WO2022139813A1 - Dispositifs et procédés d'établissement de points de référence pour la distribution d'échantillon - Google Patents

Dispositifs et procédés d'établissement de points de référence pour la distribution d'échantillon Download PDF

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Publication number
WO2022139813A1
WO2022139813A1 PCT/US2020/066610 US2020066610W WO2022139813A1 WO 2022139813 A1 WO2022139813 A1 WO 2022139813A1 US 2020066610 W US2020066610 W US 2020066610W WO 2022139813 A1 WO2022139813 A1 WO 2022139813A1
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WO
WIPO (PCT)
Prior art keywords
sample
shuttle
carriage
planar surface
sample preparation
Prior art date
Application number
PCT/US2020/066610
Other languages
English (en)
Inventor
Alan Robert ARTHUR
Kevin Ken KURAMURA
Alan Shibata
Kevin WITKOE
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/US2020/066610 priority Critical patent/WO2022139813A1/fr
Publication of WO2022139813A1 publication Critical patent/WO2022139813A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • G01N35/1067—Multiple transfer devices for transfer to or from containers having different spacing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • G01N35/1072—Multiple transfer devices with provision for selective pipetting of individual channels
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • G01N35/1074—Multiple transfer devices arranged in a two-dimensional array
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • G01N2035/00039—Transport arrangements specific to flat sample substrates, e.g. pusher blade
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1011—Control of the position or alignment of the transfer device

Definitions

  • sample preparation devices can be challenging due to many moving parts in the devices, for example to move a carriage holding a cassette of sample preparation cartridge modules and/or sample dispensing containers, relative to sample receiving wells that are of a different pitch than the sample preparation cartridge modules and/or sample dispensing containers.
  • Figure 1 A is a perspective view of block diagram of an example device with datuming devices.
  • Figure 1 B is a top view the example device of Figure 1 A.
  • Figure 2A is a perspective view of an example sample preparation device that incorporates the device of Figure 1 .
  • Figure 2B is a block diagram of the device of Figure 2A.
  • Figure 3 is a block diagram showing the device of Figure 2A, with a carriage in a sample dispensing position and a shuttle in a sample receiving position.
  • Figure 4A shows a top view of a portion of the device of Figure 1 showing alignment between sample receiving positions of a shuttle and sample preparation cartridge module positions of a carriage, when the shuttle and the carriage are at a relative given angle.
  • Figure 4B shows a top view of a portion of the device of Figure 1 showing the shuttle in a subset of sample receiving positions.
  • Figure 5A and Figure 5B respectively show a portion of components of the device of Figure 2A with a planar surface in an internal position and an external position, respectively.
  • Figure 6 shows a front view of the device of Figure 2A with a planar surface in an external position and/or a well loading position and a carriage in a sample loading position.
  • Figure 7 is a block diagram showing a controller and a memory of the device of Figure 2A.
  • Figure 8 is a flow diagram of an example method for dispensing in the device of Figure 2A.
  • 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 preparation cartridge modules relative to sample receiving wells.
  • the cartridge may hold a plurality of the sample preparation cartridge modules or sample preparation devices or sample preparation cartridge modules which contain different respective biological samples.
  • 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 preparation cartridge modules 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 preparation cartridge modules 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 a 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 devices can be challenging due to many moving parts in the devices, for example to move a carriage holding a cassette of sample preparation cartridge modules relative to sample receiving wells.
  • the cassette may hold a plurality of the sample preparation cartridge module which contain different respective biological samples from humans.
  • the carriage, and/or the cassette may hold the sample preparation cartridge modules in a line; similarly, the sample receiving wells may be held in a line in a well carriage, which is alternatively referred to herein as a shuttle.
  • sample preparation cartridge modules may have a larger pitch in the carriage and/or the cassette, than the sample receiving wells in the shuttle, it may not be possible to align the sample preparation cartridge modules with the sample receiving wells on a line by line basis within the sample preparation device.
  • the larger pitch of the sample preparation cartridge modules may be due to apparatuses interior to the sample preparation cartridge modules that are used to process a sample placed inside a sample preparation cartridge module.
  • a pitch of the sample receiving wells may be set by a PCR assay device, and the like, into which a well holder, that holds the sample receiving wells, is placed, once the samples are dispensed into the sample receiving wells.
  • a device that includes a carriage to hold sample preparation cartridge modules linearly arranged according to a first pitch (e.g. in a cassette) and a shuttle to: receive sample receiving wells linearly arranged according to a second pitch different from the first pitch.
  • the device includes complementary mating devices to hold the carriage in a sample dispensing position at a relative given angle to the shuttle. The relative given angle may be determined from the first pitch and the second pitch such that, at a sample receiving positions of the shuttle along a linear path thereof, a sample preparation cartridge module is aligned with a respective sample receiving well.
  • the shuttle may be on a planar surface that rotates in and out of the device, for example via a door.
  • the planar surface When the planar surface is rotated to inside the device, the planar surface is oriented such that the carriage and the shuttle are at the relative given angle.
  • the planar surface when the planar surface is rotated to outside the device (or at least partially outside the device), the planar surface is oriented such that the carriage and the shuttle are about parallel to each other.
  • the planar surface may be rotated outside the device for a loading process to receive the sample receiving wells while, concurrently, the carriage is raised out of the device to a sample loading position, to receive a cassette containing the sample preparation cartridge modules that hold the samples.
  • the sample preparation cartridge modules are then lowered into the device for processing while the planar surface is rotated into the device according to the relative given angle. Once dispensing occurs, the planar surface may again be rotated out of the device.
  • the sample preparation cartridge modules and the sample receiving wells may be loaded into the device, or unloaded from the device, while respective linear arrangements thereof are about parallel to each other.
  • a user performing the loading or unloading visually associates a first sample preparation cartridge module, holding a first sample, for example, on a left hand side of the cassette and/or the carriage, with a respective sample receiving well on a left hand side of the shuttle and/or a well holder into which the first sample is to be dispensed after processing.
  • Such visual cues may assist with reducing confusion as to which sample preparation cartridge module is associated with which sample when dispensed into the wells and retrieved from the device for insertion into a PCR device.
  • a first aspect of the present specification provides a device comprising: a planar surface; a carriage to hold sample preparation cartridge modules linearly arranged according to a first pitch, the carriage to move relative to the planar surface, into a sample dispensing position; a shuttle on the planar surface, the shuttle to receive sample receiving wells linearly arranged according to a second pitch different from the first pitch, the shuttle and the carriage to move relative to each other such that the shuttle is at sample receiving positions relative to the carriage and the shuttle is between the planar surface and the sample preparation cartridge modules when the carriage is in the sample dispensing position; and complementary mating devices, at the planar surface and the carriage, to hold the carriage in the sample dispensing position at a relative given angle to the shuttle, the relative given angle determined from the first pitch and the second pitch such that, at the sample receiving positions of the shuttle, a sample preparation cartridge module is aligned with a respective sample receiving well.
  • respective numbers of the sample preparation cartridge modules, the sample receiving wells and the sample receiving positions may be of a same given number.
  • the carriage may be to move about perpendicular to the planar surface, into the sample dispensing position.
  • the complementary mating devices may comprise holes and pins.
  • the first pitch may be larger than the second pitch.
  • the planar surface may be rotatable between an external position extending out of the device and/or extending perpendicularly out of the device, to receive the sample receiving wells, and an internal position in the device at the relative given angle.
  • the device of the first aspect may further comprise respective motors for moving the carriage and the shuttle.
  • a second aspect of the present specification provides a device comprising: a chassis having an opening; a planar surface rotatable between an external position and an internal position via the opening; a carriage to hold sample preparation cartridge modules linearly arranged according to a first pitch, the carriage to move about relative to the planar surface at the internal position; a shuttle on the planar surface, the shuttle to: receive sample receiving wells linearly arranged according to a second pitch different from the first pitch; and move linearly along the planar surface into sample receiving positions, between the planar surface and the sample preparation cartridge modules, the planar surface, at the external position, to receive, at the shuttle, the sample receiving wells about parallel to the sample preparation cartridge modules when held by the carriage, the planar surface, at the internal position, holding the shuttle at a relative given angle to the carriage, the relative given angle determined from the first pitch and the second pitch such that, at the sample receiving positions of the shuttle, a sample preparation cartridge module is aligned with a respective sample receiving well.
  • the device of the second aspect may further comprise a door that is: open at the external position of the planar surface; and closed at the internal position of the planar surface.
  • the first pitch may be larger than the second pitch.
  • the device of the second aspect may further comprise a rotational mechanism to rotate the planar surface between the external position and the internal position.
  • a third aspect of the present specification provides a method comprising: moving, at a sample preparation device, a carriage to a sample loading position to receive sample preparation cartridge modules linearly arranged according to a first pitch, the carriage to move relative to a planar surface holding a shuttle; rotating, at the sample preparation device, the planar surface to an external position to receive, at the shuttle, sample receiving wells linearly arranged according to a second pitch different from the first pitch; rotating, at the sample preparation device, the planar surface to an internal position such that the sample receiving wells and the sample preparation cartridge modules are at a relative given angle determined from the first pitch and the second pitch such that, at sample receiving positions of the shuttle, a sample preparation cartridge module is aligned with a respective sample receiving well; moving, at the sample preparation device, the carriage towards the shuttle into a sample dispensing position; moving, at the sample preparation device the shuttle into the sample receiving positions relative to the sample preparation cartridge modules; and
  • the method of the third aspect may further comprise opening and closing a door at an opening of the sample preparation device as the as the planar surface is respectively rotated to the external position and the internal position.
  • the shuttle in the external position of the planar surface, the shuttle may be about parallel to the carriage such that the sample receiving wells are about parallel with the sample preparation cartridge modules.
  • moving the shuttle into the sample receiving positions relative to the sample preparation cartridge modules may comprise moving the shuttle linearly along the planar surface between the sample receiving positions and stopping therebetween to receive the respective sample into the respective sample receiving well.
  • the method of the third aspect may further comprise, in response to a last sample being dispensed into a last sample receiving well: moving the carriage away from the shuttle; and rotating the planar surface to the external position for retrieval of the sample receiving wells from the shuttle.
  • Figure 1A and Figure 1 B show block diagrams of an example device 100 with datuming devices, in a perspective view and a top view, respectively. While describe in more detail below, it is understood that components of the device 100 may be components of a larger device used for medical testing of samples including, but not limited to, sample preparation. 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 2A and Figure 2B.
  • the device 100 generally comprises a planar surface 102, a shuttle 104, which, as depicted, is to move linearly along the planar surface 102 (e.g. along a linear path 106), and a carriage 108, which is to move (e.g. as represented by a path 110) relative to the shuttle 104 and/or the planar surface 102 and/or linear path 106, for example into a sample dispensing position, described in more detail below.
  • the carriage 108 may be to move about perpendicular to the planar surface 102, into the sample dispensing position, however the carriage 108 may move in any suitable manner relative to the planar surface 102.
  • the shuttle 104 is to move linearly along the planar surface 102 into sample receiving positions, between the planar surface 102 and sample preparation cartridge modules held by the carriage 108.
  • the carriage 108 is depicted as being above the planar surface 102 and the shuttle 104, for example at a location along the path 110, away from a sample dispensing position.
  • the carriage 108 may be at the sample dispensing position. The sample dispensing position is described in more detail below with respect to Figure 3.
  • the carriage 108 is generally further to hold sample preparation cartridge modules linearly arranged according to a first pitch 112.
  • the sample preparation cartridge modules may be held by a cassette received at the carriage 108; as such the carriage 108 may alternatively be referred to herein as the cassette carriage 108. While details of the carriage 108 are not depicted, it is understood that the carriage 108 and/or the device 100 may include any suitable combination of features to move the carriage 108 along the path 110 such as guiderails, motors and the like. In general, the carriage 108 may be to move along the path 110 to different positions as described in further detail below. Further, the carriage 108 may include any suitable combination of features to receive and hold the sample preparation cartridge modules for example at the cassette.
  • the carriage 108 may comprise any suitable combination of features (e.g. openings, apertures and the like) which enables a sample processing device, for example as described below with respect to Figure 2A, Figure 2B and Figure 3, to perform sample processing on samples held by the sample preparation cartridge modules.
  • a sample processing device for example as described below with respect to Figure 2A, Figure 2B and Figure 3, to perform sample processing on samples held by the sample preparation cartridge modules.
  • the shuttle 104 is to receive sample receiving wells linearly arranged according to a second pitch 114 different from the first pitch 112.
  • the sample dispensing wells may be held by a holder received at the shuttle 104; as such the shuttle 104 may alternatively be referred to herein as the well carriage 108.
  • the first pitch 112 is larger than the second pitch 114, for example due to apparatuses in the sample preparation cartridge modules used to process samples received in the sample preparation cartridge modules, described in more detail below with respect to Figure 2B.
  • the carriage 108 and the shuttle 104 are empty of containers and/or wells, respective positions thereof are shown at the carriage 108 and the shuttle 104.
  • the carriage 108 includes eight sample preparation cartridge module positions 116, labelled 1 , 2, 3, 4, 5, 6, 7, 8 at a top of the carriage 108, which are linearly arranged along a length of the carriage 108.
  • the shuttle 104 includes eight corresponding well positions 118, also labelled 1 , 2, 3, 4, 5, 6, 7, 8 at a top of the shuttle 104, which are linearly arranged along a length of the shuttle 104.
  • the first pitch 112 is hence depicted as being a center-to-center distance between adjacent sample preparation cartridge module positions 116
  • the second pitch 114 is hence depicted as being a center-to-center distance between adjacent well positions 118.
  • a first sample preparation cartridge module position 116 is understood to be the sample preparation cartridge module position 116 labelled “1”
  • a second sample preparation cartridge module position 116 is understood to be the sample preparation cartridge module position 116 labelled “2”, etc.; similarly, a first well position 118 is understood to be the well position 118 labelled “1”, a second well position 118 is understood to be the well position 118 labelled “2”, etc.
  • the carriage 108 includes any suitable combination of apparatuses, slots, grooves, windows, and/or any other physical features that enable the carriage 108 to receive, and hold, sample preparation cartridge modules (and/or a cassette hold the sample preparation cartridge modules) at the sample preparation cartridge module positions 116 and/or enables a sample preparation device (e.g. as described below with respect to Figure 2A and Figure 2B), into which the device 100 is incorporated, to interact with the sample preparation cartridge modules to process samples held therein.
  • a sample preparation device e.g. as described below with respect to Figure 2A and Figure 2B
  • the shuttle 104 is understood to include any suitable combination of apparatuses, slots, grooves, and/or any other physical features that enable the shuttle 104 to receive, and hold, sample wells (and/or a holder hold the wells) at the well positions 118.
  • the first sample preparation cartridge module position 116 may be aligned with the first well position 118; in a second sample receiving position of the shuttle 104, the second sample preparation cartridge module position 116 may be aligned with the second well position 118.
  • respective numbers of the sample preparation cartridge modules e.g. when present at the carriage 108
  • the sample receiving wells e.g. when present at the shuttle 104
  • the sample receiving positions may be of a same given number, for example, as depicted, “eight”.
  • the respective numbers of the sample preparation cartridge modules (e.g. when present at the carriage 108), the sample receiving wells and the sample receiving positions may be any suitable respective numbers which may be the same (as depicted) or different from each other.
  • Such sample receiving positions of the shuttle 104 may be predetermined and stored at a memory of the device 100 and/or a sample preparation device into which the device 100 is incorporated, as described below with respect to Figure 7.
  • the relative given angle 120 may be determined by rotating the carriage 108 and the shuttle 104, relative to each other, until the first sample preparation cartridge module position 116 aligns with the first well position 118 along the linear path 106, the second sample preparation cartridge module position 116 aligns with the second well position 118 along the linear path 106, etc.
  • the relative given angle 120 may be determined from (e.g. the law of cosines):
  • Equation (1) 0 is the relative given angle 120, P2 is the second pitch 114 and Pi is the first pitch 112. Equation (1) assumes that a line through the centers of the well positions 118 of the shuttle 104 is perpendicular to the linear path 106; however, in other examples, a line through the centers of the well positions 118 of the shuttle 104 may not be perpendicular to the linear path 106 and/or the linear path 106 may be at a different angle to the carriage 108 as that depicted, and Equation (1) may be modified accordingly, for example to a more generic equation that takes into account such geometric conditions between the positions 116, 118 and the linear path 106.
  • the device 100 further comprises complementary mating devices 122-1 , 122-2 (e.g. respectively) at the carriage 108 and the planar surface 102, to hold the carriage 108 in the sample dispensing position at the relative given angle 120 to the shuttle 104.
  • the complementary mating devices 122-1 , 122-2 are interchangeably referred to hereafter, collectively, as the mating devices 122 (or the mating devices 122-1 , or the mating devices 122-2) and, generically, as a mating device 122 (or a mating device 122-1 , or a mating device 122-2).
  • the complementary mating devices 122 may alternatively be referred as datuming devices as the complementary mating devices 122 hold the carriage 108 in the sample dispensing position at the relative given angle 120 relative to the shuttle 103 to provide a reference position for positioning of the shuttle 104 into the sample receiving positions.
  • the mating devices 122-1 comprise pins and/or posts extending from a shuttle-facing surface of the carriage 108, at opposite ends (e.g. opposite longitudinal ends) of the carriage 108.
  • the mating devices 122-2 comprise holes complementary the pins and/or posts of the mating devices 122-1 , the holes located at the planar surface 102 at positions corresponding to the pins and/or posts of the mating devices 122-1 .
  • locations of a mating device 122-1 and a complementary mating device 122-2 may be reversed (e.g. a hole may be at the carriage 108 and a complementary pin/post may be at the planar surface 102).
  • the mating devices 122 may comprise any suitable mating devices.
  • the pins and/or posts of the mating devices 122-1 mate with, and/or are inserted into, the holes of the mating devices 122-2.
  • Such mating is indicated by respective dashed lines between the mating devices 122-1 and corresponding mating devices 122-2.
  • the pins (and/or posts) and holes have diameters that are similar such that the pins (and/or posts) insert into the holes “tightly”, but removably, so that the carriage 108 is firmly held in place by the mating devices 122 and/or with no give/play and/or minimized give/play.
  • the tolerance of the mating devices 122 is selected to be as small as possible to reduce and/or minimize lateral movement (e.g.
  • the mating devices 122 may comprise any suitable mating devices that hold the carriage 108 in the sample dispensing position at a relative given angle to the shuttle 104 with minimal lateral play, and the like.
  • the depth of the holes may be selected to hold the carriage 108 at a given height from the planar surface 102 in the sample dispensing position such that the shuttle 104 may move between the planar surface 102 and sample preparation cartridge modules in the carriage 108.
  • the pins and/or posts of the mating devices 122-1 may include a region that is larger than a diameter of the holes of the mating devices 122-2, to hold the carriage 108 at a given height from the planar surface 102 in the sample dispensing position such that the shuttle 104 may move between the planar surface 102 and sample preparation cartridge modules in the carriage 108.
  • the planar surface 102 and the shuttle 104 may include any suitable combination of apparatuses for guiding the shuttle 104 along the linear path 106, such as grooves, complementary protrusions, and the like.
  • Two example guides 124 e.g. grooves
  • the shuttle 104 may comprise protrusions that mate with the guides 124 such that the shuttle 104 slides along the guides 124 along the linear path 106.
  • the planar surface 102 may alternatively be to as a horizontal carriage guide (e.g. assuming the linear path 106 is horizontal).
  • the device 100 may further include a shuttle motor to move the shuttle 104 along the linear path 106, and a carriage motor to move the carriage 108 relative to the linear path 106 (e.g. along the path 110 and/or perpendicularly, and/or in any suitable manner).
  • Such motors may comprise respective optical encoders.
  • the shuttle 104 may be moved along the linear path 106 to a predetermined sample receiving position, stored at a memory of the device100, until an optical encoder of the shuttle motor indicates the predetermined sample receiving position.
  • the carriage 108 may be moved along the path 110 to a predetermined sample dispensing position, stored at the memory of the device100, until an optical encoder of the carriage motor indicates the predetermined sample dispensing position.
  • Other predetermined positions of the shuttle 104 and the carriage 108, such as loading positions, etc. may be controlled in a similar manner.
  • the device 100 may comprise a controller (e.g. see Figure 7) for controlling positions of the shuttle 104 and the carriage 108 and/or respective motors of the shuttle 104 and the carriage 108; such a controller may be in communication with the motors and respective optical encoders.
  • a controller e.g. see Figure 7 for controlling positions of the shuttle 104 and the carriage 108 and/or respective motors of the shuttle 104 and the carriage 108; such a controller may be in communication with the motors and respective optical encoders.
  • the carriage 108 and/or the planar surface 102 may move relative to the shuttle 104 (e.g. along a path similar to the linear path 106 such that the shuttle 104 and/or the carriage 108 and/or the planar surface 102 move relative to each other such that the shuttle 104 is at sample receiving positions relative to the carriage 108 and the shuttle 104 is between the planar surface and the sample preparation cartridge modules when the carriage 108 is in the sample dispensing position.
  • the shuttle 104 may be held stationary at the planar surface 102, and the pins and holes of the mating devices 122 may be replaced with protrusions at the carriage 108 that made with guides and/or rails and/or grooves and, and the like, at the planar surface 102 that both hold the carriage 108 in the sample dispensing position at the relative given angle to the shuttle 104, and enable the carriage 108 to move along the linear path 106.
  • the shuttle 104 and the carriage 108 are to move relative to each other such that the shuttle 104 is at sample receiving positions relative to the carriage 108 and the shuttle 104 is between the planar surface 102 and the sample preparation cartridge modules when the carriage 108 is in the sample dispensing position.
  • Figure 1 A and Figure 1 B further depict a rotational mechanism 126 of the planar surface 102, which may comprise a hinge, a rotational pin, and the like, that joins the planar surface 102 to a surface “under” the planar surface 102 such that the planar surface 102 rotates about the rotational mechanism 126 and/or about a rotational axis 128 normal to the planar surface 102 at the rotational mechanism 126.
  • a rotational mechanism 126 of the planar surface 102 which may comprise a hinge, a rotational pin, and the like, that joins the planar surface 102 to a surface “under” the planar surface 102 such that the planar surface 102 rotates about the rotational mechanism 126 and/or about a rotational axis 128 normal to the planar surface 102 at the rotational mechanism 126.
  • the rotational mechanism 126 is understood to enable the planar surface 102 to rotate between: an external position perpendicularly (and/or in any suitable direction) extending out of the device 100 (and/or a larger sample preparation device into which the device 100 is incorporated), to receive sample receiving wells at the shuttle 104; and an internal position in the device 100 at the relative given angle 120.
  • Figure 1A and Figure 1 B are understood to show the planar surface 102 at an internal position. The rotation and external position is described in more detail below with respect to Figure 5A and Figure 5B.
  • the device 100 may further include respective components (e.g. motors) for rotating the planar surface 102 between the external and internal position via the rotational mechanism 126.
  • respective components e.g. motors
  • Figure 2A and Figure 2B respectively depict a perspective view and a block diagram of an example sample preparation device 200 that incorporates aspects of the device 100 of Figure 1 .
  • the planar surface 102, the shuttle 104 and the carriage 108 are shown in side views.
  • a pin/post of a mating device 122-1 is shown as extending (e.g. perpendicularly and/or in any suitable direction) from a shuttle-facing side of the carriage 108, and a hole of a mating device 122-2, and a portion of the rotational mechanism 126 inside the planar surface 102, is shown in outline in the planar surface 102 to show their relative positions in the planar surface 102.
  • the sample preparation device 200 (interchangeably referred to hereafter as the device 200) includes a chassis 202 that includes a cassette access door 204 for loading a cassette 206 that includes a sample preparation cartridge module 208 and/or sample preparation cartridge modules 208 therein, the sample preparation cartridge module 208 holding a sample for testing as described hereafter. While the sample preparation cartridge modules 208 are depicted herein as being in an elongate shape and/or in the form of a column, the sample preparation cartridge modules 208 may be any suitable shape.
  • the chassis 202 further includes a well access door 210 for loading a well holder 212 containing a well 214 and/or wells for receiving processed samples dispensed from the sample preparation cartridge module 208 after processing by the device 200. While only one sample preparation cartridge module 208 is depicted, and eight wells 214 (to show loading of well holder 212 into the shuttle 104), it is understood that the cassette 206 may hold a same number of sample preparation cartridge modules 108 as there are wells 214 at the well holder 212. For example, as depicted, there may be eight sample preparation cartridge modules 208 and eight wells, as described above.
  • the components of the device 200 may cause the cassette 206 and the well holder 212 to be loaded into the device 200 in any suitable relative orientation including, but not limited to, about parallel to one another such that a line of the sample preparation cartridge modules 208 is about aligned with a line of the wells 214, as described below with respect to Figure 6.
  • the device 200 further comprises an input device 218, such as a touch screen display, and the like, which may be used to control the device 200 into a loading mode, amongst other possibilities, which causes the cassette access door 204 and the well access door 210 to open such that the cassette 206 and the well holder 212, with the wells 214, may be manually loaded into the device 200.
  • a sample preparation cartridge module 208 is loaded with a sample 238 (e.g. such as a biological sample retrieved from a human by medical personnel), and the like, via a port 220.
  • the input device 218 may also be used to set given temperatures to which the sample preparation cartridge module 208 is to be heated and/or a heating cycle of the sample preparation cartridge module 208 and/or a heating/mixing cycle (e.g. setting mixing speeds of the actuator 244 of the device 200).
  • the carriage 108 of the device 200 which may alternatively be referred to as the cassette carriage 108, as previously described, is raised along a vertical carriage guide 226 to at least partially emerge from an opening that is normally covered by the cassette access door 204, to a sample loading position.
  • the cassette 206 is then manually loaded into the cassette carriage 108 at the sample loading position.
  • the shuttle e.g. a well carriage
  • the planar surface e.g. horizontal carriage guide
  • the well holder 212 may be manually loaded into a complementary shaped depression and/or holder 231 in the shuttle 104. While the terms vertical and horizontal (as well similar terms such as above, below, and the like) are used herein with regards to a position of the device 200 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 200 (e.g. the guide 226 and the planar surface 102 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 206 into different positions in the device 200 (e.g. closing the door 204), for example along the vertical carriage guide 226, to process the sample 238 before dispensing the sample 238 from the sample preparation cartridge module 208 into a well 214.
  • the device 200 e.g. and/or the device 100 integrated into the device 200
  • the device 200 is further understood to include a motor and/or a servomotor, and the like, to move the cassette carriage 108 into different positions along the vertical carriage guide 226 (e.g. as described above with respect to Figure 1A and Figure 1 B).
  • the planar surface 102 moves inside the device 200 (e.g. closing the door 210) and the shuttle 104 is moved into a position to receive the sample 238 from the sample preparation cartridge module 208 into a corresponding well 214.
  • the shuttle 104 is moved into respective positions to receive respective samples 238 dispensed from respective sample preparation cartridge modules 208 into corresponding wells 214.
  • the shuttle 104 may be positioned at the relative given angle 120 relative to the cassette carriage 108 (e.g. as shown in Figure 1), and/or the cassette 206, such that different sample preparation cartridge modules 208 align with different wells 214 at different positions of the shuttle 104 as described below with respect to Figure 4A and Figure 4B.
  • the device 200 is further understood to include motors and/or a servomotors, and the like, to move the planar surface 102 into and out of the device 200, and to linearly move the shuttle 104 along the planar surface 102.
  • the device 200 may further include respective components (e.g. motors) for opening and closing the doors 204, 210.
  • respective components e.g. motors
  • the sample preparation cartridge module 208 may be divided into a first region 232 and a second region 234, divided by a barrier 236.
  • a sample 238 is received into the sample preparation cartridge module 208 via the port 220, and may reside at a bottom of the first region 232, at the barrier 236.
  • the sample preparation cartridge module 208 may further comprise an agitator 240 in the first region 232 which may be actuated via a mixer actuator 242 and an actuator 244, and the like of the device 200 as described below.
  • the mixer actuator 242 may include a servomotor and/or servomotors, and the like, to move/rotate the actuator 244 to mix the sample 238 via the agitator 240, while the sample 238 is heated, as described below.
  • the cassette 206 may be moved, along the vertical carriage guide 226, via the cassette carriage 108, into a heating position for heating by one or both of two heaters 246 (e.g. heaters 246-1 , 246-2) attached to respective mechanical devices 248 (e.g. mechanical devices 248-1 , 248-2).
  • two heaters 246 e.g. heaters 246-1 , 246-2
  • respective mechanical devices 248 e.g. mechanical devices 248-1 , 248-2).
  • the device 200 is understood to include respective temperature sensors at the heaters 246 and/or the mechanical devices 248 so that, in a heating position of the cassette carriage 108, the heaters 246 may be positioned adjacent the first region 232 of the sample preparation cartridge module 208 to heat the sample 238, while the agitator 240 is actuated by the actuator 244, to agitate and/or mix the sample 238 while it is being heated, for example to promote lysis in cells of the sample 238.
  • the actuator 244 itself is understood to be further moved by the mixer actuator 242 into a position to agitate and/or mix the sample 238, while it is being heated, and actuated by the mixer actuator 242 which may comprise any suitable combination of motors for moving and turning the actuator 244.
  • the first region 232 may include magnetizing microparticles having surfaces to which biological components of interest, expelled by cells of the sample 238 due to lysis, bond; hence, in some examples, the actuator 244 may comprise a magnetic agitating device which agitates the sample 238 during lysis by applying a changing magnetic field to the first region 232 to move the magnetizing microparticles; In such examples, the agitator 240 may be omitted from the sample preparation cartridge module 208.
  • the agitator 240 is generally configured to mate with the actuator 244; for example, as depicted, the agitator 240 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 244, to actuate the agitator 240, and move the sample 238 to the second region 234, for example by applying pressure to the pressure source 250 via the actuator 244 to break the barrier 236.
  • 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 244, to actuate the agitator 240, and move the sample 238 to the second region 234, for example by applying pressure to the pressure source 250 via the actuator 244 to break the barrier 236.
  • the second region 234 may further include a wash buffer which may be mixed with the biological components of interest bonded to the magnetizing microparticles (e.g. when plunged into the second region 234), by actuation of a suitable reservoir 252 of a plurality of reservoirs 252 that perform different functions for the sample preparation cartridge module 208; such reservoirs 252 may be alternatively referred to as blisters and/or pouches, and the like.
  • one reservoir 252 may hold the wash buffer, another reservoir 252 may hold chemicals to stabilize the biological components of interest, another reservoir 252 may hold a grease barrier, and yet another reservoir 252 may be for dispensing the processed sample 238, biological components of interest bonded to the magnetizing microparticles, into a well 214, for example via a needle and/or tip 254 of the sample preparation cartridge module 208.
  • the cassette 206 may hold a plurality of sample preparation cartridge modules 208 and hence the device 200 may include various devices for actuating a plurality of corresponding reservoirs 252 (e.g. concurrently) on a plurality of sample preparation cartridge modules 208 and devices for actuating individual reservoirs 252 (e.g. independent of each other) on the sample preparation cartridge modules 208.
  • the device 200 may include a multiple reservoir actuator 256 including a plurality of reservoir tips 258 (though only one is depicted) which may be used to actuate a plurality of corresponding reservoirs 252 (e.g.
  • the device 200 may include a plurality of single reservoir actuators 260 (though only one is depicted) including respective reservoir tips 262 (though, again, only one is depicted), for independently actuating respective reservoirs 252 at the plurality of sample preparation cartridge modules 208 to independently dispense samples 238 into respective wells 214 via respective tips 262.
  • the device 200 may comprise one single reservoir actuator 260 including one reservoir tip 262 that is movable within the device 200 between sample preparation cartridge modules 208.
  • the cassette carriage 108 may be moved into various suitable positions along the vertical carriage guide 226 relative to other components of the device 200, to effect actuation of the pressure source 250 and/or actuation of respective reservoirs 252 by the reservoir actuators 256, 260.
  • the carriage 108 is understood to include openings, and the like, therethrough, to enable the reservoirs 252 to be actuated, as well as enable the heaters 248, the actuator 244, the magnetic devices 264, the tips 258, 262 to interact with the sample preparation cartridge modules 208.
  • the device 200 and/or the sample preparation cartridge module 208 may include other suitable components.
  • the sample preparation cartridge module 208 may include the magnetizing microparticles in the first region 232 which have surfaces treated to bond to biological components of interest from the sample 238 when heated.
  • the second region 234 may include a wash buffer density gradient, when the wash buffer is introduced into the second region 234; in particular, the second region 234 may comprise a fluid density gradient which isolates and/or purifies the biological components of interest bonded to the magnetizing microparticles.
  • the device 200 may include a magnetic device 264, which may be actuated via a magnetic actuator 266 to move the magnetic device 264 adjacent the sample preparation cartridge module 208 as the sample preparation cartridge module 208 is moved along the vertical carriage guide 226, for example to attract the magnetizing microparticles in the processed sample 238 and move the processed sample 238, including the biological components of interest bonded to the magnetizing microparticles, towards the tip 254 and/or through the wash buffer density gradient in the second region 234, for example to isolate and/or purify the biological component of interest bonded to the magnetizing microparticles.
  • a magnetic device 264 which may be actuated via a magnetic actuator 266 to move the magnetic device 264 adjacent the sample preparation cartridge module 208 as the sample preparation cartridge module 208 is moved along the vertical carriage guide 226, for example to attract the magnetizing microparticles in the processed sample 238 and move the processed sample 238, including the biological components of interest bonded to the magnetizing microparticles, towards the tip 254 and/or through the wash buffer density gradient in the second
  • the device 200 further includes a cooler and/or air-intake port 268 and/or tube which may include a fan, and the like (not depicted) for drawing air into the device 200 via a filter 270, and an exhaust port 272 (which may also include a fan) for expelling air drawn into the device 200 via the cooler port 268 via a respective filter 274.
  • the ports 268, 272 may provide passive and/or active cooling at the device 200 to cool the sample 238 when heated.
  • the ports 268, 272 may be located in any respective suitable positions at the device 200.
  • the cassette carriage 108 may be moved into a sample dispensing position relative to the shuttle 104 and/or the wells 214 to dispense samples 238, including the biological components of interest bonded to the magnetizing microparticles, into the wells 214 from the sample preparation cartridge modules 208; the shuttle 104 may be moved into sample receiving positions, relative to the carriage 108, to position the wells 214 relative to the sample preparation cartridge modules 208 to receive the processed samples 238 as dispensed.
  • the device 200 may be operated to move the wells 214 out of the device 200 (e.g. via the planar surface 102 and shuttle 104 being moved out of the device 200 via the access door 210) where the wells 214 holding the samples 238 may be moved to a PCR assay device.
  • Figure 3 is substantially similar to Figure 2B with like components having like numbers.
  • the cassette 206 has been loaded into the cassette carriage 108, and the carriage access door 204 has been closed.
  • the sample 238 has undergone lysis via heating by the heaters 246, and moved to the second region 234 of the sample preparation cartridge module 208 via the pressure source 250 being actuated (e.g. by moving the cassette carriage 108 to move the sample preparation cartridge module 208 towards the actuator 244 so that the actuator 244 actuates the pressure source 250 to break the barrier 236, for example by pushing the agitator 240 towards the barrier 236).
  • the reservoirs 252 containing the wash buffer, the stabilizing chemicals and the grease barrier have been actuated by the multiple reservoir actuator 256 and the reservoir tips 258.
  • the processed sample 238, including the biological components of interest bonded to the magnetizing microparticles has been drawn through the wash buffer density gradient/fluid density gradient to isolate and/or purify the biological components of interest bonded to the magnetizing microparticles.
  • the processed sample 238, including the biological components of interest bonded to the magnetizing microparticles m is depicted at being at the tip 254 of the sample preparation cartridge module 208, while other portions of the sample 238 remain in the second region 234 (e.g. as represented by different patterned areas of the second region 234)
  • the carriage 108 has been moved to the sample dispensing position.
  • the wells 214 have been loaded into the well holder 212 at the shuttle 104, and the planar surface 102, with the shuttle 104, has been moved/rotated into the device 200 from an external position to an internal position, with the well access door 210 closed.
  • the shuttle 104 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 214 is aligned with the sample preparation cartridge module 208, and specifically the tip 254 thereof.
  • a single reservoir actuator 260 has been controlled to move the reservoir tip 262 to actuate a dispensing reservoir 252 (not depicted in Figure 3, but nonetheless understood to be present).
  • sample 238, including the biological components of interest bonded to the magnetizing microparticles, at the tip 254 is being dispensed into a corresponding well 214.
  • the wells 214 and/or regions around the tip 254 at the sample preparation cartridge module 208 may include splash guards, and the like, to assist with reducing cross-contamination between the wells 214.
  • the shuttle 104 While the shuttle 104 is depicted as being at one sample receiving position, the shuttle 104 may be moved to other sample receiving positions (e.g. up to eight sample receiving positions, one for each well 214 and corresponding sample preparation cartridge module 208 when there are eight of each; sample preparation cartridge modules 208, that do not contain a sample may be skipped in the dispensing process). Such sample receiving positions are next described.
  • sample receiving positions e.g. up to eight sample receiving positions, one for each well 214 and corresponding sample preparation cartridge module 208 when there are eight of each; sample preparation cartridge modules 208, that do not contain a sample may be skipped in the dispensing process.
  • Figure 4A and Figure 4B depict top views of the device 100 including the planar surface 102, the shuttle 104 and the carriage 108. While in Figure 4A the guides 124 are not depicted, they are nonetheless understood to be present. Furthermore, in Figure 4A, the shuttle 104 and the carriage 108 are understood to be empty of wells 214 and sample preparation cartridge modules 208 while, in Figure 4B, wells 214 and sample preparation cartridge modules 208 are respectively present at the shuttle 104 and the carriage 108. In particular, Figure 4B is understood to show the sample 238 being dispensed into the wells 214 at different sample receiving positions via a single reservoir actuator 260 and a respective tip 262 (which, while not depicted, are understood to be present).
  • Figure 4A is provided to show linear alignment between respective positions 116, 118 along the linear path 106, when the carriage 108 and the shuttle 104 are at the relative given angle 120.
  • the shuttle 104 is depicted in a loading position, away from the carriage 108.
  • broken lines 402 between respective positions 116, 118 indicate that, when the carriage 108 and the shuttle 104 are at the relative given angle 120, the first sample preparation cartridge module position 116 is aligned with the first well position 118 along the linear path 106, the second sample preparation cartridge module position 116 is aligned with the second well position 118 along the linear path 106, etc.
  • the shuttle 104 may be moved into different sample receiving positions where a well 214 aligns with a respective sample preparation cartridge module 208 and, more specifically, a tip 254 thereof.
  • Figure 4B shows the shuttle 104 in odd-numbered sample receiving positions 404-1 , 404-3, 404-5, 404-7 (e.g. every second sample receiving position 404) along the linear path 106. While even numbered sample receiving positions 404 of the shuttle 104 are not depicted (e.g. to better show a portion of the sample receiving positions 404 in Figure 4B), it is understood that there are a same number of sample receiving positions 404 as there are positions 116, 118.
  • respective numbers of the sample preparation cartridge modules 208 and/or sample preparation cartridge module positions 116, the wells 214 and/or well positions 404, and the sample receiving positions 404 may be of a same given number, for example, as depicted, eight of each.
  • there are eight sample receiving positions 404-1 , 404-2, 404-3, 404-4, 404-5, 404-6, 404-8, 404-8 of the shuttle 104 e.g. show in Figure 4A).
  • a given well 214 is at a given well position 118 is understood to be aligned with a tip 254 of a respective sample preparation cartridge module 208 at a corresponding/aligned sample preparation cartridge module position 116.
  • a first well 214-1 at a first well position 118 is understood to be aligned with a tip 254 of a first sample preparation cartridge module 208-1 at a first sample preparation cartridge module position 116.
  • the first well 214-1 is hidden by the carriage 108, a position of the first well 214-1 is depicted in broken lines relative to the sample preparation cartridge module 208-1 showing the alignment.
  • the shuttle 104 is moved (not depicted) to the second sample receiving position 404-2 where a second well 214 at the second well position 118 is understood to be aligned with a tip 254 of a second sample preparation cartridge module 208-2 at the second sample preparation cartridge module position 116.
  • a respective sample 238 is dispensed from the second sample preparation cartridge module 208-2 into a second well 214.
  • the process then continues, to move the shuttle 104 to respective sample receiving positions 404 until respective samples 238 from the eight sample preparation cartridge modules 208 are dispensed into respective wells 214.
  • respective wells 214-1 , 214-3, 214-5, 214-7 are shown as aligned with respective sample preparation cartridge modules 208-1 , 208-3, 208-5, 208-7 and a respective sample 238 is dispensed into a respective well 214-1 , 214-3, 214-5, 214-7.
  • respective samples 238 are dispensed from respective sample preparation cartridge modules 208-2, 208-4, 208-6, 208-8 into respective wells 214.
  • respective samples 238 are depicted as being in wells 214 (e.g. represented as shaded areas) into which samples 238 have already been dispensed.
  • the carriage 108 may be moved to an unloading position (e.g. similar to the loading position in Figure 2B) for unloading of the cassette 206 and/or replacement by a new cassette 206.
  • the shuttle 104 may be moved to an unloading position (e.g. similar to the loading position in Figure 4B) and rotated out of the device 100 and/or the device 200 for unloading of the wells 214 and/or the holder 212 and/or replacement by a new wells 214 and/or a new holder 212.
  • Figure 5A and Figure 5B depict a portion of the device 200, showing a top view of the planar surface 102, the shuttle 104 in a loading/unloading position and the carriage 108, as well as an outline of the chassis 202 and the well access door 210, relative to the other depicted components, the show relative positions therebetween.
  • Figure 5A shows the planar surface 102 in an internal position within the device 200, with the well access door 210 closed, with the carriage 108 and the shuttle 104 at the relative given angle 120; and
  • Figure 5B shows the planar surface 102 in an external position within the device 200, with the well access door 210 open. While other components of the device 200 are not depicted, they are nonetheless understood to be present.
  • Figure 5A and Figure 5B it is understood that the carriage 108 has been raised out of the sample dispensing position so that the planar surface 102 may rotate out of, and into, the device 200, for example about the rotational mechanism 126, as indicated by the arrow 501.
  • Figure 5B also shows the mating devices 122-2 in the planar surface 102.
  • the shuttle 104 In the external position of the planar surface 102, the shuttle 104 is understood to be external to the device 200 for loading, or unloading, of the wells 214 and/or the well holder 212.
  • at least a portion of the planar surface 102 extends (e.g. perpendicularly and/or in any suitable direction) out of the device 200, for example out of the well access door 210.
  • Figure 5A and Figure 5B illustrate that the planar surface 102 is rotatable between an external position extending e.g. perpendicularly and/or in any suitable direction) out of the device 200, to receive the sample receiving wells, and an internal position in the device 200, defined by the relative given angle 120.
  • first and last sample receiving position 118-1 , 118-8 are in a same relative orientation as (and/or correspond with), first and last sample preparation cartridge module positions 116-1 , 116-8.
  • Such same relative orientations may assist with reducing confusion as to which sample preparation cartridge module 208 is associated with which sample when dispensed into the wells 214 when the sample preparation cartridge modules 208 and the wells 214 are loaded or unloaded, from the device 200, for example for insertion into a PCR device.
  • Figure 6 depicts a front view of the device 200 with the doors 204, 210 open, for loading.
  • the device 200 may be in a loading mode, as indicated by the touch screen display of the input device 218, such that a user may load the cassette 206 holding sample preparation cartridge modules 208 in a line (e.g. eight sample preparation cartridge modules 208) into the carriage 108, and a well holder 212 holding wells 214 (e.g. eight wells 214) in a respective line, into the shuttle 104.
  • a line e.g. eight sample preparation cartridge modules 208
  • wells 214 e.g. eight wells 214
  • the carriage 108 is depicted as being raised out of an opening of the door 204 to a sample loading position, and the planar surface 102 and the shuttle 104 are depicted as having being rotated out of an opening of the door 210 into the external position of Figure 5B.
  • the cassette 206 is being loaded/lowered into the carriage 108 and the well holder 212 is being loaded/lowered into the shuttle 104.
  • Figure 6 further shows that the sample preparation cartridge modules 208 are held in the cassette 206 at the first pitch 112, and the wells 214 are held in the holder 212 at the second pitch 114.
  • planar surface 102 at the external position, is to receive, at the shuttle 104, the sample receiving wells 214 about parallel to the sample preparation cartridge modules 208 when held by the carriage 108.
  • the sample preparation cartridge modules 208 and the sample receiving wells 214 may be loaded into the device 200, or unloaded from the device 200, while respective linear arrangements of the sample preparation cartridge modules 208 and the sample receiving wells 214 are about parallel to each other.
  • a user performing the loading or unloading visually associates a first sample preparation cartridge module 208-1 , holding a first sample, for example, on a left hand side of the cassette 206 and/or the carriage 108, with a respective first sample receiving well 214-1 on a left hand side of the shuttle 104 and/or the well holder 212 into which the first sample is to be dispensed after processing.
  • the user visually associates a last sample preparation cartridge module 208-8, holding a last sample, for example, on a right hand side of the cassette 206 and/or the carriage 108, with a respective last sample receiving well 214-8 on a right hand side of the shuttle 104 and/or the well holder 212 into which the last sample is to be dispensed after processing.
  • first and last are used herein merely to illustrate orientations of the wells 214 and the sample preparation cartridge modules 208, and the like.
  • Such visual cues may assist with reducing confusion as to which sample preparation cartridge module 208 is associated with which sample when dispensed into the wells 214 and retrieved from the device 200 for insertion into a PCR device.
  • the user may interact with the input device 218 to cause the planar surface 102 to rotate into the device 200 and further cause the carriage 108 to lower into the device 200 to process the samples 238.
  • the device 200 may generally comprise: a chassis 202 having an opening (e.g. of the door 210); a planar surface 102 rotatable between an external position and an internal position via the opening; a carriage 108 to hold sample preparation cartridge modules 208 linearly arranged according to a first pitch 112, the carriage 108 to move about relative and/or perpendicularly to the planar surface 102 at the internal position; a shuttle 104 on the planar surface 102, the shuttle 104 to : receive sample receiving wells 214 linearly arranged according to a second pitch 114 different from the first pitch 112; and move linearly along the planar surface 102 into sample receiving positions 404, between the planar surface 102 and the sample preparation cartridge modules 208, the planar surface 102, at the external position, to receive, at the shuttle 104, the sample receiving wells 214 about parallel to the sample preparation cartridge modules 208 when held by the carriage 108, the planar surface 102, at the internal position, holding the shuttle
  • the device 200 is understood to comprise a door 210 that is: open at the external position of the planar surface 102; and closed at the internal position of the planar surface 102.
  • FIG. 7 is a block diagram of control components of the device 200 that includes a controller 700 and a memory 702. While other components of the device 200 are not depicted, they are nonetheless understood to be present.
  • the controller 700 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
  • functionality of the controller 700 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).
  • the controller 700 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 702 may comprise instructions 704 for controlling the controller 700 and/or a processor thereof to perform the various processes described herein.
  • a memory 702 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, readonly 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 Disc (DVD), a paper storage device, flash memory, readonly memory, non-volatile RAM, etc.
  • the instructions 704 may be provided in the form of a module and/or software modules (e.g., as used herein, a “module” and/or “software module” is a set of instructions that when executed or interpreted by a processor or stored at a processor-readable medium realizes a component or performs a method). Hence, for example, the instructions 704 may alternatively be replaced with an instruction module.
  • the memory 702 further stores a carriage sample dispensing position 706, which has been predetermined and may be provided in the form of an optical encoder position of a carriage motor, the carriage sample dispensing position 706 corresponding to the carriage sample dispensing position of the carriage 108 shown in Figure 3.
  • the memory 702 further stores shuttle sample receiving positions 708, which have been predetermined and may be provided in the form optical encoder positions of a shuttle motor, the shuttle sample receiving positions 708 corresponding to the sample receiving positions 404.
  • the memory 702 further stores other predetermined carriage positions 710 and predetermined shuttle positions 712 which may be provided in the form of optical encoder positions and may be used to respectively move the carriage 108 and the shuttle 104 to various positions so that they move as described herein (e.g. so that the carriage 108 and the shuttle 104 may move to loading/unloading positions, etc.).
  • predetermined carriage positions 710 and predetermined shuttle positions 712 may be provided in the form of optical encoder positions and may be used to respectively move the carriage 108 and the shuttle 104 to various positions so that they move as described herein (e.g. so that the carriage 108 and the shuttle 104 may move to loading/unloading positions, etc.).
  • method 800 to perform dispensing in a sample preparation device is depicted.
  • method 800 may be performed with the device 200 (e.g. via the controller 700 implementing the instructions 704).
  • the method 800 may be one way in which the device 200 may be configured.
  • the following discussion of method 800 may lead to a further understanding of the device 200, and its various components.
  • method 800 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.
  • the device 200 moves the carriage 108 to a sample loading position (e.g. as depicted in Figure 6) to receive sample preparation cartridge modules 208 linearly arranged according to a first pitch 112, the carriage 108 to move relative (e.g. perpendicularly and/or in any suitable direction) to the planar surface 102 holding the shuttle 104.
  • a sample loading position e.g. as depicted in Figure 6
  • the carriage 108 to move relative (e.g. perpendicularly and/or in any suitable direction) to the planar surface 102 holding the shuttle 104.
  • the device 200 rotates the planar surface 102 to an external position (e.g. as depicted in Figure 5B and Figure 6) as to receive, at the shuttle 104, sample receiving wells 214 linearly arranged according to a second pitch 114 different from the first pitch 112. It is understood that, in the external position of the planar surface 102, the shuttle 104 is about parallel to the carriage 108 such that the sample receiving wells 214 are about parallel with the sample preparation cartridge modules 208.
  • an external position e.g. as depicted in Figure 5B and Figure 6
  • the shuttle 104 is about parallel to the carriage 108 such that the sample receiving wells 214 are about parallel with the sample preparation cartridge modules 208.
  • the device 200 rotates the planar surface 102 to an internal position (e.g. as depicted in Figure 1A, Figure 1 B and Figure 5A) such that the sample receiving wells 214 and the sample preparation cartridge modules 208 are at the relative given angle 120 determined from the first pitch 112 and the second pitch 114 such that, at sample receiving positions 404 of the shuttle 104, a sample preparation cartridge module 208 is aligned with a respective sample receiving well 214.
  • an internal position e.g. as depicted in Figure 1A, Figure 1 B and Figure 5A
  • the device 200 moves the carriage 108 towards the shuttle 104 (e.g. perpendicularly and/or in any suitable direction) into a sample dispensing position (e.g. as depicted in Figure 3).
  • the device 200 moves the shuttle 104 into the sample receiving positions 404 relative to the sample preparation cartridge modules 208.
  • the device 200 dispenses a respective sample 238 into a respective sample receiving well 214 at a respective sample receiving position 404.
  • Instances of the blocks 810, 812 may be performed for respective sample receiving positions 404.
  • moving the shuttle 104 into the sample receiving positions 404, at the block 810, relative to the sample preparation cartridge modules 208 may comprise moving the shuttle 104 linearly along the planar surface 102 between the sample receiving positions 404 and stopping therebetween to receive a respective sample 238 into the respective sample receiving well 214 at the block 812.
  • the method 800 may further comprise the device 200 opening and closing a door 210 at an opening of the device 200 as the as the planar surface 102 is respectively rotated to the external position and the internal position.
  • the method 800 may further comprise the device 200, in response to a last sample 238 being dispensed into a last sample receiving well 214: moving the carriage 108 (e.g. perpendicularly and/or in any suitable direction) away from the shuttle 104 (e.g.
  • a sample unloading position similar to the sample loading position in Figure 6 so that the cassette 206 may be unloaded and/or replaced with a new cassette 206 with new sample preparation cartridge modules 208); and rotating the planar surface 102 to the external position for retrieval of the sample receiving wells 214 from the shuttle 104, for example for unloading of the wells 214 (and/or the holder 212) with the samples 238 dispensed therein and/or the holder 212 and/or for replacement with new wells 214 and/or a new holder 212.
  • the unloaded wells 214 may be transferred to a PCR device for PCR processing of the samples 238 in the wells 214.

Abstract

Un dispositif, donné à titre d'exemple, comprend un chariot destiné à contenir des modules de cartouche de préparation d'échantillons, agencés linéairement selon un premier pas ; et une navette destinée à recevoir des puits récepteurs d'échantillons, agencés linéairement selon un second pas différent du premier pas, la navette et le chariot se déplaçant l'un par rapport à l'autre de telle sorte que la navette se trouve au niveau de positions de réception d'échantillons par rapport au chariot lorsque le chariot se trouve dans la position de distribution d'échantillons. Le dispositif, donné à titre d'exemple, comprend en outre des dispositifs complémentaires d'appariement qui maintiennent le chariot dans la position de distribution d'échantillons, à un angle donné relatif par rapport à la navette, l'angle donné relatif étant déterminé à partir du premier pas et du second pas, de telle sorte que, au niveau des positions réceptrices d'échantillons de la navette, un module de cartouche de préparation d'échantillon est aligné avec un puits respectif.
PCT/US2020/066610 2020-12-22 2020-12-22 Dispositifs et procédés d'établissement de points de référence pour la distribution d'échantillon WO2022139813A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060210433A1 (en) * 2005-03-10 2006-09-21 Gen-Probe Incorporated Signal measuring system having a movable signal measuring device
EP2752668A2 (fr) * 2010-07-23 2014-07-09 Beckman Coulter, Inc. Système ou procédé comprenant des unités analytiques
US20150226759A1 (en) * 2014-01-10 2015-08-13 Idexx Laboratories, Inc. Chemical analyzer

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060210433A1 (en) * 2005-03-10 2006-09-21 Gen-Probe Incorporated Signal measuring system having a movable signal measuring device
EP2752668A2 (fr) * 2010-07-23 2014-07-09 Beckman Coulter, Inc. Système ou procédé comprenant des unités analytiques
US20150226759A1 (en) * 2014-01-10 2015-08-13 Idexx Laboratories, Inc. Chemical analyzer

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