CN117813515A - System and related manifold assembly - Google Patents

Abstract

Systems and related manifold assemblies are disclosed. According to one implementation, an apparatus includes or includes a cartridge assembly of a aspirator manifold assembly that includes or has a cartridge housing, one or more aspirator tubes, one or more aspirator couplings, and one or more biasing elements. The one or more extractor tubes include or have a proximal end and a distal end. The one or more aspirator couplings are movably coupled to the cartridge housing, a proximal end of the aspirator tube is coupled to the aspirator coupling. The one or more biasing elements bias the one or more aspirator couplings. The one or more biasing elements allow relative movement between the extractor tube and the cartridge housing.

Description

System and related manifold assembly

Related patent application

The present application claims the benefit and priority of U.S. provisional patent application No. 63/273,608, filed on 29 a 10 month of 2021, and U.S. provisional patent application No. 63/344,872, filed on 23 a 5 month of 2022, the contents of each of these provisional patent applications being incorporated herein by reference in their entirety for all purposes.

Background

The sequencing platform may include valves and pumps. Valves and pumps may be used to perform various fluid operations.

Disclosure of Invention

According to a first implementation, a device includes or comprises a reagent reservoir receptacle, a sample cartridge receptacle, a reagent aspirator manifold assembly, an actuator, and a sample aspirator manifold assembly. The reagent reservoir receptacle is for receiving a reagent reservoir and the sample cartridge receptacle is for receiving a sample cartridge. The reagent aspirator manifold assembly includes or has a first end and a second end, and includes or contains one or more reagent aspirators. The actuator is coupled to the first end of the reagent aspirator manifold assembly to move the reagent aspirator manifold assembly relative to the reagent reservoir receptacle, and the sample aspirator manifold assembly includes or has one or more sample aspirators. The second end of the reagent aspirator manifold assembly engages the sample aspirator manifold assembly and moves the one or more sample aspirators toward the sample cartridge receptacle in response to the actuator moving the reagent aspirator manifold assembly toward the reagent reservoir receptacle.

According to a second implementation, an apparatus includes or includes a cartridge assembly of a aspirator manifold assembly that includes or has a cartridge housing, one or more aspirator tubes, one or more aspirator couplings, and one or more biasing elements. The one or more extractor tubes include or have a proximal end and a distal end. The one or more aspirator couplings are movably coupled to the cartridge housing, a proximal end of the aspirator tube is coupled to the aspirator coupling. The one or more biasing elements bias the one or more extractor couplings and allow relative movement between the extractor tube and the cartridge housing.

According to a third implementation, an apparatus includes or includes a sample cartridge including or having a housing, one or more sample tubes movably coupled to the housing, and a biasing element biasing the one or more sample tubes.

According to a fourth implementation, a method comprises or comprises: the reagent aspirator manifold assembly is moved toward the reagent reservoir receptacle. The reagent aspirator manifold assembly includes or has a first end and a second end, and includes or contains one or more reagent aspirators. The method further comprises or comprises: in response to moving the reagent aspirator manifold assembly toward the reagent reservoir receptacle, engaging the second end of the reagent aspirator manifold assembly with a sample aspirator manifold assembly comprising or having a sample aspirator and moving the sample aspirator toward a sample cartridge receptacle.

According to a fifth implementation, an apparatus includes or includes an extractor manifold assembly having a base, a bracket, a vertical guide, and a processor. The base carries a first sensor and a second sensor vertically spaced apart from the first sensor. The bracket carries a suction and a first flag and a second flag defining an aperture. The vertical guide couples the base and the bracket. The processor is to identify that the extractor manifold assembly is in a first position based on the first sensor sensing the first flag and not sensing the aperture, and the processor is to identify that the extractor manifold assembly is in a second position based on the second sensor sequentially sensing the second flag and then sensing the aperture.

According to a sixth implementation, a method comprises or comprises: the first sensor that identifies the aspirator manifold assembly is in a closed state. The aspirator manifold assembly has a base carrying the first sensor and a second sensor vertically spaced apart from the first sensor and a bracket carrying an aspirator. The method comprises or comprises the following steps: determining that the aspirator manifold assembly is in a first position based on the first sensor being in the closed state; moving the carriage toward a second position; and identifying that the second sensor of the aspirator manifold assembly is in a closed state. The method comprises or comprises the following steps: moving the carriage toward the second position a threshold distance; identifying that the second sensor of the aspirator manifold assembly is in an open state; and determining that the aspirator manifold assembly is in the second position based on the second sensor being in the closed state sequentially and then in the open state after the bracket has moved the threshold distance.

Further in accordance with the foregoing first, second, third, fourth, fifth, and/or sixth implementations, an apparatus and/or method may further comprise or comprise any one or more of:

According to one implementation, the device further comprises or comprises a biasing element that couples the reagent aspirator manifold assembly and the sample aspirator manifold assembly.

According to another embodiment, the biasing element is a spring.

According to another implementation, the second end of the reagent aspirator manifold assembly includes or has lips, and the sample aspirator manifold assembly includes or has lips that engage when the second end of the reagent aspirator manifold assembly engages the sample aspirator manifold assembly and moves the one or more sample aspirators toward the sample cartridge receptacle.

According to another embodiment, the apparatus further comprises or comprises: a flow cell receptacle for receiving a flow cell; and a sample fluid line coupled to each sample aspirator and fluidly coupled to the flow cell.

According to another implementation, the reagent reservoir receptacle includes or has a surface engageable by the sample aspirator manifold assembly.

According to another embodiment, the apparatus further comprises or comprises: a platform comprising or having the surface.

According to another implementation, the sample aspirator manifold assembly includes or comprises a base, a bracket, and a vertical guide. The bracket includes or has a first side and a second side. The second side includes or comprises the lip and is operatively coupled to the second end of the reagent aspirator manifold assembly. The vertical guide couples the base and the first side of the bracket.

According to another implementation, the device includes or includes a guide coupled to the base and defining one or more apertures corresponding to the one or more sample aspirators, and the one or more sample aspirators pass through the one or more apertures.

According to another implementation, the apparatus includes or includes a horizontal guide that couples the base and the guide.

According to another implementation, the apparatus includes or includes a lead screw assembly coupled to the base and the guide.

According to another implementation, the lead screw assembly includes or includes a lead screw carried by the base and a lead nut carried by the guide.

According to another implementation, the device includes or contains a cartridge assembly that carries the one or more sample aspirators and is coupled to the carrier.

According to another implementation, the cartridge housing defines a cartridge cavity, and the one or more aspirator couplings are disposed within the cartridge cavity.

According to another implementation, the one or more extractor tubes comprise a plurality of extractor tubes, and the one or more extractor couplings comprise a plurality of extractor couplings.

According to another implementation, each aspirator coupling includes or has a corresponding biasing element.

According to another implementation, each aspirator coupling includes or contains a spring seat, and the one or more biasing elements include or contain one or more springs positioned between each spring seat and the cartridge housing.

According to another implementation, the extractor coupling and the corresponding extractor tube are independently movable.

According to another implementation, the device includes or has a guide plate coupled to the cartridge housing and defining one or more slots. Each aspirator coupling includes or has a protrusion movable within a corresponding slot.

According to another implementation, each slot has opposing stops engageable by a corresponding tab.

According to another implementation, the sample aspirator manifold assembly includes or has a base, a bracket, and a vertical guide. The bracket carries the cartridge assembly and the vertical guide couples the base and the first side of the bracket.

According to another implementation, the device further includes or comprises a guide coupled to the base and defining one or more apertures corresponding to the one or more sample aspirators, and the one or more sample aspirators pass through the one or more apertures.

According to another implementation, the apparatus includes or includes a horizontal guide that couples the base and the guide.

According to another implementation, the device includes or comprises a vertical guide that couples the guide and the cartridge assembly.

According to another implementation, the vertical guide includes or comprises a rod coupled to the guide and an aperture of the cartridge housing that receives the rod.

According to another implementation, the one or more extractor tubes comprise or include a plurality of extractor tubes coupled to the extractor coupling.

According to another implementation, the extractor tube moves together.

According to another implementation, the distal end of each of the extractor tubes comprises or has a first surface positioned at a first angle relative to the longitudinal axis of the corresponding extractor tube and a second surface positioned at a second angle relative to the longitudinal axis of the corresponding extractor tube.

According to another implementation, the apparatus includes or includes a horizontal linear guide that couples the cartridge assembly and the bracket.

According to another implementation, the one or more sample tubes comprise or contain a plurality of sample tubes.

According to another implementation, the sample tubes are independently movable relative to the housing.

According to another implementation, the sample tubes are coupled together and include or have flanges that engage the biasing element.

According to another implementation, the biasing element comprises foam.

According to another implementation, the one or more sample tubes include or have a tapered portion that tapers toward a recessed portion.

According to another embodiment, the method further comprises or comprises: a liquid impermeable barrier covering a sample aperture received within the cartridge receptacle is pierced.

According to another implementation, piercing the liquid impermeable barrier comprises or comprises: the aspirator coupling of the sample aspirator engages the stop and the distal end of the sample aspirator pierces the liquid-impermeable barrier.

According to another embodiment, the method comprises or comprises: the sample aspirator is moved relative to a carriage of the aspirator manifold assembly.

According to another implementation, moving the sample aspirator includes or comprises: the sample aspirator is moved against the biasing force.

According to another implementation, the biasing force is provided by one or more springs.

According to another implementation, the biasing force is provided by the foam.

According to another implementation, there is at least one of the following: 1) The second end of the reagent aspirator manifold assembly has a lip that engages the aspirator manifold assembly when the second end of the reagent aspirator manifold assembly engages the sample aspirator manifold assembly and moves the one or more sample aspirators toward the sample cartridge receptacle, or 2) the sample aspirator manifold assembly has a lip that engages the second end of the reagent aspirator manifold assembly when the second end of the reagent aspirator manifold assembly engages the sample aspirator manifold assembly and moves the one or more sample aspirators toward the sample cartridge receptacle.

According to another implementation, the aspirator manifold assembly includes or comprises a reagent aspirator manifold assembly.

According to another implementation, the first location and the second location are a first distance apart and the first sensor and the second sensor are a second distance apart. The first distance is greater than the second distance.

According to another implementation, the first distance is about 74 millimeters.

According to another implementation, the second sensor senses that the orifice includes or comprises: the second sensor is in an open state.

According to another implementation, the processor identifying that the aspirator manifold assembly is in the second position includes or comprises: the second sensor is successively in a closed state and then in an open state.

According to another implementation, the second sensor being in the open state comprises or includes: the second sensor senses the orifice.

According to another implementation, the apparatus includes or comprises a flag assembly including the first flag and the second flag.

According to another implementation, the flag assembly includes or comprises a body from which the first flag and the second flag extend.

According to another implementation, the apparatus includes or comprises a sensor assembly including or comprising a sensor plate, the first sensor, and the second sensor.

According to another implementation, the apparatus includes or includes a lead screw assembly coupled to the base and the bracket.

According to another implementation, the threshold distance is about 2.75 millimeters.

According to another implementation, the bracket carries a first flag and a second flag defining an aperture.

According to another implementation, determining that the aspirator manifold assembly is in the second position based on the second sensor being sequentially in the closed state and then in the open state comprises or includes: the second sensor senses the second flag and the aperture sequentially.

According to another implementation, the aperture comprises or includes a through hole.

According to another embodiment, the aperture comprises or includes a slit.

It is to be understood that all combinations of the foregoing concepts and additional concepts discussed in more detail below (assuming such concepts are not mutually inconsistent) are contemplated as being part of the subject matter disclosed herein and/or may be combined to achieve certain benefits of certain aspects. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are contemplated as being part of the subject matter disclosed herein.

Drawings

Fig. 1 shows a schematic diagram of a specific implementation of a system according to the teachings of the present disclosure.

Fig. 2 is an isometric view of an exemplary sample aspirator manifold assembly that may be used to implement the sample aspirator manifold assembly of fig. 1.

Figure 3 illustrates an expanded isometric view of the extractor manifold assembly of figure 2 including a cartridge assembly.

FIG. 4 illustrates an exemplary manifold assembly in a first position and/or raised position that may be used to implement the system of FIG. 1.

Fig. 5 shows the reagent aspirator manifold assembly of fig. 4 and the carrier of fig. 4 in a second position and/or foil piercing position.

Fig. 6 shows the reagent aspirator manifold assembly of fig. 4 and the carrier of fig. 4 in a third and/or lowered position.

Fig. 7 is a detailed cross-sectional view of the distal end of the extractor tube of the sample extractor manifold assembly of fig. 2 and the sample aperture of the sample cartridge of fig. 4-6.

Fig. 8 is an isometric view of another cartridge assembly that may be used with the sample aspirator manifold assembly of fig. 1 and/or 2.

Fig. 9 is an isometric view of an exemplary sample cartridge that may be used to implement the sample cartridge of fig. 1.

Fig. 10 illustrates an isometric view of an exemplary sample tube that may be used with the sample cartridge of fig. 9.

Fig. 11 shows a flow chart of a method of using the system of fig. 1, the sample aspirator manifold assembly of fig. 1 and 2, and the reagent aspirator manifold assembly of fig. 1 and 4, or any other implementation disclosed herein.

Fig. 12 is a side view of an exemplary aspirator manifold assembly that may be used to implement the reagent aspirator manifold assembly of fig. 1.

Fig. 13 is a side view of the aspirator manifold assembly of fig. 12 in a second position.

Figure 14 is a side view of an alternative flag assembly that may be used to implement the flag assembly of figure 12.

Detailed Description

While the following text discloses a detailed description of a specific implementation of the method, apparatus and/or article of manufacture, it should be understood that the legal scope of the title is defined by the words of the claims set forth at the end of this patent. Accordingly, the following detailed description is to be taken merely as examples and does not describe every possible implementation since describing every possible implementation would be impractical, if not impossible. Many alternative implementations may be realized using the current technology or technology developed after the filing date of this patent. It is contemplated that such alternative implementations will still fall within the scope of the claims.

Implementations disclosed herein relate to aspirator manifold assemblies that reduce dead volume of a sample within a sample tube (e.g., a library tube) and reduce the likelihood of tip/distal end damage of the aspirator tube. The dead volume may be reduced to, for example, about 10 microliters (μl). The tip of the extractor tube is used to penetrate a liquid impermeable barrier, such as a foil, covering the sample aperture of the sample cartridge and thus reduce damage to the tip of the extractor tube and increase the service life of the extractor tube.

Reducing the dead volume in the sample tube may be useful because the volume of the sample provided by the source may be limited and/or several samples with unique identifiers may be pooled into the sample volume. In some cases where a larger dead volume is allowed, some portion of the limited sample may not be extracted or some limited amount may be extracted from the sample tube and/or some sample of the aggregate sample volume may not be extracted or some limited amount may be extracted from the sample tube. Reducing dead volume may be achieved by implementations described herein to achieve better extraction of limited sample volumes. Furthermore, if the dead volume is reduced, a greater number of samples may be pooled together because the likelihood of extracting a limited amount may be reduced. In addition, reducing dead volume may reduce the volume of reagents used for on-board sample preparation, thereby also reducing the size, volume, and/or cost of the instrument and/or sequencing samples.

The aspirator manifold assembly in some implementations disclosed herein has a cartridge assembly including a cartridge housing, aspirator tubes, and aspirator couplings movably coupled within the cartridge housing and the aspirator tubes coupled to the aspirator couplings. The cartridge assembly also includes one or more biasing elements, such as springs or foam, positioned between the extractor links and the cartridge housing that allow the extractor links and associated extractor tubes to move relative to the cartridge housing. These extractor coupling and extractor tube may be moved independently or together (e.g. in linkage). The movable coupling between the extractor couplings/extractor tubes and the cartridge housing advantageously allows the distal ends of the extractor tubes to have a low force interaction with the sample aperture, thereby preventing damage to the extractor tubes.

The distal end of each of the extractor tubes has a first surface positioned at a first angle relative to the longitudinal axis of the corresponding extractor and a second surface positioned at a second angle relative to the longitudinal axis of the corresponding extractor defining an opening of the extractor tube. The second angle is greater than the first angle. Thus, the first surface may engage a corresponding surface of the sample aperture while the second surface remains at least partially spaced apart from the surface of the sample aperture, allowing the opening to remain unobstructed. These sample tubes may also include a tapered portion and a recessed portion (e.g., a dimple) that further prevents damage to the distal end of the aspiration tube and/or reduces dead volume.

Fig. 1 shows a schematic diagram of a specific implementation of a system 100 according to the teachings of the present disclosure. The system 100 may be used to perform analysis on one or more samples of interest. The sample may include one or more clusters of DNA that have been linearized to form single stranded DNA (sstDNA). In the illustrated implementation, the system 100 has a reagent reservoir receptacle 102 that receives a reagent reservoir 104, a sample cartridge receptacle 106 that receives a sample cartridge 108, and a flow cell receptacle 110 that receives a flow cell cartridge assembly 112. The system 100 also includes a reagent aspirator manifold assembly 114 having one or more reagent aspirators 115, an actuator 116, a sample aspirator manifold assembly 118 having one or more sample aspirators 119, and a pump manifold assembly 120. The system 100 also includes a sample loading manifold assembly 121, a drive assembly 122, a controller 124, an imaging system 126, and a waste reservoir 128. Controller 124 is electrically and/or communicatively coupled to reagent aspirator manifold assembly 114, actuator 116, sample aspirator manifold assembly 118, pump manifold assembly 120, sample loading manifold assembly 121, drive assembly 122, controller 124, and imaging system 126, and is adapted to cause reagent aspirator manifold assembly 114, actuator 116, sample aspirator manifold assembly 118, pump manifold assembly 120, sample loading manifold assembly 121, drive assembly 122, controller 124, and imaging system 126 to perform various functions as disclosed herein.

Reagent aspirator manifold assembly 114 has a first end 130 to which actuator 116 is coupled to move reagent aspirator manifold assembly 114 relative to reagent reservoir 104 and a second end 132. In operation, actuator 116 moves reagent aspirator manifold assembly 114 toward reagent reservoir receptacle 102, causing second end 132 of reagent aspirator manifold assembly 114 to engage sample aspirator manifold assembly 118 and move sample aspirator 119 toward sample cartridge receptacle 106. The actuator 116 may be a linear actuator. Reagent reservoir receptacle 102 also has a surface 133 formed as a land 134 that sample aspirator manifold assembly 118 can engage when sample aspirator 119 aspirates fluid from sample cartridge 108.

In the illustrated implementation, biasing element 135, shown as spring 136, couples reagent and sample aspirate manifold assemblies 114, 118 and serves to force sample aspirate 115 away from sample cartridge receptacle 106 as reagent aspirate manifold assembly 114 moves away from reagent reservoir receptacle 102. The biasing element 135 may be referred to as a return spring. However, the manifold assemblies 114, 118 may be coupled in different ways.

The second end 132 of the reagent aspirator manifold assembly 114 has a lip 138 and the sample aspirator manifold assembly 118 has a lip 140. When reagent aspirator manifold assembly 114 engages sample aspirator manifold assembly 118 and moves sample aspirator 119 toward sample cartridge receptacle 106, lips 138, 140 engage. Biasing element 135 is shown coupled to and between lips 138, 140. However, the biasing element 135 may be coupled to the manifold assemblies 114, 118 in different locations. In some implementations, there is only one of the following: the second end 132 of the reagent aspirator manifold assembly 114 has a lip 138, or the sample aspirator manifold assembly 118 has a lip 140. For example, the lip 138 may engage a surface of the sample aspirator manifold assembly 118 to move the sample aspirator 119 toward the sample cartridge receptacle 106 as the reagent aspirator manifold assembly 114 moves. In another implementation, the lip 140 may engage a surface of the reagent aspirator manifold assembly 114 to move the sample aspirator 119 toward the sample cartridge receptacle 106 as the reagent aspirator manifold assembly 114 moves.

The sample cartridge 108 carries one or more samples of interest (e.g., analytes) in the sample aperture 142 and may be received in the sample cartridge receptacle 106. The sample aspirator 119 is used to aspirate a sample from the sample well 142 and the sample is delivered to the flow cell 144 of the flow cell cartridge assembly 112 through a sample fluid line 146. The sample aperture 142 may be referred to as a sample reservoir. One of the sample fluid lines 146 is coupled to each sample aspirator 119, and the sample fluid line 146 is fluidly coupled to the flow cell 144 by, for example, the sample loading manifold assembly 121. The sample cartridge 108 also includes a priming aperture 148 and one or more wash apertures 150 that can contain wash buffers and/or cleaning solutions, such as bleach.

Sample loading manifold assembly 121 includes one or more sample valves 152 and pump manifold assembly 120 includes one or more pumps 154, one or more pump valves 156, and a cache 158. One or more of the valves 152, 156 may be implemented by rotary valves, pinch valves, flat valves, solenoid valves, check valves, piezoelectric valves, and/or three-way valves. Other types of fluid control devices may prove suitable. One or more of the pumps 154 may be implemented by syringe pumps, peristaltic pumps, and/or diaphragm pumps. Other types of fluid delivery devices may prove suitable. The cache 158 may be a serpentine cache and may be adapted to accommodate a volume of about 4 milliliters (mL). The cache 158 may temporarily store one or more reactive components during, for example, a bypass maneuver of the system 100 of fig. 1. Although the cache 158 is shown as being included in the pump manifold assembly 120, the cache 158 may be located in a different location. The cache 158 may be included in the reagent aspirator manifold assembly 114 or in another location.

In operation, sample aspirator manifold assembly 118 aspirates one or more samples from sample aperture 142 and sample loading manifold assembly 121 and pump manifold assembly 120 flow one or more samples of interest from sample cartridge 108 through fluid line 160 toward flow cell cartridge assembly 112. The flow cell cartridge assembly 112 includes a flow cell 144 having a plurality of channels (e.g., two channels, four channels, eight channels). However, the flow cell 144 may have a single channel, or the flow cell 144 may be omitted and/or replaced with another detection device. The sample loading manifold assembly 121 may be adapted to automatically load/address each channel of the flow cell 144 with a sample of interest individually using the system 100 of fig. 1.

The sample cartridge 108 and sample loading manifold assembly 118 are positioned downstream of the flow cell cartridge assembly 112. Accordingly, the sample loading manifold assembly 121 may load a sample of interest into the flow cell 144 from the rear of the flow cell 144. Loading the sample of interest from the rear of the flow cell 144 may be referred to as "post-loading" and may reduce contamination. Sample loading manifold assembly 121 is coupled between flow cell cartridge assembly 112 and pump manifold assembly 120.

Pump 154 pumps hybridization buffer through flow cell 144 to perfuse system 100 with, for example, hybridization buffer and/or to remove air from system 100, and sample aspirator manifold assembly 118 dispenses hybridization buffer into perfusion holes 148 once system 100 is perfused. Sample of interest is then aspirated from sample cartridge 108 using sample aspirator 119, and sample valve 152, pump valve 156, and/or pump 154 are selectively actuated to force the sample of interest toward pump manifold assembly 120. The sample cartridge 108 is shown as including sample apertures 142 that are selectively fluid accessible via corresponding sample aspirators 119. Thus, each sample may be selectively isolated from the other samples using a corresponding sample aspirator 119 and a corresponding sample valve 152.

The sample valve 152 for the corresponding sample of interest may be opened or released to fluidly connect the sample well 142 to the instrument fluid system in order to aspirate the sample of interest from one of the sample wells 142. The corresponding pump 154 of the pump manifold assembly 120 may be actuated to draw a sample of interest from the sample aperture 142 and into a fluid line, such as the fluid line and/or another fluid line of the pump manifold assembly 120. The corresponding pump valve 156 may be opened, closed, and/or moved from the first position to the second position to fluidly couple the corresponding pump 154 to the fluid line for the corresponding sample aperture 142. In some implementations, pump valve 156 may be selectively isolated from other pumps 154 and/or pump valves 156, and samples of interest may be temporarily stored in the line volume between pump valve 156 and/or sample valve 152 and the corresponding pump 154.

Sample valve 152, pump valve 156, and/or pump 154 may be selectively actuated to force the sample of interest toward flow cell cartridge assembly 112 and into the respective channels of flow cell 144 so as to flow the sample of interest individually toward one or more corresponding channels of flow cell 144 and away from pump manifold assembly 120. For example, after a sample of interest is drawn into the line volume, the sample valve 152 may be closed, thereby fluidly disconnecting the sample aperture 142 from the line volume. In some cases, sample valve 152 may be movable from a first position to a second position to fluidly couple corresponding pump 154 to one or more corresponding channels via sample loading manifold assembly 121. The pump 154 may then push the sample of interest into one or more corresponding channels of the flow cell 144. In some implementations, the corresponding pump valve 156 may be opened, closed, and/or moved from the second position to the first position to fluidly couple the corresponding pump 154 to one or more corresponding channels. In some implementations, each of the plurality of channels of the flow cell 144 receives a sample of interest, and one or more of the channels may selectively receive a sample of interest, and other ones of the channels may not receive a sample of interest. For example, the channels of the flow cell 144 that may not receive the sample of interest may alternatively receive a wash buffer.

The drive assembly 122 interfaces with the reagent aspirator manifold assembly 114 and the pump manifold assembly 120 to flow one or more reagents that interact with the sample at the flow cell 144 through the flow cell cartridge assembly 112. In one implementation, a reversible terminator with an identifiable tag is attached to the reagent to allow incorporation of a single nucleotide by sstDNA within each cycle. In some such implementations, one or more nucleotides have a unique fluorescent label that emits a color when excited. The color (or absence of color) is used to detect the corresponding nucleotide. In the illustrated implementation, the imaging system 126 may be adapted to excite one or more of the identifiable markers (e.g., fluorescent markers) and then obtain image data of the identifiable markers. The markers may be excited by incident light and/or laser light, and the image data may include one or more colors emitted by the respective markers in response to excitation. The image data (e.g., detection data) may be analyzed by the system 100. The imaging system 126 may be a fluorescence spectrophotometer that includes an objective lens and/or a solid state imaging device. The solid-state imaging device may include a Charge Coupled Device (CCD) and/or a Complementary Metal Oxide Semiconductor (CMOS).

In some implementations, after image data is obtained, the drive assembly 122 interfaces with the reagent aspirator manifold assembly 114 and the pump manifold assembly 120 to flow another reactive component (e.g., reagent) through the flow cell 144, which is then received by the waste reservoir 128 via the main waste fluid line 162 and/or otherwise expelled by the system 100. Some of the reaction components were subjected to a washing operation that chemically cleaved the fluorescent label and reversible terminator from sstDNA. The sstDNA is then ready for another cycle. In some implementations, the sample aspirator 119 is cleaned between operations of the system 100 by immersing the sample aspirator 119 in a wash well 150 containing a cleaning solution (such as bleach) or wash buffer. The cleaning solution may be removed by immersing the sample aspirate 119 in a perfusion well 148 containing hybridization buffer. However, other methods of cleaning the sample aspirate 119 may be suitable.

A primary waste fluid line 162 is coupled between the pump manifold assembly 120 and the waste reservoir 128. The pump 154 and/or pump valve 156 of the pump manifold assembly 120 selectively flow the reaction components from the flow cell cartridge assembly 112 through the fluid line 160 and the sample loading manifold assembly 118 to the main waste fluid line 162.

The flow cell cartridge assembly 112 may be received in the flow cell receptacle 110 and may be coupled with the flow Chi Jiekou 164. However, the flow cell receptacle 110 may be eliminated and the flow cell cartridge assembly 112 may be directly coupled to the flow cell interface 164.

The flow cell cartridge assembly 112 is coupled to the central valve 166 via flow Chi Jiekou 164. An auxiliary waste fluid line 168 is coupled to the central valve 166 and the waste reservoir 128. In some implementations, the auxiliary waste fluid line 168 is adapted to receive any excess fluid of the sample of interest from the flow cell cartridge assembly 112 via the central valve 166 and to flow the excess fluid of the sample of interest to the waste reservoir 128 when the sample of interest is post-loaded into the flow cell 144, as described herein. That is, the sample of interest may be loaded from the rear of the flow cell 144, and any excess fluid of the sample of interest may exit from the front of the flow cell 144. Different samples may be separately loaded into corresponding channels of the flow cell 144 by post-loading the samples of interest into the flow cell 144, and a single manifold may couple the front of the flow cell 144 to the central valve 166 to direct excess fluid of each sample of interest to the auxiliary waste fluid line 168 and reduce the likelihood of sample contamination between the channels of the flow cell 144. A single manifold may be used to deliver a common reagent to each channel of the flow cell 144 from a front (e.g., upstream) of the flow cell 144, and the common reagent may exit the flow cell 144 from a back (e.g., downstream) of the flow cell 144. In other words, the sample and reagent of interest may flow in opposite directions through the channels of flow cell 144.

In the illustrated implementation, the reagent aspirator manifold assembly 114 includes a shared line valve 170 and a bypass valve 172. The shared line valve 170 may be referred to as a reagent selector valve. The central valve 166 and valves 170, 172 of the reagent aspirator manifold assembly 114 are selectively actuatable to control the flow of fluid through the fluid lines 174, 176, 178. One or more of the valves 166, 170, 172 may be implemented by rotary valves, pinch valves, flat valves, solenoid valves, check valves, piezo valves, etc. Other fluid control devices may prove suitable.

Reagent aspirator manifold assembly 114 may be coupled to a corresponding number of reagent reservoirs 104 via reagent aspirators 115. Reagent reservoir 104 may contain a fluid (e.g., a reagent and/or another reactive component). Reagent aspirator manifold assembly 114 includes a plurality of ports, wherein each port of reagent aspirator manifold assembly 114 can receive one of reagent aspirators 115. Reagent aspirator 115 may be referred to as a fluid line.

In the illustrated implementation, the shared line valve 170 of the reagent aspirator manifold assembly 114 is coupled to the central valve 166 via a shared reagent fluid line 174. Different reagents may flow through the shared reagent fluid line 174 at different times. When performing a flush operation prior to changing between one reagent and another reagent, pump manifold assembly 120 may draw wash buffer through shared reagent fluid line 174, central valve 166, and flow cell cartridge assembly 112. Thus, the shared reagent fluid line 174 may involve a flushing operation. Although one shared reagent fluid line 174 is shown, any number of shared fluid lines may be included in the system 100.

Bypass valve 172 of reagent aspirator manifold assembly 114 is coupled to central valve 166 via dedicated reagent fluid lines 176, 178. The central valve 166 may have one or more dedicated ports corresponding to dedicated reagent fluid lines 176, 178, and each of the dedicated reagent fluid lines 176, 178 may be associated with a single reagent. Fluids that may flow through dedicated reagent fluid lines 176, 178 may be used during a sequencing operation, and may include cleavage reagents, integration reagents, scanning reagents, cleavage detergents, and/or wash buffers. Thus, when a flushing operation is performed prior to a change between one reagent and another reagent associated with bypass valve 172, reagent aspirator manifold assembly 114 may aspirate wash buffer through central valve 166 and/or flow cell cartridge assembly 112. However, the dedicated reagent fluid lines 176, 178 themselves may not be flushed, as only a single reagent may flow through each of the dedicated reagent fluid lines 176, 178. Methods involving dedicated reagent fluid lines 176, 178 may be advantageous when the system 100 uses reagents that can react adversely with other reagents. Furthermore, reducing the number of fluid lines or the length of fluid lines flushed as it varies between different reagents reduces reagent consumption and flush volume, and may reduce the cycle time of the system 100. Although two dedicated reagent fluid lines 176, 178 are shown, any number of dedicated fluid lines may be included in the system 100.

The bypass valve 172 is also coupled to the cache 158 of the pump manifold assembly 120 via a bypass fluid line 180. One or more reagent priming operations, hydration operations, mixing operations, and/or delivery operations may be performed using the bypass fluid line 180. The priming operation, the hydration operation, the mixing operation, and/or the delivery operation may be performed independently of the flow cell cartridge assembly 112. Thus, operation using the bypass fluid line 145 may be performed during, for example, incubation of one or more samples of interest within the flow cell cartridge assembly 112. That is, the shared line valve 170 may be utilized independently of the bypass valve 172 such that the bypass valve 172 may utilize the bypass fluid line 180 and/or the cache 158 to perform one or more operations while the shared line valve 170 and/or the central valve 166 perform other operations simultaneously, substantially simultaneously, or counter-synchronously. Performing multiple operations simultaneously using system 100 may reduce runtime. Bypass valve 172 and bypass fluid line 180 may be used to flow hybridization buffer through pump manifold assembly 120 to sample loading manifold assembly 121 and allow hybridization buffer to follow the sample of interest through flow cell 144. Thus, the order in which fluid flows through flow cell 144 may be: 1) Hybridization buffer from a perfusion operation; 2) A sample sucked from the sample hole 142 via the sample suction 121; and 3) hybridization buffer entering via bypass valve 172 and bypass fluid valve 180.

Referring now to the drive assembly 122, in the illustrated implementation, the drive assembly 122 includes a pump drive assembly 182 and a valve drive assembly 184. The pump drive assembly 182 may be adapted to interface with one or more pumps 154 to pump fluid through the flow cell 144 and/or to load one or more samples of interest into the flow cell cartridge assembly 112. The valve drive assembly 184 may be adapted to interface with one or more of the valves 152, 156, 166, 170, 172 to control the position of the corresponding valve 152, 156, 166, 170, 172. In one implementation, the shared line valve 170 and/or the bypass valve 172 is implemented by a rotary valve having a first position blocking flow to the flow cell 144 and a second position allowing flow from the reagent reservoir 104 to the flow cell 144. However, any of the valves 170, 172 may be positioned in any number of positions to allow any one or more of the first reagent, buffer reagent, second reagent, etc. to flow to the flow cell cartridge assembly 112. As one example, the bypass valve 172 may be rotatable between a first position that allows fluid to pass from one or more of the reagent reservoirs 104 through the bypass valve 172 and to the central valve 166, and a second position that allows fluid to pass from one or more of the reagent reservoirs 104 through the bypass valve 172 and into the bypass fluid line 180. Other arrangements may prove suitable. For example, bypass valve 172 may be positioned to allow fluid to pass from bypass fluid line 180 through bypass valve 172 and to the mixing reservoir of reagent reservoir 104.

Referring to the controller 124, in the illustrated implementation, the controller 124 includes a user interface 185, a communication interface 186, one or more processors 188, and a memory 190 that stores instructions executable by the one or more processors 188 to perform various functions including the disclosed implementations. The user interface 185, the communication interface 186, and the memory 190 are electrically and/or communicatively coupled to the one or more processors 188.

In one implementation, the user interface 185 is adapted to receive input from a user and provide information to the user associated with the operation and/or ongoing analysis of the system 100. The user interface 185 may include a touch screen, display, keyboard, speaker, mouse, trackball, and/or voice recognition system. The touch screen and/or display may display a Graphical User Interface (GUI).

In one implementation, the communication interface 186 is adapted to enable communication between the system 100 and a remote system (e.g., a computer) via a network. The network may include the internet, an intranet, a Local Area Network (LAN), a Wide Area Network (WAN), a coaxial cable network, a wireless network, a wired network, a satellite network, a Digital Subscriber Line (DSL) network, a cellular network, a bluetooth connection, a Near Field Communication (NFC) connection, and so forth. Some of the communications provided to the remote system may be associated with analysis results, imaging data, etc., generated or otherwise obtained by the system 100. Some of the communications provided to the system 100 may be associated with fluid analysis operations, patient records, and/or protocols to be performed by the system 100.

The one or more processors 188 and/or the system 100 may include one or more of a processor-based system or a microprocessor-based system. In some implementations, the one or more processors 188 and/or the system 100 include one or more of a programmable processor, a programmable controller, a microprocessor, a microcontroller, a Graphics Processing Unit (GPU), a Digital Signal Processor (DSP), a Reduced Instruction Set Computer (RISC), an Application Specific Integrated Circuit (ASIC), a Field Programmable Gate Array (FPGA), a Field Programmable Logic Device (FPLD), logic circuitry, and/or another logic-based device that performs the functions described herein, including the functions described herein.

Memory 190 may include one or more of semiconductor memory, magnetically readable memory, optical memory, hard drive (HDD), optical storage drive, solid state storage device, solid State Drive (SSD), flash memory, read-only memory (ROM), erasable programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), random Access Memory (RAM), non-volatile RAM (NVRAM) memory, compact Disk (CD), compact disk read-only memory (CD-ROM), digital Versatile Disk (DVD), blu-ray disk, redundant Array of Independent Disks (RAID) system, cache, and/or any other storage device or storage disk in which information is stored for any duration (e.g., permanently, temporarily, for a long period of time, for buffering, for caching).

Fig. 2 is an isometric view of an exemplary sample aspirator manifold assembly 200 that may be used to implement sample aspirator manifold assembly 118 of fig. 1. In the illustrated implementation, the extractor manifold assembly 200 has a base 202, a bracket 204 having a first side 206 and a second side 206, and a vertical guide 209 coupling the base 202 and the first side 208 of the bracket 204. The vertical guides 209 are shown as a pair of guide rails 210 coupled to the base 202 and a pair of guide blocks 212 coupled to the carriage 204. The guide rail 210 and the guide block 212 are coupled and guide the movement of the carriage 204 in a direction generally indicated by arrow 214. In some implementations, a single rail 210 may be provided. The base 202 includes a stop 216 that is engaged by a top surface 218 of the carriage 204 to limit movement of the carriage 204 and maintain the coupling between the guide rail 210 and the guide block 212.

Sample aspirator manifold assembly 200 also includes guide 220, horizontal guide 222 coupling base 202 and guide 220, and cartridge assembly 233 carrying sample aspirator 119 and coupled to bracket 204. The guide 220 may be referred to as a guide plate and defines apertures 224 through which the sample aspirators 119 pass. The interaction between the sample aspirator 119 and the guide 220 reduces the effective length of the sample aspirator 119 and the likelihood of the sample aspirator 119 buckling and/or bending.

The horizontal guide 222 includes a linear rail 226 carried by the guide 220 and a channel 228 defined by sides 230, 232 of the base 202 that receives the linear rail 226. The coupling between the linear rail 226 and the groove 228 guides the movement of the guide 220 in a direction generally indicated by arrow 234. The sample aspirator manifold assembly 200 may include one or more sensors 235 for determining the y-position and/or z-position of the carriage 204.

Sample aspirator manifold assembly 200 also includes a lead screw assembly 236 coupled to base 202 and guide 220 and configured to move guide 220 in a direction generally indicated by arrow 234. The lead screw assembly 236 includes a lead screw 238 carried by the base 202 and a lead nut 240 carried by the guide 220. The lead screw assembly 223 also includes a motor 242 for driving the lead screw 238 and moving the guide 220. Although the sample aspirator manifold assembly 200 is mentioned as having a lead screw assembly 236 for moving the guide 220 relative to the base 202, the sample aspirator manifold assembly 200 may include different types of actuators.

Fig. 3 illustrates an expanded isometric view of the extractor manifold assembly 200 of fig. 2 including the cartridge assembly 233. In the illustrated implementation, the cartridge assembly 233 includes a cartridge housing 246, a sample extractor tube 119 including an extractor coupling 248 and an extractor tube 249, and a biasing element 250. The aspiration tubes 249 each have a proximal end 252 and a distal end 254, with the proximal end 252 coupled to the corresponding aspiration coupling 248, and each of the distal ends 254 has a tip 256 for penetrating the liquid impermeable barrier covering one or more of the apertures 142, 148, 150 of the sample cartridge 108. Biasing element 250 is shown as coil springs 258 that bias the aspirator coupling 248 in a direction generally indicated by arrow 260 and permit relative movement between the sample aspirator 119 and cartridge housing 246. The movable coupling between the sample aspirator tube 119 and the cartridge housing 244 advantageously allows the distal end 254 of the aspirator tube 249 to have a low force interaction with the apertures 142, 148, 150 of the sample cartridge 108, thereby preventing damage to the sample aspirator 119. The low force interaction allows the tip 256 to remain relatively sharp to penetrate the liquid impermeable barrier even after repeated use of the system 100.

Still referring to cartridge assembly 233, cartridge housing 246 defines a cartridge cavity 262, and extractor coupling 248 is disposed within cartridge cavity 262. Each of the aspirator couplings 248 is biased by a corresponding spring 258 positioned within a cartridge cavity 262. The aspirator couplings 248 each have a spring seat 264, and the springs 258 are positioned between the spring seat 264 and a surface 266 of the cartridge housing 246. Thus, the sample aspirate 119 can be independently moved to accommodate, for example, height differences and/or manufacturing tolerances between the holes 142, 148, 150 of the sample cartridge 108. The sample aspirator 119 can accommodate height variations of about +/-3 millimeters or different heights.

By providing independent movability of the sample aspirators 119, the cartridge assembly 233 may allow each sample aspirators 119 to independently reduce the dead volume of each corresponding sample tube into which the sample aspirators 119 are inserted to a minimum. Such independent reduction may be useful in implementations where the sample tube may have a variable depth (either intentionally or due to manufacturing tolerance variations). As noted above, reducing the dead volume to a minimum volume may be used to achieve better extraction of a limited sample size, increase the number of samples that can be pooled together, and/or reduce the volume of reagents used for on-board sample preparation, thereby also reducing the size, volume, and/or cost of the instrument and/or sequencing samples.

Cartridge assembly 233 also has a guide plate 268 coupled to cartridge housing 246 by fasteners 270 that pass through guide plate 268 and are received within corresponding apertures 272 of cartridge housing 246. The guide plate 268 defines a slot 274 and each of the extractor couplings 248 has a protrusion 276 movable within the corresponding slot 274. The opposite side 277 of the cartridge assembly 233 may include additional guide plates having slots, and the extractor coupling 248 may have additional protrusions 286 receivable within those slots. The extractor couplings 248 may each have two opposing protrusions 275 (see, e.g., fig. 4-6), and the cartridge assemblies 233 may have opposing slots.

The protrusion 276 interacts with a surface of the guide plate 268 defining the slot 274 to guide the sample aspirate 119 linearly in a direction generally indicated by arrow 260. The slot 274 also has opposing stops 278, 280 that may be engaged by the projections to limit travel of the sample aspirate 119. When the extractor tube 249 engages the liquid impermeable barrier covering the apertures 142, 148, 150, the protrusions 276 move toward and engage the upper stops 278, thereby allowing the extractor tube 249 to deliver a threshold amount of force to the liquid impermeable barrier to penetrate the liquid impermeable barrier. Although the slot 274 and the protrusion 276 are stadium shaped, the slot 274 and/or the protrusion 276 may be differently shaped.

Fig. 4, 5 and 6 are cross-sectional views of a portion of an exemplary implementation of the sample and reagent aspirator manifold assembly 200, 300 of fig. 2 in different positions. The reagent aspirator manifold assembly 300 of fig. 4-6 may be used to implement the reagent aspirator manifold assembly 114 of fig. 1.

Fig. 4 illustrates the manifold assemblies 200, 300 in a first and/or raised position and illustrates the lips 138, 140 spaced apart from one another. Sample aspirator manifold assembly 200 has vertical guide 302 coupling guide 220 and cartridge assembly 233. In the illustrated implementation, the vertical guide 302 includes a rod 304 and an aperture 306 that receives the rod 304. The rod 304 may be referred to as a vertical rod. The stem 304 is coupled to the guide 220 and extends from the guide 220 toward the cartridge assembly 233, and the cartridge housing 246 defines the aperture 306. The rod 304 and the surface of the cartridge housing 246 defining the aperture 306 interact to guide movement of the carriage 204 in a direction generally indicated by arrow 307. Sample aspirator manifold assembly 200 also has a horizontal linear guide 308 that couples cartridge assembly 233, and bracket 204 includes a rod 310 and an aperture 312. The rod 310 extends between the first side 206 and the second side 208 of the bracket 204 and the cartridge housing 246 defines an aperture 312. The rod 310 interacts with the surface of the cartridge housing 246 defining the aperture 312 to guide movement of the cartridge assembly 233 in a direction generally indicated by arrow 314.

Fig. 5 illustrates the reagent aspirator manifold assembly 300 and the carrier 204 in the second position and/or foil piercing position, as well as the base 202 of the engagement platform 134. The lips 138, 140 are shown engaged with one another, the protrusion 276 is shown engaging a stop 278 of the slot 274, and the distal end 254 of the extractor tube 249 is shown positioned to pierce a liquid impermeable barrier 316 covering the sample aperture 142.

Fig. 6 illustrates the reagent aspirator manifold assembly 300 and the carriage 204 in a third position and/or lowered position. The distal end 254 of the extractor tube 249 is shown engaging the bottom surface 318 of the sample aperture 142, and the biasing element 250 is shown slightly compressed, thereby preventing deflection and/or damage of the sample extractor tube 119.

Fig. 7 is a detailed cross-sectional view of the distal end 254 of the extractor tube 249 of the sample extractor manifold assembly 200 of fig. 2 and the sample aperture 142 of the sample cartridge 108 of fig. 4-6. The extractor tubes 249 each have an opening 320 at the distal end 254, and a tip 256. In the illustrated implementation, the tip 256 is formed by a first surface 322 positioned at a first angle relative to a longitudinal axis 324 of the extractor tube 249 and a second surface 326 positioned at a second angle relative to the longitudinal axis 295. The surfaces 322, 326 may be referred to as facets. The opening 320 is defined by a second surface 326. The first angle is shown as about 30 ° and the second angle is shown as about 50 °. The surfaces 322, 326 may include the same angular arrangement at different angles.

The difference between the first angle and the second angle deflects the tip 256 away from the longitudinal axis 295 and allows the opening 320 to be spaced apart from the tip 256. The first surface 322 engages the bottom surface 318 of the sample aperture 142, allowing the opening 320 to be less likely to engage the bottom surface 318 of the sample aperture 142 and thus become occluded and/or obstructed. Since the extractor tube 249 may be used to repeatedly penetrate the seal of the sample tube 249, deformation of the tip 256 via impact or collision with the bottom of the sample tube 249 may reduce the effectiveness of the extractor tube 249 to penetrate and/or extract samples of future sample tubes 249. Thus, reducing the likelihood of the tip 256 striking or striking the bottom of the sample aperture 142 may increase the life and usefulness of the extractor tube 249 for future use. In the illustrated implementation, the first surface 322 and the bottom surface 318 of the sample aperture 142 have corresponding tapers, the second surface 326 does not flush engage the bottom surface 318, and the tip 256 extends across the opening 320. The bottom surface 318 of the sample aperture 142 has a tapered portion 328 and a recessed portion 330, wherein the tapered portion 328 tapers toward the recessed portion 330 to further reduce the amount of dead volume present within the sample aperture 142. Although the distal end 254 is referred to as having two surfaces 322, 326, the distal end 254 may have three facets or another number of facets.

Fig. 8 is an isometric view of another exemplary cartridge assembly 400 that may be used with the sample aspirator manifold assembly 200 of fig. 1 and/or 2. In the illustrated implementation, the cartridge assembly 400 includes a cartridge housing 402, a extractor coupling 404 movably coupled to the cartridge housing 402, and an extractor tube 249 coupled to the extractor coupling 404. Thus, movement of the single extractor coupling 404 moves the extractor tube 249 together.

The proximal end 252 of the extractor tube catheter 249 threadably engages the extractor coupling 404, and the linear guide 406 guides the movement of the extractor coupling 404 relative to the cartridge housing 402. The linear guide 406 includes a pair of rods 408, a pair of apertures 410 that receive the rods 408, and a pair of biasing elements 412 shown as coil springs 414 that bias the aspirator coupling 404. The lever 408 is coupled to and between opposite portions 416, 418 of the cartridge housing 402, and the extractor coupling 404 defines an aperture 410.

Fig. 9 is an isometric view of an exemplary sample cartridge 450 that may be used to implement the sample cartridge 108 of fig. 1. The illustrated sample cartridge 450 includes a housing 452, a sample tube 454 movably coupled to the housing 452, and a biasing element 456, shown as foam 458, that biases one or more sample tubes 454. The movable coupling between the sample tube 454 and the housing 452 advantageously allows the sample aspirator 119 to have a low force interaction with the sample tube 454. The sample tube 454 is shown with flanges 460 engaged against the foam 458 and separated from each other, allowing the sample tube 454 to move independently relative to the housing 452. However, the sample tubes 454 may be coupled together such that the sample tubes 454 move together. The sample tube 454 may be implemented with the independently movable sample aspirator tubes 119 and/or sample tubes 249 of fig. 2-7 or with the set of aspirator tubes 249 of fig. 8, such that the compliance of the biasing element 456 advantageously allows the sample aspirator 119 and/or sample tubes 249 to further reduce low force interactions with the sample tube 454.

The housing 452 is a clamshell arrangement having a first portion 462 and a second portion 464 that define an alignment aperture 466 through which the sample tube 454 passes. Foam 458 and flange 460 are positioned between portions 462, 464. Although the sample cartridge 450 is shown as including foam 458 as the biasing element 456, a different biasing element such as a spring may be used.

Fig. 10 illustrates an isometric view of an exemplary sample tube 454 that may be used with the sample cartridge 450 of fig. 9. The sample tube 454 is coupled to the peripheral flange 468 by frangible members 470 that allow relative movement between the sample tube 454 and the peripheral flange 468. Thus, frangible member 470 acts as a biasing element. The frangible members 470 can be broken to allow the sample tubes 454 to be separated from one another. The sample tube 454 of fig. 10 has ends 472, 474, 476, 478 that include tapered portions 480, 482, 484, 486 having different angles and with and without recessed portions 330. These angles may include, for example, 40 °, 46 °, 50 °, and the like. However, other angles may prove suitable.

Fig. 11 shows a flow chart of a method of using the system 100 of fig. 1, the sample aspirator manifold assemblies 118, 200 of fig. 1 and 2, and the reagent aspirator manifold assemblies 114, 300 of fig. 1 and 4, or any other implementations disclosed herein. In the flow chart of fig. 11, blocks surrounded by solid lines may be included in an implementation of process 500, while blocks surrounded by dashed lines may be optional in an implementation of the process. However, regardless of the manner in which the boundaries of the blocks are presented in FIG. 11, the order of execution of the blocks may be changed, and/or some of the blocks described may be changed, eliminated, combined, and/or sub-divided into multiple blocks.

The process 500 of fig. 11 begins with the reagent aspirator manifold assembly 114, 300 being moved toward the reagent reservoir receptacle 102 (block 502). Reagent aspirator manifold assemblies 114, 300 have a first end 130 and a second end 132 and include one or more reagent aspirators 115. In response to moving the reagent aspirator manifold assembly 114, 300 toward the reagent reservoir receptacle 102, the second end 132 of the reagent aspirator manifold assembly 114, 300 engages with the sample aspirator manifold assembly having the sample aspirator 119 (block 504), and the sample aspirator 119 is moved toward the sample cartridge receptacle 106 (block 506). The process 500 also includes puncturing a liquid-impermeable barrier 316 covering a sample aperture 142 received within the sample cartridge receptacle 106 (block 508). In some implementations, the liquid-impermeable barrier 316 is pierced based on the aspirator couplings 248, 404 engaging the stop 278 and the distal end 254 of the sample aspirator 119 piercing the liquid-impermeable barrier 316. By moving the sample aspirate 119 against the biasing force provided by the one or more springs 136 and/or the foam 458, the sample aspirate 119 can move relative to the carriage 204 of the aspirate manifold assembly 200 (block 508).

Fig. 12 is a side view of an exemplary aspirator manifold assembly 600 that may be used to implement the reagent aspirator manifold assembly 114 of fig. 1. The aspirator manifold assembly 600 may be referred to as a reagent aspirator manifold assembly. The aspirator manifold assembly 600 includes a base 602, a bracket 604, and a vertical guide 606 coupling the base 602 and the bracket 604. The base 602 carries a first sensor 608 and a second sensor 610 vertically spaced apart from the first sensor 608. The carriage 604 carries a suction device 611, a first flag 612 and a second flag 613 defining an aperture 614. In the illustrated implementation, the aperture 614 is shown as a cutout. The aperture 614 may alternatively be a through hole 702 (see fig. 14) or another configuration.

In operation, the processor 188 identifies the aspirator manifold assembly 600 in a first position (shown in fig. 12) based on the first sensor 608 sensing the first flag 612 and not sensing the orifice 614, and identifies the aspirator manifold assembly 600 in a second position (shown in fig. 13) based on the second sensor 610 sequentially sensing the second flag 613 and then sensing the orifice 614. The first position is a raised position of the extractor manifold assembly 600 and the second position is a lowered position of the extractor manifold assembly 600.

The first and second locations are shown as being a first distance 615 from each other, and the first and second sensors 608, 610 are shown as being a second distance 616 from each other. In some implementations, the first distance 615 is greater than the second distance 616, and the first distance 615 may be approximately 74 millimeters.

In some implementations, the processor 188 identifies that the aspirator manifold assembly 600 is in the second position based on the second sensor 610 sequentially sensing the second flag 613 and then the orifice 614. The second sensor 610 sensing that the second flag 613 includes the second sensor 610 being in a closed state and the second sensor 610 sensing that the orifice 614 includes the second sensor 610 being in an open state. Thus, the processor 188 identifies that the aspirator manifold assembly 600 is in the second position includes the second sensor 610 being sequentially in the closed state and then the second sensor 610 being in the open state.

For example, after the second sensor 610 senses one of the first flag 612 or the second flag 613 or when the second sensor 610 is in the closed state, the processor 188 may cause the carriage 604 to move a threshold distance in a direction generally indicated by arrow 618. After the carriage 604 is moved a threshold distance, the processor 188 determines a status of the second sensor 610. The threshold distance may be about 2.75mm or another distance. The aperture 614 of the second flag 613 is aligned with the second sensor 610 when the second sensor 610 is in an open state after the aspirator manifold assembly 600 has been moved a threshold distance, and the first flag 612 is aligned with the second sensor 610 when the second sensor 610 is in a closed state after the aspirator manifold assembly 600 has been moved a threshold distance. When the aperture 614 is aligned with the second sensor 610, the processor 188 may not cause the carriage 604 to move further in the direction generally indicated by arrow 618.

The extractor manifold assembly 600 includes a flag assembly 619 that includes a first flag 612 and a second flag 613. A flag assembly 619 is carried by the carriage 604 and includes a body 620 from which the first and second flags 612, 613 extend. The extractor assembly 600 also includes a sensor assembly 622 and a lead screw assembly 624. The sensor assembly 622 includes a sensor board 626, a first sensor 608, and a second sensor 610. A sensor assembly 622 is carried by the base 602. Lead screw assembly 624 is coupled to base 602 and carriage 604 and is used to move carriage 604 relative to base 602. For example, the processor 188 may use the flags 612, 612 and the sensors 608, 610 to control movement of the aspirator 611 to reduce the likelihood that the aspirator 611 contacts the bottom of the aperture of the reagent reservoir 104 containing the reagent. The bottom of the engagement hole of the aspirator 611 may blunt the aspirator 611 and reduce its useful life.

Fig. 13 is a side view of the aspirator manifold assembly 600 of fig. 12 in a second position.

Figure 14 is a side view of an alternative flag assembly 700 that may be used to implement the flag assembly 619 of figure 12. The flag assembly 700 is similar to the flag assembly 619 of fig. 12, but the aperture 614 is shown as a through hole 702 rather than as a cutout.

An apparatus, the apparatus comprising: a reagent reservoir receptacle for receiving a reagent reservoir; a sample cartridge receptacle for receiving a sample cartridge; a reagent aspirator manifold assembly having a first end and a second end and comprising one or more reagent aspirators; an actuator coupled to the first end of the reagent manifold assembly to move the reagent manifold assembly relative to the reagent reservoir; and a sample aspirator manifold assembly having one or more sample aspirators. The second end of the reagent aspirator manifold assembly engages the sample aspirator manifold assembly and moves the one or more sample aspirators toward the sample cartridge receptacle in response to the actuator moving the reagent aspirator manifold assembly toward the reagent reservoir receptacle.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, the apparatus further comprising: a biasing element that couples the reagent aspirator manifold assembly and the sample aspirator manifold assembly.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, the biasing element is a spring.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, the second end of the reagent aspirator manifold assembly having lips and the sample aspirator manifold assembly having lips that engage when the second end of the reagent aspirator manifold assembly engages the sample aspirator manifold assembly and moves the one or more sample aspirators toward the sample cartridge receptacle.

An apparatus according to any one or more of the preceding examples and/or any one or more of the examples disclosed below, the apparatus further comprising: a flow cell receptacle for receiving a flow cell; and a sample fluid line coupled to each sample aspirator and fluidly coupled to the flow cell.

The device of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the reagent reservoir receptacle has a surface engageable by the sample aspirator manifold assembly.

An apparatus according to any one or more of the preceding examples and/or any one or more of the examples disclosed below, the apparatus further comprising: a platform having the surface.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the sample aspirator manifold assembly comprises: a base; a bracket having a first side and a second side, the second side including the lip and being operatively coupled to the second end of the reagent aspirator manifold assembly; and a vertical guide coupling the base and the first side of the bracket.

An apparatus according to any one or more of the preceding examples and/or any one or more of the examples disclosed below, the apparatus further comprising: a guide coupled to the base and defining one or more apertures corresponding to the one or more sample aspirators, and the one or more aspirators pass through the one or more apertures.

An apparatus according to any one or more of the preceding examples and/or any one or more of the examples disclosed below, the apparatus further comprising: a horizontal guide coupling the base and the guide.

An apparatus according to any one or more of the preceding examples and/or any one or more of the examples disclosed below, the apparatus further comprising: a lead screw assembly coupled to the base and the guide.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the lead screw assembly includes a lead screw carried by the base and a lead nut carried by the guide.

An apparatus according to any one or more of the preceding examples and/or any one or more of the examples disclosed below, the apparatus further comprising: a cartridge assembly carrying the one or more sample pickups and coupled to the bracket.

An apparatus, the apparatus comprising: a cartridge assembly of an aspirator manifold assembly, the cartridge assembly comprising: a cartridge housing; one or more extractor tubes having a proximal end and a distal end; one or more aspirator couplings, the proximal end of the aspirator tube coupled to the one or more aspirator couplings, and the one or more aspirator couplings movably coupled to the cartridge housing; one or more biasing elements for biasing the one or more aspirator couplings. The one or more biasing elements allow relative movement between the extractor tube and the cartridge housing.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the cartridge housing defines a cartridge cavity and the one or more aspirator couplings are disposed within the cartridge cavity.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the one or more extractor tubes comprise a plurality of extractor tubes and the one or more extractor couplers comprise a plurality of extractor couplers.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein each aspirator coupling has a corresponding biasing element.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein each aspirator coupling comprises a spring seat, and the one or more biasing elements comprise one or more springs positioned between each spring seat and the cartridge housing.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the extractor couplings and corresponding extractor tubes are independently movable.

An apparatus according to any one or more of the preceding examples and/or any one or more of the examples disclosed below, the apparatus further comprising: a guide plate coupled to the cartridge housing and defining one or more slots, and wherein each extractor coupling has a protrusion movable within a corresponding slot.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein each slot has opposing stops engageable by a corresponding tab.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the sample aspirator manifold assembly further comprises: a base; a bracket carrying the cartridge assembly; and a vertical guide coupling the base and the first side of the bracket.

An apparatus according to any one or more of the preceding examples and/or any one or more of the examples disclosed below, the apparatus further comprising: a guide coupled to the base and defining one or more apertures corresponding to the one or more sample aspirators, and the one or more aspirators pass through the one or more apertures.

An apparatus according to any one or more of the preceding examples and/or any one or more of the examples disclosed below, the apparatus further comprising: a horizontal guide coupling the base and the guide.

An apparatus according to any one or more of the preceding examples and/or any one or more of the examples disclosed below, the apparatus further comprising: a vertical guide coupling the guide and the cartridge assembly.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the vertical guide comprises a rod coupled to the guide and an aperture of the cartridge housing that receives the rod.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the one or more extractor tubes comprise a plurality of extractor tubes coupled to the extractor coupling.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the extractor tube moves together.

The device according to any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the distal end of each of the extractor tubes has a first surface positioned at a first angle relative to the longitudinal axis of the corresponding extractor and a second surface positioned at a second angle relative to the longitudinal axis of the corresponding extractor.

An apparatus according to any one or more of the preceding examples and/or any one or more of the examples disclosed below, the apparatus further comprising: a horizontal linear guide coupling the cartridge assembly and the bracket.

An apparatus, the apparatus comprising: a sample cartridge, the sample cartridge comprising: a housing; one or more sample tubes movably coupled to the housing; and a biasing element that biases the one or more sample tubes.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the one or more sample tubes comprise a plurality of sample tubes.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the sample tubes are independently movable relative to the housing.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the sample tubes are coupled together and have a flange that engages the biasing element.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the biasing element comprises foam.

The apparatus of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the one or more sample tubes have a tapered portion that tapers toward the recessed portion.

A method, the method comprising: moving a reagent aspirator manifold assembly toward the reagent reservoir receptacle, the reagent aspirator manifold assembly having a first end and a second end and comprising one or more reagent aspirators; engaging the second end of the reagent aspirator manifold assembly with a sample aspirator manifold assembly having a sample aspirator in response to moving the reagent aspirator manifold assembly toward the reagent reservoir receptacle; and moving the sample aspirator toward the sample cartridge receptacle.

The method according to any one or more of the preceding examples and/or any one or more of the examples disclosed below, the method further comprising: a liquid impermeable barrier covering a sample aperture received within the cartridge receptacle is pierced.

The method of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein piercing the liquid impermeable barrier comprises: the aspirator coupling of the sample aspirator engages the stop and the distal end of the sample aspirator pierces the liquid-impermeable barrier.

The method according to any one or more of the preceding examples and/or any one or more of the examples disclosed below, the method further comprising: the sample aspirator is moved relative to a carriage of the aspirator manifold assembly.

The method of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein moving the sample aspirator comprises: the sample aspirator is moved against the biasing force.

The method of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the biasing force is provided by one or more springs.

The method of any one or more of the preceding examples and/or any one or more of the examples disclosed below, wherein the biasing force is provided by a foam.

The previous description is provided to enable any person skilled in the art to practice the various configurations described herein. While the subject technology has been described in detail with reference to various figures and configurations, it should be understood that these figures and configurations are for illustrative purposes only and should not be construed as limiting the scope of the subject technology.

As used herein, an element or step recited in the singular and proceeded with the word "a" or "an" should be understood as not excluding plural said elements or steps, unless such exclusion is explicitly stated. Furthermore, references to "one implementation" are not intended to be interpreted as excluding the existence of additional implementations that also incorporate the recited features. Furthermore, unless expressly stated to the contrary, implementations "including" or "having" one or more elements having a particular attribute may include additional elements whether or not they have that attribute. Furthermore, the terms "comprising," "having," and the like, are used interchangeably herein.

The terms "substantially," "about," and "approximately" are used throughout this specification to describe and illustrate small fluctuations, such as small fluctuations due to variations in processing. For example, they may refer to less than or equal to ±5%, such as less than or equal to ±2%, such as less than or equal to ±1%, such as less than or equal to ±0.5%, such as less than or equal to ±0.2%, such as less than or equal to ±0.1%, such as less than or equal to ±0.05%.

There are many other ways to implement the subject technology. The various functions and elements described herein may be partitioned differently from those shown without departing from the scope of the subject technology. Various modifications to these implementations may be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other implementations. Accordingly, many changes and modifications may be made to the subject technology by one of ordinary skill in the art without departing from the scope of the subject technology. For example, a different number of given modules or units may be employed, one or more different types of given modules or units may be employed, given modules or units may be added or given modules or units may be omitted.

Underlined and/or italicized headings and sub-headings are used for convenience only, do not limit the subject technology, and are not referred to in conjunction with the interpretation of the description of the subject technology. All structural and functional equivalents to the elements of the various implementations described throughout this disclosure that are known or later come to be known to those of ordinary skill in the art are expressly incorporated herein by reference and are intended to be encompassed by the subject technology. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the above description.

It should be understood that all combinations of the foregoing concepts and additional concepts discussed in more detail below (assuming such concepts are not mutually inconsistent) are contemplated as being part of the subject matter disclosed herein. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are contemplated as being part of the subject matter disclosed herein.

Claim (modification according to treaty 19)

1. An apparatus, the apparatus comprising:

a reagent reservoir receptacle for receiving a reagent reservoir;

a sample cartridge receptacle for receiving a sample cartridge;

A reagent aspirator manifold assembly having a first end and a second end and comprising one or more reagent aspirators;

an actuator coupled to the first end of the reagent aspirator manifold assembly to move the reagent aspirator manifold assembly relative to the reagent reservoir receptacle; and

a sample aspirator manifold assembly having one or more sample aspirators,

wherein, in response to the actuator moving the reagent aspirator manifold assembly toward the reagent reservoir receptacle, the second end of the reagent aspirator manifold assembly engages the sample aspirator manifold assembly and moves the one or more sample aspirators toward the sample cartridge receptacle.

2. The apparatus of claim 1, the apparatus further comprising: a biasing element coupling the reagent and sample aspirator manifold assemblies.

3. The device of claim 2, wherein the biasing element is a spring.

4. The device of claim 1, wherein at least one of the following is present: 1) The second end of the reagent aspirator manifold assembly has a lip that engages the aspirator manifold assembly when the second end of the reagent aspirator manifold assembly engages the sample aspirator manifold assembly and moves the one or more sample aspirators toward the sample cartridge receptacle, or 2) the sample aspirator manifold assembly has a lip that engages the second end of the reagent aspirator manifold assembly when the second end of the reagent aspirator manifold assembly engages the sample aspirator manifold assembly and moves the one or more sample aspirators toward the sample cartridge receptacle.

5. The apparatus of any one of the preceding claims, the apparatus further comprising: a flow cell receptacle for receiving a flow cell; and a sample fluid line coupled to each sample aspirator and fluidly coupled to the flow cell.

6. The device of any one of the preceding claims, wherein the reagent reservoir receptacle has a surface engageable by the sample aspirator manifold assembly.

7. The apparatus of claim 6, the apparatus further comprising: a platform having the surface.

8. The apparatus of claim 1, wherein the sample aspirator manifold assembly comprises:

a base;

a bracket having a first side and a second side, the second side including the lip and being operatively coupled to the second end of the reagent aspirator manifold assembly; and a vertical guide coupling the base and the first side of the bracket.

9. The apparatus of claim 8, the apparatus further comprising: a guide coupled to the base and defining one or more apertures corresponding to the one or more sample aspirators, and through which the one or more sample aspirators pass.

10. The apparatus of claim 9, the apparatus further comprising: a horizontal guide coupling the base and the guide.

11. The apparatus according to any one of claims 9 to 10, further comprising: a lead screw assembly coupled to the base and the guide.

12. The device of claim 11, wherein the lead screw assembly comprises a lead screw carried by the base and a lead nut carried by the guide.

13. The apparatus according to any one of claims 8 to 12, further comprising: a cartridge assembly carrying the one or more sample aspirators and coupled to the carriage.

14. An apparatus, the apparatus comprising:

a cartridge assembly of an aspirator manifold assembly, the cartridge assembly comprising:

a cartridge housing;

one or more extractor tubes having a proximal end and a distal end;

one or more aspirator couplings, the proximal end of the aspirator tube coupled to the one or more aspirator couplings, and the one or more aspirator couplings movably coupled to the cartridge housing; and

One or more biasing elements for biasing the one or more aspirator couplings,

wherein the one or more biasing elements allow relative movement between the extractor tube and the cartridge housing.

15. The device of claim 14, wherein the cartridge housing defines a cartridge cavity, and the one or more aspirator couplings are disposed within the cartridge cavity.

16. The device of any one of claims 14 to 15, wherein the one or more extractor tubes comprise a plurality of extractor tubes and the one or more extractor couplings comprise a plurality of extractor couplings.

17. The device of claim 16, wherein each aspirator coupling has a corresponding biasing element.

18. The device of claim 14, wherein each aspirator coupling comprises a spring seat and the one or more biasing elements comprise one or more springs positioned between each spring seat and the cartridge housing.

19. The device of any one of claims 14 to 18, wherein the extractor coupling and corresponding extractor tube are independently movable.

20. The apparatus of claim 14, the apparatus further comprising: a guide plate coupled to the cartridge housing and defining one or more slots, and wherein each extractor coupling has a protrusion movable within a corresponding slot.

21. The device of claim 20, wherein each slot has opposing stops engageable by a corresponding tab.

22. The apparatus of claim 14, wherein the sample aspirator manifold assembly further comprises:

a base;

a bracket carrying the cartridge assembly; and

a vertical guide coupling the base and the first side of the bracket.

23. The apparatus of claim 22, the apparatus further comprising: a guide coupled to the base and defining one or more apertures corresponding to the one or more sample aspirators, and the one or more aspirators pass through the one or more apertures.

24. The apparatus of claim 23, the apparatus further comprising: a horizontal guide coupling the base and the guide.

25. The apparatus of any one of claims 23 to 24, further comprising: a vertical guide coupling the guide and the cartridge assembly.

26. The device of claim 25, wherein the vertical guide comprises a rod coupled to the guide and an aperture of the cartridge housing that receives the rod.

27. The device of any one of claims 14-15 and 22-26, wherein the one or more extractor tubes comprise a plurality of extractor tubes coupled to the extractor coupling.

28. The device of any one of claims 14, 15 and 22 to 27, wherein the extractor tube moves together.

29. The device of any one of claims 14-28, wherein the distal end of each of the extractor tubes has a first surface positioned at a first angle relative to a longitudinal axis of the corresponding extractor tube and a second surface positioned at a second angle relative to the longitudinal axis of the corresponding extractor tube.

30. The apparatus of any one of claims 22 to 29, further comprising: a horizontal linear guide coupling the cartridge assembly and the bracket.

31. An apparatus, the apparatus comprising:

a sample cartridge, the sample cartridge comprising:

a housing;

one or more sample tubes movably coupled to the housing; and

a biasing element that biases the one or more sample tubes.

32. The device of claim 31, wherein the one or more sample tubes comprise a plurality of sample tubes.

33. The device of claim 32, wherein the sample tube is independently movable relative to the housing.

34. The device of claim 32, wherein the sample tubes are coupled together and have flanges that engage the biasing element.

35. The device of any one of claims 31 to 34, wherein the biasing element comprises foam.

36. The device of any one of claims 31 to 35, wherein the one or more sample tubes have a tapered portion that tapers towards a recessed portion.

37. A method, the method comprising:

moving a reagent aspirator manifold assembly toward a reagent reservoir receptacle, the reagent aspirator manifold assembly having a first end and a second end and comprising one or more reagent aspirators;

Engaging the second end of the reagent aspirator manifold assembly with a sample aspirator manifold assembly having a sample aspirator in response to moving the reagent aspirator manifold assembly toward the reagent reservoir receptacle; and

the sample aspirator is moved toward the sample cartridge receptacle.

38. The method of claim 37, the method further comprising: a liquid impermeable barrier covering a sample aperture received within the cartridge receptacle is pierced.

39. The method of claim 38, wherein piercing the liquid impermeable barrier comprises: the aspirator coupling of the sample aspirator engages a stop and the distal end of the sample aspirator pierces the liquid-impermeable barrier.

40. The method of any one of claims 37 to 39, further comprising: the sample aspirator is moved relative to a carriage of the aspirator manifold assembly.

41. The method of claim 40, wherein moving the sample aspirator comprises: the sample aspirator is moved against a biasing force.

42. The method of claim 41, wherein the biasing force is provided by one or more springs.

43. The method of claim 41, wherein the biasing force is provided by foam.

44. An apparatus, the apparatus comprising:

an aspirator manifold assembly, the aspirator manifold assembly comprising:

a base carrying a first sensor and a second sensor vertically spaced apart from the first sensor;

a carriage carrying the aspirator and a first flag and a second flag defining an aperture;

a vertical guide coupling the base and the bracket; and

a processor for identifying that the aspirator manifold assembly is in a first position based on the first sensor sensing the first flag and not sensing the aperture, and for identifying that the aspirator manifold assembly is in a second position based on the second sensor sequentially sensing the second flag and then sensing the aperture.

45. The apparatus of claim 44, wherein the aspirator manifold assembly comprises a reagent aspirator manifold assembly.

46. The device of any one of claims 44 to 45, wherein the first location and the second location are a first distance apart and the first sensor and the second sensor are a second distance apart, the first distance being greater than the second distance.

47. The apparatus of claim 46, wherein the first distance is about 74 millimeters.

48. The apparatus of any one of claims 44 to 47, wherein the second sensor sensing the aperture comprises: the second sensor is in an open state.

49. The apparatus of any one of claims 44 to 48, wherein the processor identifying that the aspirator manifold assembly is in the second position comprises: the second sensor is successively in a closed state and then in an open state.

50. The apparatus of claim 49, wherein the second sensor being in the open state comprises: the second sensor senses the aperture.

51. The apparatus of any one of claims 44 to 50, further comprising: a flag assembly including the first flag and the second flag.

52. The device of claim 51, wherein the flag assembly comprises a body from which the first flag and the second flag extend.

53. The apparatus of any one of claims 44 to 52, further comprising: a sensor assembly including a sensor plate, the first sensor, and the second sensor.

54. The apparatus of any one of claims 44 to 53, further comprising: a lead screw assembly coupled to the base and the bracket.

55. A method, the method comprising:

identifying that a first sensor of an aspirator manifold assembly is in a closed state, the aspirator manifold assembly comprising a base carrying the first sensor and a second sensor vertically spaced apart from the first sensor, and a bracket carrying an aspirator;

determining that the aspirator manifold assembly is in a first position based on the first sensor being in the closed state;

moving the carriage toward a second position;

identifying that the second sensor of the aspirator manifold assembly is in a closed state;

moving the carriage toward the second position a threshold distance;

identifying that the second sensor of the aspirator manifold assembly is in an open state; and

the aspirator manifold assembly is determined to be in the second position based on the second sensor being in the closed state sequentially and then in the open state after the carriage has moved the threshold distance.

56. The method of claim 55, wherein the threshold distance is about 2.75 millimeters.

57. The method of any of claims 55 to 56, wherein the bracket carries a first flag and a second flag defining an aperture.

58. The method of claim 57, wherein determining that the aspirator manifold assembly is in the second position based on the second sensor being sequentially in the closed state and then in the open state comprises: the second sensor senses the second flag and the orifice sequentially.

59. The method of any one of claims 57 to 58, wherein the aperture comprises a through-hole.

60. The method of any one of claims 57 to 58, wherein the aperture comprises a slit.

61. A device according to any one of claims 1 to 3, wherein at least one of the following is present: 1) The second end of the reagent aspirator manifold assembly has a lip that engages the aspirator manifold assembly when the second end of the reagent aspirator manifold assembly engages the sample aspirator manifold assembly and moves the one or more sample aspirators toward the sample cartridge receptacle, or 2) the sample aspirator manifold assembly has a lip that engages the second end of the reagent aspirator manifold assembly when the second end of the reagent aspirator manifold assembly engages the sample aspirator manifold assembly and moves the one or more sample aspirators toward the sample cartridge receptacle.

62. The device of any one of claims 1 to 7 and 61, wherein the sample aspirator manifold assembly comprises:

a base;

a bracket having a first side and a second side, the second side including the lip and being operatively coupled to the second end of the reagent aspirator manifold assembly; and

a vertical guide coupling the base and the first side of the bracket.

63. The device of any one of claims 14 to 17, wherein each aspirator coupling comprises a spring seat, and the one or more biasing elements comprise one or more springs positioned between each spring seat and the cartridge housing.

64. The apparatus of any one of claims 14 to 19 and 63, further comprising: a guide plate coupled to the cartridge housing and defining one or more slots, and wherein each extractor coupling has a protrusion movable within the corresponding slot.

65. The device of any one of claims 14 to 21, 63 and 64, wherein the sample aspirator manifold assembly further comprises:

a base;

a bracket carrying the cartridge assembly; and

A vertical guide coupling the base and the first side of the bracket.

Claims (65)

1. An apparatus, the apparatus comprising:

a reagent reservoir receptacle for receiving a reagent reservoir;

a sample cartridge receptacle for receiving a sample cartridge;

a reagent aspirator manifold assembly having a first end and a second end and comprising one or more reagent aspirators;

an actuator coupled to the first end of the reagent aspirator manifold assembly to move the reagent aspirator manifold assembly relative to the reagent reservoir receptacle; and

a sample aspirator manifold assembly having one or more sample aspirators,

wherein, in response to the actuator moving the reagent aspirator manifold assembly toward the reagent reservoir receptacle, the second end of the reagent aspirator manifold assembly engages the sample aspirator manifold assembly and moves the one or more sample aspirators toward the sample cartridge receptacle.

2. The apparatus of claim 1, the apparatus further comprising: a biasing element coupling the reagent and sample aspirator manifold assemblies.

3. The device of claim 2, wherein the biasing element is a spring.

4. The device of claim 1, wherein at least one of the following is present: 1) The second end of the reagent aspirator manifold assembly has a lip that engages the aspirator manifold assembly when the second end of the reagent aspirator manifold assembly engages the sample aspirator manifold assembly and moves the one or more sample aspirators toward the sample cartridge receptacle, or 2) the sample aspirator manifold assembly has a lip that engages the second end of the reagent aspirator manifold assembly when the second end of the reagent aspirator manifold assembly engages the sample aspirator manifold assembly and moves the one or more sample aspirators toward the sample cartridge receptacle.

5. The apparatus of any one of the preceding claims, the apparatus further comprising: a flow cell receptacle for receiving a flow cell; and a sample fluid line coupled to each sample aspirator and fluidly coupled to the flow cell.

6. The device of any one of the preceding claims, wherein the reagent reservoir receptacle has a surface engageable by the sample aspirator manifold assembly.

7. The apparatus of claim 6, the apparatus further comprising: a platform having the surface.

8. The apparatus of claim 1, wherein the sample aspirator manifold assembly comprises:

a base;

a bracket having a first side and a second side, the second side including the lip and being operatively coupled to the second end of the reagent aspirator manifold assembly; and a vertical guide coupling the base and the first side of the bracket.

9. The apparatus of claim 8, the apparatus further comprising: a guide coupled to the base and defining one or more apertures corresponding to the one or more sample aspirators, and through which the one or more sample aspirators pass.

10. The apparatus of claim 9, the apparatus further comprising: a horizontal guide coupling the base and the guide.

11. The apparatus according to any one of claims 9 to 10, further comprising: a lead screw assembly coupled to the base and the guide.

12. The device of claim 11, wherein the lead screw assembly comprises a lead screw carried by the base and a lead nut carried by the guide.

13. The apparatus according to any one of claims 8 to 13, further comprising: a cartridge assembly carrying the one or more sample aspirators and coupled to the carriage.

14. An apparatus, the apparatus comprising:

a cartridge assembly of an aspirator manifold assembly, the cartridge assembly comprising:

a cartridge housing;

one or more extractor tubes having a proximal end and a distal end;

one or more aspirator couplings, the proximal end of the aspirator tube coupled to the one or more aspirator couplings, and the one or more aspirator couplings movably coupled to the cartridge housing; and

one or more biasing elements for biasing the one or more aspirator couplings,

Wherein the one or more biasing elements allow relative movement between the extractor tube and the cartridge housing.

15. The device of claim 14, wherein the cartridge housing defines a cartridge cavity, and the one or more aspirator couplings are disposed within the cartridge cavity.

16. The device of any one of claims 14 to 15, wherein the one or more extractor tubes comprise a plurality of extractor tubes and the one or more extractor couplings comprise a plurality of extractor couplings.

17. The device of claim 16, wherein each aspirator coupling has a corresponding biasing element.

18. The device of claim 14, wherein each aspirator coupling comprises a spring seat and the one or more biasing elements comprise one or more springs positioned between each spring seat and the cartridge housing.

19. The device of any one of claims 14 to 18, wherein the extractor coupling and corresponding extractor tube are independently movable.

20. The apparatus of claim 14, the apparatus further comprising: a guide plate coupled to the cartridge housing and defining one or more slots, and wherein each extractor coupling has a protrusion movable within a corresponding slot.

21. The device of claim 20, wherein each slot has opposing stops engageable by a corresponding tab.

22. The apparatus of claim 14, wherein the sample aspirator manifold assembly further comprises:

a base;

a bracket carrying the cartridge assembly; and

a vertical guide coupling the base and the first side of the bracket.

23. The apparatus of claim 22, the apparatus further comprising: a guide coupled to the base and defining one or more apertures corresponding to the one or more sample aspirators, and the one or more aspirators pass through the one or more apertures.

24. The apparatus of claim 23, the apparatus further comprising: a horizontal guide coupling the base and the guide.

25. The apparatus of any one of claims 23 to 24, further comprising: a vertical guide coupling the guide and the cartridge assembly.

26. The device of claim 25, wherein the vertical guide comprises a rod coupled to the guide and an aperture of the cartridge housing that receives the rod.

27. The device of any one of claims 14-15 and 22-26, wherein the one or more extractor tubes comprise a plurality of extractor tubes coupled to the extractor coupling.

28. The device of any one of claims 14, 15 and 22 to 27, wherein the extractor tube moves together.

29. The device of any one of claims 14-28, wherein the distal end of each of the extractor tubes has a first surface positioned at a first angle relative to a longitudinal axis of the corresponding extractor tube and a second surface positioned at a second angle relative to the longitudinal axis of the corresponding extractor tube.

30. The apparatus of any one of claims 22 to 29, further comprising: a horizontal linear guide coupling the cartridge assembly and the bracket.

31. An apparatus, the apparatus comprising:

a sample cartridge, the sample cartridge comprising:

a housing;

one or more sample tubes movably coupled to the housing; and

a biasing element that biases the one or more sample tubes.

32. The device of claim 31, wherein the one or more sample tubes comprise a plurality of sample tubes.

33. The device of claim 32, wherein the sample tube is independently movable relative to the housing.

34. The device of claim 32, wherein the sample tubes are coupled together and have flanges that engage the biasing element.

35. The device of any one of claims 31 to 34, wherein the biasing element comprises foam.

36. The device of any one of claims 31 to 35, wherein the one or more sample tubes have a tapered portion that tapers towards a recessed portion.

37. A method, the method comprising:

moving a reagent aspirator manifold assembly toward a reagent reservoir receptacle, the reagent aspirator manifold assembly having a first end and a second end and comprising one or more reagent aspirators;

engaging the second end of the reagent aspirator manifold assembly with a sample aspirator manifold assembly having a sample aspirator in response to moving the reagent aspirator manifold assembly toward the reagent reservoir receptacle; and

the sample aspirator is moved toward the sample cartridge receptacle.

38. The method of claim 37, the method further comprising: a liquid impermeable barrier covering a sample aperture received within the cartridge receptacle is pierced.

39. The method of claim 38, wherein piercing the liquid impermeable barrier comprises: the aspirator coupling of the sample aspirator engages a stop and the distal end of the sample aspirator pierces the liquid-impermeable barrier.

40. The method of any one of claims 37 to 39, further comprising: the sample aspirator is moved relative to a carriage of the aspirator manifold assembly.

41. The method of claim 40, wherein moving the sample aspirator comprises: the sample aspirator is moved against a biasing force.

42. The method of claim 41, wherein the biasing force is provided by one or more springs.

43. The method of claim 41, wherein the biasing force is provided by foam.

44. An apparatus, the apparatus comprising:

an aspirator manifold assembly, the aspirator manifold assembly comprising:

a base carrying a first sensor and a second sensor vertically spaced apart from the first sensor;

A carriage carrying the aspirator and a first flag and a second flag defining an aperture;

a vertical guide coupling the base and the bracket; and

a processor for identifying that the aspirator manifold assembly is in a first position based on the first sensor sensing the first flag and not sensing the aperture, and for identifying that the aspirator manifold assembly is in a second position based on the second sensor sequentially sensing the second flag and then sensing the aperture.

45. The apparatus of claim 44, wherein the aspirator manifold assembly comprises a reagent aspirator manifold assembly.

46. The device of any one of claims 44 to 45, wherein the first location and the second location are a first distance apart and the first sensor and the second sensor are a second distance apart, the first distance being greater than the second distance.

47. The apparatus of claim 46, wherein the first distance is about 74 millimeters.

48. The apparatus of any one of claims 44 to 47, wherein the second sensor sensing the aperture comprises: the second sensor is in an open state.

49. The apparatus of any one of claims 44 to 48, wherein the processor identifying that the aspirator manifold assembly is in the second position comprises: the second sensor is successively in a closed state and then in an open state.

50. The apparatus of claim 50, wherein the second sensor being in the open state comprises: the second sensor senses the aperture.

51. The apparatus of any one of claims 44 to 50, further comprising: a flag assembly including the first flag and the second flag.

52. The device of claim 51, wherein the flag assembly comprises a body from which the first flag and the second flag extend.

53. The apparatus of any one of claims 44 to 52, further comprising: a sensor assembly including a sensor plate, the first sensor, and the second sensor.

54. The apparatus of any one of claims 44 to 53, further comprising: a lead screw assembly coupled to the base and the bracket.

55. A method, the method comprising:

identifying that a first sensor of an aspirator manifold assembly is in a closed state, the aspirator manifold assembly comprising a base carrying the first sensor and a second sensor vertically spaced apart from the first sensor, and a bracket carrying an aspirator;

determining that the aspirator manifold assembly is in a first position based on the first sensor being in the closed state;

moving the carriage toward a second position;

identifying that the second sensor of the aspirator manifold assembly is in a closed state;

moving the carriage toward the second position a threshold distance;

identifying that the second sensor of the aspirator manifold assembly is in an open state; and

the aspirator manifold assembly is determined to be in the second position based on the second sensor being in the closed state sequentially and then in the open state after the carriage has moved the threshold distance.

56. The method of claim 55, wherein the threshold distance is about 2.75 millimeters.

57. The method of any of claims 55 to 56, wherein the bracket carries a first flag and a second flag defining an aperture.

58. The method of claim 57, wherein determining that the aspirator manifold assembly is in the second position based on the second sensor being sequentially in the closed state and then in the open state comprises: the second sensor senses the second flag and the orifice sequentially.

59. The method of any one of claims 57 to 58, wherein the aperture comprises a through-hole.

60. The method of any one of claims 57 to 58, wherein the aperture comprises a slit.

61. A device according to any one of claims 1 to 3, wherein at least one of the following is present: 1) The second end of the reagent aspirator manifold assembly has a lip that engages the aspirator manifold assembly when the second end of the reagent aspirator manifold assembly engages the sample aspirator manifold assembly and moves the one or more sample aspirators toward the sample cartridge receptacle, or 2) the sample aspirator manifold assembly has a lip that engages the second end of the reagent aspirator manifold assembly when the second end of the reagent aspirator manifold assembly engages the sample aspirator manifold assembly and moves the one or more sample aspirators toward the sample cartridge receptacle.

62. The device of any one of claims 1 to 7 and 61, wherein the sample aspirator manifold assembly comprises:

a base;

a bracket having a first side and a second side, the second side including the lip and being operatively coupled to the second end of the reagent aspirator manifold assembly; and

a vertical guide coupling the base and the first side of the bracket.

63. The device of any one of claims 14 to 17, wherein each aspirator coupling comprises a spring seat, and the one or more biasing elements comprise one or more springs positioned between each spring seat and the cartridge housing.

64. The apparatus of any one of claims 14 to 19 and 63, further comprising: a guide plate coupled to the cartridge housing and defining one or more slots, and wherein each extractor coupling has a protrusion movable within the corresponding slot.

65. The device of any one of claims 14 to 21, 63 and 64, wherein the sample aspirator manifold assembly further comprises:

a base;

a bracket carrying the cartridge assembly; and

A vertical guide coupling the base and the first side of the bracket.