WO2022139820A1

WO2022139820A1 - Devices to control magnetizing microparticles in fluid density columns

Info

Publication number: WO2022139820A1
Application number: PCT/US2020/066645
Authority: WO
Inventors: Keith William Joseph JARIABKA; Michelle Forshager ELLIS; Alan Shibata; Dawn M. Beachnau Hood
Original assignee: Hp Health Solutions Inc.
Priority date: 2020-12-22
Filing date: 2020-12-22
Publication date: 2022-06-30

Abstract

An example device includes: a carriage to move along a path, the carriage having a lateral axis perpendicular to the path; and first magnetic devices and second magnetic devices independently controllable from one another and the carriage, the first magnetic devices and the second magnetics actuatable to respective positions at the carriage from a same given side of the carriage, respective opposing edges of the first magnetic devices and the second magnetic devices laterally offset from each other along the lateral axis, the first magnetic devices and the second magnetic devices alternating with each other along the lateral axis, and offset along the path.

Description

DEVICES TO CONTROL MAGNETIZING MICROPARTICLES IN FLUID DENSITY COLUMNS

BACKGROUND

[0001] Washing magnetizing microparticles in a fluid density column is important to remove contaminants.

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 is a block diagram of an example device to control magnetizing microparticles in fluid density columns.

[0004] Figure 2A shows the example device of Figure 1 with a carriage holding a sample containers that includes fluid density columns and magnetizing microparticles therein.

[0005] Figure 2B shows a perspective view of further details of the example device of Figure 1 with a carriage holding a cassette that includes sample containers, which includes respective fluid density columns.

[0006] Figure 3 is a perspective view of example fluid density columns showing example relative positions thereto of magnetic devices of the example device of Figure 1 .

[0007] Figure 4 shows a top view of relative positions of magnetic devices to example fluid density columns, with the fluid density columns in cross-section through a plane parallel to the magnetic devices.

[0008] Figure 5A shows a top view of an example of the magnetic devices mounted to respective plates and respective actuators thereof.

[0009] Figure 5B shows a side view of the example of Figure 5A.

[0010] Figure 6A, Figure 6B, Figure 6C and Figure 6D show a sequence to control magnetizing microparticles in fluid density columns. [0011] Figure 7 show different path geometries for magnetizing microparticles that may be implemented in the example device of Figure 1 .

[0012] Figure 8A is a perspective view of an example sample preparation device that incorporates the device of Figure 1 .

[0013] Figure 8B is a block diagram of the device of Figure 8A.

[0014] Figure 8C is a block diagram of the device of Figure 8A with a carriage in a magnetizing microparticle washing position.

[0015] Figure 9 is a flow diagram of a method to control magnetizing microparticles in fluid density columns.

DETAILED DESCRIPTION

[0016] 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.

[0017] 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.

[0018] 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.

[0019] 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).

[0020] 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.

[0021] 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.

[0022] 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.

[0023] In one particular example, a biological component of interest, bonded to magnetizing microparticles, may be dragged towards an output via a fluid density column to wash the magnetizing microparticles to isolate and/or purify a biological component of interest to remove contaminants. Furthermore, to improve throughput at the sample preparation device, washing magnetizing microparticles concurrently in the sample containers may occur.

[0024] Hence, provided herein is a device that includes a carriage to hold sample preparation cartridge modules that include respective fluid density columns with respective magnetizing microparticles therein. The device further includes first magnetic devices and second magnetic devices independently controllable from one another and the carriage. The first and second magnetic devices may be used to alternately apply respective magnetic fields to sides of alternating fluid density columns, after the carriage is moved to, and pauses at, given positions, relative to the magnetic devices. Magnetic fields of first and second magnetic devices may then concurrently drag and/or move the magnetizing microparticles, with a biological component bonded thereto (e.g. a virus and the like) in different path geometries in the fluid density columns. [0025] A first aspect of the present specification provides a device comprising: a carriage to move along a path, the carriage having a lateral axis perpendicular to the path; and first magnetic devices and second magnetic devices independently controllable from one another and the carriage, the first magnetic devices and the second magnetics actuatable to respective positions at the carriage from a same given side of the carriage, respective opposing edges of the first magnetic devices and the second magnetic devices laterally offset from each other along the lateral axis, the first magnetic devices and the second magnetic devices alternating with each other along the lateral axis, and offset along the path.

[0026] At the device of the first aspect, a first portion the respective positions may correspond to gaps between adjacent fluid density columns of sample preparation cartridge modules holdable by the carriage in a row and a second portion of the respective positions correspond to respective outer sides of respective fluid density columns of respective outer sample preparation cartridge modules in the row.

[0027] At the device of the first aspect, a portion of the first magnetic devices that are actuatable to outer respective positions may be smaller in width along the lateral axis than others of the first magnetic devices or the second magnetic devices.

[0028] At the device of the first aspect, respective opposing edges of the first magnetic devices and the second magnetic devices may be laterally offset from each other along the lateral axis by a distance defined by fluid density columns of sample preparation cartridge modules holdable by the carriage, such that a fluid density column fits between the respective opposing edges.

[0029] At the device of the first aspect, the first magnetic devices and the second magnetic devices may be further to alternate moving towards, and away from, the carriage.

[0030] A second aspect of the present specification provides a device comprising: a carriage to move along a path, the carriage having a lateral axis perpendicular to the path; first magnetic devices and a first actuator to actuate the first magnetic devices to first positions at the carriage; and second magnetic devices and a second actuator to actuate the second magnetic devices to second positions at the carriage, the first actuator, the second actuator, and the carriage being controllable independent of one another, the first positions corresponding to first gaps between adjacent fluid density columns of sample preparation cartridge modules holdable the carriage and the second positions corresponding to second gaps between the adjacent fluid density columns, the first positions alternating with the second positions, the first magnetic devices and the second magnetic devices offset along the path.

[0031] At the device of the second aspect, the first magnetic devices may be mounted at a first edge of a first plate, the first actuator to actuate the first plate to actuate the first magnetic devices to the first positions, and the second magnetic devices may be mounted at a second edge of a second plate, the second actuator to actuate the second plate to actuate the second magnetic devices to the second positions, the first plate and the second plate laterally offset from each other along the path of the carriage to offset the first magnetic devices and the second magnetic devices along the path.

[0032] At the device of the second aspect, the first actuator and the second actuator may be further to alternate actuation of the first magnetic devices and the second magnetic devices to the first positions and the second positions at the carriage such that either the first magnetic devices are at the first positions or the second magnetic devices are at the second positions.

[0033] At the device of the second aspect, the first actuator and the second actuator may be further to actuate the first magnetic devices and the second magnetic devices to the first positions and the second positions at the carriage simultaneously.

[0034] At the device of the second aspect, the first magnetic devices and the second magnetic devices may further comprise mechanical centering features to mechanically interact with sides of the adjacent fluid density columns to about center a magnetic device between the adjacent fluid density columns.

[0035] A third aspect of the present specification may provide a method comprising: controlling, at a sample preparation device, the sample preparation cartridge modules to move to a first position, the sample preparation cartridge modules including fluid density columns and magnetizing microparticles therein; controlling, at the sample preparation device, while the sample preparation cartridge modules are paused at the first position, first magnetic devices to apply respective first magnetic fields between first adjacent fluid density columns for a first given time period and to outer sides of end fluid density columns; controlling, at the sample preparation device, the first magnetic devices to remove the respective first magnetic fields from the fluid density columns; controlling, at a sample preparation device, the sample preparation cartridge modules to move to a second position; controlling, at the sample preparation device, while the sample preparation cartridge modules are paused at the second position, second magnetic devices to apply respective second magnetic fields between second adjacent fluid density columns for a second given time period, the first adjacent fluid density columns alternating with the second adjacent fluid density columns; and controlling, at the sample preparation device, the second magnetic devices to remove the respective second magnetic fields from the fluid density columns.

[0036] At the method of the third aspect, the first given time period and the second given time period may be selected to drag the magnetizing microparticles to respective sides of the fluid density columns while the first magnetic devices and the second magnetic devices are applying the respective first magnetic fields and the respective second magnetic fields at the fluid density columns.

[0037] The method of the third aspect may further comprise, prior to moving the sample preparation cartridge modules to the first position and the second position: controlling both the first magnetic devices and the second magnetic devices to concurrently apply, for a third given time period, the respective first magnetic fields and the respective second magnetic fields to between the first adjacent fluid density columns, the second adjacent fluid density columns and the outer sides of the end fluid density columns. [0038] At the method of the third aspect, the third time period may be selected to drag the magnetizing microparticles to respective opposite sides of the fluid density columns to form respective clumps or groups of the magnetizing microparticles at the respective opposite sides.

[0039] The method of the third aspect may further comprise, continuing to control the first magnetic devices and the second magnetic devices to alternately apply the respective first magnetic fields and the respective second magnetic fields at the fluid density columns as the carriage moves to, and pauses at, different positions.

[0040] Figure 1 and Figure 2A are block diagrams of an example device 100 to control magnetizing microparticles in fluid density columns. Figure 2B shows a perspective view of details of a particular example device 100. While described in more detail below, it is understood that components of the device 100 may be components of a larger device used for sample preparation of biological samples. Such a sample preparation device is described below with respect to Figure 8A, Figure 8B and Figure 8C.

[0041] In particular, Figure 1 shows the device 100 without sample preparation cartridge modules and Figure 2A shows the device 100 with sample preparation cartridge modules 102-1 , 102-2, 102-3, 102-4, 102-5, 102-6, 102-7, 102-8, which are interchangeably referred to hereafter, collectively, as the sample preparation cartridge modules 102 and, generically, as a sample preparation cartridge module 102. This convention will be used throughout the present specification. The sample preparation cartridge modules 102 include respective fluid density columns 104 and respective magnetizing microparticles 106. While only one respective fluid density column 104 and one group of respective magnetizing microparticles 106 are numbered in Figure 2A, it is understood that all the sample preparation cartridge modules 102 include a respective fluid density column 104 and respective magnetizing microparticles 106. Figure 2B shows particular details of the device 100 with the sample preparation cartridge modules 102 held in a cassette 107.

[0042] The device 100 comprises a carriage 108 to hold the sample preparation cartridge modules 102, the carriage to move along a path 110, for example via a vertical carriage guide of the sample preparation device described below. The carriage further includes a lateral axis 111 perpendicular to the path 110.

[0043] While details of the carriage 108 are not depicted in Figure 1 and Figure 2A, 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 apertures for guiderails (e.g. of a vertical carriage guide described below with respect to Figure 8B), 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.

[0044] Further, the carriage 108 may include any suitable combination of features to receive and hold the sample preparation cartridge modules 102 which, for example, may be provided in the cassette 107 holding a plurality of sample preparation cartridge modules 102 holding respective samples, which may be processed concurrently in the sample preparation device described below. As such, the carriage 108 is depicted as holding eight sample preparation cartridge modules 102, though the carriage 108 may hold any suitable number of sample preparation cartridge modules 102, for example by receiving the cassette 107 of sample preparation cartridge modules 102 which hold the sample preparation cartridge modules 102 in a row, about parallel to one another, for example along the lateral axis 111.

[0045] With reference to Figure 1 and Figure 2A, various sample container positions in the carriage 108 are indicated in Figure 1 by apertures 112 in the carriage 108 through which dispensing tips 114 of the sample preparation cartridge modules 102 may extend to dispense samples therefrom. However, in the particular example of Figure 2B, it is understood that such apertures 112 may be in the cassette 107, and/or may correspond to one larger aperture in the cassette 107 holding the sample preparation cartridge modules 102 rather than the carriage 108 itself (e.g. which, as depicted in Figure 2B, may include a larger aperture at a side through which the dispensing tips 114 of the sample preparation cartridge modules 102 may extend as held in the cassette 107). [0046] As depicted, there are eight apertures 112, again indicating that the carriage 108 and/or the cassette 107 may hold as many as eight sample preparation cartridge modules 102, though the carriage 108 and/or the cassette 107 may hold any suitable number of sample preparation cartridge modules 102.

[0047] Hence, while present examples are described with respect to eight sample preparation cartridge modules 102, the device 100 may be adapted to process samples in any suitable number of sample preparation cartridge modules 102.

[0048] As depicted, the device 100 further comprises first magnetic devices 116-1 and second magnetic devices 116-2 (e.g. magnetic devices 116 and/or a magnetic device 116). The first magnetic devices 116-1 and the second magnetic devices 116-2 are independently controllable from one another, for example in groups, via respective actuators thereof described in further detail below with respect to Figure 5A and Figure 5B.

[0049] The first magnetic devices 116-1 and the second magnetic 116-2 are generally actuatable to respective positions at the carriage 108 from a same given side of the carriage 108. For example, as depicted, the magnetic devices 116 are generally to move relative to the path 110 of the carriage 108, for example about perpendicular to the path 110 of the carriage 108, along respective paths 118-1 , 118-2 (e.g. paths 118 and/or a path 118). As depicted, the paths 118 are about parallel to one another. However, the magnetic devices 116 may move along any suitable paths to effect functionality as described herein.

[0050] As will be explained in further detail below, to effect the magnetic devices 116 being generally actuatable to respective positions at the carriage 108 from a same given side of the carriage 108, respective opposing edges 119 of the first magnetic devices 116-1 and the second magnetic devices 116-2 are laterally offset from each other along the lateral axis 111 (e.g. as best seen in Figure 5B, described below); furthermore the first magnetic devices 116-1 and the second magnetic devices 116-2 alternate with each other along the lateral axis 111 (e.g. as best seen in Figure 4, described below); furthermore, the first magnetic devices 116-1 and the second magnetic devices 116-2 are offset from each other along the path 110 (e.g. as seen in Figure 1 and Figure 2A, and as further seen in Figure 5B, described below).

[0051] It is understood, however that the respective opposing edges 119 of the first magnetic devices 116-1 and the second magnetic devices116-2 are laterally offset from each other along the lateral axis 111 by a distance defined by the fluid density columns 104 of the sample preparation cartridge modules 102 holdable by the carriage 108, such that a fluid density column 104 fits between the respective opposing edges 119; as such, one first magnetic device 116-1 and one second magnetic device 116-2 may be positioned on opposite sides 120 of a given fluid density column 104, for example to move and/or wash magnetizing microparticles 106 thereof, as described in more detail below with respect to Figure 6A, Figure 6B, Figure 6C and Figure 6D.

[0052] To show movement along respective paths 118, the magnetic devices 116 are each depicted in two respective positions along the respective paths 118. For example, the first magnetic devices 116-1 are depicted in Figure 1 and Figure 2A, in solid lines in first positions that correspond to gaps between first adjacent fluid density columns 104 of adjacent sample preparation cartridge modules 102, and respective outer sides 120 of respective fluid density columns 104 of respective outer sample preparation cartridge modules 102 in the row of sample preparation cartridge modules 102 (e.g. the first and last sample preparation cartridge modules 102-1 , 102-8 in the row). For example, as depicted, respective first magnetic device 116-1 are respectively between: adjacent fluid density columns 104 of respective adjacent sample preparation cartridge modules 102-2, 102-3; adjacent fluid density columns 104 of respective adjacent sample preparation cartridge modules 102-4, 102-5; and adjacent fluid density columns 104 of respective adjacent sample preparation cartridge modules 102-6, 102-7.

[0053] As such, as depicted, there are five first magnetic devices 116-1 : two at respective outer sides of respective fluid density columns 104 of respective outer sample preparation cartridge modules 102-1 , 102-8, and three between adjacent fluid density columns 104 of respective adjacent sample preparation cartridge modules 102.

[0054] However, the first magnetic devices 116-1 are also depicted in second positions in broken lines along respective paths 118-1 , away from the sample preparation cartridge modules 102.

[0055] Similarly, the second magnetic devices 116-2 are depicted in Figure 1 and Figure 2A, in broken lines in respective first positions that correspond to gaps between second adjacent fluid density columns 104, that alternate with the first adjacent fluid density columns 104 between which the first magnetic devices 116- 1 may be located. However, the second magnetic devices 116-2 are also depicted in second positions in solid lines along respective paths 118-2, away from the sample preparation cartridge modules 102.

[0056] While in Figure 2B, the first magnetic devices 116-1 are shown at the first sides 120-1 of the fluid density columns 104, and the second magnetic devices 116-2 are shown away from the second sides 120-2 of the fluid density columns 104, without showing the paths 118 and/or other positions of the magnetic devices 116, in Figure 2B the paths 118 and/or other positions of the magnetic devices 116 are nonetheless understood to be similar to as depicted in Figure 1 and Figure 2A.

[0057] With reference to Figure 2B, as depicted, respective second magnetic device 116-2 are respectively between: adjacent fluid density columns 104 of respective adjacent sample preparation cartridge modules 102-1 , 102-2; adjacent fluid density columns 104 of respective adjacent sample preparation cartridge modules 102-3, 102-4; adjacent fluid density columns 104 of respective adjacent sample preparation cartridge modules 102-5, 102-6; and adjacent fluid density columns 104 of respective adjacent sample preparation cartridge modules 102-7, 102-8.

[0058] As such, as depicted, there are four second magnetic devices 116-2 between adjacent fluid density columns 104 of respective adjacent sample preparation cartridge modules 102. [0059] Hence, a total number of the magnetic devices 116 is nine, though the total number of the magnetic devices 116 and/or respective numbers of the first magnetic devices 116-1 and the second magnetic devices 116-2 generally depend on the number of sample preparation cartridge modules 102 with, for example, one more magnetic device 116 than there are sample preparation cartridge modules 102 such the magnetic device 116 may be positioned on opposite sides of all the fluid density columns 104 of the sample preparation cartridge modules 102.

[0060] Furthermore, a portion of the first magnetic devices 116-1 are between first adjacent fluid density columns 104 (e.g. at respective gaps therebetween), and the second magnetic devices 116-1 are between second adjacent fluid density columns 104(e.g. at respective gaps therebetween), and pairs of the first adjacent fluid density columns 104 alternate with respective pairs of the second magnetic devices 116-2, with the magnetic devices 116 arranged accordingly.

[0061] Furthermore, as also seen in Figure 1 and Figure 2A a portion of the first magnetic devices 116-1 that are actuatable to outer respective positions (e.g. at respective outer sides of respective fluid density columns 104 of the respective outer sample preparation cartridge modules 102-1 , 102-8 in the row) may be smaller in width along the lateral axis 111 than others of the first magnetic devices 116-1 , for example to fit between inner sides of the carriage 108 and/or a cassette holding the sample preparation cartridge modules 102, and the respective outer sides of the fluid density columns 104 of the respective outer sample containersl 02-1 , 102-8.

[0062] To move the magnetic devices 116 along the paths 118, device 100 is further understood to include any suitable combination of actuators, motors, robotic arms, and the like, to move the magnetic devices 116 along the respective paths 118, for example independent from each other, towards the sample preparation cartridge modules 102, and away from the sample preparation cartridge modules 102, for example to between adjacent fluid density columns 104 and/or to the outer sides 120 of respective fluid density columns 104 of the respective outer sample preparation cartridge modules 102. However, it is understood that the first magnetic devices 116-1 are movable as a group and the second magnetic devices 116-2 are movable as a respective group, independent from the group of the first magnetic device 116-1.

[0063] Similarly, when the magnetic devices 116 comprise electromagnets, the device 100 is understood to include (and/or be powered by) any suitable combination of power supplies to independently control magnetic fields of the magnetic devices 116 (e.g. in groups). Hence, it is understood that first magnetic fields of the first magnetic devices 116-1 may be controllable as a first group and second magnetic fields of the second magnetic devices 116-2 may be controllable as a second group, independent from the first group of the first magnetic device 116-1.

[0064] In particular, the first magnetic devices 116-1 and the second magnetic devices 116-2 may be further to alternate moving towards, and away from, the carriage 108, for example as respective groups, such that the first magnetic devices 116-1 or the second magnetic devices 116-2 may be at the fluid density columns 104 (e.g. between respective adjacent fluid density columns 104 and/or at the outer sides of the outer fluid density columns 104) at any given time. However, the magnetic devices 116 may all be moved to the fluid density columns 104 at any given time.

[0065] Similarly, the carriage 108 may be moved independent of the magnetic devices 116 such that the carriage 108 and the magnetic devices 116 may be controlled to any suitable relative positions along the respective paths 110, 118.

[0066] Furthermore, as is apparent in Figure 2A, the magnetic devices 116 are positioned along the paths 118 to move to the fluid density columns 104 to respectively apply magnetic fields to sides 120 of the fluid density columns 104, which may be used to concurrently control path geometries (e.g. a wash path geometries) of the magnetizing microparticles 106 in the fluid density columns 104, as described below with respect to Figure 6A, Figure 6B, Figure 6C and Figure 6D.

[0067] Figure 2A further show example opposite sides 120-1 , 120-2 (e.g. sides 120 and/or a side 120) of one of the fluid density columns 104; in particular, the side 120-1 is further understood to be an outer side 120 of the fluid density column 104 of the outer sample preparation cartridge module 102-1.

[0068] The magnetic devices 116 are generally to alternate applying magnetic fields at opposite sides 120 of the fluid density columns 104 to move the magnetizing microparticles 106 between the opposite sides of the fluid density column 104 to wash the magnetizing microparticles 106 in the fluid density column 104, the magnetic devices 116 being controllable to apply the magnetic fields independent of each other to control a path geometry (e.g. a wash path geometry) of the magnetizing microparticles 106 in the fluid density columns 104, as described below with respect to Figure 6A, Figure 6B, Figure 6C and Figure 6D.

[0069] In some examples, the magnetic devices 116 may comprise electromagnetic magnetics which may be positioned at respective opposite sides 120 of the fluid density column 120 and turned on and/or turned off, independent of each other, to alternate applying magnetic to the opposite sides 120. However, the magnetic devices 116 may comprise any suitable combination of magnets and/or permanent magnets, including, but not limited to, rare earth magnets, and the like, which may be used to apply magnetic fields to the magnetizing microparticles 106 in the fluid density column 104. Furthermore, the magnetic devices 116 may have any suitable polarities, which may be the same, or different, relative to the sides 120.

[0070] Furthermore, the magnetic devices 116 may further comprise respective frames, and the like to hold a respective magnet at respective ends thereof (e.g. which extend towards the carriage 108) such that, when a magnetic device 116 is between adjacent fluid density columns 104, the magnets thereof are against backplanes thereof, for example as describe below with respect to Figure 4.

[0071] While hereafter, functionality of the magnetic devices 116 is described with respect to moving the magnetic devices 116 along the paths 118 to alternate applying magnetic fields at the opposite sides 120, it is understood that such alternation of magnetic fields, and/or general control of the magnetic devices 116 to apply or remove magnetic fields at the opposite sides 120, alternately or currently may occur in any suitable manner.

[0072] Similarly, while hereafter functionality of the magnetic devices 116 is described with respect to moving the magnetic devices 116 along the paths 118, it is understood that, alternatively, the carriage 108 may move relative to the magnetic devices 116 to effect the paths 118. Hence, is understood that such alternation of magnetic fields, and/or general control of the magnetic devices 116 to apply or remove magnetic fields at the opposite sides 120, alternately or currently, may occur in any suitable manner by moving the magnetic devices 116 and/or the carriage 108 to effect the paths 118.

[0073] In particular, as will be explained in more detail below, the magnetic devices 116 may be to alternate applying magnetic fields to respective opposite sides of the fluid density columns 104 to move respective magnetizing microparticles 106 therein between the opposite sides to wash the magnetizing microparticles 106 in the fluid density column 104, to isolate and/or purify biological components bonded thereto. The magnetic devices 116 are generally controllable and/or movable independent of each other (e.g. in groups) and the carriage 108, to control a path geometry of the magnetizing microparticles 106 in the fluid density columns 104.

[0074] For reference, an “XYZ” coordinate system 122 is also depicted in Figure 1 and Figure 2A and which will be used throughout the present specification to show relative positions of components of the device 100. For example, a “Z” direction may be along the path 110 of the carriage 108, a “Y” direction may be along the paths 118 of the magnetic devices 116 (e.g. when the paths 110, 118 are perpendicular to each other), and an X” direction may be perpendicular to the “Y” and “Y” directions and/or along the lateral axis 111 . The XYZ coordinate system 122 is provided on further figures herein to show relative orientations of the device 100, and the like, between the figures.

[0075] Some further details of the sample preparation cartridge module 102 are next described. For example, while not depicted in Figure 1 and Figure 2A, the sample preparation cartridge modules 102 may comprise respective ports for receiving respective biological samples that includes a biological component of interest which may bond to the magnetizing microparticles 106.

[0076] The respective biological samples (hereafter referred to the samples) may be received into the sample preparation cartridge modules 102 and heated in a region of the sample preparation cartridge modules 102 different from the fluid density columns 104 to perform lysis on the sample to release respective biological component of interest from cells in the samples. The magnetizing microparticles 106 may initially be provided in the lysis regions of the sample preparation cartridge modules 102 so that the biological component of interest may bond to surfaces of the magnetizing microparticles 106. After lysis, the samples, with the magnetizing microparticles 106, may be moved into the fluid density columns 104 for washing, and which may include introducing various chemicals into the fluid density column for example via actuation of reservoirs and/or blisters and/or pouches, and the like, at the sample preparation cartridge modules 102 that include such chemicals. The washing may result in isolation and/or purification of the biological component of interest bonded to the magnetizing microparticles 106. In particular, in some examples, the terms “wash” and/or “washing” may include, but is not limited to, a moving action of the magnetizing microparticles 106 when dragged toward and/or through the fluid density column 104. In some specific examples, the terms “wash” and/or “washing” may refer to actions of elimination of components that are present in the biological sample that are not the biological component of interest (e.g. that are not bonded to the magnetizing microparticles 106).

[0077] Further details of the sample preparation cartridge modules 102, and associated sample processing, are described in further detail below with respect to Figure 8A, Figure 8B and Figure 8C.

[0078] The magnetizing microparticles 106 may be in the form of paramagnetic microparticles, superparamagnetic microparticles, diamagnetic microparticles, or a combination thereof, for example. In some examples, the magnetizing microparticles 106 are paramagnetic microparticles. The term “magnetizing microparticles” or “magnetizing microparticle” is defined herein to include microparticles that may not be magnetic in nature unless and until a magnetic field is introduced at a strength and proximity to cause them to become magnetic. Their magnetic strength can be dependent on the magnetic field applied, for example by the magnetic devices 116, and may get stronger as the magnetic field is increased, or the magnetizing microparticles 106 get closer to a magnet applying the magnetic field. In more specific detail, “paramagnetic microparticles” have these properties, in that they have the ability to increase in magnetism when a magnetic field is present; however, paramagnetic microparticles are not magnetic when a magnetic field is not present. In some examples, the paramagnetic microparticles can exhibit no residual magnetism once the magnetic field is removed. A strength of magnetism of the paramagnetic microparticles can depend on the strength of the magnetic field, the distance between a source of the magnetic field and the paramagnetic microparticles, and a size of the paramagnetic microparticles. As a strength of the magnetic field increases and/or a size of the paramagnetic microparticles increases, the strength of the magnetism of the paramagnetic microparticles increases. As a distance between a source of the magnetic field and the paramagnetic microparticles increases, the strength of the magnetism of the paramagnetic microparticles decreases. “Superparamagnetic microparticles” can act similar to paramagnetic microparticles; however, they can exhibit magnetic susceptibility to a greater extent than paramagnetic microparticles in that the time it takes for them to become magnetized appears to be near zero seconds. “Diamagnetic microparticles,” on the other hand, can display magnetism due to a change in the orbital motion of electrons in the presence of a magnetic field.

[0079] The magnetizing microparticles 106 can be surface-activated to selectively bind with a biological component or can be bound to a biological component from a biological sample, for example the aforementioned viruses. Hence, it is understood that while present examples are described with respect to viruses, the device 100 may be used to process any suitable samples having any suitable biological component that may bind to the magnetizing microparticles 106. In particular, an exterior of the magnetizing microparticles 106 can be surface-activated with interactive surface groups that can interact with a biological component of a biological sample or may include a covalently attached ligand. In some examples, the ligand can include proteins, antibodies, antigens, nucleic acid primers, nucleic acid probes, amino groups, carboxyl groups, epoxy groups, tosyl groups, sulphydryl groups, or the like. In one example, the ligand can be a nucleic acid probe. The ligand can be selected to correspond with and to bind with the biological component. The ligand may vary based on the type of biological component targeted for isolation from the biological sample. For example, the ligand can include a nucleic acid probe when isolating a biological component that includes a nucleic acid sequence. In another example, the ligand can include an antibody when isolating a biological component that includes antigen. In one example, the magnetizing microparticles 106 can be surface-activated to bind to nucleic acids. Thus nucleic acid molecules (DNA or RNA) can be bound to the surface of the magnetizing microparticles 106. Commercially available examples of magnetizing microparticles 106 that are surface-activated include those sold under the trade name DYNABEADS®, available from ThermoFischer Scientific (USA).

[0080] In some examples, the magnetizing microparticles 106 can have an average microparticle size that can range from 10 nm to 50,000 nm. In yet other examples, the magnetizing microparticles 106 can have an average microparticle size that can range from 500 nm to 25,000 nm, from 10 nm to 1 ,000 nm, from 25,000 nm to 50,000 nm, or from 10 nm to 5,000 nm. The term “average microparticle size" describes a diameter or average diameter, which may vary, depending upon the morphology of the individual microparticle. A shape of the magnetizing microparticles 106 can be spherical, irregular spherical, rounded, semi-rounded, discoidal, angular, sub-angular, cubic, cylindrical, or any combination thereof. In one example, the microparticles can include spherical microparticles, irregular spherical microparticles, or rounded microparticles. The shape of the magnetizing microparticles 106 can be spherical and uniform, which can be defined herein as spherical or near- spherical, e.g., having a sphericity of >0.84. Thus, any individual microparticles having a sphericity of <0.84 are considered non-spherical (irregularly shaped). The microparticle size of the substantially spherical microparticle may be provided by its diameter, and the microparticle size of a non-spherical microparticle may be provided by its average diameter (e.g., the average of multiple dimensions across the microparticle) or by an effective diameter, e.g., the diameter of a sphere with the same mass and density as the non-spherical microparticle.

[0081] Attention is next directed to Figure 3 and Figure 4. Figure 3 depicts a perspective view of a specific example four fluid density columns 104 of the sample preparation cartridge modules 102 (e.g. similar to as depicted in Figure 2B) showing one set of example relative positions thereto of the magnetic devices 116 in one position of the carriage 108 with exemplary paths 118 of two magnetic devices 116. Figure 4 schematically depicts a top view of Figure 3, but with the fluid density column 104 (e.g. and a backplane thereof) depicted in cross-section through a plane parallel to the magnetic devices 116 and with both the first magnetic devices 116-1 and the second magnetic devices 116-1 located at the opposite sides 120 of the fluid density columns 104.

[0082] Figure 4 depicts a top view of four fluid density columns 104 of a subset of the sample preparation cartridge modules 102 (e.g. and half of one sample preparation cartridge module 102) with the fluid density columns 104 (and backplanes thereof) depicted in cross-section through a plane parallel to the magnetic devices 116.

[0083] It is furthermore understood that the example fluid density columns 104 of Figure 3 are depicted without, for example, a lysis region or a port to receive a sample, but which are nonetheless understood to be present. For example, a sample that has undergone lysis may be introduced into the example fluid density column 104 from a lysis region, via respective apertures 124 at ends of the example fluid density columns 104 opposite the dispensing tips 114. It is further understood that the fluid density column 104 becomes narrower the closer to the dispensing tip 114 (e.g. and/or the further from the aperture 124). Indeed, the fluid density columns 104 may have any suitable cross-section, or cross-sections, but are understood to becomes narrower the closer to the dispensing tip 114 (e.g. and/or the further from the aperture 124).

[0084] As depicted, the example fluid density columns 104 is understood to be held by respective backplanes 126, and the like, such that the example fluid density columns 104 extend from respective backplanes 126. A backplane 126 and a fluid density column 104 may be provided as integrated unit.

[0085] As sides 120 of the example fluid density columns 104 extend outward from the backplane 126 (e.g. in the “Y” direction”, an associated sample preparation cartridge module 102 may be held by the carriage 108 such that the paths 118 of the magnetic devices 116 are on a same side of the carriage 108.

[0086] Attention is next specifically directed to Figure 4, which further depict both the first magnetic devices 116-1 and the second magnetic devices 116-2 against the backplanes 126, and between respective gaps 127-1 , 127-2 between the fluid density columns 104. For example, the first magnetic devices 116-1 are in first gaps 127-1 , other than an outer first magnetic device 116-1 at the first sample preparation cartridge module 102-1 , and the second magnetic devices 116-2 are in second gaps 127-2.

[0087] Furthermore, in Figure 3 and Figure 4 (e.g. and also in Figure 2B), it is understood that only a magnet portion of the magnetic devices 116 are shown, along with, in Figure 4, respective polarities of edges 119 thereof, with “N” indicating a north polarity and “S” indicating a south polarity. For example, the magnetic devices 116 may be longer along the paths 118 then as depicted in Figure 3 and Figure 4, but portions of the magnetic devices 116 that apply magnetic fields at the sides 120 may be smaller than an overall magnetic device 116; for example, the portions of the magnetic devices 116 depicted in Figure 3 and Figure 4 may comprise permanent magnets and/or electromagnets, with the remainder of the magnetic devices 116 comprising respective frames for holding the permanent magnets and/or the electromagnets, and attaching to an actuator, and the like (e.g. as described below with respect to Figure 5A and Figure 5B).

[0088] As best seen in Figure 4, the magnets of the magnetic devices 116 are positioned with opposite polarities facing each other across the fluid density column 104 therebetween; such a configuration may be more efficient for washing the magnetizing microparticles 106, as described below, and/or such a configuration may be for more efficient for collecting dispersed magnetizing microparticles 106 into clumps, as described below with respect to Figure 6A, Figure 6B, Figure 6C and Figure 6D. However, the polarities may be arranged in any suitable manner. Put another way, the magnetic devices 116 may have opposing polarities across the fluid density column 104.

[0089] Figure 4 further shows that the first magnetic devices 116-1 and the second magnetic devices 116-2 alternate with each other along the lateral axis 111 , as are respective opposing edges 119 of the first magnetic devices 116-1 and the second magnetic devices 116-2. In other words, a given fluid density column 104 is between opposing edges 119 of a pair of adjacent magnetic devices 116-1 , 116-2 (e.g. a given first magnetic device 116-1 and an adjacent second magnetic device 116-2).

[0090] Attention is next directed to Figure 5A and Figure 5B which respectively depict top and side views of block diagrams of the device 100 with specific example actuators and motors thereof. In particular, actuators, motors and plates to which the magnetic devices 116 are attached are depicted in detail, but the carriage 108 is depicted in block diagram form to show a relative position to the magnetic devices 116.

[0091] In particular, as depicted, the first magnetic devices 116-1 may be mounted at a first edge of a first plate 129-1 , for example an edge of the plate 129-1 facing the carriage 108, and the device 100 may further comprise a first actuator 131-1 to actuate the first plate 129-1 to actuate the first magnetic devices 116-1 to respective positions (e.g. first positions as depicted in Figure 1 and Figure 2A) at the carriage 108, adjacent respective fluid density columns 104 as described herein, for example along the paths 118-1. As depicted, the first actuator 131-1 may comprise a first motor 133-1 , such as stepper motor, and the like. The first actuator 131-1 may further comprise any suitable combination of guide rails, drive screws, and the like which may operated via the first motor 133-1 to move the plate 129-1 , and hence the first magnetic device 116-1 (e.g. as a group) towards, and away from, the carriage 108.

[0092] Similarly, as depicted, the second magnetic devices 116-2 may be mounted at a second edge of a second plate 129-2, for example an edge of plate 129-2 facing the carriage 108, and the device 100 may further comprise a second actuator 131-2 to actuate the second plate 129-2 to actuate the second magnetic devices 116-2 to respective positions at the carriage 108 (e.g. second positions as compared to first positions of the first magnetic devices 116-1 , such second positions corresponding the to the magnetic devices 116-2 depicted in broken lines in Figure 1 and Figure 2A), adjacent respective fluid density columns 104 as described herein, for example along the paths 118-2. As depicted, the second actuator 131-2 may comprise a second motor 133-2, such as stepper motor, and the like. The second actuator 131-2 may comprise any suitable combination of guide rails, drive screws, and the like which may be operated via the second motor 133-2 to move the plate 129-2, and hence the second magnetic device 116-2 (e.g. as a group) towards, and away from, the carriage 108.

[0093] As depicted, the device 100 further comprises a chassis 135, and the like, supporting the plates 129, the actuators 131-1 , 131-2 (e.g. the actuators 131 and/or an actuator 131) and the motors 133-1 , 133-2 (e.g. the motors 133 and/or a motor 133), such that the magnetic devices 116, the plates 129, the actuators 131 and the motors 133 may be provided as a single unit which may be integrated with the sample preparation device of Figure 8A, Figure 8B and Figure 8C.

[0094] It is further understood that the respective actuators 131 , motors 133 and may be to actuate the magnetic devices 116 to respective positions at the opposite sides 120 of the fluid density column 104, as depicted in Figure 1 , Figure 2A, Figure 2B, Figure 3 and/or Figure 4. In other examples, the respective actuators 131 , motors 133 and may be to actuate the magnetic devices 116 towards the carriage 108 until respective motors 133 thereof stall due the magnetic devices 116 encountering the backplanes 126.

[0095] As depicted, the magnetic devices 116 further comprise mechanical centering features 137, for example, as depicted, beveled edges facing the carriage 108, and set back from a carriage-facing edge of the magnetic devices 116. The mechanical centering features 137 of one magnetic device 116 generally mechanically interact with sides 120 of adjacent fluid density columns 104 (e.g. across a gap 127) to about center a magnetic device 116 between the adjacent fluid density columns 104 and/or space a magnetic device 116 about evenly between center lines of the adjacent fluid density columns 104 (e.g. center lines along lengths of the adjacent fluid density columns 104). As such, the mechanical centering features 137 are of a shape and position to mechanically interact with sides 120 of adjacent fluid density columns 104 that face each other across a gap 127. As has been previously described, the fluid density columns 104 may taper and/or narrow towards the tips 114. Hence, the closer to the tips 114, the larger the gaps 127 and/or the further apart are opposing sides 120 of adjacent fluid density columns 104. Hence, away from tips 114 of adjacent fluid density columns 104 (e.g. closer to the apertures 124), a width of a magnetic device 116 in the “X” direction may be similar to a width of a gap 127, which may assist with centering the magnetic device 116 in a gap 127, as ends of the magnetic devices 116 proximal sides 120 of adjacent fluid density columns 104 may be mechanically positioned in a gap 127 by the sides 120. However, the closer a magnetic device 116 is to tips 114 of adjacent fluid density columns 104, the further the sides 120 of adjacent fluid density columns 104 are from the magnetic devices 116; as such, the mechanical centering features 137 may center a magnetic device 116 in gap 127 regardless of a size of a gap 127. Furthermore, the mechanical centering features 137 may ensure consistent positioning of a magnetic device 116 between adjacent fluid density columns 104 along a length of the adjacent fluid density columns 104 (e.g. in the “Y” direction).

[0096] Furthermore, while outer first magnetic devices 116-1 may not include the mechanical centering features 137, as the first magnetic devices 116-1 are attached to the same plate 129-1 , mechanical centering features 137 at one, or more than one, of the first magnetic devices 116-1 may cause all the first magnetic devices 116-1 to center accordingly as force applied to one or more than one, of the first magnetic devices 116-1 by one, or more than one, set of mechanical centering features 137 is translated to the plate 129-1 which in turn moves to center the first magnetic devices 116-1 attached thereto. The mechanical centering features 137 of the second magnetic devices 116-2, attached to the second plate 129-2, cause the second magnetic devices 116-2 and the second plate 129-2 to behave in a similar manner.

[0097] Furthermore, as best seen in Figure 5B, the plates 129-1 , 129-2 (e.g. plates 129 and/or a plate 129) may be offset along the path 110, and/or the “Z” direction, so as to not interfere with respective actuation thereof. Hence, the first magnetic devices 116-1 and the second magnetic devices 116-2 are also offset along the path 110 and/or the “Z” direction. Furthermore, the locations of the plates 129-1 , 129-2 and/or the first magnetic devices 116-1 and the second magnetic devices 116-2 may be reversed at the path 110 and/or in the “Z” direction. Indeed, comparing Figure 5A and Figure 5B to Figure 1 , and Figure 2A, Figure 2B, the positions of the first magnetic devices 116-1 and the second magnetic devices 116-2 are reversed along the “Z” direction.

[0098] Furthermore, the offset of the first magnetic devices 116-1 and the second magnetic devices 116-2 may be of any suitable distance that effects the functionality as described herein, though the offset may be selected to be as small as possible given the geometries and/or dimensions of the magnetic devices 116, the plates 129, the actuators 131 and/or the motors 133.

[0099] Attention is next directed to Figure 6A, Figure 6B, Figure 6C and Figure 6D which depict block diagrams of two adjacent the fluid density columns 104-1 , 104-2 with one second magnetic device 116-2 between the fluid density columns 104 (e.g. in a gap 127) and first magnetic devices 116-1 at sides 120 of the fluid density columns 104 which are opposite sides 120 at which the second magnetic device 116-2 is located. For example, at the fluid density column 104- 1 , a first magnetic device 116-1 is at a side 120-1 , and the second magnetic device 116-2 is at an opposite side 120-1 ; similarly, at the fluid density column 104-2, a first magnetic device 116-1 is at a side 120-2, and the second magnetic device 116-2 is at an opposite side 120-2. [00100] In particular, Figure 6A, Figure 6B, Figure 6C and Figure 6D show a sequence of steps “A”, “B”, “C”, “D”, “E”, “F”, “G” to wash the magnetizing microparticles 106 in the fluid density columns 104 to isolate and/or purify biological components of interest attached thereto; the sequence of steps “A”, “B”, “C”, “D”, “E”, “F”, “G” are understood to occur, one after the other, at the device 100. Furthermore, at Figure 6A, Figure 6B, Figure 6C and Figure 6D, while the fluid density columns 104 and the magnetic devices 116 are shown without the carriage 108 and the actuators 131 , etc., the carriage 108 and the actuators 131 are nonetheless understood to be present and may be controlled to move along the path 110, for example to move the fluid density columns 104, concurrently, along the path 110 in “steps” and/or given distances (described in more detail below). Furthermore, in Figure 6A, Figure 6B, Figure 6C and Figure 6D, it is understood that the magnetizing microparticles 106 have been introduced into respective fluid density columns 104 from a lysis region of a respective sample preparation cartridge module 102.

[00101] It is further understood that the fluid density columns 104 contains fluid for washing the magnetizing microparticles 106 which may be introduced via actuation of a reservoir at the sample preparation cartridge module 102 containing such a wash fluid, and the like. The fluid density column 104 may, however, contain any suitable combination of fluids such that, initially, the magnetizing microparticles 106 are suspended and/or dispersed in a fluid in the fluid density column 104 at an end opposite that of the tip 114, as in step “A”.

[00102] Furthermore, in Figure 6A, Figure 6B, Figure 6C and Figure 6D, the magnetic devices 116 are depicted in either solid lines or broken lines. When a magnetic device 116 is depicted in solid lines, it is understood that the magnetic device 116 has been controlled to apply a respective magnetic field at a respective side 120 (or respective sides 120) which may include, but is not limited to: a magnetic device 116 moving along a respective path 118 to be in a first position adjacent a respective side 120 of a fluid density column 104, for example, similar to the first magnetic device 116-1 in Figure 2A; and/or an electromagnet of a magnetic device 116 being turned on. [00103] However, when a magnetic device 116 is depicted in broken lines, it is understood that the magnetic device 116 has been controlled to remove a respective magnetic field from a respective side 120 (or respective sides 120) which may include, but is not limited to: a magnetic device 116 moving along a respective path 118 (e.g. “out” of the page in Figure 6A, Figure 6B, Figure 6C and Figure 6D) to be in a second position away from a respective side 120 of the fluid density column 104, for example, similar to the second position of the second magnetic device 116-2 in Figure 2A (e.g. the second position of the second magnetic device 116-2 depicted in solid lines in Figure 1 and Figure 2A); and/or an electromagnet of a magnetic device 116 being turned off.

[00104] Hence, while hereafter the magnetic devices 116 are described as applying, or removing, magnetic fields via movement along the paths 118, it is understood that the same functionality may be achieved when the magnetic devices 116 include electromagnets by positioning both the magnetic devices 116 at the fluid density column 104 and turning the electromagnets on and off.

[00105] Furthermore, while the example of Figure 6A, Figure 6B, Figure 6C and Figure 6D is described with respect to two fluid density columns 104, it is understood that similar processes may occur at all the fluid density columns 104 by actuating the first magnetic devices 116-1 , and the second magnetic devices 116-2, as respective groups, along their respective paths 118 (and/or turning electromagnetic fields on or off) such that the magnetic devices 116 are controlled to be apply (or remove) magnetic fields on opposite sides 120 of any given fluid density column 104.

[00106] With attention first directed to step “A”, the carriage 108 may be controlled to move the fluid density columns 104 to an initial position relative to the magnetic devices 116 so that the magnetic devices 116 may be controlled to move along the paths 118 to be adjacent respective opposite sides 120 of the fluid density columns 104, at the end opposite that of the tip 114 and/or at an end adjacent a lysis region of the sample preparation cartridge modules 102. The magnetic devices 116 pause in these positions and exert respective magnetic fields on the magnetizing microparticles 106, which, as depicted in step “B” cause the magnetizing microparticles 106 to be dragged to both of the sides 120 of respective fluid density columns 104, at sides 120 adjacent respective magnetic devices 116 where they form respective clumps and/or groups. For example, depending on an initial position of a magnetizing microparticle 106 in a fluid density column 104, some magnetizing microparticles 106 are dragged and/or pulled to a respective first side 120-1 , and other magnetizing microparticles 106 are dragged and/or pulled to a respective second side 120-2.

[00107] As depicted in step “C”, in Figure 6B, one group of the magnetic devices 116 may be controlled to move away from the fluid density columns 104; for example, as depicted, the first magnetic device s116-1 may be controlled to move away from the fluid density columns 104, removing a respective magnetic fields from the magnetizing microparticles 106, such that the magnetizing microparticles 106 are dragged and/or pulled to a respective side 120 by the second magnetic device 116-2, and may form a clump and/or a group at the respective sides 120. For example, at the first fluid density column 104-1 , respective magnetizing microparticles 106 form a clump at the side 120-2 adjacent the second magnetic device 116-2, and at the second fluid density column 104-2, respective magnetizing microparticles 106 form a clump at the side 120-1 adjacent the second magnetic device 116-2.

[00108] While the process of steps “A”, “B” and “C” may be optional, such a process may assist with magnetizing the magnetizing microparticles 106, and the like. In addition, as the magnetizing microparticles 106 may initially be dispersed in fluid in the fluid density column 104, the process of steps “A”, “B” and “C” may be used to collect the magnetizing microparticles 106, for example in a clump, at a respective side 120 of a fluid density column 104 to assist with the steps that are next described to wash the magnetizing microparticles 106.

[00109] With attention directed to step “D”, and with the magnetizing microparticles 106 at respective sides 120 of the fluid density columns 104, the magnetic devices 116 are controlled to move away from their respective sides 120 along the paths 118. When the magnetic devices 116 are moved away and stopped, the carriage 108 is controlled to move the fluid density columns 104 along the path 110 (for example as represented by the arrows 128) by a given distance 130 for example in the “Z” direction, which positions the magnetic devices 116 closer to the dispensing tips 114. Hence, it is understood in step “D”, that the fluid density columns 104 have moved relative to the magnetic devices 116 in the “Z” direction while the magnetic devices 116 have not moved in the “Z” direction. The position of the carriage 108 at step “D” (e.g. as represented by the fluid density columns 104 relative to the magnetic devices 116) may be referred to as a first position of the carriage 108.

[00110] Furthermore, at step “D”, after the carriage 108 moves through the given distance 130 to the first position, the magnetizing microparticles 106 are offset from the magnetic devices 116 in the “Z” direction.

[00111] Attention is next directed to step “E”, depicted in Figure 6C. With the carriage 108 paused (e.g. after moving through the given distance 130), the first magnetic devices 116-1 are controlled to move along their respective paths 118- 1 to be adjacent respective sides 120 of the fluid density columns 104 and the first magnetic devices 116-1 are paused in this position for a first given time period.

[00112] As such, magnetic fields of the first magnetic devices 116-1 are applied to the respective magnetizing microparticles 106 of the fluid density columns 104 to pull and/or drag the magnetizing microparticles 106 through the fluid of the fluid density column 104 to respective sides 120, adjacent the first magnetic devices 116-1 , as represented by the arrows 132, and the magnetizing microparticles 106 depicted in broken lines about midway between the opposite sides 120-1 , 120-2 of the fluid density columns 104. The magnetizing microparticles 106 again form a clump and/or group at the respective sides 120 adjacent the first magnetic devices 116-1 . The first given time period may be selected to ensure that the magnetic field of the first magnetic devices 116-1 pulls and/or drags the magnetizing microparticles 106 to the adjacent sides 120, though any suitable first given time period is within the scope of the present specification. [00113] It is understood that, as the magnetizing microparticles 106 move through the fluid of the fluid density column, the magnetizing microparticles 106 may be washed, for example to isolate and/or purify biological components bonded to the magnetizing microparticles 106 (e.g. viruses), and furthermore may disperse during such movement, for example as individual magnetizing microparticles 106 follow respective magnetic field lines of the magnetic fields applied by the first magnetic devices 116-1 . Such dispersing is represented by the magnetizing microparticles 106 depicted in broken lines which are further apart than at the sides 120.

[00114] With attention next directed to step “F”, which is similar to step “D”, the first magnetic devices 116-1 are controlled to move away from their respective sides 120 along respective paths 118-1 and, when stopped, the carriage 108 is again controlled to move the fluid density columns 104 along the path 110 (for example as represented by the arrows 134) by a given distance 136 for example in the “Z” direction, which may the same as, or (as depicted) different from, the given distance 130. Such movement again positions the magnetic devices 116 closer to the dispensing tip 114 and the magnetizing microparticles 106 are again offset from the magnetic devices 116 in the “Z” direction. The position of the carriage 108 at step “F” (e.g. as represented by the fluid density column 104 relative to the magnetic devices 116) may be referred to as a second position of the carriage 108.

[00115] Attention is next directed to step “G”, in Figure 6D, which is similar to step “E” but performed with the second magnetic device 120-2. With the carriage 108 paused (e.g. after moving through the given distance 134 to the second position), the second magnetic device 116-2 is controlled to move along the path 118-2 to be adjacent the respective sides 120 of the fluid density columns 104 and the second magnetic device 116-2 is paused in this position for a second given time period which may be the same as, or different from the first given time period for which the first magnetic devices 116-1 are paused in step “D”. As such, a magnetic field of the second magnetic device 116-2 is applied to the magnetizing microparticles 106 at both of the adjacent fluid density columns 104, to again pull and/or drag the magnetizing microparticles 106 through the fluid of the fluid density column 104 to the respective sides 120, adjacent the second magnetic device 116-2, as represented by the arrows 138, and the magnetizing microparticles 106 depicted in broken lines about midway between the respective opposite sides 120-1 , 120-2 of the fluid density columns 104 (e.g. which are dispersed relative to at the sides 120). The magnetizing microparticles 106 again form a clump and/or group at the respective sides 120 adjacent the second magnetic device 116-2. The second given time period may be selected to ensure that the magnetic field of the second magnetic device 116-2 pulls and/or drags the magnetizing microparticles 106 to the respective sides120, though any suitable second given time period is within the scope of the present specification.

[00116] It is again understood that, as the magnetizing microparticles 106 move through the fluid of the fluid density column, the magnetizing microparticles 106 may be washed, for example to isolate and/or purify biological components bonded to the magnetizing microparticles 106, and furthermore may disperse during such movement, for example as individual magnetizing microparticles 106 follow respective magnetic field lines of the magnetic field applied by the second magnetic device 116-2.

[00117] The process shown in step “D” to step “G” may be repeated any suitable number of times to move the magnetizing microparticles 106 towards the dispensing tips 114, washing the magnetizing microparticles 106 for example to control a path geometry of the magnetizing microparticles 106.

[00118] In particular, the magnetic devices 116 may be controlled to alternate applying magnetic fields to the opposite sides 120 of the fluid density columns 104 to move the magnetizing microparticles 106 between respective opposite sides 120 of the fluid density columns 104, the carriage 108 being moved along the path 110 between the magnetic devices 116 alternately applying magnetic fields to the opposite sides 120.

[00119] Furthermore, as the first magnetic devices 116-1 and the second magnetic devices 116-2 are moved in groups, the washing, etc., of the magnetizing microparticles 106 occurs concurrently at the fluid density columns 104.

[00120] Furthermore, the respective arrows 132, 138 at the fluid density columns 104 are understood to present a path of the magnetizing microparticles 106 through the fluid density columns 104 which may be changed and/or controlled by controlling the given distances 130, 136, and/or subsequent given distances of movement of the carriage 108 as the process shown in step “D” to step “G” is repeated, as well as the first given time period and the second given time period (e.g. pause times) that the magnetic devices 116 respectively pause to drag and/or pull the magnetizing microparticles 106 through the fluid density column 104.

[00121] In particular, as depicted, the arrows 132, 138, represent a zig-zag pattern of a path geometry of the magnetizing microparticles 106 through the fluid density column 104, which may attempt balance a time to implement the washing, with maximizing the washing.

[00122] Furthermore, the given distances 130, 136, which may be referred to as “steps” (e.g. in this context a step of the carriage 108 may be distances through which the carriage 108 is moved and then paused), and the pause times of the magnetic devices 116 may be varied to control the path geometry. For example, a step size and/or a pause time may be varied according to a distance the magnetic devices 116 are from the dispensing tips 114, for example to take into account the narrowing of the fluid density columns 104 from the apertures 124 to the dispensing tips 114.

[00123] It is further noted that pause times of the magnetic devices 116 may be controlled to be of a duration (e.g. which may be determined heuristically) to clump the magnetizing microparticles 106 at a side 120. However, in some examples, in particular during a final movement of the magnetizing microparticles 106 prior to dispensing, a pause time of the magnetic devices 116 may be reduced (e.g. relative to other pause times), such that a clump of the magnetizing microparticles 106 is pulled from an opposing side 120, but not given enough time to ‘re-clump’ and densely pack on a side 120 wall closest to a magnetic device 116 applying a magnetic field, for example to better position the magnetizing microparticles 106 away from the sides 120 to dispense out of the tip 114. Such applying of a magnetic field may assist with efficient dispensing of the magnetizing microparticles 106 with biological components of interest bonded thereto, for example to reduce a possibility of the magnetizing microparticles 106 being “stuck” at the sides 120 during dispensing.

[00124] Attention is next directed to Figure 7 which shows different path geometries 702, 704, 706 showing different respective paths for the magnetizing microparticles 106 that may be implemented in the fluid density columns 104 using the example device 100 of Figure 1 .

[00125] For example, using the steps depicted in Figure 6A, Figure 6B, Figure 6C and Figure 6D, the path geometry 702 may be achieved to take into account the narrowing of the narrowing of a fluid density column 104 from an aperture 124 to a dispensing tip 114. For example, the closer the magnetic devices 116 are to a dispensing tip 114, the shorter their respective pause times, as the diagonal distance that the magnetizing microparticles 106 may travel may be reduced; similarly, a last pause may be to pull the magnetizing microparticles 106 into about a center of a fluid density column 104 rather than to clump against a side 120. However, the step size of the carriage 108 may also be shortened or lengthened, the closer the magnetic devices 116 are to the dispensing tips 114, for example to decrease or increase an angle of movement of the magnetizing microparticles 106 between the sides 120. The mechanical centering features 137 may further be used to consistently position the magnetic devices 116 between the fluid density columns 104.

[00126] For example, a path geometry 704 includes diagonal regions from a second side 120-2 to a first side 120-1 , which are all of respective equal distances, and “horizontal" regions from the first side 120-1 to the second side 120-2 (e.g. movement between the sides 120 that is not diagonal) which are also all of respective equal distances. Such a path geometry 704 may be achieved by moving the carriage 108 a same distance prior to applying a magnetic field to the first side 120-1 (e.g. by one, or another, of a first magnetic device 116-1 or a second magnetic device 116-2), and not moving the carriage 108 prior to applying a magnetic field to the second side 120-2. Hence, for example, the step “F” may be eliminated and/or a step size thereof (e.g. the distance 136) may be reduced to achieve such a path geometry 704. Furthermore, the path geometry 704 illustrates that the pause times of the magnetic devices 116 may be controlled such that the magnetizing microparticles 106 may not be dragged and/or pulled all the way to the sides 120. While such a path geometry 704 may not be preferred, the path geometry 704 illustrates the many different path geometries that may be achieved using the device 100.

[00127] Similarly, the path geometry 706 is provided to show that movement between the sides 120 and parallel to the sides 120, and the like, may be achieved using the device 100. Such a path geometry 706 may be achieved by modifying the step “E” and/or the step “F” such that the carriage 108 moves the along the path 110 while a magnetic device 116 is adjacent a respective side 120 and/or by eliminating step “F” and/or reducing a step size thereof (e.g. the distance 136). Again, while such a path geometry 706 may not be preferred, the path geometry 706 illustrates the many different path geometries that may be achieved using the device 100.

[00128] By now it may be understood that in some examples, the device 100 may comprise: the carriage to move along the path 110, the carriage 108 having the lateral axis 111 perpendicular to the path 110; the first magnetic devices 116- 1 and the first actuator 131-1 to actuate the first magnetic devices 116-1 to first positions at the carriage 108; and the second magnetic devices 116-2 and the second actuator 131-2 to actuate the second magnetic devices 116-2 to second positions at the carriage 108, the first actuator 131 -1 , the second actuator 131- 2, and the carriage 108 being controllable independent of one another. In general, the first positions of the first magnetic devices 116-1 correspond to the first gaps 127-1 between adjacent fluid density columns 104 of the sample preparation cartridge modules 102 holdable the carriage 108 and the second positions the second magnetic devices 116-2 correspond to the second gaps 127-2 between the adjacent fluid density columns 104, the first positions alternating with the second positions. Furthermore, the first magnetic devices 116-1 and the second magnetic devices 116-2 are offset along the path 110, for example to accommodate the plates 129 and the actuators 131 .

[00129] For example, as has already been described, the first magnetic devices 116-1 may mounted at a first edge of the first plate 129-1 (e.g. facing the carriage 108), and the first actuator 131-1 may be actuate the first plate to actuate the first magnetic devices 116-1 to the first positions; and the second magnetic devices 116-2 may be mounted at a second edge plate (e.g. facing the carriage 108) of the second plate 129-2, the second actuator 131-2 to actuate the second plate 129-2, to actuate the second magnetic devices 116-2 to the second positions. The first plate 129-1 and the second plate 129-2 may be laterally offset from each other along the path 110 of the carriage 108 to offset the first magnetic devices 116-1 and the second magnetic devices 116-2 along the path 110.

[00130] The first actuator 131-1 and the second actuator 131-2 may be further to alternate actuation of the first magnetic devices 116-1 and the second magnetic devices 116-2 to the first positions and the second positions at the carriage 108 such that either the first magnetic devices 116-1 are at the first positions or the second magnetic devices 116-2 are at the second positions. However, the first actuator 131-1 and the second actuator 131-2 may be further to actuate the first magnetic devices 116-1 and the second magnetic devices 116-2 to the first positions and the second positions at the carriage 108 simultaneously.

[00131] In particular, the first actuator 131-1 and the second actuator 131-2 may be to actuate the first magnetic devices 116-1 and the second magnetic devices 116-2 to the first positions and the second positions by moving the first magnetic devices 116-1 and the second magnetic devices 116-2 towards the carriage 108 until respective motors 133 thereof stall due the first magnetic devices 116-1 and the second magnetic devices 116-2 encountering a backplane 126, or backplanes 126, of the sample preparation cartridge modules 102 holdable by the carriage 108.

[00132] 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.

[00133] As depicted, the sample preparation device 800 (interchangeably referred to hereafter as the device 800) includes a chassis 802 that includes a cassette access door 804 for loading a cassette 107 that includes the sample preparation cartridge module 102 and/or sample preparation cartridge modules 102 therein, the sample preparation cartridge module 102 holding a sample for testing as described hereafter. While the sample preparation cartridge modules 102 are depicted herein as being in an elongate shape and/or in the form of a column, similar to Figure 2A and Figure 3, the sample preparation cartridge modules 102 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 dispensed from the sample preparation cartridge module 102 after processing by the device 800. While only one sample preparation cartridge module 102 is depicted, and eight wells 814, it is understood that the cassette 107 may hold a same number of sample containers 108 as there are wells 814 at the well holder 812. For example, as depicted, similar to as described with respect to Figure 1 and Figure 2A, there may be eight sample preparation cartridge modules 102 and hence eight wells 814. Furthermore, while the cassette 107 is depicted in an end view showing only one sample preparation cartridge module 102, 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 107 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 102 is about aligned with a line of the wells 814.

[00134] 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 cassette access door 804 and the well access door 810 to open such that the cassette 107 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 102 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 102 is to be heated and/or a heating cycle of the sample preparation cartridge module 102 and/or a heating/mixing cycle (e.g. setting mixing speeds of an actuator 844 of the device 800) and/or the input device 818 may be used to control step sizes of the carriage 108 and/or pause times of the magnetic devices 116 to control path geometry of the magnetizing microparticles 106.

[00135] 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 to at least partially emerge from an opening that is normally covered by the cassette access door 804. The cassette 107 may then be manually loaded into the carriage 108.

[00136] 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 (and the device 100) 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).

[00137] Once loaded, the cassette carriage 108 moves the cassette 107 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, to process the sample 838, for example at least by washing the magnetizing microparticles

106 after lysis, before dispensing the sample 838 from the sample preparation cartridge module 102 into a well 814.

[00138] 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 102 into a corresponding well 814. When there a plurality of sample preparation cartridge modules 102 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 102 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

107 such that different sample preparation cartridge modules 102 align with different wells 814 at different positions of the shuttle 828.

[00139] 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.

[00140] While not depicted, the device 800 may further include respective components for opening and closing the doors 804, 810.

[00141] To effect processes of the device 800, a sample preparation cartridge module 102 may be divided into a first region 832 and a second region 834 (e.g. that includes the fluid density column 104, for example as depicted in Figure 3), divided by a barrier 836. A sample 838 is received into the sample preparation cartridge module 102 via the port 820, and may reside at a bottom of the first region 832, at the barrier 836; as depicted, the magnetizing microparticles 106 are initially located in the first region 832. The sample preparation cartridge module 102 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.

[00142] For example, the cassette 107 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).

[00143] 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 102 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, 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 106; in such examples, the agitator 840 may be omitted from the sample preparation cartridge module 102.

[00144] 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 850, 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.

[00145] Once lysis is performed on the sample 838, biological components of interest may be released from cells of the sample 838 and bond to the magnetizing microparticles 106. While not depicted, the second region 834 (e.g. the fluid density column 104) may further include a wash buffer which may be mixed with mixed with the biological components of interest (e.g. bonded to the magnetizing microparticles) (e.g. when plunged into the second region 834), by actuation of a suitable reservoir 852 of a plurality of reservoirs 852 that perform different functions for the sample preparation cartridge module 102. The reservoirs 852 may alternatively be referred to as blisters and/or pouches, and the like. For example, one reservoir 852 may hold the wash buffer, another reservoir 852 may hold chemicals to stabilize the biological component of interest, another reservoir 852 may hold a grease barrier, and yet another reservoir 852 may be for dispensing the sample 838, including the magnetizing microparticles 106 with the biological component of interest bonded thereto, into a well 214, for example via the tip 114 of the sample preparation cartridge module 102.

[00146] As mentioned above, the cassette 107 may hold a plurality of sample preparation cartridge modules 102 and hence the device 800 may be to actuate a plurality of corresponding reservoirs 852 (e.g. concurrently) on a plurality of sample preparation cartridge modules 102 for sample processing, and to actuate individual reservoirs 852 (e.g. independent of each other) on the sample preparation cartridge modules 102 for sample dispensing. For example, as depicted, the device 800 may include a multiple reservoir actuator 856 including a plurality of reservoir tips 858 (though only one is depicted) which may be used to actuate (e.g. concurrently) a plurality of corresponding reservoirs 852 on a plurality of sample preparation cartridge modules 102, 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 102 (e.g. and the fluid density columns 104). However, the device 800 may include a plurality of single reservoir actuators 860 (though only one is depicted) including respective reservoir tips 862 (though, again, only one is depicted), for independently actuating respective reservoirs 852 at the plurality of sample preparation cartridge modules 102 to independently dispense samples 838 into respective wells 814 via respective tips 862. In other examples, as depicted, the device 800 may comprise one single reservoir actuator 860 including one reservoir tip 862 that is movable within the device 800 between sample preparation cartridge modules 102.

[00147] As has already been described, the device 800 may include the magnetic devices 116, which may be actuated via a magnetic actuator and/or magnetic actuators 866 to move the magnetic devices 116 adjacent the sample preparation cartridge module 102, as described above, to attract the magnetizing microparticles 106 in the sample 838 to wash the magnetizing microparticles 106 to isolate and/or purify biological components of interest bonded thereto, and move the sample 838 towards the tip 114 and/or through the fluid density column 104 in the second region 834, as described with respect to Figure 5, Figure 6, and Figure 7, for example in combination with moving the sample preparation cartridge modules 102 via the carriage 108.

[00148] 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.

[00149] 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 102; 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 102 to receive the samples 838 as dispensed via actuation of individual suitable reservoirs 852 by the single reservoir actuator 860. The wells 814 may be moved back out of the device 800 via the planar surface 830 and the well access door 810 and transferred to, for example, a PCR assay device. [00150] 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.).

[00151] 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 magnetic devices 116 as described herein, among other possibilities. 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.

[00152] 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 107 has been loaded into the cassette carriage 108, and the carriage access door 804 has been closed. Similarly, the wells 814 have been loaded into the shuttle 828 and the planar surface 830 (with the shuttle 828) has been moved into the device 800, and the well access door 810 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 102 via the pressure source 850 being actuated (e.g. by moving the cassette carriage 108 to move the sample preparation cartridge module 102 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). Furthermore, reservoirs 852 containing the wash buffer, have been concurrently actuated by the multiple reservoir actuator 856 and the tips 858. As such, the reservoirs 852 associated with the wash buffer are no longer seen at the sample preparation cartridge module 102. Further, the sample 838 including the magnetizing microparticles 106 with the biological component of interest bonded thereto, is located at a “top” of the fluid density column 104 (e.g. an end opposite the tip 114).

[00153] In particular in Figure 8C, the carriage 108 has been moved to a magnetizing microparticle washing position, similar to that of step “A, “B” and/or “C” and the magnetic actuators 131 have moved the magnet devices 116 to opposite sides 120 of the fluid density column 104 to begin washing of the magnetizing microparticles 106.

[00154] Referring to Figure 9, a flow diagram of an example method 900 to control magnetizing microparticles in fluid density columns 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.

[00155] At a block 902, the processor 890 and/or the device 800 controls the sample preparation cartridge modules 102 (e.g. by controlling the carriage 108) to move to a first position (e.g. as seen in step “D” of Figure 6B), the sample preparation cartridge modules 102 including fluid density columns 104 and magnetizing microparticles 106 therein.

[00156] At a block 904, the processor 890 and/or the device 800 controls, while the sample preparation cartridge modules 102 are paused at the first position, first magnetic devices 116-1 (e.g. by controlling the actuator 131-1) to apply respective first magnetic fields between first adjacent fluid density columns 104 for a first given time period and to outer sides 120 of end fluid density columns 104 (e.g. as seen in step “E” of Figure 6C).

[00157] At a block 906, the processor 890 and/or the device 800 controls the first magnetic devices 116-1 to remove the respective first magnetic fields from the fluid density columns 104 (e.g. as seen in step “F” of Figure 6C).

[00158] At a block 908, the processor 890 and/or the device 800 controls, the sample preparation cartridge modules 102 to move to a second position (e.g. as also seen in step “F” of Figure 6C).

[00159] At a block 910, the processor 890 and/or the device 800 controls, while the sample preparation cartridge modules 102 are paused at the second position, second magnetic devices 116-2 to apply respective second magnetic fields between second adjacent fluid density columns 104 for a second given time period (e.g. as seen in step “G” of Figure 6D), the first adjacent fluid density columns 104 alternating with the second adjacent fluid density columns 104.

[00160] At a block 912, the processor 890 and/or the device 800 controls the second magnetic devices 116-2 to remove the respective second magnetic fields from the fluid density columns 104 (e.g. as seen in step “D” of Figure 6B or step “F of Figure 6C).

[00161] The first given time period and the second given time period may be selected to drag the magnetizing microparticles 106 to respective sides 120 of the fluid density columns 104 while the first magnetic devices 116-1 and the second magnetic devices 116-2 are applying the respective first magnetic fields and the respective second magnetic fields at the fluid density columns 104.

[00162] The method 900 may further comprise the processor 890 and/or the device 800, prior to moving the sample preparation cartridge modules 102 to the first position and the second position: controlling both the first magnetic devices 116-1 and the second magnetic devices 116-2 to concurrently apply, for a third given time period, the respective first magnetic fields and the respective second magnetic fields to between the first adjacent fluid density columns 104, the second adjacent fluid density columns 104 and the outer sides 120 of the end fluid density columns 104 (e.g. as seen in step “B” of Figure 6A). The third time period may be selected to drag the magnetizing microparticles 106 to respective opposite sides 120 of the fluid density columns 104 to form respective clumps or groups of the magnetizing microparticles 106 at the respective opposite sides 120.

[00163] The method 900 may further comprise the processor 890 and/or the device 800, continuing to control the first magnetic devices 116-1 and the second magnetic devices 116-2 to alternately apply the respective first magnetic fields and the respective second magnetic fields at the fluid density columns 104 as the carriage moves to, and pauses at, different positions.

[00164] 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

47 CLAIMS

1 . A device comprising: a carriage to move along a path, the carriage having a lateral axis perpendicular to the path; and first magnetic devices and second magnetic devices independently controllable from one another and the carriage, the first magnetic devices and the second magnetics actuatable to respective positions at the carriage from a same given side of the carriage, respective opposing edges of the first magnetic devices and the second magnetic devices laterally offset from each other along the lateral axis, the first magnetic devices and the second magnetic devices alternating with each other along the lateral axis, and offset along the path.

2. The device of claim 1 , wherein a first portion the respective positions correspond to gaps between adjacent fluid density columns of sample preparation cartridge modules holdable by the carriage in a row and a second portion of the respective positions correspond to respective outer sides of respective fluid density columns of respective outer sample preparation cartridge modules in the row.

3. The device of claim 1 , wherein a portion of the first magnetic devices that are actuatable to outer respective positions are smaller in width along the lateral axis than others of the first magnetic devices or the second magnetic devices.

4. The device of claim 1 , wherein respective opposing edges of the first magnetic devices and the second magnetic devices laterally offset from each other along the lateral axis by a distance defined by fluid density columns of sample preparation cartridge modules holdable by the carriage, such that a fluid density column fits between the respective opposing edges.

5. The device of claim 1 , wherein the first magnetic devices and the second magnetic devices are further to alternate moving towards, and away from, the carriage.

49

6. A device comprising: a carriage to move along a path, the carriage having a lateral axis perpendicular to the path; first magnetic devices and a first actuator to actuate the first magnetic devices to first positions at the carriage; and second magnetic devices and a second actuator to actuate the second magnetic devices to second positions at the carriage, the first actuator, the second actuator, and the carriage being controllable independent of one another, the first positions corresponding to first gaps between adjacent fluid density columns of sample preparation cartridge modules holdable the carriage and the second positions corresponding to second gaps between the adjacent fluid density columns, the first positions alternating with the second positions, the first magnetic devices and the second magnetic devices offset along the path.

7. The device of claim 6, wherein: the first magnetic devices are mounted at a first edge of a first plate, the first actuator to actuate the first plate to actuate the first magnetic devices to the first positions, and the second magnetic devices are mounted at a second edge of a second plate, the second actuator to actuate the second plate to actuate the second magnetic devices to the second positions, the first plate and the second plate laterally offset from each other along the path of the carriage to offset the first magnetic devices and the second magnetic devices along the path.

8. The device of claim 6, wherein the first actuator and the second actuator are further to alternate actuation of the first magnetic devices and the second magnetic devices to the first positions and the second positions at the carriage such that either the first magnetic devices are at the first positions or the second magnetic devices are at the second positions. 50

9. The device of claim 6, wherein the first actuator and the second actuator are further to actuate the first magnetic devices and the second magnetic devices to the first positions and the second positions at the carriage simultaneously.

10. The device of claim 6, wherein the first magnetic devices and the second magnetic devices further comprise mechanical centering features to mechanically interact with sides of the adjacent fluid density columns to about center a magnetic device between the adjacent fluid density columns.

11. A method comprising: controlling, at a sample preparation device, the sample preparation cartridge modules to move to a first position, the sample preparation cartridge modules including fluid density columns and magnetizing microparticles therein; controlling, at the sample preparation device, while the sample preparation cartridge modules are paused at the first position, first magnetic devices to apply respective first magnetic fields between first adjacent fluid density columns for a first given time period and to outer sides of end fluid density columns; controlling, at the sample preparation device, the first magnetic devices to remove the respective first magnetic fields from the fluid density columns; controlling, at a sample preparation device, the sample preparation cartridge modules to move to a second position; controlling, at the sample preparation device, while the sample preparation cartridge modules are paused at the second position, second magnetic devices to apply respective second magnetic fields between second adjacent fluid density columns for a second given time period, the first adjacent fluid density columns alternating with the second adjacent fluid density columns; and controlling, at the sample preparation device, the second magnetic devices to remove the respective second magnetic fields from the fluid density columns.

12. The method of claim 11 , wherein the first given time period and the second given time period are selected to drag the magnetizing microparticles to respective sides of the fluid density columns while the first magnetic devices and the second magnetic devices are applying the respective first magnetic fields and the respective second magnetic fields at the fluid density columns.

13. The method of claim 11 , further comprising, prior to moving the sample preparation cartridge modules to the first position and the second position: controlling both the first magnetic devices and the second magnetic devices to concurrently apply, for a third given time period, the respective first magnetic fields and the respective second magnetic fields to between the first adjacent fluid density columns, the second adjacent fluid density columns and the outer sides of the end fluid density columns.

14. The method of claim 13, wherein the third time period is selected to drag the magnetizing microparticles to respective opposite sides of the fluid density columns to form respective clumps or groups of the magnetizing microparticles at the respective opposite sides.

15. The method of claim 11 , further comprising: continuing to control the first magnetic devices and the second magnetic devices to alternately apply the respective first magnetic fields and the respective second magnetic fields at the fluid density columns as the carriage moves to, and pauses at, different positions.