WO2022139802A1

WO2022139802A1 - Sample preparation

Info

Publication number: WO2022139802A1
Application number: PCT/US2020/066556
Authority: WO
Inventors: Wesley R. Schalk; Kris M. English; Alan Shibata; Si-Lam J. Choy; Alan R. Arthur
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 is to receive a sample preparation cartridge and includes a first carriage, a second carriage, and a number of modules. The first carriage is to enable movement of the cartridge in a first direction. The second carriage is to enable movement of a well cartridge in a second direction. The number of modules is to interact with the sample preparation cartridge and include: a mixer module, a temperature control module, a magnetic module, a pocket actuation module, or a combination thereof. The first carriage and the second carriage are arranged with respect to one another such that the well cartridge is to be presented to the sample preparation cartridge at a non-orthogonal angle.

Description

SAMPLE PREPARATION

BACKGROUND:

[0001] In certain types of situations, analysis is performed on biological fluid samples. Examples includes tests of blood and other biological fluids for the presence of pathogens, such as viruses. The analysis may include an initial stage of preparing biological fluids, such as lysis, purification, and amplification of the biological component of interest (e.g., nucleic acid).

BRIEF DESCRIPTION OF THE DRAWINGS

[0002] Various examples will be described below by referring to the following figures.

FIGS. 1A-1 E illustrate various portions, aspects, and views of an example sample preparation device;

FIG. 2A is a block diagram of an example sample preparation device;

FIG. 2B is a block diagram illustrating an example system in which an example sample preparation device may operate;

FIG. 3 is a flowchart illustrating a possible process for operation of an example sample preparation device within an example system;

FIG. 4 is a block diagram illustrating an example computer-readable medium and controller used by a sample preparation device;

FIG. 5 is an example sample preparation cartridge;

FIG. 6 shows different modules of an example preparation device;

FIGS. 7A and 7B are flowcharts illustrating example methods for an example preparation device; and

FIGS. 8A-8O show an example preparation device at different moments in time corresponding to methods of operation, such as shown in FIGS. 7A and 7B.

[0003] Reference is made in the following detailed description to accompanying drawings, which form a part hereof, wherein like numerals may designate like parts throughout that are corresponding and/or analogous. It will be appreciated that the figures have not necessarily been drawn to scale, such as for simplicity and/or clarity of illustration. DETAILED DESCRIPTION

[0004] References throughout this specification to one implementation, an implementation, one example, an example, and/or the like means that a particular feature, structure, characteristic, and/or the like described in relation to a particular implementation and/or example is included in at least one implementation and/or example of claimed subject matter. Thus, appearances of such phrases, for example, in various places throughout this specification are not necessarily intended to refer to the same implementation and/or example or to any one particular implementation and/or example. Furthermore, it is to be understood that particular features, structures, characteristics, and/or the like described are capable of being combined in various ways in one or more implementations and/or examples and, therefore, are within intended claim scope. In general, of course, as has always been the case for the specification of a patent application, these and other issues have a potential to vary in a particular context of usage. In other words, throughout the disclosure, particular context of description and/or usage provides helpful guidance regarding reasonable inferences to be drawn; however, likewise, “in this context” in general without further qualification refers to the context of the present disclosure.

[0005] Preparation of biological samples (e.g., liquids, such as blood, saliva, etc.) for analysis may include a number of manual stages, which may be performed by lab technicians, researchers, doctors, and nurses, by way of example. A “biological sample” can refer to a fluid ora dried or lyophilized material obtained for analysis from a living or deceased organism. Failure to properly prepare a sample for analysis may lead to erroneous test results (e.g., false negatives, false positives, etc.). Of note, manual preparation of a sample may be time-consuming and expensive, such as by using expensive tools, materials, and experts. Preparation of a biological sample, refers to, for example, performing action on the sample in order to isolate a biological component of interest. As used herein, the term “biological component” refers 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. Isolating the biological component from other components of the biological sample can permit subsequent analysis (e.g., without potential interference by those other components, which can therefore 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.

[0006] Consequently, there are a number of automated solutions for preparing and/or analyzing samples. By way of illustration, some systems may automate the analysis of prepared samples. Other systems may automate the complete process of preparing and analyzing samples, such as within proprietary test beds and using proprietary disposable cartridges. For example, some systems may have a proprietary receptacle for receiving different samples across an array of wells, and each well may be spaced closely (e.g., at a pitch of 8 or 9 mm). Other systems may space their sample wells further apart (e.g., at a pitch of 10 mm or more). As used herein, the term “well” refers to a portion of a receptacle, the portion for receiving prepared samples. [0007] Additionally, while there may be a desire to space wells closely together in a receptacle, such as to enable maximizing a number of samples that can be analyzed at one time, such close spacing may render the process of preparing the samples more challenging. For instance, if tubes containing samples are packed tightly together in a preparation cartridge, it may be challenging to automate the preparation of each sample, such as due to a lack of space between preparation tubes.

[0008] With the foregoing in mind, there may be a desire for an approach for preparing samples (e.g., biological samples) while also facilitating sample preparation independent of the spacing of wells on a well tray. As should be appreciated, such an approach would also have the benefit of providing an automated sample preparation device that may be used on a number of different well spacings and/or arrangements.

[0009] The present description proposes devices and methods that enable the use of a sample preparation cartridge having a first pitch to dispense into a well cartridge having a second pitch. Specifically, the present description proposes presenting the well cartridge to the sample preparation cartridge at a non- orthogonal angle.

[0010] The difference in pitches between a sample preparation cartridge and a well cartridge is illustrated in FIG. 1A. As shown, a sample preparation cartridge 102 is illustrated as having a number of sample preparation tubes, of which example sample preparation tubes 104a and 104b are labeled, each sample preparation tube containing a primary fluid passage leading from an input portion (e.g., for a fluid sample) to an output portion (e.g., a needle via which a prepared sample is to be dispensed). A pitch, or distance between a central axis of each of sample preparation tube 104a and 104b, is labeled as A. Meanwhile, a pitch, or distance between a central axis of wells 108a and 108b of well cartridge 106 is labeled as B. As should be readily apparent, the length A is not equal to the length B. In one example, B may be 9 mm. Of course, other pitches are contemplated by the present disclosure, including, but not limited to, 7 mm, 8 mm, 10 mm, etc. In one example, A may be 18 mm. Of course, other pitches are also contemplated by the present disclosure, including, but not limited to, 15 mm, 16 mm, 19 mm, etc.

[0011] To illustrate how it may be possible to automate a sample preparation process using sample preparation cartridges (e.g., sample preparation cartridge 102) having a first pitch to dispense prepared samples into a well cartridge with wells of a second pitch, a number of block diagrams are presented in FIGS. 1 B- 1 E to show, first arrangement, and then operation, of the components. FIG. 1 B illustrates an example device 100, which may be used to prepare a sample, such as in a sample preparation cartridge 102, and dispense the prepared sample into a well cartridge, such as well cartridge 106.

[0012] Device 100 includes a number of modules 110. Modules refer to a combination of hardware and software that are designed to interact with sample preparation cartridge 102 and well cartridge 106. FIG. 1 B illustrates three possible modules, labeled with “1 ,” “2,” and “n” to illustrate an open set of possible modules. Example modules may include a mixer module, a temperature control module, a magnetic module, a pocket actuation module, among others, as will be discussed in greater detail hereinafter. Examples of additional possible modules will also be discussed in greater detail hereinafter.

[0013] Device 100 also includes a carriage 112 that is to cause movement of sample preparation cartridge 102 (illustrated within the block representing carriage 112). In one example, carriage 112 is designed to move along one axis (e.g., in one direction on that axis, such as up, and then to return in an opposite direction along that same axis, such as down). In another example, carriage 112 may be designed to move along multiple axes (e.g., up and down, as described in the previous example, as well as along another axis, such as side-to-side, by way of non-limiting example). Carriage 112 may use carriage guides and actuators such as motors. In one example, this may come in the form of a combination of carriage guide posts and electric motors.

[0014] Device 100 also includes a carriage 114 that is designed to move well cartridge 106 along another axis (e.g., in one direction on that axis, such as backwards, and then to return in an opposite direction along that same axis, such as forwards). In another example, carriage 114 may also be capable of moving along other axes and/or pivoting.

[0015] Movement of carriages 112 and 114 is illustrated in FIGS. 1 C and 1 D, according to one example. As shown in FIG. 1 C, which views device 100 from a side, carriage 112 is arranged within device 100 and can receive sample preparation cartridge 102. Carriage 112 moves along an axis, in an up-and-down direction, as indicated by arrow 116a. A position of carriage 112 at one extremity of its path of movement is shown by the lower carriage 112’ position, which is in closer proximity to carriage 114, and the path carriage 114 takes along a different axis.

[0016] Carriage 114 is shown moving in a left-and-right direction, as indicated by arrow 116b. At one extremity of this movement, carriage 114 extends beyond device 100 to receive well cartridge 106. FIG. 1C shows carriage 114 partially outside of device 100. However, in other implementations carriage 114 may extend completely beyond a housing of device 100. For instance, carriage 114 may be arranged upon a tray and the tray may allow carriage 114 to exit a housing of device 100 completely.

[0017] FIG. 1 C shows carriage 114 in another position, as indicated by carriage 114’, which refers to another extremity of movement of carriage 114 along an axis, as illustrated by arrow 116b. While the carriages (carriage 112 and 114) are in the positions indicated by carriage 112’ and carriage 114’, respectively, it may be possible for prepared samples to be dispensed from a sample preparation cartridge (e.g., cartridge 102) into wells of a well cartridge (e.g., well cartridge 106). It is noted that due to the point of view of FIG. 1C, there may be multiple directional components that describe movement of carriage 114. For example, in one implementation, movement of carriage 114 may include a rotational component, such as due to rotation of carriage 114 about a point. And the movement of carriage 114 may also include a lateral component, such as due to carriage 114 moving from right to left, as illustrated in the figure. However, it should be understood that rotational movement may also contribute to movement of carriage 114 and well cartridge 106 into a housing of device 100. Thus, for ease of illustration, only a single directional component is labeled in FIG. 1 C, but it should thus be understood that this is done without limitation.

[0018] FIG. 1 D illustrates an implementation of carriage 114, such as to enable a non-orthogonal arrangement between well cartridge 106 and sample preparation cartridge 102. The block diagram of FIG. 1 D is illustrated as viewed from above. In this example, carriage 114 may pivot about a point, as illustrated by pivot point 120, so as to present well cartridge 106 at a non-orthogonal angle with respect to the sample preparation cartridge. At a first position (e.g., a state for receiving well cartridge 106), carriage 114 may extend beyond a housing of device 100. Axes are included in FIG. 1 D showing a central axis 118a of carriage 114, which intersects pivot point 120. A central axis 118b of well cartridge 106 is also shown.

[0019] In one example, to bring well cartridge 106 into the housing of device 100, carriage 114 will be caused to pivot inside of device 100. Carriage 114’ illustrates carriage 114 in a position or state representative of being loaded within device 100. An angle, 0, represents an angle at which carriage 114 pivots into device 100, and is shown as the difference between a position of axis 118a (initial or loading state of carriage 114) and a position of axis 118a’ (subsequent or loaded state of carriage 114’). The angle, 0, may correspond to a non-orthogonal angle, such as may be created between an axis of a sample preparation cartridge and an axis of a well cartridge 106 (e.g., represented by axis 118b’). It is noted that the angle 0 represents a rotational component of movement, such as may contribute to movement of carriage 114 illustrated in FIG. 1 C and labeled with arrow 116b. [0020] Once loaded into device 100, carriage 114 may move along axis 118a’ to move well cartridge 106 into proximity with the sample preparation cartridge. This arrangement between cartridges is illustrated in FIG. 1 E, as shown from above. FIG. 1 E shows sample preparation cartridge 102 in a lowered position, such as was illustrated by carriage 112’ in FIG. 1C. FIG. 1 E also shows well cartridge 106 in an angled position, such as illustrated by cartridge 106’ and carriage 114’ in FIG. 1 D. FIG. 1 E shows three possible arrangements of sample preparation cartridge 102 and well cartridge 106: a first position, illustrated in (a), a second position, illustrated in (b), and a third position, illustrated in (n). It is noted that axes 118a’ (an axis of carriage 114) and 118b’ (an axis of well cartridge 106) are illustrated, as shown in FIG. 1 D. Also illustrated is an axis 118c of sample preparation cartridge 102. As illustrated, an angle of intersection between axis 118c and axis 118a’ forms an angle, illustrated by p. And an angle of intersection between axis 118c and axis 118b’ forms an angle, illustrated by p. As shall be discussed, these non-orthogonal angles allow a sample preparation cartridge having a first pitch (e.g., sample preparation cartridge 102 having a pitch A) to dispense prepared fluids into a well cartridge having a second pitch (e.g., well cartridge 106 having a pitch B). The relevant angles and p may be between 30 and 60° depending on particular pitch differences.

[0021] As illustrated in FIG. 1 E, in a first position, as illustrated in (a), carriage 114 and well cartridge 106 may be caused to move towards sample preparation cartridge 102. As illustrated, carriage 114 may move along guides of a well carriage module 122, such as a tray. A direction of movement of carriage 114 and well cartridge 106 is illustrated by an arrow 116b (see, also FIG. 1 C). It should be appreciated that the angles p and p make it possible for prepared samples to be dispensed from the eight illustrated sample preparation tubes of sample preparation cartridge 102 into eight corresponding wells of well cartridge 106, one at a time.

[0022] The angle p represents the angle at which well cartridge 106 is to be presented to sample preparation cartridge 102 to enable cartridges of different pitches being used together. For example, as illustrated in (b) of FIG. 1 E, sample preparation cartridge 102 and well cartridge 106 are shown arranged such that a first prepared sample may be dispensed into a first well of well cartridge 106. Subsequently, well cartridge 106 and carriage 114 may move in a direction illustrated by arrow 116b’ to align subsequent corresponding tubes and wells. Indeed, as illustrated in (n) of FIG. 1 E, a last (eighth, in this example) sample preparation tube of sample preparation cartridge 102 and well of well cartridge 106 are aligned to enable dispensing of prepared sample into the last well of well cartridge 106. Subsequently, well cartridge 106 and carriage 114 may continue in direction arrow 116b’ and may pivot back into an open/loading position (e.g., rotating from a position depicted by carriage 114’ in FIG. 1 D to position depicted by carriage 114 in FIG. 1 D, consistent with a rotational component depicted by angle 0) so that well cartridge 106 may be removed from device 100, such as to enable analysis thereof.

[0023] With the foregoing in mind, an example device (e.g., device 100) is to receive a sample preparation cartridge (e.g., sample preparation cartridge 102) and the device includes a first carriage (e.g., carriage 112), a second carriage (e.g., carriage 114) and a number of modules (e.g., modules 110). The first carriage is to enable movement of the sample preparation cartridge in a first direction (e.g., direction indicated by arrow 116a in FIG. 1C). The second carriage is to enable movement of a well cartridge (e.g., well cartridge 106) in a second direction (e.g., direction indicated by arrow 116b in FIG. 1 C). The number of modules are to interact with the sample preparation cartridge and include a mixer module, a temperature control module, a magnetic module, a pocket actuation module, or a combination thereof. Further, the first carriage and the second carriage are arranged with respect to one another such that the well cartridge is to be presented to the sample preparation cartridge at a non-orthogonal angle (see, e.g., FIGS. 1 D and 1 E).

[0024] In another example, a method of preparing a sample in a device (e.g., device 100) includes causing a first carriage (e.g., carriage 112) of the device conveying a sample preparation cartridge (e.g., sample preparation cartridge 102) to move in a first direction (e.g., direction indicated by arrow 116a). The method also includes causing a second carriage (e.g., carriage 114) of the device conveying the well cartridge to pivot from a load position partially external to a housing of the device into a concealed position within the housing to present the well cartridge at the non-orthogonal angle with respect to the sample preparation tubes (see, e.g., FIGS. 1 D and 1 E).

[0025] As should be apparent by the foregoing, by presenting cartridges at non- orthogonal angles, it may be possible to use cartridges having different pitches together in an automated preparation process/device.

[0026] FIG. 2A is a block diagram illustrating an example sample preparation device. It is noted that in FIG. 2A and subsequent figures, like numbers are used to denote similar components. For instance, sample preparation cartridge 202 may be similar in structure and/or operation with sample preparation cartridge 102, discussed previously. However, it is to be understood that particular arrangements and operations discussed in FIG. 2A (and subsequent figures) are not necessarily to be understood as necessarily being present in more general discussions, such as those of earlier figures. For instance, a particular implementation discussed in FIG. 2A for sample preparation cartridge 202 are not to be understood as necessarily being present in sample preparation cartridge 102. Etc. It is also noted that for brevity, the term “preparation” is alternatively referred to at times as “prep.” Thus, for example, sample preparation cartridge 202 may alternatively be referred to as sample prep cartridge 202.

[0027] Returning to FIG. 2A, sample prep device 200 is illustrated as having a first carriage, sample carriage 212, which is to convey sample prep cartridge 202, and a second carriage, well carriage 214, which is to convey well cartridge 206. At times, there may be a desire for device 200 to prepare sample prep cartridges, such as sample prep cartridge 202, which contains actuatable pockets containing a substance, such as a dry or liquid reagent, which may be pushed into a fluid passage of sample prep cartridge 202, such as in response to an application of pressure to the actuatable pocket. The application of pressure may cause an interior partition of the actuatable pocket to rupture and through which the contents of the pocket may travel into the fluid passage of sample prep cartridge 202. A module of device 200 may be configured to apply pressure to such actuatable pockets and is illustrated as pocket actuation module 232 in FIG. 2A.

Pocket actuation module 232 will be discussed in greater detail hereinafter. [0028] In addition to pocket actuation module 232, other modules of modules 210 may interact with sample prep cartridge 202. For instance, a mixer module 224 is to mix different components of sample prep cartridge 202, heater module 226 is to apply heat to sample prep cartridge 202, and magnetic module 230 is to apply an electromagnetic field to sample prep cartridge 202. Of note, heater module 226 may correspond to the temperature control module referred to, above. In one implementation, the temperature control module may include distinct heating and cooling components (e.g., heater module 226). In other implementations, the temperature control module may include heating and cooling components in an integrated temperature control module. Hereinafter, the former case is illustrated, such as to facilitate description by providing distinct modules for distinct functionality. However, it is to be understood that this is done without limitation.

[0029] With the foregoing in mind, a method of preparing a sample, such as using an example device (e.g., device 200) includes moving a first carriage (e.g., carriage 212) in a first direction and moving a second carriage (carriage 214) in a second direction. Movement of the first carriage is to cause movement of a sample preparation cartridge (e.g., sample prep cartridge 202). Movement of the second carriage is to cause movement of a well cartridge (e.g., well cartridge 206). The method also includes causing a number of modules (e.g., modules 210) to interact with the sample preparation cartridge including: a mixer module, a heater module, a magnetic module, a pocket actuation module, or a combination thereof. [0030] FIG. 2B illustrates an example overall system 250 in which a preparation device, such as device 100 discussed in FIGS. 1A-1 E may operate. FIG. 2B is a block diagram that illustrates components of system 250, while not necessarily showing exact arrangements.

[0031] In FIG. 2B, sample preparation cartridge 202 is illustrated and is made up of a number of sample preparation tubes 204 (referred to hereinafter alternatively as SPTs), of which, one is illustrated, and includes a number of components, including a plunger 260, an agitator 262, a sample 264 (when in use; otherwise, there is a portion of SPT 204 reserved to receive the sample; it is noted that in some examples, sample 264 will be a biological sample containing the biological component of interest), a port 266 through which sample 264 is received, a reagent 268 (which may include multiple reagents), an actuatable pocket 270 (which may include multiple pockets, such as including different reagents, among other things), and a needle 272 through which a prepared sample may be dispensed, such as into wells of well cartridge 206. As noted, above, actuatable pockets, such as actuatable pocket 270, refer to portions of sample prep cartridge 202 with an interior partition designed to be breakable upon an application of pressure. An example of actuatable pocket 270 includes a foil blister, without limitation.

[0032] Plunger 260 refers to a structural component that can be actuated in order to cause sample 264 to move from one preparation stage of SPT 204 to a subsequent stage. For instance, actuation of plunger 260 may break or pierce a barrier designed to hold sample 264 in a particular position within SPT 204, such as during mixing and heating operations. Agitator 262 refers to a structural component that can be actuated to cause agitation or mixing of sample 264, such as with reagent 268, among other things. Agitator may be caused to rotate about a central axis in an example.

[0033] As discussed previously, prep device 200 may include a sample carriage 212, for conveying sample preparation cartridge 202 through device 200. Device 200 may also include a number of modules (see, e.g., modules 110 in FIG. 1 B) including, but not limited to, a mixer module 224 (for enabling agitation of a sample and to enable actuation of plunger 260), a heater module 226 for imparting heat to sample preparation cartridge 202, a magnetic module 230 for applying an electromagnetic field to sample preparation cartridge 202, a cooling module 234, and pocket actuation module 232, which may include a number of structures for actuating actuatable pockets 270 of SPTs 204. Each of these modules may interact directly with sample preparation cartridge 202. Additionally, sample carriage drive module 240 is to cause operation of sample carriage 212 and well carriage drive module 242 is to cause operation of well carriage 214. A well tray module 238 may hold well carriage 214 and enable movement thereof, such as via guides and motors.

[0034] One aspect of device 200 that may be of interest in some implementations is pressurization levels within the housing of device 200. For instance, by achieving a lower pressurization level within the housing of device 200 (such as compared with the pressure levels of the environment surrounding device 200), it may be possible to reduce fluid leaks (e.g., including air, such as partially contaminated air), such as from sample prep cartridge 202. Desired pressurization levels of device 200 may be achieved using exhaust module 228 and cooling module 234 in combination. For instance, cooling module 234 may pull cooler air into the housing of device 200 (e.g., from outside of the housing of prep device 200) at a first rate while exhaust module 228 may cause air to exit the housing at a second rate, higher than the first rate. Such an imbalance in air intake and exhaust may be used to control pressurization of device 200.

[0035] Furthermore, cooling module 234 may be of interest to maintain certain desired temperatures for portions of sample prep cartridge 202. For instance, in one example, the contents of an actuatable pocket 270 may have a temperature threshold to not cross (e.g., 24°C for some PCR master mixes), and cooling module 234 may operate to help enable such a temperature. Further, other portions of the sample may need to be kept reasonably cool (as well as components of device 200, such as motors), and cooling module 234 may act to help achieve such cooling. It is noted that some implementations of prep device 200 may omit cooling module 234.

[0036] A sensor module 236, which may be optional in some implementations, may include a number of different sensing capabilities, such as temperature sensing, pressure sensing, humidity sensing, sample prep cartridge presence detection, well cartridge presence detection, access door status detection, and well carriage home detection, among other things. The operation of the many modules of device 200, including sensor module 236, and its reaction (e.g., changes in operation) to readings detected by sensor module 236 may be controlled by controller 274 in response to execution of instructions, such as may be stored in a computer-readable medium (CRM) 276. As used herein, controller

274 refers to refers to a processing mechanism comprising a combination of hardware and/or software (but not software per se) capable of receiving instructions, such as in the form of signals or states, and executing the received instructions to enable functionality of the controller and/or other parts of the device (e.g., modules 110). Example controllers include field-programmable gate arrays (FPGAs), application-specific integrated circuits (ASICs), and general-purpose processing units, by way of non-limiting example. And CRM 276 refers to different forms of volatile and non-volatile computer-readable media (but not transitory media). Example computer-readable media include, but are not limited to, random access memory (RAM), read-only memory (ROM), flash memory, resistive memory, magnetic memory, erasable programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), and the like.

[0037] Device 200 may also include a number of modules and components to facilitate sample preparation and analysis. For instance, FIG. 2B includes scanner module 246, which may be optional, and which refers to a combination of software and hardware to read identifiers of a sample or a patient and enable association of that sample or patient with a particular sample preparation tube and/or well. In other examples, scanner module 246 may be capable of scanning sample vials, sample preparation cartridges, well cartridges, and user ID. In one example, scanner module 246 may include an emitter to emit electromagnetic radiation, such as in the visible or non-visible spectrum, and a receiver to read reflected electromagnetic radiation to detect an identifier. In another example, scanner module 246 may include a camera and software to receive light and interpret the detected light to correspond to an identifier. Etc. FIG. 2B shows scanner partially overlapping preparation device 200. This is to indicate that in some examples, scanner module 246 may be included as a part of device 200 (e.g., integrated therein). However, in other examples, scanner module 246 may be external (e.g., wired or wireless connection) and distinct from device 200. The readings from scanner module 246 may be used in a larger system, such as including local and remote storage and computing components, such as shall be discussed in greater detail hereinafter with respect to mobile application 254, cloud information system 256, and lab information system 258.

[0038] Example prep device 200 may also include a user interface (III) 244, which refers to a combination of hardware and software (e.g., buttons, switches, a screen, and the like along with underlying software and firmware) to allow users to interact with device 200. For instance, the user may interact with III 244 to cause doors in a housing of prep device 200 to open to receive sample prep cartridge 202 and well cartridge 206. Further interactions may enable starting a sample preparation cycle by way of example, without limitation.

[0039] A well magnetic module 248 is also illustrated as partially overlapping prep device 200 and may be optional in some implementations. Well magnetic module 248 refers to a component to cause a prepared sample (e.g., including a magnetic particulate substrate, in some examples, paramagnetic beads) to concentrate towards a bottom of wells of well cartridge 206. In one example, well magnetic module 248 may be included within prep device 200. However, in other examples, well magnetic module 248 may be part of an intermediate stage before transferring well cartridge 206 into analysis device 252 and may thus be distinct from prep device 200. [0040] Analysis device 252 refers to a device, distinct from prep device 200, comprising a combination of hardware and software for analyzing the contents of a prepared sample, as found in well cartridge 206. In one example, analysis device 252 may be capable of nucleic acid amplification, such as, for example, polymerase chain reaction (PCR) testing, pulse-controlled amplification (PCA) testing, strand displacement assay (SDA), or transcription mediated assay (TMA), by way of example. As discussed, above, the pitch of well cartridge 206 may be dictated by analysis device 252. In some cases it may be 8 mm, 9 mm, etc. and different from a pitch between SPTs 204 of sample prep cartridge 202 (see, e.g., FIG. 1A).

[0041] As noted above, there may be a desire for other external tools to help manage and store data, verify sample identity, and provide data to users. For instance, in some examples of system 250, a mobile application 254 may be used in order to help users interact directly with prep device 200 and/or system 250. Mobile application 254 may also be used by end user patients for whom tests are being performed and may therefore communicate test status, test results, and the like. The potential details of such a system are beyond the scope of the present application, but it suffices to say that information collected at scanner module 246 and/or III 244 may be used to link a particular sample to a user identifier, and that user identifier may be used by mobile application 254 in order to allow end user patients to view test status and/or results.

[0042] Part of such functionality will rely upon a cloud information system 256, comprising a combination of remote computing resources (e.g., servers comprising processors, memory, and network connections, such as in the form of a distributed computing network) to send and receive data packets between prep device 200 (e.g., via lab information system 258, discussed in a subsequent paragraph) and a mobile application 254. In one example, much of the processing and/or data storage to enable operation of mobile application 254 may be performed by cloud information system 256. For instance, mobile application 254 may make queries to cloud information system 256 based on a user identifier (e.g., stored in a table of a database or other like data structure) and, in response, receive data in response indicative of test status and/or results, among other things.

[0043] In some implementations, device 200 and analysis device 252 may be communicatively connected directly (e.g., via wired and/or wireless connections) to cloud information system 256. However, in other examples, a local information technology system, such as comprising local processing components (e.g., microprocessors), memory, and network connections may serve to provide intermediate processing and storage resources. Lab information system 258 represents such local processing structures. In one example, prep device 200 and analysis device 252 may be communicatively connected to a local computing device, such as via a wired (e.g., wired ethernet or USB connection, etc.) or wireless (e.g., WiFi (e.g., 802.11 b, 802.11 a/g, etc.), Bluetooth (e.g., 802.15.1), near-field-communication (NFC), etc.) connection. For instance, it may be desirable to limit processing and storage functions of device 200 and analysis device 252, and perform local processing and storage functions on a connected local computing device, such as of lab information system 258. For instance, the lab information system 258 may store a unique user ID associated with a particular patient and/or a unique sample ID. Each SPT of SPTs 204 may have an associated ID that may be scanned by scanner module 246 prior to inserting sample prep cartridge 202 into device 200. Additionally, each well of well cartridge 206 may also include an associated ID that may also be scanned before inserting well cartridge 206 into device 200 and/or after removing well cartridge 206 from device 200. Lab information system 258 may associate identifiers, store status information, test result information, etc. It may be desirable for lab information system 258 to also store information about the preparation and analysis process. For instance, the system may automatically store readings from sensor module 236, such as to refer back to tests to confirm integrity of a result. Lab information system 258 may be communicably connected to cloud information system 256 in order to provide information to cloud information system 256, such as in response to queries.

[0044] Detailed discussion of operation of an example sample preparation device, such as prep device 200, will be provided hereinafter. However, a brief example will now be provided to illustrate how device 200 may be used in one example case illustrated in associated FIG. 3, which illustrates an example of operation of system 250. It is to be understood that this example is not intended to be limiting. One or more components or modules may be added or omitted without departing from claimed subject matter.

[0045] In this example, an end user patient may install a mobile application 254 on their mobile device and may receive a unique user identifier, such as based on an email address. Mobile application 254 may allow the user to schedule a test. This information may be transmitted, such as via a cloud information system 256, to lab information system 258, which may enable preparing for the end user patient, such as printing SPT/sample prep cartridge labels, well cartridge labels, etc. Upon arriving for the appointment, lab information system 258 may enable checking the end user patient in, confirming identity, etc. Fluid samples may be taken from the end user patient and inserted into a SPT 204 of sample prep cartridge 202, such as via port 266 of SPT 204. This is shown at blocks 305 and 310 of method 300 in FIG. 3. In one example, sample preparation may be performed on a single sample by device 200. However, in other examples, it may be more efficient to combine multiple samples (e.g., multiple SPTs, each with a different end user patient sample) in sample prep cartridge 202. Labels may be applied to sample prep cartridge 202 and/or SPTs 204 and well cartridge 206, such as identifying samples and linking samples to an end user patient.

[0046] A user (e.g., lab technician) may interact with prep device 200 and/or scanner module 246. Sample carriage 212 may be raised to receive sample prep cartridge 202 (and a door of a housing of prep device 200 be open to receive sample prep cartridge 202). This is shown at block 315 of method 300 in FIG. 3. Likewise, well carriage 214 may move out of a housing of prep device 200 to receive well cartridge 206. The user may interact with prep device 200 and both sample carriage 212 and well carriage 214 may retract within device 200 (and doors of the housing may close). Sample carriage 212 may cause sample prep cartridge 202 to move to different locations within prep device 200 to enable the different modules to interact with sample prep cartridge. Movement of sample carriage 212 may be enabled by sample carriage drive module 240. Likewise, movement of well carriage 214 is to be enabled by well carriage drive module 242 and well tray module 238. Meanwhile, cooling module 234, heater module 226, and/or exhaust module 228 may operate to achieve a desired pressurization, humidity level and/or temperature within prep device 200, such as based on readings made by sensor module 236.

[0047] Mixer module 224 may interact with sample prep cartridge 202. For instance, mixer module 224 may cause agitator 262 of SPTs 204 to mix the samples with a reagent. Heater module 226 may be used to apply heat to the biological sample and reagent mixture. In one example, heater module 226 may cause the biological sample to be heated to 80°C. Sensor module 236 may be used to confirm temperature. However, in other cases, such as based on empirical evidence, the system may automate application of heat for a set period of time found to reach the desired temperature (e.g., based on external temperature characteristics, barometric pressure, humidity measurements, etc.). The mixing and heating is illustrated at block 320 of method 300 in FIG. 3. Heater module 226 may retract and cease application of heat to the biological sample to allow cooling, such as to a desired temperature (e.g., 56°C in one example). Further, convective cooling from cooling module 234 may be used to reduce to the desired temperature. It may be desirable for mixer module 224 to continue to cause agitator 262 to agitate the biological sample during the heating and cooling phases. This cooling and mixing is shown at block 325 of method 300 in FIG. 3.

[0048] A pocket actuation module 232 may actuate an actuatable pocket 270 containing a wash buffer to enable purification of the biological sample. In one example, pocket actuation module 232 may include an array of posts or actuation tips to interact with actuatable pockets 270 and may actuate a number of times (e.g., in one example, a first press may be used followed by a second press by the actuation tips of pocket actuation module 232 to empty a desired amount of wash buffer into SPTs 204). Operation of pocket actuation module 232 is shown at block 330 in method 300 in FIG. 3. Plunger 260 of SPTs 204 may be actuated to release the biological sample into the primary fluid passage of SPTs 204. In one example, plunger 260 may be actuated by a structure of mixer module 224. Plunging using mixer module 224 is shown at block 335 in FIG. 3. Subsequently, magnetic module 230 may interact with sample prep cartridge 202, such as to cause the magnetic particulate substrate (e.g., paramagnetic beads) within the biological sample to move through the wash buffer, as shown at block 340 in FIG. 3. In some examples, the magnetic particulate substrate, such as paramagnetic beads, will be bound to the biological component of interest from the biological sample (such as nucleic acid), and the magnetic particulate substrate enables extraction and separation from the biological fluid. Such magnetic particulate substrate might be separated from the sample and moved towards an output by an externally generated (para)magnetic force that may be generated by magnetic module 230.

[0049] In the example of a PCR or PCA test, pocket actuation module 232 may interact with another actuatable pocket 270 of SPTs 204 to cause a release of a master mix. Similar to the release of the wash buffer, pocket actuation module 232 may interact multiple times with the actuatable pockets 270 containing the master mix (e.g., a mixture containing precursors and enzymes) to empty the contents into SPTs 204. This operation of pocket actuation module 232 is shown at block 345 in FIG. 3. In some examples, pocket actuation module 232 may again interact with yet another actuatable pocket 270 of SPTs 204 to release a barrier substance to cause release of but a desired substance into wells (e.g., to cause the wash barrier to remain suspended while releasing but the purified sample. In some examples, the desired substances would be the magnetic particulate substrate that is bound to the biological component of interest from the biological sample. In some other examples, the desired substances would be paramagnetic beads bound to nucleic acid (such as DNA or RNA). This desired substance is referred to alternatively herein as a “prepared sample,” referring to the biological component of interest (e.g., nucleic acid) bound to a magnetic particulate substrate, such as paramagnetic beads. Block 345 of FIG. 3 is intended to also illustrate this functionality.

[0050] Next, the SPTs 204 will be prepared to dispense prepared samples. This includes uncapping needle 272, as illustrated at block 350 in FIG. 3. Pocket actuation module 232 may interact with a final actuatable pocket 270 of SPT s 204 to push a controlled volume containing the prepared sample into out of SPT 204 via needle 272 and into a well of well cartridge 206. In this pocket actuation, a single actuator tip of pocket actuation module 232 may interact with but a single actuatable pocket of a single SPT 204 at a time because, as was noted above, each SPT 204 is not aligned with a corresponding well of well cartridge 206 at a same time. This is shown at block 355 of FIG. 3. Then, as shown at block 360 of FIG. 3, needle 272 may be resealed. Subsequently, well carriage 214 may be moved to align subsequent wells of well cartridge 206 with subsequent SPTs 204 of sample prep cartridge 202. A single actuation tip of pocket actuation module 232 may actuate corresponding actuatable pockets 270 to fill each well of well cartridge 206. This is shown at block 365 of FIG. 3. At block 365, a determination is made as to whether the dispense stage has been completed for all wells across well cartridge 206. If not, method 300 loops back up and performs the functionality of blocks 350, 355, and 360 until all wells have been filled.

[0051] Once each well of well cartridge 206 has received a prepared sample, well carriage 214 may be moved outside of device 200 and sample prep cartridge 202 may also be moved outside of device 200. Additionally, a cover may be placed over well cartridge 206 (e.g., as shown at block 370). Sample prep cartridge 202 is disposed of and well cartridge 206 may be arranged over the top of well magnetic module 248 to cause the magnetic particulate substrate (e.g., paramagnetic beads) of the fluid sample to settle to the bottom of the wells of well cartridge 206. Well cartridge 206 may be inserted into analysis device 252 and desired analytical tests performed. This is shown at block 375 of FIG. 3. The results of the tests may be communicated automatically, such as via lab information system 258, cloud information system 256, and/or mobile application 254. It is noted that such operation is enabled by execution of instructions (e.g., such as may be stored with, fetched from, etc.) in CRM 276 by controller 274.

[0052] With the foregoing in mind, an example method (e.g., method 300) of preparing a sample includes sensing a humidity, a temperature, or a combination thereof within a housing of the device using a sensor module (e.g., sensor module 236) of the device.

[0053] In another example, an example computer-readable medium (e.g., CRM 276) includes instructions that when executed by a controller (e.g., controller 274) of a device (e.g., prep device 200) are to cause a carriage (e.g., sample carriage 212) of the device to move a sample preparation cartridge (e.g., sample prep cartridge 202) into a housing of the device. The instructions also are to cause a mixer module (e.g., mixer module 224) of the device to agitate liquids within the sample preparation cartridge. The instructions are also to cause a heater module (e.g., heater module 226) of the device to heat the to be agitated liquids. The instructions are also to cause a pocket actuation module (e.g., pocket actuation module 232) of the device to activate an actuatable pocket (e.g., pocket 270) of the sample preparation cartridge. The instructions are also to cause a magnetic module (e.g., magnetic module 230) of the device to engender movement of paramagnetic beads within the sample preparation cartridge. And the instructions are also to cause the pocket actuation module to activate an actuatable pocket to dispense a prepared sample into a well of a well cartridge (e.g., well cartridge 206) arranged at a non-orthogonal angle with respect to the sample preparation cartridge (see, e.g., FIGS. 1 D and 1 E). FIG. 4 is a block diagram illustrating the relationship between the controller and CRM of the preparation device. Controller 474 refers to a processing structure, similar in structure and operation to controller 274 in FIG. 2B. And CRM 476 refers to a computer readable storage medium, similar in structure and operation to CRM 276 in FIG. 2B. FIG. 4 includes a number of sample instructions, such as instructions 478a for causing pressurization within a housing of the preparation device. It is to be understood that these instructions are merely provided by way of example, and are not intended to be a closed set.

[0055] By way of example, pressurization instructions 478a, when executed by controller 474 may cause a cooling module (e.g., cooling module 234 of FIG. 2B) and an exhaust module (e.g., exhaust module 228 of FIG. 2B) to operate to achieve a desired pressurization, such as compared with a pressure level external to the prep device. This may include reception of data from a sensor module (e.g., sensor module 236 of FIG. 2B), operation of fans and vents of the cooling and exhaust modules, and the like.

[0056] Carriage movement instructions 478b, upon execution by controller 474, may cause operation of a sample carriage and a well carriage (e.g., sample carriage 212 and well carriage 214 of FIG. 2B). For instance, upon execution of instructions 478b by controller 474, a sample carriage drive module (e.g., sample carriage drive module 240 in FIG. 2B) may the cause sample carriage to move up and down along a guide, such as by motors or other actuators. Likewise, the well carriage drive module may cause movement of a well tray module (e.g., well tray module 238), such as pivoting (as shown in FIG. 1 D) into and out of a housing of the device and causing movement of the well carriage (e.g., such as along a guide as shown in FIGS. 1C and 1 E). It is noted that carriage movement instructions 478b may also be executed in conjunction with other instructions (e.g., mixer module operation instructions 478c, heater module operation instructions 478d, magnetic module operation instructions 478e, and pocket actuation module operation instructions 478f) such as to facilitate operation of respective modules.

[0057] Mixer module operation instructions 478c may cause operation of a mixer module (e.g., mixer module 224 in FIG. 2B) such as causing interaction with an agitator and a plunger of an SPT (e.g., agitator 262 and plunger 260 of SPT 204 of FIG. 2B) as described, above. [0058] Heater module operation instructions 478d, upon execution by controller 474, may cause operation of the heater module (e.g., heater module 226 in FIG. 2B). In one example, the heater module may include multiple heater components (e.g., a front side heater and a back side heater) and upon execution by controller 474, motors or other actuators may cause the heater components to move into proximity to the sample prep cartridge and retract therefrom. Additionally, in response to execution of instructions by controller 474, heating elements of the heater module may heat up to enable heating of the sample prep cartridge (e.g., via radiant heating, conductive heating, etc.).

[0059] Magnetic module operation instructions 478e, upon execution by controller 474, may cause magnets of the magnetic module (e.g., magnetic module 230) to move with respect to the sample prep cartridge and its SPTs. Example movement includes moving into proximity with the sample prep cartridge and moving away from the sample prep cartridge. Other movement can include moving side to side in proximity to the sample prep cartridge, such as to attract magnetic particulate substrate (e.g., paramagnetic beads) within the SPTs to move in a side-to-side motion with respect to the sides of the SPTs. Similarly, in some cases, the sample carriage may cause the sample prep cartridge to move in an upward direction while the magnetic module is in proximity to the SPTs to cause the magnetic particulate substrate (e.g., paramagnetic beads) to travel downwards through the SPTs (e.g., towards a needle thereof).

[0060] Pocket actuation module operation instructions 478f, upon execution by controller 474, causes structural elements of a pocket actuation module (e.g., pocket actuation module 232 in FIG. 2) to move towards and actuate actuatable pockets of SPTs. For instance, in the example of an actuatable pocket with a flexible film structure surrounding a reservoir, application of pressure by an actuation tip of the pocket actuation module may cause pressure to exceed a threshold and break an internal barrier of the actuatable pocket thus causing the contents of the pocket to enter a primary fluid passage of the SPT. The contents of the actuatable pockets may include reagents, wash liquids, barrier materials, air, and other such compositions to enable preparation of a sample. In one example, the pocket actuation module may have multiple components. A first component may include an array of actuation tips such that all corresponding actuatable pockets of an array of SPTs are all actuated concurrently (or approximately concurrently). Meanwhile, a second component of the pocket actuation module may include a single actuation tip to actuate but a single actuatable pocket of a single SPT at a time, such as to dispense a prepared sample one SPT at a time.

[0061] It is noted that other instructions are included on CRM, such as instructions to enable operation of III 244. Therefore, the foregoing is provided to illustrate possible operation enabled by controller 474 and CRM 476. Indeed, the following discussion and figures illustrate an example of sample preparation for a COVID-19 PCR test. The discussion will span multiple figures and reference to relevant figures will be noted in the description. It is to be understood that operation of the preparation device is controlled by the execution of instructions by a controller, such as controller 474.

[0062] With the foregoing in mind, an example device (e.g., prep device 200 of

FIG. 2B) includes a controller (e.g., controller 474) to execute instructions (e.g., instructions 478b and 478c) to cause a first carriage (e.g., sample carriage 212 of FIG. 2B) to move to enable interaction between sample preparation cartridge (e.g., sample prep cartridge 202 in FIG. 2B) and a mixer module (e.g., mixer module 224 of FIG. 2B). The execution of instructions is also to cause the mixer module to interact with the sample preparation cartridge and mix a liquid within the sample preparation cartridge.

[0063] In another example, the controller is further to execute instructions (e.g., instructions 478d) to cause a heater module (e.g., heater module 226 of FIG. 2B) to apply heat to a liquid within the sample preparation cartridge.

[0064] In another example, the controller is further to execute instructions (e.g., instructions 478b and 478e) to cause the first carriage to move to enable interaction between the sample preparation cartridge and a magnetic module (e.g., magnetic module 230 of FIG. 2B). Execution of the instructions is also to cause the magnetic module to interact with the sample preparation cartridge to cause movement of paramagnetic beads within the sample preparation cartridge. [0065] In another example, the controller is further to execute instructions (e.g., instructions 478b and 478f) to cause the first carriage to move to enable interaction between the sample preparation cartridge and a pocket actuation module (e.g., pocket actuation module 232 of FIG. 2B). The execution of instructions is also to cause the pocket actuation module to interact with the sample preparation cartridge to actuate an actuatable pocket (e.g., actuatable pocket 270 of FIG. 2B) on the sample preparation cartridge.

[0066] In another example, the execution of instructions (e.g., instructions 478a) by the controller is to cause a cooling module (e.g., cooling module 234 of FIG. 2B), and an exhaust module (e.g., exhaust module 228 of FIG. 2B) to create a pressurization within a housing of the device that is lower than a pressure level of the environment surrounding the housing. In another example, the pressurization within the housing is based on an imbalance between air entering the housing via the input module and air exiting the housing via the exhaust module.

[0067] FIG. 5 illustrates an example sample preparation cartridge 502. Sample preparation cartridge 502 includes an array of sample preparation tubes (SPTs) 504 (of which one is labeled). Each SPT 504 includes a port 566 via which samples are to be inserted into SPT 504. In some cases, port 566 may include an opening and closing cap capable of sealing shut. Port 566 may lead to a portion of SPT 504 that includes a reagent and/or magnetic particulate substrate (e.g., paramagnetic beads). Though not visible in FIG. 5, each SPT may include a plunger and an agitator (e.g., plunger 260 and agitator 262 shown in FIG. 2B) to enable mixing of a biological sample and piercing a barrier intended to keep the biological sample in a particular portion of SPT 504 during a mixing, heating, and cooling process.

[0068] Each SPT 504 also includes a number of actuatable pockets 570a- 570d. As noted, this example number of actuatable pockets 570a-570d is relevant for the particular example preparation process, and other numbers of actuatable pockets 570a-570d may be used in different implementations and for different tests. In this example, actuatable pocket 570a may include a pocket of air designed to expel a controlled amount of prepared sample into a well. Actuatable pocket 570b may include a wash buffer. Actuatable pocket 570c may include a barrier material (e.g., a material selected based on, among other things, to mitigate against collapse of the fluid column during dispense operations; one example may include a grease barrier having a high viscosity). And actuatable pocket 570d may include a PCR master mix, such as including enzymes and precursors. Each actuatable pocket 570a-570d may form a reservoir including an outer surface of a higher strength than an inner partition, which separates the contents of the reservoir from the primary fluid passage of SPT 504. As noted, above, a pocket actuation actuator may move its actuating tip into contact with actuatable pockets 570a-570d and exert a pressure that is large enough to cause the inner partition to break and release the contents of the pocket. In some implementations, actuatable pockets 570a-570d may include a multi-part actuation structure. For instance, a smaller pocket may be used to open a channel between each actuatable pocket 570a-570d and the primary fluid passage of SPT 504, and then the larger bubble of actuatable pocket 570a-570d may be subsequently actuated one, two, or other number of times to dispense a desired amount of the contents into the tube of SPT 504.

[0069] Finally, FIG. 5 shows an approximate portion of SPT 504 containing a needle 572, which refers to a portion of SPTs 504 to facilitate dispensing a prepared sample. In some implementations, such as illustrated in FIG. 5, needle 572 may include a cap structure, which may be opened and closed, such as by a module of a preparation device.

[0070] As discussed above, a cartridge, such as sample prep cartridge 502, may be desirable such as being usable to fill a well cartridge without being tied to a proprietary analysis system. The benefits of such a cartridge shall be more clear in view of the discussion referring to the remaining figures and the non-limiting example of a PCR test.

[0071] FIG. 6 is an exploded view of a number of components and modules of a preparation device, such as prep device 200 in FIG. 2B. FIG. 6 illustrates a mixer module 624, a heater module 626, a magnetic module 648, a pocket actuation module 632, a sample prep cartridge carriage module 621 , and a well tray module 638, which can all be arranged within a chassis 680 of a preparation device. Each of these modules were discussed previously, however, a few features are noted here to provide context for previous and subsequent discussion. And as noted above, each module may operate in response to execution of instructions by a processor, such as described in reference to FIG. 4.

[0072] Example mixer module 624 includes a number of mixers 686, which are structural protrusions designed to interface with a plunger and an agitator of an SPT. Each mixer 686 may be connected to a motor or other actuator to cause rotation thereof. Additionally, mixer module 626 may be capable of moving towards and away from sample prep cartridge carriage module 621 , such as using motors.

[0073] Sample prep cartridge carriage module 621 includes a number of carriage guides 611 upon which carriage 612 may run. This example includes a motor and post with teeth to engage teeth of a sprocket. However, other forms of causing movement of carriage 612 are also contemplated by the present disclosure. [0074] Well tray module 638 includes a pivot point 620 (see, e.g., discussion of FIG. 1 D) to enable a tray portion to rotate between two states: a state in which well tray module 638 is entirely within a housing of the device, and a state in which well tray module 638 extends partially beyond an opening in the housing to receive well cartridge 606 into a well carriage 614 and also to present well cartridge 606 to the user after prepared samples have been dispensed therein. Well tray module 638 also includes horizontal carriage guides 641 (of which one is labeled) upon which well carriage 614 may travel similar to the movement of sample preparation carriage 612, such as by motors or other actuators.

[0075] Heater module 626 includes a front portion and a rear portion. For instance, the rear portion is angled to show heating elements 684, which may include resistive heaters that generate heat when electrical current is pulsed through the heating elements. The front portion also includes heating elements, but they are not visible from the angle at which heater module 626 is arranged. Carriage module 621 will be arranged between the rear and front portions of heater module 626 such that a rear portion of sample prep cartridge 602 will be exposed to heat from the rear portion of heater module 626 (e.g., by heating elements 684) and a front portion of sample prep cartridge 602 will be exposed to heat from the front portion of heater module 626 (e.g., and corresponding heating elements). An actuator device will be used to move the front and rear portions of heater module 626 towards and away from carriage module 621 . The view of heater module 626 also shows an exhaust vent 682, which may have a fluid connection to a fan or like mechanism to pull air and heat away from heater module 626 and push the air out of the housing. Exhaust vent 682 may be part of an exhaust module 682, which may also include, among other things, motors and filters.

[0076] Magnetic module 648 includes a motor or actuator of some form to cause magnets 688 to move into proximity of carriage module 621 and to retract. As illustrated, and similar to front and rear portions of heater module 626, magnetic module 648 and pocket actuation module 632 are to be arranged on opposing sides of carriage 612 and sample prep cartridge 602 such that carriage 612 may move in an up-and-down motion with respect to magnetic module 648 and pocket actuation module 632.

[0077] Pocket actuation module 632 also includes a motor or actuator of some type to cause actuator tips 690 to move into proximity of and actuate actuatable pockets of sample prep cartridge 602 and to retract. In one example, pocket actuation module 632 includes multiple portions: in a first portion, an array of actuator tips concurrently actuates all corresponding actuatable pockets of sample prep cartridge 602 (e.g., each actuatable pocket 570a of each SPT 504, as illustrated in FIG. 5). In another portion, a single actuator tip actuates a single actuatable pocket of a single SPT at a time while leaving corresponding actuatable pockets of the remaining SPTs untouched (e.g., actuating only actuatable pocket 570a of a single SPT 504, of FIG. 5 at a time while not interacting with the other actuatable pockets 570a of the other SPTs 504).

[0078] FIGS. 7A and 7B illustrate example methods 700 and 730, respectively, of preparing a sample using a device, such as device 200 from FIG. 2B. In discussing methods 700 and 730, reference will be made to other figures to provide context to the reader. For instance, the description will refer to FIGS. 8A- 80, which provide block diagram side views of an example device 800 at different moments in time. While method 700 illustrates a method of operation at a broader level, such as for a number of different tests and presenting a well cartridge to a sample prep cartridge at a non-orthogonal angle, method 730 provides more description for different example processes that may be performed in the example of preparing a sample for a PCR test and presenting the well cartridge to the sample prep cartridge at a non-orthogonal angle.

[0079] Starting first with example method 700, at block 705, a sample prep cartridge (e.g., sample prep cartridge 802 in FIG. 8A) is received into a carriage (e.g., carriage 812) of a device (e.g., device 800).

[0080] At the illustrated point in time shown by FIG. 8A carriage 814 is shown extending beyond housing 805 of device 800, carriage 814 arranged on a horizontal carriage guide 841.

[0081] Returning to method 700 and FIG. 7A, at block 710 components (e.g., modules of FIG. 8A, and combinations thereof) of the device are to interact with the sample prep cartridge. For instance, FIGS. 8D and 8E show a mixer 886 interacting with the agitators of sample prep cartridge 802 and heater actuators 825a and 825b and heater blocks 884a and 884b moving into proximity with the sample prep cartridge 802, applying heat, and retracting. FIG. 8F shows pocket actuation actuator 833a and pocket actuation tip 890a actuating an actuatable pocket of sample prep cartridge 802. Etc.

[0082] Returning, again, to method 700 and FIG. 7A, at block 715, prepared sample is dispensed into wells of a well cartridge (e.g., well 808 of well cartridge 806 in FIGS. 8L-8N), which is presented to the sample prep cartridge at a non- orthogonal angle (e.g., well cartridge 106 and sample prep cartridge 102 of FIG. 1 E).

[0083] With the foregoing in mind, an example method (e.g., method 700) includes receiving in a device (e.g., device 800), a cartridge (e.g., sample prep cartridge 802) containing sample preparation tubes having a first pitch (see, e.g., FIG. 1A and block 705 of FIG. 7A). The method also includes causing components of the device to interact with the cartridge including between the sample preparation tubes to yield a prepared sample in the sample preparation tubes (see, e.g., block 710). And the method also includes dispensing the prepared samples into wells of a well cartridge having a second pitch by presenting the well cartridge at a non-orthogonal angle with respect to the sample preparation tubes (see, e.g., FIG. 1 E and block 715 in FIG. 7A).

[0084] Moving to method 730 illustrated in FIG. 7B, an example of preparing a sample for an PCR test is illustrated. At block 735, a sample prep cartridge (e.g., sample prep cartridge 802 in FIG. 8A) is received into a carriage (e.g., carriage 812) of a device (e.g., device 800). As shown, sample prep cartridge 802 may include a number of components, such as a port 866, a plunger 860, an agitator 862, a barrier 803 and a sample 864. A number of actuatable pockets 870 are illustrated (of which only one is labeled), and a needle 872 is present and via which prepared sample is to eventually be dispensed. FIG. 8A shows carriage 812 moving up towards a top of housing 805 of device 800 along a carriage guide 811 . This movement of carriage 812 may trigger opening of access door 801 , as illustrated by the corresponding arrow. [0085] At the illustrated point in time, FIG. 8A also shows carriage 814 extending beyond housing 805 of device 800, carriage 814 arranged on a horizontal carriage guide 841 . A well cartridge 806 having a number of wells 808 (of which only one is labeled) is received in carriage 814. Movement of carriage 814 out of housing 805 may also cause access door 819 to open. FIG. 8B shows sample prep cartridge 802 secured within carriage 812 and well cartridge 806 within well carriage 814.

[0086] At block 740 of method 730 in FIG. 7B, the carriage is caused to move. For instance, FIG. 8C shows carriage 812 moving in a downward direction. This motion of carriage 812 back down into housing 805 may cause access door 801 to close. Likewise, FIG. 8C shows carriage 814 moving in a horizontal direction back into housing 805, which may also cause access door 819 to close. Because the next block in method 730 is for the mixer module to interact with the sample prep cartridge, FIG. 8C shows carriage 812 moving below mixer 886. It is noted that because access doors 801 and 819 are closed, exhaust vent 882 and cooler 835 may operate to cause air to be pulled into housing 805 and leave housing 805 at a controlled rate, such as to achieve a desired pressurization level. In one implementation, a fan connected to exhaust vent 882 may run at a higher rate than a fan connected to an inlet of cooler 835, by way of example. FIG. 8C also shows filters 829, which may be used in some implementations, such as to control particles entering and leaving housing 805.

[0087] Thus, in an example, a method of preparation includes opening and closing doors of the housing responsive to movement of the first carriage and the second carriage, as described above with respect to blocks 735 and 740 and FIGS. 8A-8C.

[0088] At block 745, the mixer module (e.g., mixer module 224 of FIG. 2B or mixer module 624 of FIG. 6) is caused to interact with the sample prep cartridge. For example, looking at FIG. 8D, mixer actuator 807 is caused to move mixer 886 into position to interact with SPTs of cartridge 802 and cause agitator 862 to rotate. Meanwhile, as illustrated at block 750, heater actuators 825a and 825b cause heater blocks (e.g., comprising heating elements) 884a and 884b, respectively, to move into proximity of sample 864. In one example, heater blocks 884a and 884b may be brought into contact with portions of sample prep cartridge 802, such as for conductive heating. In other examples, convective heating may be used. FIG. 8D also shows carriage 812 moving up to the appropriate vertical position to enable interactions with the mixer module and the heater module. FIG. 8E shows heater actuators 825a and 825b retracting heater blocks 884a and 884b while continuing to cause agitator 862 to rotate. Further, at this point in time, the sample 864 may be allowed to cool and/or convectively cooled, such as by cooler 835. While FIG. 8E illustrates both heater actuator 825a and 825b retracting, different combinations of heater actuators may retract and/or remain in place, such as to achieve a desired rate of cooling and avoid falling below a temperature threshold. In other cases, there may be a desired thermal profile for sample 864, and as such, in some cases (e.g., in response to readings by a sensor module, such as sensor module 236 of FIG. 2B), the heater module may remain engaged in whole or in part for a longer period of time. [0089] Thus, in an example, a method (e.g., method 730) includes causing a rear heater module (e.g., heater actuator 825a and heater block 884a) of the device to move into proximity of a rear portion of the sample preparation tubes and a front heater module (e.g., heater actuator 825b and heater block 884b) of the device to move into proximity of a front portion of the sample preparation tubes and impart heat to a portion of contents of the sample preparation tubes, such as shown at block 750 and FIG. 8D.

[0090] At block 755, the carriage may be caused to move. FIG. 8F shows carriage 812 lowering to be in proximity to the pocket actuation module, including pocket actuation actuator 833a and pocket actuation tip 890a. Pocket actuation actuator 833a may cause pocket actuation tip 890a to come into contact with an actuatable pocket of cartridge 802, as illustrated at block 760 of FIG. 7B. As described above, actuation of an actuatable pocket may comprise several presses in order to cause a desired amount of the contents of the actuatable pocket to be expelled into the primary fluid passage of the SPT. In this example, this actuation of the actuatable pocket is to cause a wash buffer to be released. FIG. 8F shows wash buffer 861 at the bottom of the SPT.

[0091] At block 765 of method 730, carriage 812 is caused to move again, as shown in FIG. 8G. In this example, movement of carriage 812 results in mixer 886 contacting plunger 860 and breaking barrier 803 such that sample 864 (corresponding to a biological sample) is released down into the primary fluid passage of the SPT. FIG. 8G also shows pocket actuation actuator 833a retracting. [0092] Continued movement of carriage 812 causes carriage 812 to be in proximity to the magnetic module. At block 770 of FIG. 7B, magnetic actuator 831 causes magnets 888 to move into proximity to sample prep cartridge 802. The application of a magnetic field, by magnets 888, to sample 864 will cause magnetic particulate substrate (e.g., paramagnetic beads) in sample 864 to gather and move together. For example, magnetic actuator 831 can cause the magnetic particulate substrate (e.g., paramagnetic beads) to move in different directions (e.g., side to side) and, along with movement of carriage 812, can cause the magnetic particulate substrate (e.g., paramagnetic beads) to move down through wash buffer 861 . FIG. 8I shows the upward movement of carriage 812, such as described at block 775 of method 730, and the movement of magnetic particulate substrate 863 (e.g., paramagnetic beads) down through wash buffer 861.

[0093] Thus, in one example, a method (e.g., method 730) includes causing a magnetic module (e.g., magnetic actuator 831 and magnet 813) of the device to move in proximity of back surfaces and peripheral surfaces of the sample preparation tubes (e.g., block 770 and FIGS. 8H and 8I).

[0094] FIG. 8J shows carriage 812 moving back downward while magnetic actuator causes magnets 888 to retract. Additionally, and as shown at block 780 of FIG. 7B, the pocket actuation module may be caused to interact with actuatable pockets of sample prep cartridge, such as shown in FIG. 8J. Indeed, pocket actuation actuator 833a may cause pocket actuation tip 890a to actuate an actuatable pocket. In this example, the actuatable pocket corresponds to a master mix 865, which is shown released just above magnetic particulate substrate 863 (e.g., paramagnetic beads).

[0095] FIG. 8K shows yet another interaction between the pocket actuation module and cartridge 802, as also shown at block 785 of FIG. 7B. In this example, pocket actuation actuator 833a causes pocket actuation tip 890a to actuate yet another actuatable pocket. In this case, the actuatable pocket contains a grease barrier 867, which may be used to keep previously used liquids, such as the wash buffer, out of the needle, among other things. FIG. 8K shows the stack comprising grease barrier 867, master mix 865, and then magnetic particulate substrate 863 (e.g., paramagnetic beads).

[0096] Subsequently, the carriage 812 may move again, such as to move the needle of the SPT into proximity with a well 808 of well cartridge 806. At this point in the process, and as illustrated at block 790 of FIG. 7B and FIG. 8L, pocket actuator module may again interact with an actuatable pocket of cartridge 802. In this case, rather than actuating all corresponding actuatable pockets concurrently, actuatable pockets are actuated one at a time, to enable dispensing of a prepared sample 869 into wells of well cartridge 806 one at a time (see, e.g., FIG. 1 E). In this case, such behavior is caused by pocket actuation actuator 833b causing movement of pocket actuator tip 890b to actuate an actuatable pocket corresponding to a fluid to cause dispensing of the prepared sample. For instance, the actuatable pocket may include air or some other gas sufficient to dispense prepared sample 869, but not the wash buffer or grease barrier. This process (and block 790) may be repeated for each SPT of cartridge 802 and cause prepared sample 869 to be dispensed into successive wells of well cartridge 806. This may mean that carriage 812 is to retract, then well carriage 814 is to move, and then carriage 812 is to redescend and dispense until all of the wells have been filled with prepared sample 869, as shown in FIG. 8N.

[0097] Thus, in one example, a method (e.g., method 730) includes causing a multiple pocket actuation module (e.g., pocket actuation actuator 833a and pocket actuation tip 890a) of the device to concurrently actuate corresponding actuatable pockets of the sample preparation tubes (e.g., block 785 and FIG. 8K). The method also includes causing a single pocket actuation module (e.g., pocket actuation actuator 833b and pocket actuation tip 890b) of the device to activate an actuatable pocket of one sample preparation tube of the sample preparation tubes without activating corresponding actuatable pockets of remaining sample preparation tubes of the sample preparation tubes (e.g., block 790 and FIG. 8L). [0098] Block 795 of FIG. 7B shows movement of well carriage module to cause well cartridge 808 to be presented to the user, as shown in FIG. 80, such that prepared samples 869 may be analyzed. Similarly, carriage 812 may move upward to eject (and allow for the disposal of) cartridge 802.

[0099] As should be apparent from the foregoing, there may be a desire to present a well cartridge having a first pitch at a non-orthogonal angle to a sample prep cartridge having a second pitch. As described, such an approach may be beneficial, such as enabling the use of an intermediate sample preparation cartridge that is independent of a particular proprietary well cartridge, and the reduction of manual intervention in the sample preparation process.

[00100] The present description uses direction terms, such as “over” are understood in a similar manner as the terms “up,” “down,” “top,” “bottom,” “left,” “right,” “side-to-side,” and so on. These terms may be used to facilitate discussion, but are not intended to necessarily restrict scope of claimed subject matter. For example, the term “over,” as an example, is not meant to suggest that claim scope is limited to only situations in which an example is right side up, such as in comparison with the example being upside down, for example. Thus, if an object, as an example, is within applicable claim scope in a particular orientation, such as upside down, as one example, likewise, it is intended that the latter also be interpreted to be included within applicable claim scope in another orientation, such as right side up, again, as an example, and vice-versa, even if applicable literal claim language has the potential to be interpreted otherwise. Of course, again, as always has been the case in the specification of a patent application, particular context of description and/or usage provides helpful guidance regarding reasonable inferences to be drawn.

[00101] Unless otherwise indicated, in the context of the present disclosure, the term “or” if used to associate a list, such as A, B, or C, is intended to mean A, B, and C, here used in the inclusive sense, as well as A, B, or C, here used in the exclusive sense. With this understanding, “and” is used in the inclusive sense and intended to mean A, B, and C; whereas “and/or” can be used in an abundance of caution to make clear that all of the foregoing meanings are intended, although such usage is not required. In addition, terms “at least,” “one or more,” and/or similar terms is used to describe any feature, structure, characteristic, and/or the like in the singular, “and/or” is also used to describe a plurality and/or some other combination of features, structures, characteristics, and/or the like. Failure to use such terms does not indicate an intention to recite a closed set. Furthermore, the terms “first,” “second”’ “third,” and the like are used to distinguish different aspects, such as different components, as one example, rather than supplying a numerical limit or suggesting a particular order, unless expressly indicated otherwise.

[00102] In the preceding description, various aspects of claimed subject matter have been described. For purposes of explanation, specifics, such as amounts, systems and/or configurations, as examples, were set forth. In other instances, well-known features were omitted and/or simplified so as not to obscure claimed subject matter. While certain features have been illustrated and/or described herein, many modifications, substitutions, changes and/or equivalents will now occur to those skilled in the art. It is, therefore, to be understood that the appended claims are intended to cover all modifications and/or changes as fall within claimed subject matter.

Claims

CLAIMS What is claimed is:

1. A device to receive a sample preparation cartridge, the device comprising: a first carriage to enable movement of the sample preparation cartridge in a first direction; a second carriage to enable movement of a well cartridge in a second direction; and a number of modules to interact with the sample preparation cartridge, the number of modules comprising: a mixer module, a temperature control module, a magnetic module, a pocket actuation module, or a combination thereof; wherein the first carriage and the second carriage are arranged with respect to one another such that the well cartridge is to be presented to the sample preparation cartridge at a non-orthogonal angle.

2. The device of claim 1 further comprising: a controller; and a cooling module and an exhaust module; wherein the controller is to execute instructions to cause the cooling module and the exhaust module to create a pressurization within a housing of the device that is lower than a pressure level of the environment surrounding the housing.

3. The device of claim 2, wherein the pressurization within the housing is based on an imbalance between air entering the housing via the cooling module and air exiting the housing via the exhaust module.

4. The device of claim 1 further comprising: a controller to execute instructions to cause: the first carriage to move to enable interaction between the sample preparation cartridge and the mixer module; and

48 the mixer module to interact with the sample preparation cartridge and mix a liquid within the sample preparation cartridge.

5. The device of claim 4, wherein the controller is further to execute instructions to cause the heater module to apply heat to a liquid within the sample preparation cartridge.

6. The device of claim 5, wherein the controller is further to execute instructions to cause: the first carriage to move to enable interaction between the sample preparation cartridge and the magnetic module; and the magnetic module to interact with the sample preparation cartridge to cause movement of paramagnetic beads within the sample preparation cartridge.

7. The device of claim 6, wherein the controller is further to execute instructions to cause: the first carriage to move to enable interaction between the sample preparation cartridge and the pocket actuation module; and the pocket actuation module to interact with the sample preparation cartridge to actuate an actuatable pocket on the sample preparation cartridge.

8. A method comprising: receiving in a device, a cartridge containing sample preparation tubes having a first pitch; causing components of the device to interact with the cartridge between the sample preparation tubes to yield a prepared sample in the sample preparation tubes; and dispensing the prepared samples into wells of a well cartridge having a second pitch by presenting the well cartridge at a non-orthogonal angle with respect to the sample preparation tubes.

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9. The method of claim 8 further comprising: causing a rear heater module of the device to move into proximity of a rear portion of the sample preparation tubes and a front heater module of the device to move into proximity of a front portion of the sample preparation tubes and impart heat to a portion of contents of the sample preparation tubes.

10. The method of claim 8 further comprising: causing a multiple pocket actuation module of the device to concurrently actuate corresponding actuatable pockets of the sample preparation tubes; and causing a single pocket actuation module of the device to activate an actuatable pocket of one sample preparation tube of the sample preparation tubes without activating corresponding actuatable pockets of remaining sample preparation tubes of the sample preparation tubes.

11 . The method of claim 8 further comprising: causing a first carriage of the device conveying the sample preparation cartridge containing the sample preparation tubes to move in a first direction; and causing a second carriage of the device conveying the well cartridge to pivot from a load position partially external to a housing of the device into a concealed position within the housing to present the well cartridge at the non-orthogonal angle with respect to the sample preparation tubes.

12. The method of claim 8 further comprising sensing a humidity, a temperature, or a combination thereof within a housing of the device using a sensor module of the device.

13. The method of claim 8 further com prising causing a magnetic module of the device to move in proximity of back surfaces and peripheral surfaces of the sample preparation tubes.

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14. A computer-readable medium comprising instructions that when executed by a controller of a device are to cause: a carriage of the device to move a sample preparation cartridge into a housing of the device; a mixer module of the device to agitate liquids within the sample preparation cartridge; a heater module of the device to heat the to be agitated liquids; a pocket actuation module of the device to activate an actuatable pocket of the sample preparation cartridge; a magnetic module of the device to engender movement of paramagnetic beads within the sample preparation cartridge; and the pocket actuation module to activate an actuatable pocket to dispense a prepared sample into a well of a well cartridge arranged at a non-orthogonal angle with respect to the sample preparation cartridge.

15. The computer-readable medium of claim 14 further comprising instructions that when executed by the controller are to cause: doors of the housing to open and close in response to movement of the first carriage and the second carriage.

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