which, together, hold a chemical, and the like, for example in fluid form, and the like (e.g. which may include, but is not limited to gel form, and the like) in the given reservoir 106. The inner foil barrier may be adjacent a respective aperture in a sample preparation cartridge module 104 that acts as a passage between the given reservoir 106 and a portion of the sample preparation cartridge module 104 within which sample processing and/or sample dispensing occurs. As such, the reservoir actuating force applied to a row of reservoirs 106 by the tips 128 (e.g. as provided by the second actuator 138), is understood to be sufficient to press on the outer plastic shell and break the inner foil barrier to release a respective chemical into the sample preparation cartridge module 104 and/or perform any other suitable process associated with actuating a reservoir 106.
[0063] Furthermore, the actuator device 110 and the carriage 108 may be operated to position the tips 128 at different rows of the reservoirs 106 (for example in a sequence), for example by mating the pins of the second mating device 118 with different pairs of V-grooves of the first mating device 116; when the pins of the second mating device 118 are mated with a given pairs of V- groove of the first mating device 116, the second actuator 138 may be operated to concurrently actuate a respective row of reservoirs 106.
[0064] As such, the actuator device 110 may be positioned at a plurality of given positions, corresponding to the pins of the second mating device 118 being mated with different V-grooves of the first mating device 116, and the given positions of the actuator device 110 may be respective positions at which the tips 128 are about aligned with a respective row of reservoirs 106 to actuate respective row of reservoirs 106.
[0065] While described in more detail below, it is understood that, in the depicted example, the device 100 further comprises a pair of arms 140 (only one of which is visible in Figure 1 A and Figure 1 B), and that the tips 128 extends between the pair of arms 140; for example, opposite ends of the block 134, to which the tips 128 are attached, may be rotationally attached to the arms 140 and/or the block 134 may extend between the arms 140. Furthermore, as depicted, the pair of pins of the second mating device 118 may be respectively located at the pair of arms 140, for example at positions that allow the pins to move into a pair of V-shaped grooves of the first mating device 116. In particular, in this example, the first actuator 126 is to move the pins of the second mating device 118, to mate with respective V-shaped grooves of the first mating device 116, by moving the pair of arms 140 to move the pair of pins into the pair of V-shaped grooves. Furthermore, in this example, the second actuator 138 is to actuate the reservoir actuating tips 128 towards the carriage 108 and/or a row of reservoirs 106, by pivoting and/or rotating the pair of arms 140 around the pair of pins mated with the pair of V-shaped grooves, which further moves the reservoir actuating tips towards the carriage and/or a row of reservoirs 106.
[0066] In some examples, as depicted, the device 100 further comprises a biasing mechanism and/or, as depicted, biasing mechanisms 142-1 , 142-2, which are interchangeably referred to hereafter as the biasing mechanisms 142 and/or a biasing mechanism 142. The biasing mechanism 142 is to move the actuator device 110 into the given position (and/or one of the given positions), relative to the carriage 108, when the second mating device 118 mates with the first mating device 116. While only a first biasing mechanism 142-1 , present at the carriage 108, is visible in Figure 1A and Figure 1 B, it is understood that a second biasing mechanism 142-2 is associated with the actuator device 110, and will be describe in more detail with respect to Figure 6, and further is visible in Figure 2, Figure 3A, Figure 3B, Figure 4A, Figure 4B, Figure 5A, and Figure 5B.
[0067] For example, as depicted, the first biasing mechanism 142-1 may comprise a pair of chamfered grooves in the carriage 108 (only one of which is visible in Figure 1A and Figure 1 B), into which respective complementary shaped chamfered arms (e.g. the second biasing mechanism 142-2) are inserted (e.g. mated) when the second actuator 138 moves the tips 128 towards the carriage 108. In particular, the biasing mechanism 142 may shift and/or move the actuator device 110 into the given position in the “X” direction to more precisely position the tips 128 relative to a row of reservoirs 106. Furthermore, the actuator device 110 may be biased (e.g. using a spring, and the like) in the “X” direction such that, when the biasing mechanisms 142 are mated, and the like, the second biasing mechanism 142-2 exerts a stabilizing force on the first biasing mechanism 142-1 to assist with holding the actuator device 110 into the given position relative to the carriage 108.
[0068] It should now be apparent that the XYZ coordinate system 107 may alternatively be defined with respect to the device 100 without the carriage 108. For example, the “Z” direction may be understood to be along the path 125 of the carriage 108, the “X” direction may be understood to be along a row of the tips 128 which are about perpendicular to the path 125, and the “Y” direction may be understood to be perpendicular to the path 125 and row of the tips 128 and/or in a direction of movement of the tips 128 towards and away from the carriage 108. The XYZ coordinate system 107 is provided on further figures herein to show relative orientations of the device 100, and the like, between the figures.
[0069] Attention is next directed to Figure 2 which depicts a portion of the device 100 showing details of one pair of the mating devices 116, 118 and, in particular, pins of the second mating device 118 as mated with one pair of V- shaped grooves 144-1 of the first mating device 116. In particular, Figure 2 shows that the second mating device 118 includes six pairs of V-shaped grooves 144-1 , 144-2, 144-3, 144-4, 144-5, 144-6. While only pin of the second mating device 118 is depicted, and only one V-shaped groove of the six pairs of V-shaped grooves 144-1 , 144-2, 144-3, 144-4, 144-5, 144-6 is depicted, it is understood that pins and V-shaped grooves are provided in pairs as shown in Figure 1A and Figure 1 B. The V-shaped grooves 144-1 , 144-2, 144-3, 144-4, 144-5, 144-6 are interchangeably referred to hereafter, collectively, as the V- shaped grooves 144 and/or a V-shaped groove 144.
[0070] Also depicted in Figure 2 is a rear of the block 134, with two reservoir actuating tips 128 shown in outline to indicate the row of the tips 128 are on an opposite side of the block 134. Also depicted in Figure 2 are reservoirs 106 of two of the sample preparation cartridge modules 104 (e.g. the reservoirs 106 are depicted without the remainder of the sample preparation cartridge modules 104) to show that an example sample preparation cartridge module 104 may include six reservoirs 106-1 , 106-2, 106-3, 106-4, 106-5 (e.g. indicated as 106- 5A and 106-5B), 106-6. The reservoir 106-5 is understood to include a larger volume of fluid and/or chemical therein, as compare to the other reservoirs 106, and hance includes two regions 106-5A and 106-5B which may be individually actuated to dispense such a larger volume. As depicted, the reservoirs 106 of a given sample preparation cartridge module 104 may be provided as a unit attachable to a remainder of the given sample preparation cartridge module 104 (e.g. using glue and the like).
[0071] Furthermore, it is understood that one of the reservoirs 106, for example, the reservoir 106-6, may be for dispensing a sample from a sample preparation cartridge module 104, but the remaining reservoirs 106-1 , 106-2, 106-3, 106-4, 106-5 may be to release chemicals into the sample preparation cartridge module 104 for sample processing, and the like, though some of the remaining reservoirs 106-1 , 106-2, 106-3, 106-4, 106-5 may be used to assist with puncturing an inner foil of an adjacent reservoir 106-1 , 106-2, 106-3, 106-4, 106-5, and/or mixing chemicals therein, and the like. Regardless, it is understood that the reservoirs 106-1 , 106-2, 106-3, 106-4, 106-5 are to be actuated by the reservoir actuating tips 138, and the reservoir 106-6, for sample dispensing, is to be actuated by the tip 136 of the second actuator device 112, described in more detail below.
[0072] In particular, as depicted, the pins of the second mating device 118 are mated with the first V-shaped grooves 114-1 , which aligns the tips 128 with a row of the first reservoirs 106-1 . Similarly, when the pins of the second mating device 118 are mated with the second V-shaped grooves 114-2, the tips 128 are aligned with a row of the second reservoirs 106-2. Similarly, when the pins of the second mating device 118 are mated with the third V-shaped grooves 114-3, the tips 128 are aligned with a row of the third reservoirs 106-3. Similarly, when the pins of the second mating device 118 are mated with the fourth V-shaped grooves 114-4, the tips 128 are aligned with a row of the fourth reservoirs 106-4. However, when the pins of the second mating device 118 are mated with the fifth V-shaped grooves 114-5, the tips 128 are aligned with a row of the fifth reservoirs 106-5 corresponding to the portion labelled as “106-5A”. Similarly, when the pins of the second mating device 118 are mated with the sixth V- shaped grooves 114-6, the tips 128 are aligned with a row of the fifth reservoirs 106-5 corresponding to the portion labelled as “106-5B”.
[0073] Hence, dimensions of the arms 140, distances between the V-shaped grooves 144 and/or dimensions of other suitable components of the device 100 are selected such that, when the pins of the second mating device 118 are mated with a V-shaped groove 144 of the first mating device 116, the tips 128 are aligned with a respective row of reservoirs 106, which may then be concurrently actuated via the second actuator 138 moving the tips 128 towards the row of reservoirs 106.
[0074] Figure 2 also shows one arm of the second biasing mechanism 142-2, which is understood to be located at end of a row of the tips 128, with the other arm of the second biasing mechanism 142-2 located at an opposite end of the row of tips 128.
[0075] Attention is next directed to Figure 3A and Figure 3B, Figure 4A and Figure 4B, and Figure 5A and Figure 5B which show the device 100 implementing a process for actuating the row of the tips 128 against a row of reservoirs 106.
[0076] For example, Figure 3A, Figure 4A, and Figure 5A show a perspective view of different configurations the device 100 as the first actuator 126 mates the mating devices 116, 118 (e.g. in Figure 3A and Figure 4A and as the second actuator 138 moves the tips 128 to concurrently acuate a row of reservoirs 106 (e.g. in Figure 5A). Figure 3B, Figure 4B, and Figure 5B show side views respectively corresponding to the configurations of Figure 3A, Figure 4A, and Figure 5A. For clarity, in Figure 3A, Figure 3B, Figure 4A, Figure 4B, Figure 5A and Figure 5B, the carriage 108, cassette 102 and sample preparation cartridge modules 104 are removed, other than the reservoirs 106 (e.g. similar to Figure 2. Furthermore, in Figure 3B, Figure 4B, and Figure 5B, some other components of the device 100 are omitted, such as the first actuator 126, but are nonetheless understood to be present.
[0077] Figure 3A, Figure 4A, and Figure 5A further show details of the arms 140 (e.g. both of which are depicted in Figure 3A, Figure 4A, and Figure 5A) and components of the second actuator 138 that pivot the arms 140 around the pair of pins of the second mating device 118, when mated with a pair of V-shaped grooves 144 (e.g. as depicted, the V-shaped grooves 144-1) of the first mating device 116.
[0078] In particular, the second actuator 138 may comprise a frame 146, and the like, to which respective ends of the arms 140 are attached, for example ends opposite respective ends of the arms 140 at which the pins of the second mating device 116 are attached. The frame 146 may slide on a guide rail 148 in a direction that is towards and/or away from the carriage 108, and (e.g. the “Y” direction) via a lead and/or drive screw 150 (or multiple drive screws) via a motor (not depicted). The arms 140 may be pivotably attached to the frame 146 via respective hinges and/or pivot mechanisms 152 and the like. The second actuator 138 may hence pivot the pair of arms 140 around the pair of pins of the second mating device 118, when mated with the pair of V-shaped grooves 144- 1 , which moves the tips 128 towards the carriage 108 and/or a row of reservoirs 106-1.
[0079] Similarly, the first actuator 126 may comprise a frame 154, and the like, to which respective ends of the arms 140 are attached, for example ends at which the pins of the second mating device 116 are attached. The frame 154 may slide on a guide rail 156 in a direction that is towards and/or away from the carriage 108, and (e.g. the “Y” direction) via a lead and/or drive screw 158 (or multiple drive screws) via a motor (not depicted). The arms 140 may be pivotably attached to the frame 154 via respective hinges and/or pivot mechanisms which may be coincident with the pins of the second mating device 118. The first actuator 126 may hence move the pair of pins of the second mating device 118, to mate with the pair of V-shaped grooves 144-1 by moving the arms 140 towards the carriage 108 via the guide rail 156 and the drive screws 158, which causes the arms 140 to pivot accordingly around the pivot mechanisms 152.
[0080] Furthermore, as best seen in Figure 3B, the V-shaped grooves 144 may be asymmetrically shaped to accommodate an approach angle and/or an approach path of the pins of the second mating device 118, for example to “catch” the pins of the second mating device 118 into the V-shaped grooves 144 as they approach the V-shaped grooves 144 and push them into a deepest portion of the V-shaped grooves 144. The asymmetry of the V-shaped grooves 144 may be such that an “upper” portion of a V-shaped groove 144 is angled closer to 90° than a “lower” portion with the pins being biased towards the upper” portions of the V-shaped grooves 144 by a suitable biasing mechanism.
[0081] Also depicted in Figure 3A, Figure 3B, Figure 4A, Figure 4B, Figure 5A and Figure 5B are the arms of the biasing mechanism 142-2 associated with the second actuator 138 which, as depicted, are attached to respective arms 140, for example at opposite ends of the row of tips 128. In particular, in Figure 3B, Figure 4B, and Figure 5B, the tips 128 and the reservoirs 106-1 are shown in outline “through” the biasing mechanism 142-2, to show relative positions thereof.
[0082] With reference to Figure 3A and Figure 3B, it is understood that the carriage 108 has been moved along the path 125 to align the pins of the second mating device 118 with the V-shaped grooves 144-1 of the first mating device 116, which further aligns the tips 128 with a row of the first reservoirs 106-1. Hence, in this configuration, the second actuator 138 has moved the frame 146 into a position where the carriage 108 may move without interference from the pins of the second mating device 118, the tips 128, and/or other components of the actuator device 110 (e.g. and similarly, the actuator device 112 has moved the tip 136 to a position where the carriage 108 may move without interference from the tip 136, as described below).
[0083] With reference to Figure 4A and Figure 4B, the first actuator 126 actuates the frame 154 along the guide rail 156 via the drive screw 158, and the like, to pivot the arms 140 and move the pins of the second mating device 118 into the V-shaped grooves 144-1 . The first actuator 126 is understood to apply a suitable force to the pins of the second mating device 118 that “holds” the pins in the V-shaped grooves 144-1. In some examples, the first actuator 126 may actuate the frame 154 along the guide rail 156 via the drive screw 158 until motor thereof stalls, which may occur when the pins of the second mating device 118 mate with the V-shaped grooves 144-1 and/or are located at a deepest position within the V-shaped grooves 144-1 such that the pins of the second mating device 118 stop (e.g. thereby stalling the motor thereof).
[0084] With reference to Figure 5A and Figure 5B, with the tips 128 in position relative to the row of the first reservoirs 106-1 , the second actuator 138 actuates the frame 146 along the guide rail 148 via the drive screw 150, and the like, to pivot the arms 140 around the pins of the second mating device 118, as indicated by the arrow 164 in Figure 5B. The arms 140 may also pivot around the pivot mechanisms 152. As also best seen in Figure 5A, the tips 128 concurrently press and/or push respective first reservoirs 106-1 to release a chemical therein into respective sample preparation cartridge modules 104.
[0085] In some examples, the second actuator 138 may actuate the frame 146 along the guide rail 148 via the drive screw 150 in a feedback loop with a motor (not depicted) that applies a torque to the drive screw 150 corresponding to a linear force that is translated to the tips 128, such that the tips 128 apply a sufficient force to the reservoirs 106-1 of the sample preparation cartridge module 104 to push and/or crush the reservoirs 106-1 .
[0086] In some examples, the second actuator 138 may partly actuate the reservoir actuating tips 128 towards, and then away from, the carriage 108 and/or the row of reservoirs 106-1 , and then fully actuating the reservoir actuating tips towards the carriage and/or the row of reservoirs 106-1 . In such examples, the reservoirs 106-1 may initially be partly actuated by the tips 128, and the tips 128 may be backed off the reservoirs 106-1 ; then the reservoirs 106-1 may fully actuated by the tips 128. In some of these examples, the reservoirs 106-1 may initially be partly actuated by the tips 128 a plurality of times, for example to different depths, which may cause the chemicals (e.g. in a fluid form) to cause turbulence, and the like, within a respective sample preparation cartridge module 104, which may assist with mixing of fluids therein.
[0087] The process shown in Figure 3A, Figure 3B, Figure 4A, Figure 4B, Figure 5A and Figure 5B may be reversed, and the carriage 108 moved to a new position to mate the pins of the second mating device 118 with another pair of V- shaped grooves 144 to acuate another row of the reservoirs 106.
[0088] Furthermore, the rows of reservoirs 106 may be actuated in any suitable order. For example, while the process shown in Figure 3A, Figure 3B, Figure 4A, Figure 4B, Figure 5A and Figure 5B is described with respect to actuating the row of reservoirs 106-1 , another row of reservoirs 106 may be first actuated and/or the rows of reservoirs 106 may be actuated in any suitable order consistent with sample processing at the sample preparation cartridge modules 104 (and hence which may depend on which chemicals are held in which row of reservoirs 106, and the like).
[0089] It is further understood in Figure 5A and Figure 5B that the second biasing mechanism 142-2 has mated with the first biasing mechanism 142-1 to better position the tips 128 relative to the reservoirs 106-1 , details of which are next described.
[0090] Attention is next directed to Figure 6 which depicts a portion of one set of the biasing mechanisms 142, with a portion of the carriage 108 that includes a groove of a first biasing mechanism 142-1 in cross-section (e.g. through a plane perpendicular to the “Z” direction and/or parallel to the “X” and Y directions). While only one set of the biasing mechanisms 142 are shown, it is understood that the device 100 may include two sets of the biasing mechanisms 142, for example at positions corresponding to the positions of the arms of the second biasing mechanisms 142-2 depicted in Figure 3A, Figure 4A and Figure 5A.
[0091] As depicted, the arm of the second biasing mechanism 142-2 has been inserted into the groove of the first biasing mechanism 142-1 which may move the arm of the second biasing mechanism 142-2, as well as the actuator device 110 and the tips 128 (e.g. not depicted in Figure 6, but nonetheless understood to be present) in a the “X” direction, as indicated by the arrow 166, to more precisely move the actuator device 110 into a given position where the tips 128 align with a reservoirs 106 of a given row thereof. As depicted, a force 168 is applied (e.g. by a spring, and the like incorporated into the first actuating device 110) in a direction opposite the movement of the arm of the second biasing mechanism 142-2 to assist with holding the tips 128 in position. As such, when the arm of the second biasing mechanism 142-2 is removed from the groove of the first biasing mechanism 142-1 , the arm of the second biasing mechanism 142-2 may move into a rest position (e.g. as depicted in Figure 3A and Figure 4A). As depicted, corners of the biasing mechanisms 142 may be chamfered and/or rounded to promote movement of the arm of the second biasing mechanism 142-2 into the groove of the first biasing mechanism 142-1. Similarly, the groove of the first biasing mechanism 142-1 may be shaped to promote movement of the arm of the second biasing mechanism 142-2 therein.
[0092] While the first actuator device 110 has been described with respect to specific features, other examples are within the scope of the present specification. For example, while not depicted, the pins and grooves of the mating devices 116, 118 may be replaced with any suitable structures, such hooks and pins in any suitable locations at the carriage 108 and/or at the first actuator device 110 and which hold and/or lock the carriage 108 in a position when a force is applied to the reservoirs 106 by the tips 128 (e.g. to prevent the carriage 108 from moving away from the tips 128). Similarly, while the tips 128 are depicted as cylindrical, the tips 128 may be any suitable shape. Similarly, while actuation of the tips 128 has been described with respect to the arms 140, as well as the frames 146, 154 etc., the tips 128 may be actuated with any suitable combination of mechanical devices.
[0093] The second actuator device 112 will next be described with reference to Figure 7A, Figure 7B and Figure 7C. Figure 7A depicts a perspective view of the second actuator device 112 relative to a row of the reservoirs 106-6. Figure 7B and Figure 7C show a cross-section of the second actuator device 112 through a line A-A in Figure 7A. As such, it is understood that, while not depicted in Figure 7A, Figure 7B and Figure 7C, the carriage 108 has been moved along the path 125 (e.g. by the motor 124, etc.) into a given position relative to the second actuator device 112 until a respective path 170 of the single reservoir actuating tip 136 aligns with the row of reservoirs 106-1 .
[0094] In particular, the second actuator device 112 comprises the single reservoir actuating tip 136, for example mounted to a rail and/or a drive screw 172 and the like. The second actuator device 112 further comprises a first actuator 174 to move the single reservoir actuating tip 136 into respective given positions relative to the carriage 108, for example where the single reservoir actuating tip 136 aligns with one respective reservoir 106-1. In particular the first actuator 174 may be to move the single reservoir actuating tip 136 along the respective path 170, perpendicular to the path 125 of the carriage 108, into respective given positions relative to the carriage 108, for example where the single reservoir actuating tip 136 aligns with one respective reservoir 106-1 . For example, the first actuator 174 may comprise any suitable combination of gears, motors, pulleys, and the like. In particular, as depicted, the first actuator 174 may comprise a worm drive that turns the drive screw 172, via a motor 175. As such, the single reservoir actuating tip 136 may be moved along the path 170 to align with any of the reservoirs 106-1 and/or along any suitable path where the single reservoir actuating tip 136 aligns with any of the reservoirs 106-1 .
[0095] Put another way, in the depicted example, the single reservoir actuating tip 136 may be mounted on a rail and/or drive screw 172 that extends along the respective path 170, and the first actuator 174 may be further to move the single reservoir actuating tip 136 along the rail and/or drive screw 172 into respective given positions that align the tip 136 with individual reservoirs 106-1.
[0096] The second actuator device 112 further comprises a second actuator 176 to actuate and/or move the single reservoir actuating tip 136 towards the carriage 108 and/or a reservoir 106-1 , for example in a manner similar to that described above with respect to the tips 128. In particular, as depicted, the second actuator 176 may comprise a frame 178, to which the first actuator 174, the drive screw 172 and the single reservoir actuating tip 136 are attached, and the frame 178 may slide on a guide rail 180 (only partially visible in Figure 7A) in a direction that is towards and/or away from the carriage 108, and (e.g. the “Y” direction) via a lead and/or drive screw 182 (or drive screws) via a motor 184 (e.g. which may be combined with the motor 175). Hence, in general, the second actuator 176 is to actuate the single reservoir actuating tip 136 towards the carriage 108, perpendicular to the respective path 170 of the single reservoir actuating tip 138, for example to actuate a reservoir 106-6.
[0097] Similarly, it is understood that, in the depicted example, the first actuator 174 comprises a first motor 175 to move the single reservoir actuating tip 136 along the respective path 172 into respective given positions (e.g. that align with respective reservoir tips 106-6), and that the second actuator 176 comprises a second motor 184 to move the single reservoir actuating tip 136 towards the carriage 108 and/or a reservoir tip 106-6.
[0098] For example, attention is next directed to Figure 7B and Figure 7C which depict the second actuator device 112 in cross section through a plane perpendicular to the “X” direction (e.g. and that includes the “Y” and “Z” directions), and which is through the single reservoir actuating tip 136. Hence, Figure 7B and Figure 7C show the second actuator device 112 from a side view that also shows the single reservoir actuating tip 136 moved to a given position by the first actuator 174 where the single reservoir actuating tip 136 is aligned with a reservoir 106-6. Figure 7B and Figure 7C further show gears, and the like, of the second actuator 176, at a rear side of the second actuator device 112 (e.g. similar as depicted in Figure 1A and Figure 1 B).
[0099] In Figure 7B, the second actuator 176 has moved the single reservoir actuating tip 136 to a position away from the carriage 108 so that, for example, the carriage 108 may move without interference by the single reservoir actuating tip 136. However, Figure 7B also shows a position of the single reservoir actuating tip 136 while repositioning along the path 170 to align with a reservoir 106-6.
[00100] However, in Figure 7C the second actuator 176 has moved the single reservoir actuating tip 136 towards the carriage 108 to actuate a reservoir 106-6 which, in Figure 7C, is depicted as pressed and/or crushed, for example to push air therein into a respective sample preparation cartridge module 104 to dispense a sample therefrom (e.g. after sample processing to isolate and/or purify a biological component of interest).
[00101] After crushing the reservoir 106-6 as in Figure 7C, the second actuator 176 may move the single reservoir actuating tip 136 to the position shown in Figure 7B such that the first actuator 174 may move the single reservoir actuating tip 136 to a next position along the path 170 (e.g. along rail and/or drive screw 172) to align with another reservoir 106-6 of another sample preparation cartridge module 104. As such, the second actuator device 112 may be used to actuate individual reservoirs 106-6 and/or any other of the reservoirs 106.
[00102] It is further understood that the samples of sample preparation cartridge modules 104 may be dispensed into sample wells in the sample preparation device (e.g. after sample processing to isolate and/or purify a biological component of interest), as described below with respect to Figure 8B, and that between dispensing events, a sample well may be aligned with a tip of a sample preparation cartridge module 104 that has a reservoir 106-6 that is next to be actuated by the second actuator device 112. Hence, actuating of individual reservoirs 106-6 may be coordinated with positioning of individual tips of the sample preparation cartridge modules 104 relative to the sample wells.
[00103] Attention is next directed to Figure 8A and Figure 8B which respectively depict a perspective view and a block diagram of an example sample preparation device 800 that incorporates aspects of the device 100 and of Figure 1.
[00104] As depicted, the sample preparation device 800 (interchangeably referred to hereafter as the device 800) includes a chassis 802 that includes a carriage access door 804 for loading the cassette 102 that includes the sample preparation cartridge module 104 and/or sample preparation cartridge modules 104 therein, the sample preparation cartridge module 104 holding a sample for testing as described hereafter. While the sample preparation cartridge modules 104 are depicted as being in an elongate shape and/or in the form of a column, similar to Figure 1 B, Figure 2 and Figure 3, the sample preparation cartridge modules 104 may be any suitable shape. The chassis 802 further includes a well access door 810 for loading a well holder 812 containing a well 814 and/or wells for receiving processed samples (e.g. after sample processing to isolate and/or purify a biological component of interest) dispensed from the sample preparation cartridge module 104 after processing by the device 800. While only one sample preparation cartridge module 104 is depicted, and eight wells 814, it is understood that the cassette 102 may hold a same number of sample preparation cartridge modules 108 as there are wells 814 at the well holder 812. For example, as depicted, similar to Figure 1 B, there may be eight sample preparation cartridge modules 104 and hence eight wells. Furthermore, while the cassette 102 is depicted in an end view showing only one sample preparation cartridge module 104, and the well holder 812 is shown in a front view showing eight wells 814, the components of the device 800 may cause the cassette 102 and the well holder 812 to be loaded into the device 800 in any suitable relative orientation including, but not limited to, about parallel to one another such that a line of the sample preparation cartridge module 104 is about aligned with a line of the wells 814.
[00105] As depicted, the device 800 further comprises an input device 818, such as a touch screen display, and the like, which may be used to control the device 800 into a loading mode, which causes the carriage access door 804 and the well access door 810 to open such that the cassette 102 and the well holder 812, with the wells 814, may be manually loaded into the device 800. Hence, it is understood that a sample preparation cartridge module 104 is loaded with a sample 838 (e.g. such as a biological sample retrieved from a human by medical personnel), and the like, via the port 820. The input device 818 may also be used to set given temperatures to which the sample preparation cartridge module 104 is to be heated and/or a heating cycle of the sample preparation cartridge module 104 and/or a heating/mixing cycle (e.g. setting mixing speeds of a actuator 844 of the device 800).
[00106] In the loading mode, the carriage 108 of the device 800, which may alternatively be referred to as the cassette carriage 108, is raised along a vertical carriage guide 826 (e.g. which may include the rails 120 and drive screws 122) to at least partially emerge from an opening that is normally covered by the carriage access door 804. The cassette 102 may then be manually loaded into the carriage 108. [00107] Similarly, in the loading mode, the shuttle (e.g. a well carriage) 828, which moves linearly on the planar surface (e.g. a horizontal carriage guide) 830, is moved out of an opening that is normally covered by the well access door 810, for example by moving and/or rotating an end of planar surface 830 at which the shuttle 828 is located in the loading mode, out of the opening. The well holder 812 is then manually loaded into a complementary shaped depression and/or holder 831 in the well carriage 108. While the terms vertical and horizontal are used herein with regards to a position of the device 800 in a normal use mode, such terms are meant for ease of description only and/or to indicate relative positions of components of the device 800 (e.g. the guide 826 and the planar surface 830 may be about perpendicular to each other as one is vertical and the other horizontal, but may be in any suitable orientation).
[00108] Once loaded, the cassette carriage 108 moves the cassette 102 into the device 800 (e.g. closing the door 804), and then into different positions in the device 800, for example along the vertical carriage guide 826 (e.g. via the rails 120, the drive screws 122 and the motor 124), to process the sample 838, for example at least by concurrently actuating rows of reservoirs 106 using the first actuating device 110, before dispensing the sample 838 from the sample preparation cartridge module 104 into a well 814, for example at least by actuating individual reservoirs 106 using the second actuating device 112.
[00109] Similarly, once loaded, the planar surface 830 moves inside the device 800 (e.g. closing the door 810) and the shuttle 828 is moved into a position to receive the sample 838 from the sample preparation cartridge module 104 into a corresponding well 814. When there a plurality of sample preparation cartridge modules 104 holding respective samples 838, once the samples 838 are processed, the shuttle 828 is moved into respective positions to receive respective samples 838 dispensed from respective sample preparation cartridge modules 104 into corresponding wells 814. As such, the shuttle 828 may be positioned at an angle relative to the cassette carriage 108 and/or the cassette 102 such that different sample preparation cartridge modules 104 align with different wells 814 at different positions of the shuttle 828. [00110] As such, while not depicted, the device 800 is further understood to include motors and/or a servomotors, and the like, to move the planar surface 830 into and out of the device 800, and to linearly move the shuttle 828 along the planar surface 830.
[00111] While not depicted, the device 800 may further include respective components for opening and closing the doors 804, 810.
[00112] To effect processes of the device 800, a sample preparation cartridge module 104 may be divided into a first region 832 and a second region 834 (e.g. depicted in Figure 3), divided by a barrier 836. A sample 838 is received into the sample preparation cartridge module 104 via the port 820, and may reside at a bottom of the first region 832, at the barrier 836. The sample preparation cartridge module 104 may further comprise an agitator 840 in the first region 832 which may be actuated via a mixer actuator 842 and an actuator 844, and the like of the device 800 as described below. In particular, the mixer actuator 842 may include a servomotor and/or servomotors, and the like, to move/rotate the actuator 844 to mix the sample 838 via the agitator 840, while the sample 838 is heated, as described below.
[00113] For example, the cassette 102 may be moved, along the vertical carriage guide 826, via the cassette carriage 108, into a heating position for heating by one or both of two heaters 846 (e.g. heaters 846-1 , 846-2) attached to respective mechanical devices 848 (e.g. mechanical devices 848-1 , 848-2).
[00114] While not depicted in Figure 8A, the device 800 is understood to include respective temperature sensors at the heaters 846 and/or the mechanical devices 848 so that, in a heating position of the cassette carriage 108, the heaters 846 may be positioned adjacent the first region 832 of the sample preparation cartridge module 104 to heat the sample 838, while the agitator 840 is actuated by the actuator 844, to agitate and/or mix the sample 838 while it is being heated, for example to promote lysis in cells of the sample 838. As such, the actuator 844 itself is understood to be further moved by the mixer actuator 842 into a position to agitate and/or mix the sample 838, while it is being heated, and actuated by the mixer actuator 842 which may comprise any suitable combination of motors for moving and turning the actuator 844. Alternatively, as will be explained in further detail below, the first region 832 (or the second region 834) may include magnetizing microparticles having surfaces to which a biological component of interest, expelled by cells of the sample 838 due to lysis, bond; hence, in some examples, the actuator 844 may comprise a magnetic agitating device which agitates the sample 838 during lysis by applying a changing magnetic field to the first region 832 to move the magnetizing microparticles; in such examples, the agitator 840 may be omitted from the sample preparation cartridge module 104.
[00115] However, as depicted, it is understood that the agitator 840 is generally configured to mate with the actuator 844; for example, as depicted, the agitator 840 may be attached to a pressure source 250, such as a plunger, and the like, an outer surface of which may be used to both mate with the actuator 844, to actuate the agitator 840, and move the sample 838 to the second region 834, for example by applying pressure to the pressure source 850 via the actuator 844 to break the barrier 836.
[00116] Once lysis is performed on the sample 838, biological components of interest may be released from and bond to magnetizing microparticles. While not depicted, the second region 834 may further include a wash buffer which may be mixed with the biological components of interest (e.g. bonded to the magnetizing microparticles) (e.g. when plunged into the second region 834), by concurrent actuation of a suitable row of reservoirs 106 that hold the wash buffer, for example by the first actuator device 110. Concurrent actuation of other rows of reservoirs 106 the first actuator device 110 by release a grease barrier into the second region 834, and chemicals to stabilize biological components of interest, another reservoir 106.
[00117] As has already been described reservoirs 106 in another row may be individually actuated by the second actuator device 112 to dispense the biological components of interest bonded to the magnetizing microparticles into a well 814, for example via a needle and/or tip 854 of the sample preparation cartridge module 104. [00118] As mentioned above, the cassette 102 may hold a plurality of sample preparation cartridge modules 104 and hence the device 800 may have the device 100 incorporated therein to actuate a plurality of corresponding reservoirs 106 (e.g. concurrently) on a plurality of sample preparation cartridge modules 104 for sample processing, and to actuate individual reservoirs 106 (e.g. independent of each other) on the sample preparation cartridge modules 104 for sample dispensing. For example, as depicted, the device 800 includes the first actuator device110 (e.g. a multiple reservoir actuator) including the row of reservoir tips 128 (though only one is depicted) which may be used to actuate a plurality of corresponding reservoirs 106 (e.g. concurrently) on a plurality of sample preparation cartridge modules 104, for example to concurrently introduce the wash buffer, or the stabilizing chemicals or the grease barrier into the second regions 834 of the plurality of sample preparation cartridge modules 104. As depicted the device 800 includes the second actuator device 112 (e.g. a single reservoir actuators) with the single reservoir tip 136, for independently actuating respective reservoirs 106 at the plurality of sample preparation cartridge modules 104 to independently dispense samples 838 into respective wells 814 via respective tips 854.
[00119] It is understood that the cassette carriage 108 may be moved into various suitable positions along the vertical carriage guide 826 relative to other components of the device 800, to effect actuation of the pressure source 850 and/or actuation of respective reservoirs 106 by the reservoir actuator devices110, 112.
[00120] The device 800 and/or the sample preparation cartridge module 104 may include other suitable components. For example, the sample preparation cartridge module 104 may include magnetizing microparticles in the first region 832 which have surfaces treated to bond to a biological component of interest from the sample 838 when heated. Furthermore, the second region 834 may include a wash buffer density gradient, when the wash buffer is introduced into the second region 834; in particular, the second region 834 may comprise a fluid density gradient isolates and/or purifies the biological components of interest bonded to magnetizing microparticles. As such the second region 834 may alternatively be referred to as a fluid density gradient region.
[00121] As depicted, the device 800 may include a magnet and/or magnets 864, which may be actuated via a magnetic actuator 866 to move the magnet(s) 864 adjacent the sample preparation cartridge module 104 to attract the magnetizing microparticles in the sample 838 to wash the magnetizing microparticles and move the sample 838 towards the tip 854 and/or through the wash buffer density gradient in the second region 834, for example in combination with moving the sample preparation cartridge modules 104 via the carriage 108.
[00122] As depicted, the device 800 further includes a cooler and/or air-intake port 868 and/or tube which may include a fan, and the like (not depicted) for drawing air into the device 800 via a filter 870, and an exhaust port 872 (which may also include a fan) for expelling air drawn into the device 800 via the cooler port 868 via a respective filter 874. In particular, the ports 868, 872 may provide passive and/or active cooling at the device 800 to cool the sample 838 when heated. Furthermore, the ports 868, 872 may be located in any respective suitable positions at the device 800.
[00123] Finally, once the samples 838 are processed as described, the cassette carriage 108 may be moved into a sample dispensing position relative to the shuttle 828 and/or the wells 814 to dispense samples 838 into the wells 814 from the sample preparation cartridge modules 104; the shuttle 828 may be moved into sample receiving positions, relative to the carriage 108, to position the wells 814 relative to the sample preparation cartridge modules 104 to receive the samples 838 as dispensed via actuation of individual suitable reservoirs 106 by the second actuator device 112.
[00124] As depicted, the device 800 further comprises a processor 890 and a memory 892. The processor 890 may include a general-purpose processor and/or controller or special purpose logic, such as a microprocessor and/or microcontroller (e.g. a central processing unit (CPU) and/or a graphics processing unit (GPU) an integrated circuit or other circuitry), an application specific integrated circuit (ASIC), a Field Programmable Gate Array (FPGA), a programmable array logic (PAL), a programmable logic array (PLA), a programmable logic device (PLD), and the like. Hence, functionality of the processor 890 may be implemented as a combination of hardware (e.g. a CPU, a GPU, etc.) and software (e.g., programming such as machine- or processorexecutable instructions, commands, or code such as firmware, a device driver, programming, object code, etc. as stored on hardware). Alternatively, the processor 890 may be implemented as a hardware element with no software elements (e.g. such as an ASIC, an FPGA, a PAL, a PLA, a PLD etc.).
[00125] The memory 892 may comprise instructions 894 for controlling the processor 890 and/or a processor thereof to perform the various processes described herein and which may include the various positions at which the carriage 108 is to be located relative the actuator devices 110, 112 as described herein. Such a memory 892 may include, but is not limited to, any suitable combination of a volatile computer-readable medium (e.g., volatile RAM, a processor cache, a processor register, etc.), a non-volatile computer-readable medium (e.g., a magnetic storage device, an optical storage device (e.g. a Digital Versatile Disc (DVD), a paper storage device, flash memory, read-only memory, non-volatile RAM, etc.), and/or the like.
[00126] Attention is next directed to Figure 8C which is substantially similar to Figure 8B with like components having like numbers. However, in Figure 8C, the cassette 102 has been loaded into the cassette carriage 108, and the carriage access door 804 has been closed. Further, the sample 838 has undergone lysis via heating by the heaters 846, and moved to the second region 834 of the sample preparation cartridge module 104 via the pressure source 850 being actuated (e.g. by moving the cassette carriage 108 to move the sample preparation cartridge module 104 towards the actuator 844 so that the actuator 844 actuates the pressure source 850 to break the barrier 836, for example by pushing the agitator 840 towards the barrier 836 via the pressure source 850). Furthermore, reservoirs 106 containing the wash buffer, the stabilizing chemicals and the grease barrier have been concurrently actuated by the first actuator device 110 and the tips 128. As such, the reservoirs 106 associated with sample processing are no longer seen at the sample preparation cartridge module 104, having been crushed by the tips 128. Further, the processed sample 838has been drawn through the wash buffer density gradient/fluid density gradient to better isolate and/or purify a biological component of interest bonded to magnetizing microparticles attached thereto.
[00127] In particular in Figure 8C, the carriage 108 has been moved to a sample dispensing position and the wells 814 have been loaded into the well holder 812 at the shuttle 828, and the planar surface 830, with the shuttle 828, has been moved/rotated into the device 800 from an external position to an internal position, with the well access door 810 closed. Furthermore, the shuttle 828 has been moved into a sample receiving position (e.g. a first sample receiving position), relative to the sample dispensing position of the carriage 108, such that a well 814 is aligned with the sample preparation cartridge module 104, and specifically the tip 854 thereof.
[00128] As depicted, in the sample dispensing position of the carriage 108, the second actuator device 106 has been controlled to move the single reservoir actuating tip 136 to actuate a dispensing reservoir 106-6 (not depicted in Figure 8C, having been crushed by the single reservoir actuating tip 136). As such, the processed sample 838 at the tip 854, now processed to isolate and/or purify the biological component of interest bonded to the magnetizing microparticles is being dispensed into a corresponding well 814. In some examples, the wells 814 and/or regions around the tip 854 at the sample preparation cartridge module 104 may include splash guards, and the like, to assist with reducing cross-contamination between the wells 814.
[00129] While the shuttle 828 is depicted as being at one sample receiving position, the shuttle 828 may be moved to other sample receiving positions (e.g. up to eight sample receiving positions, one for each well 814 and corresponding sample preparation cartridge module 104 when there are eight of each; sample preparation cartridge modules 104, that do not contain a sample may be skipped in the dispensing process), and similarly the single reservoir actuating tip 136 may be moved to respective positions along the path 170 to actuate individual reservoirs 106-6 to dispense samples. [00130] Referring to Figure 9, a flow diagram of an example method 900 to actuate reservoirs is depicted. In order to assist in the explanation of method 900, it will be assumed that method 900 may be performed with the device 800 (e.g. via the processor 890 implementing the instructions 894 stored at the memory 892). The method 900 may be one way in which the device 800 may be configured. Furthermore, the following discussion of method 900 may lead to a further understanding of the device 800, and their various components.
Furthermore, it is to be emphasized, that method 900 may not be performed in the exact sequence as shown, and various blocks may be performed in parallel rather than in sequence, or in a different sequence altogether. Furthermore, the method 900 may be performed by the device 100.
[00131] As the method 900 is described with reference to all the actuator devices of the device 100, in the discussion of the method 900, the actuators 126, 138, 174, 176 will be referred to, respectively, as the first actuator 126, the second actuator 138, the third actuator 174 and the fourth actuator 176.
[00132] At a block 902, the processor 890 and/or the device 800 controls the carriage 108 to move along the path 125, relative to the first actuator device 110, into a first carriage position (e.g. where the mating devices 116, 118 are aligned as depicted in Figure 3A and Figure 3B).
[00133] At a block 904, the processor 890 and/or the device 800 controls the first actuator 126 of the first actuator device 110 to cause respective mating devices 116, 118 of the carriage 108 and the first actuator device 110 to mate.
[00134] At a block 906, the processor 890 and/or the device 800, when the respective mating devices 116, 118 are mated, controls the second actuator 138 of the first actuator device 110 to actuate the reservoir actuating tips 128 towards, and then away from, the carriage 108 for example to actuate a respective row of reservoirs 106.
[00135] As such, at the block 904 and the block 906, controlling the first actuator 126 of the first actuator device 110 to cause the respective mating devices 116, 118 to mate aligns the reservoir actuating tips 128 with a row of reservoirs 106 of a plurality of sample preparation cartridge modules 104 held by the carriage 108 such that, when the second actuator 138 actuates the reservoir actuating tips 128 towards the carriage 108, the reservoir actuating tips 128 actuate the reservoirs 106 in the row for example which may release a chemical held by the reservoirs 106 into the plurality of sample preparation cartridge modules 104.
[00136] Furthermore, at the block 906, the controlling the second actuator 138 of the first actuator device 110 to actuate the reservoir actuating tips 128 towards, and then away from, the carriage 108 may occur by: partly actuating the reservoir actuating tips 128 towards, and then away from, the carriage 108; and then fully actuating the reservoir actuating tips 128 towards, and then away from, the carriage 108, for example to partially dispense and then fully dispense a chemical, and the like, held by the reservoirs 106 being actuated by the tips 128.
[00137] At a block 908 the processor 890 and/or the device 800 controls the first actuator 126 to unmate the respective mating devices 116, 118.
[00138] The blocks 902, 904, 906, 908 may be implemented any suitable number of times to actuate different rows of the reservoirs 106 in any suitable order.
[00139] At a block 910 the processor 890 and/or the device 800 controls the carriage 108 to move, along the path 125 into a second carriage position for example, in the second carriage position, the single reservoir actuating tip 136 may located at the row of reservoirs 106-6 of a plurality of sample preparation cartridge modules 104 held by the carriage 108.
[00140] At a block 912 the processor 890 and/or the device 800 controls a third actuator 174 of the second actuator device 112 to move the single reservoir actuating tip 136, (e.g. different from the reservoir actuating tips 128), into different positions perpendicular to the path 125 of the carriage 108, for example in the “X” direction to align with one reservoir 106-6.
[00141] At a block 914 the processor 890 and/or the device 800 at the different positions, controls a fourth actuator 176, of the second actuator device 112, to actuate the single reservoir actuating tip 136 towards, and then away from, the carriage 108, for example to actuate one reservoir 106-6, before the third actuator moves the single reservoir 106 actuating tip into a next position to actuate another reservoir 106-6.
[00142] Hence, at the block 912 and the block 914, controlling the third actuator 174 of the second actuator device 112 to move the single reservoir actuating tip 136 into the different positions causes the single reservoir actuating tipi 36 to align with one respective reservoir 106-6 at one respective sample preparation cartridge module 104, of a plurality of sample preparation cartridge modules 104, held by the carriage 108 such that, when the fourth actuator 176 actuates the single reservoir actuating tip 136 towards the carriage 108, the single reservoir actuating tip 136 actuates the respective single reservoir 106-6 for example to dispense a sample from the one respective sample preparation cartridge modules 104.
[00143] It should be recognized that features and aspects of the various examples provided above may be combined into further examples that also fall within the scope of the present disclosure.

Claims

39 CLAIMS
1 . A device comprising: a carriage comprising a first mating device; and an actuator device comprising: a second mating device that mates with the first mating device; a first actuator to move the second mating device to mate with the first mating device to position the actuator device at a given position relative to the carriage; reservoir actuating tips that are positioned, relative to the carriage, when the actuator device is positioned at the given position relative to the carriage; and a second actuator to move the reservoir actuating tips towards the carriage.
2. The device of claim 1 , further comprising a biasing mechanism to move the actuator device into the given position, relative to the carriage, when the second mating device mates with the first mating device.
3. The device of claim 1 , wherein the first mating device comprises a pair of V-shaped grooves on opposite ends of the carriage, and the second mating device comprises a corresponding pair of pins to move into the V-shaped grooves.
4. The device of claim 1 , wherein the second actuator is further to actuate the reservoir actuating tips towards the carriage with a reservoir actuating force.
5. The device of claim 1 , further comprising a pair of arms, and wherein: the reservoir actuating tips extends between the pair of arms, the first mating device comprises a pair of V-shaped grooves on opposite ends of the carriage, the second mating device comprises a pair of pins respectively located at the pair of arms, to move into the pair of V-shaped grooves, 40 the first actuator is to move the second mating device to mate with the first mating device by moving the pair of arms to move the pair of pins into the pair of V-shaped grooves, and the second actuator is to actuate the reservoir actuating tips towards the carriage by pivoting the pair of arms around the pair of pins mated with the pair of V-shaped grooves, which further moves the reservoir actuating tips towards the carriage.
41
6. A device comprising: a carriage; and an actuator device, the carriage movable into a given position relative to the actuator device, the actuator device comprising: a single reservoir actuating tip; a first actuator to move the single reservoir actuating tip into respective given positions relative to the carriage; and a second actuator to actuate the single reservoir actuating tip towards the carriage.
7. The device of claim 6, further comprising a motor to move the carriage along into the given position.
8. The device of claim 6, wherein the first actuator comprises a first motor to move the single reservoir actuating tip along a respective path perpendicular to a path of the carriage, into the respective given positions; and the second actuator comprises a second motor to move the single reservoir actuating tip towards the carriage.
9. The device of claim 6, wherein the second actuator is to actuate the single reservoir actuating tip towards the carriage, perpendicular to a path of the single reservoir actuating tip along which the single reservoir actuating tip moves into the respective given positions relative to the carriage.
10. The device of claim 6, wherein the single reservoir actuating tip is mounted on a rail that extends along a respective path along which the single reservoir actuating tip moves into the respective given positions relative to the carriage, and the first actuator is further to move the single reservoir actuating tip along the rail into the respective given positions.
11. A method comprising: controlling, at a sample preparation device, a carriage to move along a path, relative to an actuator device, into a first carriage position; controlling, at the sample preparation device, a first actuator of the actuator device to cause respective mating devices of the carriage and the actuator device to mate; when the respective mating devices are mated, controlling, at the sample preparation device, a second actuator of the actuator device to actuate reservoir actuating tips towards, and then away from, the carriage; controlling, at the sample preparation device, the first actuator to unmate the respective mating devices; controlling, at the sample preparation device, the carriage to move, along the path into a second carriage position; controlling, at the sample preparation device, a third actuator of the actuator device to move a single reservoir actuating tip, different from the reservoir actuating tips, into different positions perpendicular to the path of the carriage; and at the different positions, controlling a fourth actuator, of the actuator device, to actuate the single reservoir actuating tip towards, and then away from, the carriage, before the third actuator moves the single reservoir actuating tip into a next position.
12. The method of claim 11 , wherein controlling the first actuator of the actuator device to cause the respective mating devices to mate aligns the reservoir actuating tips with a row of reservoirs of a plurality of sample preparation cartridge modules held by the carriage such that, when the second actuator actuates the reservoir actuating tips towards the carriage, the reservoir actuating tips actuate the reservoirs in the row to release a chemical held by the reservoirs into the plurality of sample preparation cartridge modules.
13. The method of claim 11 , wherein controlling the third actuator of the actuator device to move the single reservoir actuating tip into the different positions causes the single reservoir actuating tip to align with one respective reservoir at one respective sample preparation cartridge module, of a plurality of sample preparation cartridge modules, held by the carriage such that, when the fourth actuator actuates the single reservoir actuating tip towards the carriage, the single reservoir actuating tip actuates the one respective reservoir to dispense a sample from the one respective sample preparation cartridge module.
14. The method of claim 11 , wherein the controlling the second actuator of the actuator device to actuate the reservoir actuating tips towards, and then away from, the carriage occurs by: partly actuating the reservoir actuating tips towards, and then away from, the carriage; and then fully actuating the reservoir actuating tips towards, and then away from, the carriage.
15. The method of claim 11 , wherein, in the second carriage position, the single reservoir actuating tip is located at a row of reservoirs of a plurality of sample preparation cartridge modules held by the carriage.
PCT/US2020/066651 2020-12-22 2020-12-22 Reservoir actuating devices and methods WO2022139822A1 (en)

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Citations (3)

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Publication number Priority date Publication date Assignee Title
RU2009119457A (en) * 2009-05-18 2010-11-27 Закрытое акционерное общество "Технолинк" (RU) AUTOMATIC SYSTEM OF ANALYTICAL CONTROL OF LIQUID SAMPLES AND METHOD OF SYSTEM MANAGEMENT
US20160129437A1 (en) * 2014-11-11 2016-05-12 Advanced Liquid Logic, Inc. Instrument and cartridge for performing assays in a closed sample preparation and reaction system employing electrowetting fluid manipulation
JP2019104232A (en) * 2017-12-14 2019-06-27 三緯國際立體列印科技股▲ふん▼有限公司XYZprinting, Inc. Printing module and 3d printer

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Publication number Priority date Publication date Assignee Title
RU2009119457A (en) * 2009-05-18 2010-11-27 Закрытое акционерное общество "Технолинк" (RU) AUTOMATIC SYSTEM OF ANALYTICAL CONTROL OF LIQUID SAMPLES AND METHOD OF SYSTEM MANAGEMENT
US20160129437A1 (en) * 2014-11-11 2016-05-12 Advanced Liquid Logic, Inc. Instrument and cartridge for performing assays in a closed sample preparation and reaction system employing electrowetting fluid manipulation
JP2019104232A (en) * 2017-12-14 2019-06-27 三緯國際立體列印科技股▲ふん▼有限公司XYZprinting, Inc. Printing module and 3d printer

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