Inducing dean vortices for enhanced rinsing

Abstract

A system for cleaning a probe includes a pump, a probe, and tubing having a curved portion, wherein a fluid path is formed between the pump and the probe at least in part by the tubing. The geometry of the curved portion causes fluid flowing in the fluid path to form one or more Dean vortices.

Description

INDUCING DEAN VORTICES FOR ENHANCED RINSINGCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 639,260, entitled “INDUCING DEAN VORTICES FOR ENHANCED RINSING” filed April 26, 2024, the disclosure of which is hereby incorporated by reference in its entirety for all purposes.TECHNICAL FIELD

[0002] The present disclosure relates generally to probe cleaning and, in particular, to inducing Dean vortices in a fluid flow for enhanced cleaning of probes.BACKGROUND

[0003] In vitro diagnostics (IVD) allow labs to assist in the diagnosis of disease based on assays performed on patient fluid samples. IVD includes various types of analytical tests and assays related to patient diagnosis and therapy that can be performed by analysis of a liquid sample taken from a patient’s bodily fluids, or abscesses. These assays are typically conducted with automated clinical chemistry analyzers (analyzers) onto which fluid containers, such as tubes containing patient samples have been loaded.

[0004] To conduct these assays, analyzers typically utilize hypodermic needle-like probes to aspirate and dispense fluids, such as patient samples and reagents, to transfer the fluids between vessels and containers. For example, probes are used in a clinical analyzer to transfer fluid between a reagent container and a reaction vessel and between a primary patient sample container and a dilution vessel. The probes and tubing need to be cleaned between assays and transfers to avoid “carrying over” fluids from one reaction to another. Carryover can lead to incorrect results of a patient test through either unintended introduction of trace amounts of a previously used reagent, or by introduction of analytes that were present in a previously- handled patient sample. Thus, it is important to thoroughly clean the probes and tubing between assays and transfers.

[0005] Cleaning of the probes typically requires water, although for some non-water- soluble reagents or for an absolutely thorough removal of patient sample, chemicalcleaners may be introduced. The inside of the tube tubing and internal lumen of the probe are typically cleaned of any contamination (i.e. , carryover) by flowing high velocity water through the tubing and probe. High velocity creates shear-stress that, in part, strips contamination. Turbulence, if present, aids in the diffusion between rinse water and the contamination due to chaotic mixing. The onset of turbulence is dependent on the Reynolds number.

[0006] The disadvantage with this approach is that the velocity is highly sensitive to the supply pressure as well as any restrictions between the flow source and the probe. Hence, the Reynolds number could vary significantly effecting not only the initiation of turbulence, but also the location.

[0007] A solution is needed to deliver reagents with accuracy and precision to meet the required assay performance and to automate means to clean probes (e.g., reagent probes) and other components utilized in the fluid transfer to minimize crosscontamination (i.e., carryover) from one transfer to the next.

[0008] The present disclosure is directed to overcoming these and other problems of the prior art.SUMMARY

[0009] Embodiments of the present invention address and overcome one or more of the above shortcomings and drawbacks, by providing systems, methods, and apparatuses for inducing Dean vortices for enhanced rinsing. Additional features and advantages of the invention will be made apparent from the following detailed description of illustrative embodiments that proceeds with reference to the accompanying drawings.

[0010] In an exemplary embodiment, a system for cleaning a probe includes a pump; a probe; and tubing having a curved portion, wherein a fluid path is formed between the pump and the probe at least in part by the tubing, wherein a geometry of the curved portion causes fluid flowing in the fluid path to form one or more Dean vortices.

[0011] In some embodiments, the tubing forms a ll-bend and the curved portion curves in a plane co-planar with a plane of the U-bend. In some embodiments, thetubing forms a ll-bend and the curved portion curves in a plane orthogonal to a plane of the U-bend. In some embodiments, the tubing forms a ll-bend and the curved portion curves in a plane other than co-planar and orthogonal with a plane of the U-bend. In some embodiments, the curved portion includes a first arcuate portion and a second arcuate portion. In some embodiments, the curved portion has an S-shaped curve.

[0012] In some embodiments, the system further includes a splint attached to the tubing therein to form the curved portion. In some embodiments, the splint is formed of one unitary body and configured to be slid over the tubing. In some embodiments, the geometry of the curved portion comprises a radius, wherein the radius is greater than a radius at which tubing pinches and is less than or equal to a largest radius at which secondary flow continues to increase as radius increases. In some embodiments, attachment of the splint to the tubing causes the tubing therein to conform to an internal surface area of the splint. In some embodiments, the curved portion comprises a thermally formed tubing.

[0013] In another exemplary embodiment, a splint for attaching to a system for a cleaning of a probe, the system including a tubing is provided. The splint includes an elongate member, wherein attachment of the elongate member to the system causes fluid flowing through form one or more Dean vortices. In some embodiments, the elongate member includes a first arcuate portion and a second arcuate portion. In some embodiments, the elongate member has an S-shape.

[0014] In some embodiments, the elongate member is formed of one unitary body and is configured to be slid over the tubing. In some embodiments, wherein a radius of the elongate member is greater than a radius at which tubing pinches and is less than or equal to a largest radius at which secondary flow continues to increase as radius increases. In some embodiments, attachment of the elongate member to the system includes attachment of the elongate member to the tubing, and attachment to the tubing causes the tubing to conform to an internal surface area of the elongate member.

[0015] In yet another exemplary embodiment, a method of cleaning tubing includes causing the tubing to form one or more bends configured to cause flow within thetubing to form one or more Dean vortices, flowing a rinse fluid through the tubing to cause a contaminate within the tubing to mix with the rinse fluid, and disposing of the mixture of rinse fluid and contaminate. In some embodiments, causing the tubing to form one or more bends includes installing a curved splint on an exterior wall of the tubing. In some embodiments, causing the tubing to form one or more bends includes thermally forming a curved section of tubing.

[0016] This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the detailed description. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter. Additional features and advantages of the disclosed technology will be made apparent from the following detailed description of illustrative embodiments that proceeds with reference to the accompanying drawings.BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The foregoing and other aspects of the present invention are best understood from the following detailed description when read in connection with the accompanying drawings. For the purpose of illustrating the invention, there are shown in the drawings embodiments that are presently preferred, it being understood, however, that the invention is not limited to the specific instrumentalities disclosed. Included in the drawings are the following Figures:

[0018] FIGS. 1A and 1 B illustrate a system for cleaning tubing, according to an embodiment of the disclosure;

[0019] FIG. 2 is a graph of velocity profiles of flows of a variety of Reynold’s numbers, according to an embodiment of the disclosure;

[0020] FIG. 3 is a graph of gradient in flow velocity, according to an embodiment of the disclosure;

[0021] FIG. 4 is a graph of carryover as a function of flow rate for a variety of instruments cleaning using a conventional method, according to an embodiment of the disclosure;

[0022] FIGS. 5A and 5B illustrate counter rotating vortices (i.e., Dean flow), according to an embodiment of the disclosure;

[0023] FIGS. 6A-6G illustrate rinsing reagent from a tubing’s U-bend, according to an embodiment of the disclosure;

[0024] FIGS. 7A-7C illustrate the results of CFD simulations of the breakdown of the boundary layers of tubing of various geometries, according to an embodiment of the disclosure;

[0025] FIGS. 8A-8D illustrate rinsing reagent from a tubing, according to an embodiment of the disclosure;

[0026] FIGS. 9A-9E are illustrations of an external splint, according to embodiments of the disclosure;

[0027] FIGS. 10A and 10B illustrate different axial rotations of added bends, according to embodiments of the disclosure;

[0028] FIG. 11 is a chart of carryover as a function of flow rate, according to an embodiment of the disclosure;

[0029] FIG. 12 is a figure of a geometry of an external splint, according to an embodiment of the disclosure; and

[0030] FIG. 13 is a graph of pressure drop as a function of cleaning improvement, according to an embodiment of the disclosure.DETAILED DESCRIPTION

[0031] Independent of the grammatical term usage, individuals with male, female or other gender identities are included with this term. Further, “tube” and “tubing” are used interchangeably. Unless specified otherwise, tubing can be flexible or rigid. As applied to cleaning probes and tubing, the cleaning is performed by rinsing the probes and tube with a fluid, e.g., rinse water. Thus, “cleaning” and “rinsing” are used interchangeably herein. Additionally, leftover reagent to be rinsed from a tube or probe can be referred to herein as “contamination” or “carryover.”

[0032] The present disclosure describes systems, methods, and apparatuses to enhance cleaning of tubing and probes by increasing the turbulence of rinse water within a system to an efficiently high Dean number such that Dean vortices form in the rinse water. Turbulence of the rinse water’s flow is increased by adding curved sections to otherwise straight tubing. As the rinse water flows through the curved sections (also referred to herein as “bends” or “curves”), turbulent flow occurs. When the turbulence becomes great enough, as measured by the flow’s Dean number, Dean vortices will occur. The secondary mixing caused by the Dean vortices can break down the tubing’s boundary layer (i.e., the leftover reagent accumulated on the tubing’s inner walls) and facilitate diffusion of reagent into the rinse water, leading to more efficient cleaning of the tubing and probes compared to laminar flow.

[0033] The convention relies on increasing the velocity of the rinse water while the present solutions rely on redirecting flow to generate Dean vortices, which produces secondary mixing beneficial for cleaning. Because the present solutions do not rely on the velocity of rinse water, the present solutions require lower flow rates. With reduced flow rates come reduced supply pressure and volume of water required for the cleaning process. With a reduced volume of water will come reduced energy consummation because there will be less rinse water to heat before the rinse water is pumped into the system. Additionally, because the present solution does not rely on velocity of the rinse water (unlike the convention solution), it is less sensitive to the rinse water’s flow rate, the supply pressure, and any restrictions in the tubing or probe, which can all affect the flow’s velocity.

[0034] The present solutions are also faster than the convention solution. This is due to their efficacy - the solutions described herein are more effective than the convention solution. With less time spent cleaning tubing and probes, more time can be spent using them for, e.g., assays. Thus, sample throughput can be increased.

[0035] The present disclosure also describes apparatuses that can be installed on a system to bend the system’s tubing. There are several advantages to the use of these apparatuses. They can be mechanically simple and elegant, requiring few parts and connections. Due to their elegant design, they can be manufactured inexpensively. They can also be used with unmodified legacy equipment. As will bediscussed below, in some cases, use of the apparatuses disclosed herein may bring an otherwise non-compliance piece of equipment back into its specifications.

[0036] In some embodiments, the systems, methods, and apparatuses described herein can be used, for example, in an in-vitro diagnostics (“IVD”) system, such as an immunoassay analyzer, for example, during a cleaning / rinsing operation. For example, in some embodiments, the systems, methods, and apparatuses described herein can be used to clean tubing and probes used to aspirate fluids for assays performed on diagnostic or chemistry analyzers like automated clinical diagnostic analyzers and automated clinical chemistry analyzers.

[0037] An immunoassay (“IA”) analyzer module is a clinical analyzer that automates heterogeneous immunoassays using magnetic separation and chemiluminescence readout. Immunoassays take advantage of the existence of either specific antibodies for the analytes being tested, or specific antigens for the antibodies being tested. Such antibodies will bond with the analyte in the patient's sample to form an “immune complex.” In order to use antibodies in immunoassays, they are modified in specific ways to suit the needs of the assay. In heterogeneous immunoassays, one antibody (capture antibody) is bound to a solid phase, a fine suspension of magnetic particles for the IA module, to allow separation using a magnetic field followed by a wash process. This is exemplified in sandwich assays and competitive assays. An exemplary IA module menu can include additional variations on these formats. Automated clinical analyzers, including IA analyze modules are described in further detail in US Patent No. 11 ,378,583, entitled Automated Clinical Analyzer System and Method, which is hereby incorporated by reference herein in its entirety.

[0038] FIGS. 1A and 1 B illustrate a system 100 for cleaning tubing 102 and probes 103, according to an embodiment of the disclosure. As illustrated in FIG. 1A, the system 100 can include a pump 101 , tubing 102, and a probe 103, among other elements. To wash the external surface area of the probe 102, the probe 102 can be placed in a wash station 104, as illustrated in FIG. 1 B.

[0039] As discussed above, probes can be used to transfer reagent from a storage container to a reaction container and a sample from an access position to a diluting container for one or more assays. Between assays and transfers, the probes andassociated tubing need to be cleaned to avoid carrying over fluids from one reaction to another, which can lead to incorrect results of an assay. The amount of carryover is dictated by how clean a tubing's inner wall is. The key to good cleaning of a tubing’s inner wall is diffusion of rinse water and reagent on the tubing’s inner wall. Diffusion describes the reagent particles’ movement from a high concentration area (e.g., the tubing’s inner wall) to a low concentration area (e.g., the rinse water).

[0040] In straight tubing, cleaning efficiency is driven by flow rate, which affects the flow’s Reynold’s number and its velocity gradient at the tube wall. There is no secondary mixing. FIG. 2 is a graph of velocity profiles of flows of a variety of Reynold’s numbers, with tube walls identified as reference numeral 201 , according to an embodiment of the disclosure. FIG. 3 is a graph of gradient in flow velocity, according to an embodiment of the disclosure. The gradient of dirty reagent is a measure of the dirty reagent build up that needs to be removed. The larger the gradient, the harder it is for the reagent to diffuse into the cleaning rinse water. FIG. 4 is a graph of carryover as a function of flow rate for a variety of instruments cleaning using a conventional method, according to an embodiment of the disclosure. In FIG. 4, the solid line represents the results computational fluid dynamic (“CFD”) simulations. The diffusion coefficient was adjusted to bring the CFD results in line with the experimental measurements.

[0041] The solutions disclosed herein propose adding bends to otherwise straight lengths of tubing to redirect the flow to cause the Dean vortices to form in the fluid flow. As mentioned above, Dean vortices produce secondary mixing that is beneficial for cleaning. Dean vortices are driven by energy conservation. As faster flow moves outward in a bend, pressure must balance along a streamline. High velocity fluid in the center of the tubing deflects outwards along the tubing’s bends creating counter-rotated cells (i.e. , Dean vortices, illustrated in FIGS. 5A and 5B). As the high velocity fluid deflects outward, it breaks down the boundary layer, i.e., the layer of contamination on the tubing’s wall (see FIGS. 7A-7C), which, as described above, dictates the amount of carryover. Further, Dean vortices augments the diffusion of the contamination into the rinse water.

[0042] Dean number can be calculated using the following equation:where De is Dean number, Re is Reynolds number, D is the hydraulic diameter, and Rcis the path curvature radius. An increase in Dean number (e.g., 2x) can result in an increase of secondary vortices and can significantly improve rinse efficacy. For example, an increase in Dean number can greatly increase the mixing between the dirty reagent and the rinse water in the tapered section of tubing leading into probe, which is where most carryover volume can be accumulated.

[0043] As described above, Dean vortices can present when flow travels through a bend or curve, i.e. , co-planar curves. This can make cleaning dependent on tubing curvature. Referring back to FIG. 1 A, in some embodiments, a tubing 102 can include a “ll-bend” 105 to route rinse water through the tubing 102 and into the probe 103. Use of a U-bend 105 can give flexibility to the design of the overall system 100 by, for example allowing the probe 103 to lower into and lift out of a reagent pack or a patient sample vessel. However, the routing of a U-bend 103 is determined based on geometric constraints, not to influence internal fluid dynamics but rather is based on geometric constraints. Further, the effectiveness of the Dean vortices created by flow through the U-bend 103 can diminish downstream as the flow relaminarizes. If rinse enhancement is needed upstream or along any straight portion of the tubing 102, there are no ways to externally induce internal Dean flow. Therefore, the systems, methods, and apparatuses disclosed herein add bends on tubing to induce internal Dean flow.

[0044] To illustrate the effects of Dean flow, consider FIGS. 6A-9D, which illustrate rinsing reagent from tubing, according to embodiments of the disclosure. FIGS. 6A- 6G illustrate rinsing reagent from a tubing’s U-bend, according to an embodiment of the disclosure. In FIGS. 6A-6G, rinse water enters at 610 and exits after 620. FIGS. 7A-7C illustrate the results of CFD simulations of the breakdown of the boundary layers 704 of tubing of various geometries, according to an embodiment of the disclosure. FIG. 7A illustrates the results of CFD simulations of straight tubing, FIG. 7B illustrates the same for tubing with a U-bend, and FIG. 7C illustrates the same for tubing with a U-bend and added bends. After rinsing, the straight tubing (FIG. 7A)has carryover volume of 5.23 uL, the tubing with a ll-bend (FIG. 7B) has a carryover volume of 0.778 uL, and the tubing with the U-bend and added bends (FIG. 7C) has a carryover volume of 0.0021 uL. The reduced carryover volume is due to the Dean vortices formed as a result of the added bends. FIGS. 8A-8D illustrate rinsing reagent from a tubing, according to an embodiment of the disclosure. In FIGS. 8A- 8D, rinse water enters at 810 and exits after 820. As illustrated in FIGS. 8A-8D, the tubing with added bends 850 is cleaned of carryover faster than the tubing without. Again, the faster cleaning is due to the Dean vortices formed as a result of the added bends.

[0045] Bends can be added on tubing in a variety of different ways. For example, in some embodiments, the tubing can be thermally formed to include bends; although with these embodiments, care should be taken to ensure that the bends do not lose shape over time. For another example, in some embodiments, a plurality of dowels can be connected to the tubing to cause the tubing to bend. For yet another example, in some embodiments, an external splint is used. The interior geometry of the external splint can have bends such that, when the external split is attached to a flexible tubing, the tubing bends in accordance with the external splint’s interior geometry. Although a few specific examples of how to add bends to tubing are discussed in this paragraph, the subject matter is not limited to these examples. Rather, as one of ordinary skill in the art will appreciate, any method or apparatus that can add bends to the tubing can be used.

[0046] FIGS. 9A-9E are illustrations of an external splint, according to embodiments of the disclosure. In some embodiments, an external splint 900 is provided to fixate bends on a flexible tubing such that flow within the tubing will form Dean vortices. As illustrated in FIGS. 9A-E, the external splint’s 900 internal geometry can have one or more bends 951 and, in some embodiments, be substantially in the shape of an “S” or a backwards “S,” to cause the tubing within the external splint 900 to bend according to the internal geometry. Although the external splint 900 can have one or more bends, it is not helical. A helical splint, and the resulting helical tubing, will cause separation of the rinse water and the leftover reagent rather than the desired mixing. In some embodiments, the external splint 900 has one or more “windows” 902 or holes through its side wall, as illustrated in FIG. 9B. Incorporating windows inthe external splint can have several advantages. For example, it can allow a user to view the tubing within the external splint; it can reduce the weight of the external split, which can be beneficial when the system is on a moving gantry, for example; and it can reduce the external splint’s effect on heat transfer of the fluid within the tubing.

[0047] In some embodiments, the installation and removal of the external splint 900 (or the dowels mentioned above) does not damage the tubing. The external splint 900 can be formed by one or more components. In single component embodiments, the external splint 900 can be slid over the outer diameter of the tubing. In multicomponent embodiments, the external splint 900 may be “opened” to receive the tubing and “closed” around the tubing. The components of a multi-component external splint 900 may be connected to each other by an means known in the art. For example, in some embodiments, the external splint 900 is a hinged splint with a groove inside. In other embodiments, the external splint 900 is a jig with a groove inside, with the jig held together with magnets. In yet other embodiments, the external splint 900 is a snap on groove.

[0048] The geometry of the bends, regardless of how they are added on the tubing, should cause flow within the tubing to achieve a Dean number effective to form Dean vortices effective to clean the tubing. Further, because it may not be desirable to add bends each time the tubing and probe are cleaned and remove them each time the system is used for an aspiration or a dispense, it can be important that the geometry of bends do not substantially negatively affect the system’s ability to perform aspiration and dispenses. Thus, the geometry of the bends should not significantly affect the pressure drop of the system. If the bends cause a significant pressure drop in the system 100, it may be difficult or impossible to accurately determine the volume aspirated or dispensed by an analysis of pressure in the tubing during the aspiration or dispense. Determining the specific geometry of the bends can be determined using fluid dynamic calculations and simulations including, for example, computational fluid dynamics. The geometry of the bends includes, for example, the number of bends, the radius of each bend (In some embodiments, each bend has the same radius; in other embodiments, they do not.), the arc length of each bend, the length of the external splint (if one is used), and the angle of thebends with respect to the ll-bend. In some embodiments, a bend’s radius should not be so small that it causes the tubing to kink. In some embodiments, to minimize the weight of the external splint and costs for materials, the length of the external splint should be no longer than required to accommodate the number of bends, their radii, and their arc length. For embodiments in which the bends are added by an external splint, the external splint’s interior geometry should be the same as the desired geometry of the tubing’s bends. In some embodiments, an external splint may have the geometry illustrated in FIG. 12 and be placed on 1.5” ID x 2.35” OD FEP tubing.

[0049] FIG. 13 is a graph of pressure drop as a function of cleaning improvement, according to an embodiment of the disclosure. In some embodiments, the radii of an S-bend can be determined by preparing and analyzing a graph similar to the one shown in FIG. 13. In FIG. 13, the percent increase in pressure drop and the percent improvement in cleaning is measured at radii ranging from 0 mm (i.e. , straight tubing) to a radii at which the tubing is pinched, in this case, 12 mm. Although any smaller radius (which would cause flow to achieve a larger Dean number) would improve cleaning, albeit but not as effectively, the optimal radius is the last radius before the trend line becomes vertical because any further increase in radius would not improve cleaning but it would still increase pressure drop. In the embodiment analyzed to create the graph in FIG. 13, the S-bend has two 5.5 mm bends, which results in flow having a Dean number of 632. Once a radius for the S-bends is chosen, one can verify that the increase in pressure drop of the flow at the resulting Dean number does not impact aspiration or dispense accuracy, which can be important to instrument performance.

[0050] Whether the tubing bends “out” or “in” first does not affect the internal fluid dynamics. Therefore, the tubing can be “out” first or “in” first. In other words, the tubing can bend to form the shape of an “S” or a backwards “S.” Further, the axial alignment of the bends with respect to the tubing’s plane does not affect the fluid dynamics caused by fluid flow through the bends. Therefore, the bends can be inline with the tubing plane (e.g., co-planar, FIG. 10A), traverse with the tubing plane (e.g., orthogonal, FIG. 10B), or at any angle with respect to the plane of tubing. In other words, the bends (or the external splint that adds the bends) can be rotated360° about the tubing without affecting the internal fluid dynamics, as illustrated in the table below.

[0051] As illustrated in FIGS. 10A and 10B, the bends 1050 can be added after the U-bend 1005. However, one of ordinary skill in the art will appreciate that the subject matter disclosed herein is not so limited. Instead, the bends 1050 can be added before the U-bend 1005 or in the U-bend 1005. However, inducing the bends 1050 after the U-bend 1005 may result in the greatest improvement of cleaning for at least two reasons. One, pure rinse water does not exist after the U-bend 1005. Purse rinse water enters the tubing at 1010, before the U-bend 1005, and mixes with leftover reagent as it flows through the tubing. Because the rinse water is no longer pure after it flows through the U-bend 1005, it is less effective to mix with the leftover reagent. Two, the Dean vortices formed before the U-bend 1005 will at least partially diminish as they travel through the U-bend 1005. “Before” as used herein refers the portion of the tubing between the rinse water inlet and the U-bend. “After” as used herein refers to the portion of tubing between the probe and the U-bend. To illustrate this point, the following table shows the carryover for tubing with various configurations, according to a CFD simulation.

[0052] The following discussion illustrates the solution’s superiority to the conventional solution. The influence of Dean vortices on contamination removal rate (i.e., removeable of leftover reagent) greatly reduces the sensitivity of supply pressure, flow rate, and restrictions of the tubing and the probe. The following table shows the carryover volume for various instruments when the convention solution isused (i.e. , high velocity flow) and when the solution disclosed herein (i.e., added bends that redirect flow, causing Dean vortices) is used.

[0053] FIG. 11 is a chart of carryover as a function of flow rate, according to an embodiment of the disclosure. The solid line and round dotted line represents the results of a CFD simulation, the round dotted line representing the results of using the conventional solution and the solid line representing the results of using the solutions disclosed herein. The horizontal dotted line is the carryover limit at which the amount of carryover is deemed unacceptable. The datapoints represent carryover measurements of various equipment.

[0054] As illustrated by FIG. 11 , the solutions disclosed herein are not as sensitive to flow rate as the convention solution. In addition, use of the solutions disclosed herein result in a significant reduction in carryover when compared to convention solutions - nearly 100%.

[0055] In FIG. 11 , there are two circled “X’s” and a dashed arrowed from one “X” to the other “X.” Both are measurements from the same probe cleaned once with the conventional solutions (the top “X,” 165 PPM) and cleaned once with the solutions disclosed herein (the bottom “X,” 9.6 PPM). This probe was identified as an outlier due to geometrical tolerances, but when an S-bend was added upstream of the probe, this probe was brought back into specification.

[0056] It may not be desirable to add bends each time the tubing and probe are cleaned and remove them each time the system is used for an aspiration or a dispense so it can be important that the bends do not substantially negatively affect the system’s ability to perform aspiration and dispenses. Experiments were performed on a system with an external splint installed to determine the effects the added bends have on the aspiration or dispense. Each test is described in the “TestDescriptions” table below, the acceptance criteria is provided in the “Acceptance Criteria” table below, and the results are provided in the “Test Results” table below. As illustrated by the results below, added bends have a negligible effect on the system’s ability to perform aspiration and dispenses. In these tests, the probe passed both aspiration and dispense tests.

[0057] Note that “RLU” standards for “reflect light units,” which is a measure of the concentration of solid particles against a suspension substance.

[0058] While various illustrative embodiments incorporating the principles of the present teachings have been disclosed, the present teachings are not limited to the disclosed embodiments. Instead, this application is intended to cover any variations, uses, or adaptations of the present teachings and use its general principles. Further, this application is intended to cover such departures from the present disclosure that are within known or customary practice in the art to which these teachings pertain. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

[0059] In the above detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the present disclosure are not meant to be limiting. Other embodiments may be used, and other changes may be made, without departing from the spirit or scope of the subject matter presented herein. It will be readily understood that various features of the present disclosure, as generally described herein, and illustrated in the Figures, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are explicitly contemplated herein.

[0060] These computer readable program instructions can be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions / acts specified in the flowchart and / or block diagram block or blocks. These computer readable program instructions can also be stored in a computer readable storage medium that can direct a computer, a programmable data processing apparatus, and / or other devices to function in a particular manner, such that the computer readable storage medium having instructions stored therein comprises an article of manufacture including instructions which implement aspects of the function / act specified in the flowchart and / or block diagram block or blocks.

[0061] With respect to the use of substantially any plural and / or singular terms herein, those having skill in the art can translate from the plural to the singular and / or from the singular to the plural as is appropriate to the context and / or application. The various singular / plural permutations may be expressly set forth herein for sake of clarity.

[0062] It will be understood by those within the art that, in general, terms used herein are generally intended as “open” terms (for example, the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” et cetera). While various compositions, methods, and devices aredescribed in terms of “comprising” various components or steps (interpreted as meaning “including, but not limited to”), the compositions, methods, and devices can also “consist essentially of” or “consist of” the various components and steps, and such terminology should be interpreted as defining essentially closed-member groups.

[0063] As used in this document, the singular forms “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art. Nothing in this disclosure is to be construed as an admission that the embodiments described in this disclosure are not entitled to antedate such disclosure by virtue of prior invention.

[0064] In addition, even if a specific number is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (for example, the bare recitation of “two recitations,” without other modifiers, means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to “at least one of A, B, and C, et cetera” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (for example, “a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A, B, and C together, et cetera). In those instances where a convention analogous to “at least one of A, B, or C, et cetera” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (for example, “a system having at least one of A, B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A, B, and C together, et cetera). It will be further understood by those within the art that virtually any disjunctive word and / or phrase presenting two or more alternative terms, whether in the description, sample embodiments, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or “B” or “A and B.”

[0065] In addition, where features of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.

[0066] As will be understood by one skilled in the art, for any and all purposes, such as in terms of providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, et cetera. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, et cetera. As will also be understood by one skilled in the art all language such as “up to,’’ “at least,” and the like include the number recited and refer to ranges that can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, for example, a group having 1-3 components refers to groups having 1 , 2, or 3 components. Similarly, a group having 1-5 components refers to groups having 1 , 2, 3, 4, or 5 components, and so forth.

[0067] Various of the above-disclosed and other features and functions, or alternatives thereof, may be combined into many other different systems or applications. Various presently unforeseen or unanticipated alternatives, modifications, variations or improvements therein may be subsequently made by those skilled in the art, each of which is also intended to be encompassed by the disclosed embodiments.NON-LIMITING ILLUSTRATIVE EMBODIMENTS

[0068] The following is a list of non-limiting illustrative embodiments disclosed herein.

[0069] Illustrative embodiment 1 . A system for cleaning a probe, the system comprising: a pump; a probe; and tubing comprising a curved portion, wherein a fluid path is formed between the pump and the probe at least in part by the tubing, wherein a geometry of the curved portion causes fluid flowing in the fluid path to form one or more Dean vortices.

[0070] Illustrative embodiment 2. The system of illustrative embodiment 1 , wherein the tubing forms a ll-bend, and wherein the curved portion curves in a plane coplanar with a plane of the U-bend.

[0071] Illustrative embodiment 3. The system of any one of illustrative embodiments 1-2, wherein the tubing forms a U-bend, and wherein the curved portion curves in a plane orthogonal to a plane of the U-bend.

[0072] Illustrative embodiment 4. The system of any one of illustrative embodiments 1-3, wherein the tubing forms a U-bend, wherein the curved portion curves in a plane other than co-planar and orthogonal with a plane of the U-bend.

[0073] Illustrative embodiment 5. The system of any one of illustrative embodiments 1-4, wherein the curved portion comprises: a first arcuate portion; and a second arcuate portion.

[0074] Illustrative embodiment 6. The system of any one of illustrative embodiments 1-5, wherein the curved portion has an S-shaped curve.

[0075] Illustrative embodiment 7. The system according to one of the preceding illustrative embodiments, further comprising: a splint attached to the tubing therein to form the curved portion.

[0076] Illustrative embodiment 8. The system according to one of the preceding illustrative embodiments, wherein the splint is formed of one unitary body and configured to be slid over the tubing.

[0077] Illustrative embodiment 9. The system according to one of the preceding illustrative embodiments, wherein the geometry of the curved portion comprises a radius, wherein the radius is greater than a radius at which tubing pinches and is less than or equal to a largest radius at which secondary flow continues to increase as radius increases.

[0078] Illustrative embodiment 10. The system according to one of the preceding illustrative embodiments, wherein the attachment to the tubing causes the tubing therein to conform to an internal surface area of the splint.

[0079] Illustrative embodiment 11. The system according to one of the preceding illustrative embodiments, wherein the curved portion comprises a thermally formed tubing.

[0080] Illustrative embodiment 12. A splint for attaching to a system for a cleaning of a probe, the system including a tubing, the splint comprising: an elongate member, wherein attachment of the elongate member to the system causes fluid flowing through form one or more Dean vortices.

[0081] Illustrative embodiment 13. The splint of any one of the preceding illustrative embodiments, wherein the elongate member comprises: a first arcuate portion; and a second arcuate portion.

[0082] Illustrative embodiment 14. The splint of any one of the preceding illustrative embodiments, wherein the elongate member has an S-shape.

[0083] Illustrative embodiment 15. The splint of any one of the preceding illustrative embodiments, wherein the elongate member is formed of one unitary body and is configured to be slid over the tubing.

[0084] Illustrative embodiment 16. The splint of any one of the preceding illustrative embodiments, wherein a radius of the elongate member is greater than a radius at which tubing pinches and is less than or equal to a largest radius at which secondary flow continues to increase as radius increases.

[0085] Illustrative embodiment 17. The splint of any one of the preceding illustrative embodiments, wherein the attachment of the elongate member to the system comprises attachment of the elongate member to the tubing, and wherein the attachment to the tubing causes the tubing to conform to an internal surface area of the elongate member.

[0086] Illustrative embodiment 18. A method of cleaning tubing comprising: causing the tubing to form one or more bends configured to cause flow within the tubing to form one or more Dean vortices; flowing a rinse fluid through the tubing to cause a contaminate within the tubing to mix with the rinse fluid; and disposing of the mixture of rinse fluid and contaminate.

[0087] Illustrative embodiment 19. The method of any one of the preceding illustrative embodiments, wherein causing the tubing to form one or more bends comprises installing a curved splint on an exterior wall of the tubing.

[0088] Illustrative embodiment 20. The method of any one of the preceding illustrative embodiments, wherein causing the tubing to form one or more bends comprises thermally forming a curved section of tubing.

Claims

CLAIMSW / e claim:

1. A system for cleaning a probe, the system comprising: a pump; a probe; and tubing comprising a curved portion, wherein a fluid path is formed between the pump and the probe at least in part by the tubing, wherein a geometry of the curved portion causes fluid flowing in the fluid path to form one or more Dean vortices.

2. The system of claim 1 , wherein the tubing forms a U-bend, and wherein the curved portion curves in a plane co-planar with a plane of the U- bend.

3. The system of claim 1 , wherein the tubing forms a U-bend, and wherein the curved portion curves in a plane orthogonal to a plane of the U- bend.

4. The system of claim 1 , wherein the tubing forms a U-bend, wherein the curved portion curves in a plane other than co-planar and orthogonal with a plane of the U-bend.

5. The system of claim 1 , wherein the curved portion comprises: a first arcuate portion; and a second arcuate portion.

6. The system for claim 1 , wherein the curved portion has an S-shaped curve.

7. The system of claim 1 , further comprising: a splint attached to the tubing therein to form the curved portion.

8. The system of claim 7, wherein the splint is formed of one unitary body and configured to be slid over the tubing.

9. The system of claim 7, wherein the geometry of the curved portion comprises a radius, wherein the radius is greater than a radius at which tubing pinches and is less than or equal to a largest radius at which secondary flow continues to increase as radius increases.

10. The system of claim 7, wherein the attachment to the tubing causes the tubing therein to conform to an internal surface area of the splint.

11. The system of claim 1 , wherein the curved portion comprises a thermally formed tubing.

12. A splint for attaching to a system for a cleaning of a probe, the system including a tubing, the splint comprising: an elongate member, wherein attachment of the elongate member to the system causes fluid flowing through form one or more Dean vortices.

13. The splint of claim 12, wherein the elongate member comprises: a first arcuate portion; and a second arcuate portion.

14. The splint of claim 12, wherein the elongate member has an S-shape.

15. The splint of claim 12, wherein the elongate member is formed of one unitary body and is configured to be slid over the tubing.

16. The splint of claim 12, wherein a radius of the elongate member is greater than a radius at which tubing pinches and is less than or equal to a largest radius at which secondary flow continues to increase as radius increases.

17. The splint of claim 12,wherein the attachment of the elongate member to the system comprises attachment of the elongate member to the tubing, and wherein the attachment to the tubing causes the tubing to conform to an internal surface area of the elongate member.

18. A method of cleaning tubing comprising: causing the tubing to form one or more bends configured to cause flow within the tubing to form one or more Dean vortices; flowing a rinse fluid through the tubing to cause a contaminate within the tubing to mix with the rinse fluid; and disposing of the mixture of rinse fluid and contaminate.

19. The method of claim 18, wherein causing the tubing to form one or more bends comprises installing a curved splint on an exterior wall of the tubing.

20. The method of claim 18, wherein causing the tubing to form one or more bends comprises thermally forming a curved section of tubing.

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