This disclosure, in general, relates to rotor assemblies and methods for using such rotor assemblies.
In fields such as chemistry, molecular biology, and biomedical sciences, researchers increasingly rely on small-scale sensor arrays for conducting testing. In particular, analytes, particularly analytes attached to beads or particle substrates, are deposited onto the small-scale sensor arrays for testing. As the number of sensors increases and the size of the individual sensors in the sensor array decreases, depositing analytes into the sensor array is increasingly difficult. Factors such as Brownian motion become increasingly dominant over gravity.
Therefore, an improved rotor assembly would be desirable.
In a first aspect, a fluid transfer housing to engage a sensor array having a flow cell includes a solution inlet and a solution outlet to engage ports of the flow cell; a transfer basin; a solution retainer disposed between the solution outlet and the transfer basin; and a collection reservoir in fluid communication with the transfer basin.
In a second aspect, a rotor assembly includes a rotor plate to rotate around a first axis; a bucket rotatably attached to the rotor plate and to rotate around a second axis; and a stop plate to rotate around the first axis relative to the rotor plate between an open position and a closed position. When in the closed position, the stop plate is to engage the bucket to fix an angular position of the bucket relative to a plane of rotation of the rotor assembly. The rotor assembly further includes a housing for a sensor array component. The housing is disposed in the bucket and includes a solution inlet, a solution outlet, a transfer basin, a solution retainer disposed between the solution outlet and the transfer basin, and a collection reservoir in fluid communication with the transfer basin. The solution inlet and the solution outlet engage ports of a flow cell of a sensor array.
In a third aspect, a method of loading a sensor array component includes applying a solution to a sensor array component located within a housing that includes a solution inlet, a solution outlet, a solution retainer, a transfer basin, and a collection reservoir disposed in a bucket of a rotor assembly when a stop plate of the rotor assembly is in a closed position. The method further includes spinning the rotor assembly, the bucket rotating to a horizontal or negative angle relative to a plane of rotation of the rotor assembly, and the solution flowing out of the fluid outlet, over the solution retainer, and into the transfer basin. The method also includes moving the stop plate to an open position and spinning the rotor assembly, the bucket rotating to a positive angle relative to the plane of rotation of the rotor assembly, and the solution flowing from the transfer basin into the collection reservoir. The method optionally includes removing the solution from the collection reservoir.
This invention has many advantages, including the ability to retain the solution in the collection reservoir, enabling the removal of the solution from the collection reservoir after spinning the rotor assembly.
The present disclosure may be better understood, and its numerous features and advantages made apparent to those skilled in the art by referencing the accompanying drawings.
The use of the same reference symbols in different drawings indicates similar or identical items.
In an exemplary embodiment illustrated in
The rotor assembly 100 can further include a stop plate 110. The stop plate 110 can include wings 112 to engage the buckets 104, limiting rotation of the buckets around axles 120. The stop plate 110 can further include rings 118 that can be engaged, for example, by a tip of a pipetting robot. Using a pipetting robot and optionally the associated centrifuge motor, the stop plate 110 can be rotated around the central axis 116 or relative to the rotor plate 102, moving the wings 112 from an open position as illustrated in
In addition, the rotor assembly 100 can include a coupler 114 to secure the rotor assembly 100 to the central axis 116 of a centrifuge motor.
As illustrated in
In proximity to the bucket opening 304 of the rotor plate 102, the rotor plate 102 can include an upper stop surface 312 and a rear stop surface 316. When a stop plate 110 is in a closed position, the stop plate 102 can force a bucket 104 or sensor array component into contact with the upper stop surface 312 or the backstop surface 316, limiting rotation of the bucket around the axles 120 engaging the recesses 310.
Further, the stop plate 110 includes arms 704 and distal rings 118. The rings 118 can be engaged to permit relative rotation of the stop plate 110 around the axis 116 relative to the coupler 114 and rotor plate 102 (illustrated in
As illustrated in
At a bottom surface of the bucket 104, as illustrated in
In particular, as illustrated in
To further illustrate the operation of the rotor assembly,
In particular, the rotor assembly can be used to load samples onto a sensor array component. As illustrated in
The sensor array component is inserted into a bucket, as illustrated at 1704. In particular, the bucket secures the sensor array component when the rotor assembly spins.
Optionally, the bucket is inserted into the rotor assembly, and a solution is applied to the sensor array component, as illustrated at 1706. In particular, the solution can be applied while the stop plate is in the closed position to hold the bucket in place. Alternatively, the solution can be applied prior to inserting the bucket into the rotor plate.
As illustrated at 1708, the stop plate can be positioned to an open position that permits the bucket and sensor array component to swing relative to an axis extending in the direction of the rotation of the rotor assembly. In particular, the bucket can be weighted to rotate to a positive angle around an axis that extends in a direction along a direction of rotation of the rotor assembly.
Once the stop plate has been moved into an open position, the rotor assembly including the bucket and sensor array component can be spun, as illustrated at 1710. As a result, the bucket and sensor array component can rotate to an angle of at least 45°, such as at least 75°, or even at least 80° during spinning of the rotor assembly. During spinning of the rotor assembly, the bucket may swing to a position or angle in a range of 85° to 110°, such as an angle of 85° to 105°, or even an angle of 85° to 95°, such as approximately 90°, relative to the plane of rotation of the rotor assembly.
Following spinning, the stop plate can be positioned into a closed position to limit the spin angle of the bucket and sensor array component, as illustrated at 1712. For example, the stop plate can limit the spin angle of the bucket to near zero or slightly negative. Optionally, the rotary assembly and the sensor array component can be spun, as illustrated at 1714, while the stop plate is in the closed position and limits the movement of bucket. In particular, spinning at a negative angle can facilitate removal of solution from the sensor array component.
The remaining solution can be removed from the sensor array component, as illustrated at 1716, for example, by pipetting the remaining solution from a recess in the cap. The sensor array component can then be removed from the bucket as illustrated at 1718 and used in a separate testing apparatus.
In a particular example, the sensor array component has particular use when sequencing target polynucleotides. As illustrated in the method 1800 of
As illustrated at 1804, the amplified sample, particularly beads or particle substrates, can be applied to a sensor array component. In particular, a solution including the amplified sample is applied to or loaded into the sensor array component, and undergoes spinning under various angular conditions, securing to the bead or particulate substrates into the sensor array component. The sensor array component can then be inserted into a sequencing apparatus and the amplified sample that is loaded onto the sensor array component can be sequenced, as illustrated at 1806.
Such a rotor assembly finds particular use in a pipetting robot assembly.
In operation, the translation device 1902 manipulates the position of the syringe pump 1904 to retrieve tips from the tip rack 1906 and perform the various functions of the system 1900. For example, the syringe pump 1904 can be utilized along with reagents of the reagent rack 1916 to form an emulsion including enzymes and a sample in an aqueous discontinuous phase surrounded by an immiscible continuous phase. For example, the sample and enzyme solutions can be stored in the chilled reagent block 1910. The emulsion can be formed within a tube in the reagent rack 1916. In particular, the emulsion can be generated by rapid pipetting. In another example, the emulsion can be generated by pipetting through a restriction.
Following formation of the emulsion, the emulsion can be transferred to a thermocycler plate on a thermocycler 1912 using the translation device 1902 and the syringe pump 1904. The thermocycler plate 1912 can be utilized to perform polymerase chain reaction (PCR) or recombinase polymerase amplification (RPA). Upon completion of the PCR reaction, the emulsion can be transferred from the thermocycler 1912 to one of the emulsion breaking centrifuges 1914. The emulsion can be injected into the emulsion breaking centrifuge 1914 that includes tubes having a surfactant solution. As the centrifuge rotates, the emulsion is injected into the centrifuge. When the emulsion contacts the surfactant solution within the tubes of the centrifuge 1914, aqueous phase components are driven into the solution while oil phase components are removed from the tube.
The PCR or RPA process can generate amplified beads including a number of target polynucleotides. Such amplified beads can be washed and separated from other aqueous solution components using an enrichment system. In particular, the reagent rack 1916 can be modified with the magnet system to permit enrichment using magnetic particles that bind to the amplified beads.
Following enrichment, the beads can be transferred and loaded onto a sequencing device, such as a chip configured for detecting sequencing byproducts, using the loading centrifuge 1918. For example, aliquots of the solution including the amplified beads can be injected into ports on the sequencing device disposed on the rack within the loading centrifuge 1918. The centrifuge 1918 can be positioned and spun, for example, as described above, to facilitate the loading. In particular, a tip attached to the syringe pump 1904 can be positioned in a ring of a stop plate to move the stop plate between open and closed positions. The process can be repeated one or more times to improve loading density. As a result, a sequencing device loaded with amplified particles, incorporating amplified target nucleotides from the sample, is provided with minimal human interaction.
Throughout the process, the syringe pump 1914 can utilize a variety of pipette tips acquired from the pipette tip rack 1906. Further, tips can be provided that assist with movement of magnets, loading of tubes within the emulsion breaking centrifuge 1914, configuring the loading centrifuge, or other functions. To assist with removal of the tips from the syringe pump 1904, a tip removal device can be provided.
In other embodiments, the stop plate can be formed from two separate components, the magnets can be positioned at different locations on different components, and the axles of the buckets can be secured to the buckets and be of different sizes in contrast to securing the axles to the rotor plate. While exemplary embodiments are illustrated in
As illustrated in
As illustrated in the bottom view of the upper stop plate 2006 in
As illustrated in the side view in
The rotor plate 2004 includes features similar to those described in relation to the rotor plate above. In the example illustrated in
In further example, the rotor plate 2004 can include slots 2502 to receive axles of the buckets 2002. In such an example, the axles are secured to the buckets 2002 and can be slid into the slots 2502 to rotatably couple the buckets 2002 to the rotor plate 2004. In a particular example, the slots 2502 of the rotor plate 2004 can be configured to receive axles of different size. In particular, a slot 2502 on a clockwise side of the recess to receive the buckets 2002 can have a size different from the slots on the counterclockwise side. As illustrated in
In another exemplary embodiment illustrated in
The rotor assembly 2700 can further include a stop plate 2710. The stop plate 2710 engages the buckets 2704, limiting rotation of the buckets 2704 around axles 2720. The stop plate 2710 can further include rings 2718 that can be engaged, for example, by a tip of a pipetting robot. Using a pipetting robot and optionally the associated centrifuge motor, the stop plate 2710 can be rotated around the central axis 2716 or relative to the rotor plate 2702, moving the stop plate 2710 from a closed position as illustrated in
In particular, as illustrated in
As shown in
When the housing 2705 is horizontal and viewed from a side, a lower surface or bottom of the transfer basin 3140 is higher than the lower surface or bottom of the collection reservoir 3150. In addition, when place in the rotor, the transfer basin 3140 is closer to a back edge of the housing 2705 than the collection reservoir 3150 or is disposed radially outwardly from the collection reservoir 3150. Further, the transfer basin 3140 is closer to a back edge of the housing 2705 than the solution outlet 3120 or is disposed radially outwardly from the solution outlet 3120. In an example, the collection reservoir 3150 has a conical shape to allow a pipette to draw fluid from the collection reservoir 3150 with limited fluid retention in the collection reservoir 3150.
The solution retainer 3130 is disposed between the solution outlet 3120 and the transfer basin 3140. The solution retainer 3130 can include an upper lip 3132 separating the transfer basin 3140 from the solution outlet 3120. The lower surface or bottom of the transfer basin 3140 can be lower than the lip 3132 of the solution retainer 3130.
The housing 3705 can also include clips 3170 to secure a sensor array and flow cell to a bucket. In an example, the clips 3170 can engage the sensor array and flow cell on one side and engage openings in the bucket on an opposite side.
In a further example, the housing 3705 can include gaskets 3180 to engage ports of a flow cell over a sensor array. In an example, the gaskets 3180 can be co-molded to the housing body and formed of a flexible polymeric material.
As also shown in
As shown in
In particular, the rotor assembly can be used to load samples onto a sensor array component. As illustrated in
The sensor array component is inserted into a bucket, as illustrated at 3404. In particular, the bucket secures the sensor array component when the rotor assembly spins.
Optionally, the bucket is inserted into the rotor assembly, and a solution is applied to the sensor array component, as illustrated at 3406. In particular, the solution can be applied while the stop plate is in the closed position to hold the bucket in place. Alternatively, the solution can be applied prior to inserting the bucket into the rotor plate.
The stop plate can be positioned into a closed position to limit the spin angle of the bucket and sensor array component, as illustrated at 3408. For example, the stop plate can limit the spin angle of the bucket to near zero or slightly negative. The rotary assembly and the sensor array component can be spun, as illustrated at 3410, while the stop plate is in the closed position and limits the movement of bucket. In particular, spinning at a negative angle can facilitate flowing the solution over the solution retainer and into the transfer basin of the housing.
As illustrated at 3412, the stop plate can be positioned to an open position that permits the bucket and sensor array component to swing relative to an axis extending in the direction of the rotation of the rotor assembly. In particular, the bucket can be weighted to rotate to a positive angle around an axis that extends in a direction along a direction of rotation of the rotor assembly.
Once the stop plate has been moved into an open position, the rotor assembly including the bucket and sensor array component can be spun, as illustrated at 3414. As a result, the bucket and sensor array component can rotate to an angle of at least 45°, such as at least 75°, or even at least 80° during spinning of the rotor assembly. During spinning of the rotor assembly, the bucket may swing to a position or angle in a range of 85° to 110°, such as an angle of 85° to 105°, or even an angle of 85° to 95°, such as approximately 90°, relative to the plane of rotation of the rotor assembly, and the solution can flow from the transfer basin into the collection reservoir.
The remaining solution can be removed from the sensor array component, as illustrated at 3416, for example, by pipetting the remaining solution from the collection reservoir. The sensor array component can then be removed from the bucket, as illustrated at 3418, and used in a separate testing apparatus.
In an alternative example, the stop plate can be positioned to allow the bucket to rotate around the axles following application of the solution, as illustrated at 3406, and the rotor spun prior to positioning the stop plate to limit the spin angle, as illustrated at 3408. Such an additional spinning can assist with deposition of particles and beads into alignment with sensors of the sensor array, such as with deposition of particles or beads into wells associated with the sensors.
In one embodiment, a rotor assembly includes a rotor plate to rotate around a first axis, a bucket rotatably attached to the rotor plate and to rotate around a second axis, and a stop plate to rotate around the first axis relative to the rotor plate between an open position and a closed position, when in the closed position, the stop plate is to engage the bucket to fix an angular position of the bucket relative to a plane of rotation of the rotor assembly. The bucket can include a chamfered surface to engage the chamfered surface of the stop plate. In certain embodiments, the bucket can be weighted to provide an angular position relative to a plane of rotation of the rotor assembly when the rotor assembly is spinning. The rotor assembly further includes a housing for a sensor array component, the housing disposed in the bucket and including a transfer basin, a solution retainer adjacent to the transfer basin, and a collection reservoir in fluid communication with the transfer basin. The stop plate can include a wing with a chamfered surface to engage a surface of the bucket when the stop plate is moving to the closed position. In some embodiments, the stop plate can include an arm and a ring. The rotor plate can include an opening through which the ring of the stop plate can be accessed. The ring can include a chamfered slip.
The rotor assembly can further include a coupler having a central shaft to engage the rotor plate and the stop plate. The coupler can include a stop surface to engage a stop surface of the stop plate when the stop plate is in an open or closed position. In some embodiments, the coupler can include a magnet to attract a magnet of the stop plate when the stop plate is in an open or closed position. The rotor plate can include a recess with slots to receive the wings of the coupler to engage the slots of the rotor plate.
The rotor plate can include a top stop surface to engage the bucket or a sensor array component when the stop plate is in a closed position. Alternatively, the rotor plate can include a rear stop surface to engage the bucket when the stop plate is in a closed position.
In another embodiment, a method of loading a sensor array component includes applying a solution to a sensor array component located within a housing that includes a solution retainer, a transfer basin, and a collection reservoir disposed in a bucket of a rotor assembly when a stop plate of the rotor assembly is in a closed position. The method further includes spinning the rotor assembly, the bucket rotating to a horizontal or negative angle relative to the plane of rotation of the rotor assembly, the solution flowing over the retainer into the transfer basin, moving the stop plate to an open position, spinning the rotor assembly, the bucket rotating to a positive angle relative to a plane of rotation of the rotor assembly, the solution flowing from the transfer basin into the collection reservoir, and removing the solution from the collection reservoir. The rotor assembly can include a rotor plate to rotate around a first axis, a bucket rotatably attached to the rotor plate and to rotate around a second axis, and a stop plate to rotate around the first axis relative to the rotor plate between an open position and a closed position, when in the closed position, the stop plate is to engage the bucket to fix an angular position of the bucket relative to a plane of rotation of the rotor assembly.
In a first aspect, a fluid transfer housing to engage a sensor array having a flow cell includes a solution inlet and a solution outlet to engage ports of the flow cell; a transfer basin; a solution retainer disposed between the solution outlet and the transfer basin; and a collection reservoir in fluid communication with the transfer basin.
In a second aspect, a rotor assembly includes a rotor plate to rotate around a first axis; a bucket rotatably attached to the rotor plate and to rotate around a second axis; and a stop plate to rotate around the first axis relative to the rotor plate between an open position and a closed position. When in the closed position, the stop plate is to engage the bucket to fix an angular position of the bucket relative to a plane of rotation of the rotor assembly. The rotor assembly further includes a housing for a sensor array component. The housing is disposed in the bucket and includes a solution inlet, a solution outlet, a transfer basin, a solution retainer disposed between the solution outlet and the transfer basin, and a collection reservoir in fluid communication with the transfer basin. The solution inlet and the solution outlet engage ports of a flow cell of a sensor array.
In a third aspect, a method of loading a sensor array component includes applying a solution to a sensor array component located within a housing that includes a solution inlet, a solution outlet, a solution retainer, a transfer basin, and a collection reservoir disposed in a bucket of a rotor assembly when a stop plate of the rotor assembly is in a closed position. The method further includes spinning the rotor assembly, the bucket rotating to a horizontal or negative angle relative to a plane of rotation of the rotor assembly, and the solution flowing out of the fluid outlet, over the solution retainer, and into the transfer basin. The method also includes moving the stop plate to an open position and spinning the rotor assembly, the bucket rotating to a positive angle relative to the plane of rotation of the rotor assembly, the solution flowing from the transfer basin into the collection reservoir. The method optionally includes removing the solution from the collection reservoir.
In an example of the above aspects, the solution inlet has a conical opening to receive a distal end of a pipette tip.
In another example of the above aspects and the above examples, the solution inlet and the solution outlet further include gasket material to engage the ports of the flow cell.
In a further example of the above aspects and the above examples, the housing further includes a cap disposed over the transfer basin. For example, the cap can define an opening for accessing the solution outlet. In another example, the cap can define an opening for accessing the collection reservoir. In a further example, the housing further includes a fluid path defined between the cap and the solution retainer.
In an additional example of the above aspects and the above examples, when in a horizontal position and viewed from a side, the collection reservoir has a lower bottom than the transfer basin.
In another example of the above aspects and the above examples, when in a horizontal position and viewed from a side, the transfer basin has a bottom that is lower than the top of the solution retainer.
In a further example of the above aspects and the above examples, the transfer basin is positioned radially outwardly from the solution outlet and the solution retainer.
In an additional example of the above aspects and the above examples, the transfer basin is positioned radially outwardly from the collection reservoir.
In an example of the second aspect and the above examples, the stop plate includes a wing with a chamfered surface to engage a surface of the bucket when the stop plate is moving to the closed position. For example, the bucket includes a chamfered surface to engage the chamfered surface of the stop plate.
In another example of the second aspect and the above examples, the rotor plate includes a rear stop surface to engage the bucket when the stop plate is in a closed position.
In a further example of the second aspect and the above examples, the bucket is weighted to provide an angular position relative to a plane of rotation of the rotor assembly when the rotor assembly is spinning and the stop plate is in an open position.
In a further example of the above aspects and the above examples, the transfer basin is positioned radially outwardly from the solution outlet and the solution retainer relative to the first axis.
In an additional example of the above aspects and the above examples, the transfer basin is positioned radially outwardly from the collection reservoir relative to the first axis.
In an example of the third example and the above example, the rotor assembly includes a rotor plate to rotate around a first axis, a bucket rotatably attached to the rotor plate and to rotate around a second axis, and a stop plate to rotate around the first axis relative to the rotor plate between an open position and a closed position, when in the closed position, the stop plate is to engage the bucket to fix an angular position of the bucket relative to a plane of rotation of the rotor assembly.
In another example of the third aspect and the above examples, applying the solution includes applying the solution to the fluid inlet of the housing.
In a further example of the third aspect and the above examples, in response to spinning the rotor assembly with the bucket in the horizontal or negative angle, the solution flows through the flow cell to the solution outlet.
Note that not all of the activities described above in the general description or the examples are required, that a portion of a specific activity may not be required, and that one or more further activities may be performed in addition to those described. Still further, the order in which activities are listed are not necessarily the order in which they are performed.
In the foregoing specification, the concepts have been described with reference to specific embodiments. However, one of ordinary skill in the art appreciates that various modifications and changes can be made without departing from the scope of the invention as set forth in the claims below. Accordingly, the specification and figures are to be regarded in an illustrative rather than a restrictive sense, and all such modifications are intended to be included within the scope of invention.
As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having” or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a process, method, article, or apparatus that comprises a list of features is not necessarily limited only to those features but may include other features not expressly listed or inherent to such process, method, article, or apparatus. Further, unless expressly stated to the contrary, “or” refers to an inclusive-or and not to an exclusive-or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).
Also, the use of “a” or “an” are employed to describe elements and components described herein. This is done merely for convenience and to give a general sense of the scope of the invention. This description should be read to include one or at least one and the singular also includes the plural unless it is obvious that it is meant otherwise.
Benefits, other advantages, and solutions to problems have been described above with regard to specific embodiments. However, the benefits, advantages, solutions to problems, and any feature(s) that may cause any benefit, advantage, or solution to occur or become more pronounced are not to be construed as a critical, required, or essential feature of any or all the claims.
After reading the specification, skilled artisans will appreciate that certain features are, for clarity, described herein in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features that are, for brevity, described in the context of a single embodiment, may also be provided separately or in any subcombination. Further, references to values stated in ranges include each and every value within that range.
This application claims benefit of U.S. Provisional Application No. 62/195,937, filed Jul. 23, 2015, and entitled “LIQUID GUIDE AND METHOD OF USE,” which is incorporated herein by reference in its entirety.
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