Patent Application
20050281713
The present invention relates generally to the provision of a tube assembly, system, and method for biological fluids, and, more particularly, to a tube assembly, system, and method for waste containment and sample collection.
In the field of health science, there is often a need to collect multiple biological fluid samples (including blood, urine, spinal fluid, synovial fluid, fermentation broth, etc.) from laboratory animals, human subjects, cell cultures, and fermentations. In some cases, the biological fluid may be hazardous due to the presence of infectious agents or pathogens. In other cases, the biological fluid samples may be radioactive as a result of radioisotopes inserted into the host organism to act as biomarkers. Multiple biological fluid samples are needed in preclinical research with laboratory animals or in human clinical trials to evaluate the efficacy, toxicity, stability, and pharmacokinetics of new pharmaceuticals. Multiple biological fluid samples are also needed in intensive care medicine, to monitor chemical changes that may indicate alterations in the health of the subject or indicate a need to alter a prescribed treatment, and in fermentation, to indicate changing concentrations of toxic and non-toxic agents. Such samples are collected periodically, for example, at points that are separated in time or at points based on condition(s) in order to monitor the temporal changes of the biological fluid in the subject, cell culture, or fermentation. It is important, in such a context, to avoid contamination of a current biological fluid sample with biological fluid from previous sample collections. The collection and storage of multiple biological fluid samples in individual collection vessels is labor-intensive, time-consuming, and can be difficult to accomplish if fluid samples are needed from multiple subjects at the same time.
Frequently, in the prior art, systems have been designed for the automated collection of biological fluid samples into individual collection vessels. Some of these systems function by moving a new collection vessel below a stationary dispensing needle for each sample collection, whereas other systems function by moving a dispensing needle above a stationary rack of individual collection vessels for each sample collection. In either type of system, the collection vessels are located in close physical proximity to the dispensing needle, and are often supported within a refrigerated environment or located in close physical proximity to an animal subject, i.e., situations that involve limited space.
In cases where it is desired to dispense the biological samples into sealed collection vessels, the dispensing needle in the automated sample collection system is moved down to pierce a septum in the collection vessel. A mechanism is provided to allow displaced air within the sealed collection vessel to escape as the vessel is being filled with the biological fluid sample. After the biological fluid sample is dispensed into the collection vessel, the needle is moved up and out of the collection vessel and the septum reseals the collection vessel. In these automated sample collection systems, the dispensing needle and tubing leading to the dispensing needle are flushed with a rinse solution between every biological fluid sample collection, with the resulting biological fluid waste being flushed out of the end of the dispensing needle. Flushing is performed to remove biological fluid remaining inside the dispensing needle and the tubing leading to the dispensing needle that might otherwise contaminate the subsequent biological fluid sample with biological fluid remaining from the previous biological fluid sample.
The outside of the dispensing needle is also flushed with a rinse solution between every biological sample collection. Since the dispensing needle is suspended within the sealed collection vessel while dispensing the biological fluid sample, the outside surface of the dispensing needle is in contact with the fluid sample. Some of the biological fluid sample may adhere to the outside of the dispensing needle. Any biological fluid that does adhere to the outside of the dispensing needle may contaminate the subsequent biological fluid sample when the needle dispenses the next biological fluid sample into the next collection vessel. Flushing the outside of the dispensing needle with rinse solution requires a means of moving the rinse solution to the outside of the dispensing needle, at appropriate times, and stopping rinse flow when not needed; this typically requires pumps, valves, tubing and/or software control, all of which add to the complexity and cost of the automated sample collection system.
The volume of rinse solution necessary to thoroughly flush the inside and the outside of the dispensing needle, and the tubing leading to the dispensing needle, is typically many times the volume contained within the needle and the tubing. Because flushing the dispensing needle and the tubing leading to the dispensing needle occurs between every biological fluid sample collection, a total volume of biological fluid waste is generated that is much greater than the volume of a sample collection vessel. During the flushing process, the rinse solution mixes with the residual biological fluid located inside and on the outside of the dispensing needle, and within the tubing leading to the dispensing needle. If the residual biological fluid is hazardous due to the presence of radioisotopes, infectious agents, pathogens, or other risks, then the resulting biological fluid waste, consisting of residual biological fluid and rinse solution, must be treated as hazardous waste as well.
In automated sample collection systems known in the prior art in which the dispensing needle and the tubing connected to the dispensing needle are flushed with rinse solution to remove residual biological fluid, the resulting biological fluid waste exiting from the end of the dispensing needle, and the waste generated by flushing the outside of the dispensing needle, are collected in an open, reusable, i.e., cleanable, collection vessel or vessels. The use of such a collection vessel or vessels maximizes an operator's exposure to hazardous or potentially hazardous biological fluid waste, not only by virtue of the biological fluid waste being a hazard in and of itself to an operator, but also by virtue of any surface having contact with biological fluid waste being a source of hazard to an operator. Operator exposure to contaminated surfaces may occur during the collection of biological fluid waste in an open, cleanable collection vessel, or may occur following the collection process during operator cleaning and disinfecting of the surfaces of the collection vessel that were exposed to biological fluid waste, and even through contact with surfaces that have been previously cleaned and disinfected.
Preparing an automated sample collection system for new sample collections, by cleaning and disinfecting surfaces of a collection vessel or vessels previously exposed to biological fluid waste, requires the expenditure of time and labor and can be tedious, the result of which is that surfaces exposed to biological fluid waste are not always cleaned or are not cleaned thoroughly. Biological fluids are a rich medium for vigorous microbial growth. In cases where biological fluid waste is not adequately removed by cleaning and is allowed to collect, the resulting microbial growth can obstruct fluid flow paths in the collection system, which may cause fluid to accumulate. Fluid accumulation due to obstruction from microbial growth may ultimately cause collection system instrument failures. In cases where surfaces of the automated sample collection system that are exposed to biological fluid waste are thoroughly cleaned, the cleaning process itself can expose collection system instruments to cleaning solvents and physical cleaning action that may be harmful to the instruments and detrimental to proper operation. Cleaning solvents spilled into areas of the collection system that are not intended for exposure to such chemicals may result in damage to those areas. Furthermore, cleaning solvents are often incompatible with label adhesives, which may be dissolved at inopportune times with unforeseen consequences.
Therefore, in order to overcome the aforementioned disadvantages inherent in the prior art, it is desirable that a collection vessel for biological fluid waste, associated with an automated sample collection system, be sealed, self-contained, and disposable so that potential contact with contaminated surfaces on the part of an operator is minimized and cleaning or disinfecting of contaminated surfaces is not required.
It is also desirable that a biological fluid waste collection vessel accommodate a much greater fluid volume than that of a sample collection vessel, while avoiding the necessity that such a waste collection vessel is located in close physical proximity to individual sample collection vessels, and the necessity that a dispensing needle moves automatically, to the location of such a waste collection vessel in order to dispense biological fluid waste. Such automated movement would require drive components and control software, add significantly to the complexity, size, and expense of the automated sample collection system, and reduce both its utility and its reliability.
Accordingly, it is desirable to provide a system and method of biological fluid waste collection for sample collection that offers:
Ultrafiltration is a membrane sampling technique for extracting biological fluids from probes implanted in a subject. Sample collection from ultrafiltration probes generally requires the use of a vacuum. The vacuum is used to force the fluid surrounding the probe to pass through pores in the semi-permeable membrane that filters out macromolecules. The filtered sampled fluid travels through tubing and is deposited into a collection vessel in a continuous flow process. Often the flow is fractionated or collected into multiple discrete samples in separate collection vials, with each such sample representing time periods across which the samples are collected.
In the prior art, the vacuum source used to draw the fluid through the membrane, through the tubing, into the collection vial may be provided in the collection vial itself. This is accomplished using a vacutainer. A vacutainer is an evacuated test tube having rubber stopper cap. The tubing from the probe is connected to a needle and the needle is inserted through the rubber stopper into the vacutainer. The vacuum in the sealed vial causes the fluid to filter through the probe membrane and be drawn into the vial.
Systems using vacutainers have several shortcomings. Vacutainers are unsuited for drawing small volume samples, such as is typical samples taken from small rodents, because it is difficult to remove the small sample from the relatively large vacutainer vial. Thus, a large proportion of sample may be left in the vacutainer when extracting the sample for analysis. Sample volumes may be as small as 10 uL and the smallest commercially available vacutainer holds 5000 uL volume. Also, vacutainers do not provide an indication of the level of vacuum within. Leakage through system, including leakage around the stopper, reduces the vacuum to an unknown level. In some cases, leakage may essentially result in no vacuum. Due to the relatively low flow rate of such systems, a loss of vacuum may not be discovered for some time and time sensitive samples may be lost.
The vacuum level in ultrafiltration systems is one factor that determines the rate and volume of sample collection. If ultrafiltration is used to assess changes in the availability of fluid from a particular probe location, the flow from the probe should be as consistent as possible. Vacutainers cannot assure consistent vacuum, and, therefore, cannot assure consistent flow from the probe. Further, when collecting multiple samples, vacutainers must be substituted by hand. Manual operation requires someone to be present at each time point of collection. Thus, these vacutainers are not suited for automated small volume fraction collection.
Peristaltic pumps have also been used in prior art systems as the vacuum source for the probe membrane and to move the filtered fluid from the probe to the collection vial. The pump is generally located between the probe and the collection vial. Such location of the pump allows automated fraction collection of multiple ultrafiltrate samples into refrigerated collection vials. However, this approach requires the ultrafiltrate to pass through peristaltic tubing on the way to the vial. Peristaltic tubing generally contains a relatively large volume, and large volume increases the time required for the fluid to move from the probe to the collection vial. Thus, a significant time lag results for the low flow rates associated with ultrafiltration in small rodents. Also, peristaltic tubing is formulated to be soft and pliable and have good compression characteristics. However, the plasticizing chemicals used to produce these characteristics can contaminate the fluid washing through the tube. Such contamination can create a significant interference in the assay of the analyte in the ultrafiltrate. Analyte from the ultrafiltrate may also bind to this tubing making it unavailable for analysis, and thus altering the measured concentration of analyte in the collected sample. Further, the flow characteristics from peristaltic pumps change over time as the tubing stretches from the compression of the pump rollers. This change in flow characteristics creates inconsistent flow over time and introduces uncertainty as to whether changes in flow are due to physiological factors in the subject or due to the pump and tubing.
Thus, it is desired to provide a system and method for sample collection that:
The present invention comprises a tube assembly, system, and method for waste containment when collecting biological samples or rinsing collection systems. In one embodiment, the tube assembly of the present invention includes a first tube, a second tube, a mechanism for securing the first and second tubes, and at least one container for operable connection to one or both of the first and second tubes. The securing mechanism comprises a threaded hub having a cavity, and with adhesive cured in the cavity. The securing mechanism is operable to orient the first and second tubes such that the first end of the first tube extends beyond the first end of the second tube. Further, the first end of the second tube has an inner diameter greater than the outer diameter of the first tube to create an interstitial space about the first tube at the first end of the second tube.
The tube assembly of the present invention can be used for biological fluid sample collection and for rinsing, and results in containment of waste resulting from both processes. For collection of a biological sample, the tube assembly is connected to a source of a biological fluid sample through the second end of the first tube. Connected to the second end of the second tube is a container for receipt of waste. For collection of the biological waste, the tube assembly is inserted into a collection vial having a septum. Specifically, the first tube is inserted through the septum so that the opening of the first end of the first tube resides within the interior of the collection vial and near the bottom of the vial, and such that the first end of the second tube is inserted through the septum so that the open first end resides within the interior of the collection vial near the top of the vial. This orientation results in the septum sealingly engaging the exterior of the second tube.
During operation, the fluid sample is caused to move from the second end of the first tube through the opening of the first end of the first tube into the collection vial. The contents originally residing in the collection vial, such as air, that is displaced by the biological sample deposited into the collection container travels into the interstitial space between the first and second tubes. The displaced contents of the vial then travel to the waste container. Thus, the waste container collects air displaced by the biological sample. Such air is tainted by the biological sample.
To rinse the tube assembly, a source of a rinse solution is operably connected to the second end of the first tube. The second end of the second tube is connected to a container for receipt of waste. For collection of biological sample, the tube assembly is inserted into a rinse vial containing rinse solution and having a septum. Specifically, the first tube is inserted through the septum of the rinse vial so that the opening of the first end of the first tube resides within the interior of the rinse vial and near the bottom of the vial, and such that the first end of the second tube is inserted through the septum so that the opening of the first end of the second but resides within the interior of the rinse vial near the top of the vial. The septum sealingly engages the exterior surface of the second tube.
During operation, the rinse solution is caused to move from the second end of the first tube through the opening of the first end of the first tube into the rinse vial displacing biological waste residing in the first tube into the rinse vial. Rinse solution, or other original contents of the rinse solution, that is displaced by biological waste fluid deposited into the collection container travels into the interstitial space between the first and second tubes. The displaced contents of the rinse vial then travel to the waste container. Thus, the waste container collects the contents of the rinse vial displaced by the biological waste fluid. Such contents are tainted by the biological sample residing in the rinse vial.
Continued provision of rinse solution into the rinse vial will eventually flush biological waste in the rinse vial through the interstitial space between the first and second tubes to the waste container. Any additional rinse solution will flow through the rinse vial, the exterior of the first tube and into the interstitial space, for subsequent deposit in the waste container. This results in rinsing of the interior and exterior of the first tube and interior of the second tube of any biological sample residing thereon or therein.
According to one embodiment, the ultrafiltration collection system of the present invention comprises a tube assembly as previously described. The system also includes a probe operatively connected to the second end of the first tube of the tube assembly, a trap operatively connected to the second end of the second tube of the tube assembly, and a vacuum source operatively connected to the trap. The system may also include a first container for collection of the ultrafiltration sample from the probe, the first container for connection to the tube assembly such that the first end of the first tube of the tube assembly and the first end of the second tube of the tube assembly reside within the interior of the first container. This first container may comprise a vial, with, or without a septum thereon.
One embodiment of the method of collecting a sample according to the present invention requires provision of a system as described above. The method also comprises the steps of inserting the tube assembly into the first container, activating the vacuum source to cause air to withdraw from the first container through the second tube of the tube assembly and the trap. Then, the sample is pulled through the first tube of the tube assembly into the first container.
The present invention obviates or mitigates at least one disadvantage of previous systems and methods. The tube assembly of the present invention may be used manually or with automated sample collection systems. In fact, the tube assembly may be easily integrated with existing collection systems. The system and method permit for containment of waste of fluids—both gases and liquids—that may be tainted with a biological sample during a sampling process or during the rinsing process. Collection and containment of such waste results in a safer environment, as well as improved environmental and control conditions for sample collection. The present invention results in sealed, self-contained, and disposable containment of fluid waste, and also permits for large volume containment of such waste. All surfaces of a needle assembly used in depositing a biological sample for collection can be rinsed according to the system and method of the present invention. Both the inside and outside of the needle and the inside of the cannula may be flushed and the waste collected therefrom contained. The apparati of the present invention is also comprised of simple, reliable, inexpensive components, and the methods of the present invention are retrofittable and simple to implement.
The system and method of the present invention used for ultrafiltration collection addresses several of the shortcomings of the prior art. The present invention is suitable for use in drawing small volume samples, and provides for consistent flow over time. The tubing used in the present invention is of appropriate volume, does not contaminate the fluid washing through the tube and has predictable flow characteristics. The present invention permits for control of the vacuum, control of the flow of fluid from the probe, and does not require human intervention for the collection of multiple samples. The ultrafiltration collection system and method may be accomplished manually, or may be retrofitted into existing automated collection systems.
Other aspects and features of the present invention will become apparent to those ordinarily skilled in the art upon review of the following description of specific embodiments of the invention in conjunction with the accompanying figures.
Embodiments of the present invention will now be described, by way of example only, with reference to the attached figures, wherein:
Generally, the present invention provides a tubing assembly, system, and method for biological fluid waste containment for sample collection. Referring now to
In the embodiment of
To obtain the aforementioned orientation, tube assembly 200 of
In the embodiment of
As previously stated, in the embodiment of
It will be appreciated by those of skill in the art that other mechanisms for securing needle 10 and cannula 20 to create interstitial space 25 may be used. For example, needle 10 and cannula 20 may be secured by the material of the threaded hub as the threaded hub is injection molded around the pre-aligned needle and cannula. In addition, it is possible that a single material may comprise cannula 20 and flexible tube 130, and/or exit tube 30. In such an embodiment, cannula 20, flexible tube 130, and exit tube 30 may be comprised of a semi-rigid material, for example, PEEK (polyetheretherketone) tubing.
Based on the illustrations of
This orientation of tube assembly 200 is explained in greater detail in association with
Referring again to
Needle 10 includes second end 15 for operable connection of needle 10 to flexible tubing 50. Tubing 50 is operable for connection to the source of the biological fluid and to the source of a rinse solution. This allows a biological fluid sample to pass through needle 10 into collection vial 100 or a rinse solution to pass through the needle into vial 140.
During one embodiment of the sample collection process according to the present invention, a sample is taken through tubing 50 operably connected to a source of the sample (not shown). The sample is introduced to tube assembly 200 via tubing 50. Then, sample collection vessel 100 is moved under dispensing tube assembly 200 (or tube assembly 200 is moved over sample collection vessel 100). Dispensing tube assembly 200 is moved downward (or sample collection vessel 100 is moved upward) to allow first end 12 of needle 10 to pierce septum 110 of sample collection vial 100 and reside within the interior of collection vial 100 near the bottom of vial 100, and first end 22 of cannula 20 pierces septum 110 so that first end 22 resides within the interior of collection vial 100 near the top of vial 100. Septum 110 sealingly engages the exterior surface of cannula 20. The biological sample is then disbursed into sealed vial 100 and any air from vial 100 displaced by the introduction of the biological sample into vial 100 escapes out of sealed vial 100 about first tube 10, into first end 22 of cannula 20, and through the interstitial space 25 between needle 10 and cannula 20. This escaped air travels through exit tube 30 into connecting flexible tubing 60 and ultimately into waste collection vessel 90. Allowing air to escape sealed collection vial 100 during sample collection prevents pressure from building within collection vial 100 as it fills, and thus permits more accurate volume collection of the biological sample. The displaced air is also tainted with the biological fluid, and thus, the contaminated air is collected rather than being permitted to enter the environment.
Dispensing needle assemblies similar to that of the present invention are commonly used in many automated sample collection systems to permit air to escape from sealed vials as they are filled. However, normally, the air from the vial escapes through the cannula to the atmosphere and is not captured by a waste collection vessel. Thus, any contaminants present in the escaped air are allowed to pass into the laboratory atmosphere, exposing operators, others, and equipment to the contaminated air.
After the biological sample has been dispensed into collection vial 100, dispensing tube assembly 200 is raised out of vial 100 (or vial 100 is lowered away from tube assembly 200), and septum 110 seals the biological fluid sample within vial 100. Rinse vial 140 is then brought under the dispensing tube assembly 200 (or tube assembly 200 is brought over rinse vial 140). Dispensing tube assembly 200 is brought down into sealed rinse vial 140 filled with a rinse solution (or rinse vial 140 is brought upward to tube assembly 200) so that opening 13 is inserted through septum 110 of rinse vial 140 into the interior of rinse vial 140, and such that first end 22 of cannula 20 is inserted through septum 110 so that the opening of first end 22 of cannula 20 resides within the interior of vial 140 near the top of vial 140. Septum 110 sealingly engages with the exterior surface of cannula 20. Tubing 50 is flushed with a sufficient amount of rinse solution as extracted through tubing 50 from a rinse solution source operably connected to tubing 50 (not shown). The rinse solution washes the inside of tubing 50 and the inside of needle 10 free of biological fluid waste into rinse vial 110. As rinse solution flows into rinse vial 140, the outside of needle 10 is washed, and any biological fluid adhering to needle 10 will be removed with the rinse solution. The addition of more rinse solution will displace the fluid mixture of biological waste and rinse solution out of rinse vial 140 through interstitial space 25 between needle 10 and outer cannula 20, through exit tube 30, through the connecting tubing 60, and ultimately into the waste collection vessel 90. The flushing of tubing 50 and dispensing tube assembly 200 continues until all the biological fluid waste is removed.
Since septum 110 of rinse vial 140 is pierced by the dispensing tube assembly 200 after each biological fluid sample is collected and must remain liquid tight, guide cap 120 is affixed to septum 110 to assure that the dispensing tube assembly 200 always pierces the rinse vial septum 110 in the same location. Use of the same location helps assure the septum 110 seals around the dispensing outer cannula 20 of tube assembly 200 every time.
1. Remove blood from an intravenous catheter implanted in a mammal at programmed intervals
2. Dispense a portion of the blood into sealed refrigerated (3° C.) vials
3. Return the remaining blood to the subject
4. Return sterile saline to the subject to compensate for the blood removed
5. Dispense an optional dilution volume of saline to the collected blood
6. Flush the system with saline prior to the next sample.
An example of such a blood sampling system is disclosed in U.S. Pat. No. 6,062,224, which is incorporated herein by reference.
The automated blood sampler of the embodiment of
Tube assembly 200 mounted on fraction collector 500 is connected by tubing 50 to tubing set 400 of control system 300. Like collection vials 100, rinse vial(s) 140 is(are) held in fraction collector 500 alongside collection vials 100. Flexible tubing 60 connects to exit tube 30 of needle assembly 200 and extends to waste collection vessel 90 that is mounted external to fraction collector 500. Fraction collector 500 includes a mechanism for orienting tube assembly 200 with respect to collection vials 100 and rinse vial(s) 140. As is well known in the art, such mechanism may comprise robotics to move tube assembly 200 and/or the rack(s) holding collection vial(s) 100 and rinse vial(s) 140.
During operation, a sample of blood is withdrawn from subject 350 as described in U.S. Pat. No. 6,062,224. The connection of tubing set 400 to tubing 50 allows the sample to enter tube assembly 200 mounted on fraction collector 500. Collection vial 100 is caused to move under tube assembly 200 and tube assembly 200 is caused to move downward. When moved downward, needle 10 pierces septum 110 of collection vial 100 and first end 22 of cannula 20 pierces septum 110 of collection vial 100. Septum 110 of collection vial 100 forms a seal around the outside of cannula 20. Movement of the sample, initiated by control system 300, into collection vial 100 caused displaced air from collection vial 100 to move through interstitial space 25 through tubing 60 into waste containment container 90.
After the sample collection in collection vial 100 is complete, tube assembly 200 is raised by fraction collector 500 out of collection vial 100, moved over rinse vial 140, and moved downward to allow needle 10 and first end 22 of cannula 20 to enter rinse vial 140 through septum 110 of rinse vial 140 and to allow cannula 20 to form a seal with septum 110 of rinse vial 100. The system is now in position to be rinsed.
As described in U.S. Pat. No. 6,062,224, rinse solution, saline, is caused to move from saline reservoir through tubing set 400. The connection of tubing set 400 to tubing 50 causes saline to wash the inside of tubing 50 and the inside of needle 10. The saline enters rinse vial 140 through needle 10. Rinse fluid moved into tubing 50 from control system 300 displaces fluid mixture of biological waste and rinse fluid in rinse vial 40 through interstitial space 25, through tubing 60, into waste container 90. This flushing can continue until all biological fluid waste has been removed from tube assembly 200, and from the blood sampling system.
In the operation described for the system of
One skilled in the art will recognize that collection vials used with waste collection according to the present invention do not have to be septum sealed provided leakage of air tainted with sample is acceptable. Often such leakage is acceptable, such as when collecting blood samples. If no septum is present, one may chose to use plastic caps, rather than a septum, on the collection vials. However, one skilled in the art will also recognize that the rinse vial used in waste containment according to the present invention should be septum sealed and this seal should be fluid-tight for every sample collected. Thus, it is often desired to provide a guide cap on the rinse vial to assure reliable sealing with the cannula every time the tube assembly is inserted into the rinse vial.
It will be appreciated by those of skill in the art that the tubing set, system, and method of the present invention has many salient features and advantages when compared to the prior art. First, the tubing set and system are useful manually or with existing automated sample collection systems. The invention results in sealed, self-contained, and disposable containment of biological fluid waste. Contaminated air is even captured with the present invention. The invention permits also for large volume containment of biological fluid waste.
It will be further appreciated that the present invention allows for cleaning of all surfaces that may come in contact with biological fluid. The inside and outside of the needle and the inside of the cannula are flushed. These features and advantages are all accomplished with simple, reliable, inexpensive components that are retrofitable with existing collection systems, and with straightforward, inexpensive methods.
Referring now to
The system of
First, second, and third needles 840, 841, and 842, respectively, are inserted into trap 845. Trap 845 serves as a sealed manifold, as is explained in greater detail herein. In this embodiment, first, second and third needles 840, 841, and 842 comprise 16-gauge needles, and first, second, and third needles 840, 841, and 842 are operably connected to first, second, and third tubes 830, 831, and 843 by first, second, and third luer connectors 848, 846, and 850, respectively. Trap 845 comprises a manifold, and vacuum source 844 comprises a vacuum pump, such as a standard laboratory vacuum pump made by Gast Manufacturing of Benton Harbor, Mich.
To explain the method of ultrafiltrate collection according to one embodiment of the present invention, consider the system of
When it is time to collect ultrafiltrate into another collection vial, first tube assembly 810 is moved up and out of first collection vial 800. A new collection vial (which contains air and/or other fluid inside) is brought under first tube assembly 810. The contents of the new collection vial are evacuated and ultrafiltrate is drawn into the new collection vial by the vacuum, as described above in connection with first collection vial 800. This process repeats for every sample collection desired.
Vacuum source 845 provides a constant level of vacuum so that the flow of ultrafiltrate is not affected by the vacuum source. Vacuum source 845 is sized to overcome small leaks in the system, including, any leaks through septum of the collection vial, and still provide consistent vacuum within the collection vial. It will be appreciated that the level of vacuum can be monitored and adjusted if desired. Monitoring of these factors improve the reliability of ultrafiltrate collection. Automation of sample collection is readily accomplished because any size collection vial may be used with the system of the present invention. Vacuum source 845 may also be sized to accommodate leakage of air into the collection vial. Therefore, collection vials with plastic caps, without septa, may be used. The use of plastic caps reduces cost and time spent sealing septa capped vials.
According to the present invention, vacuum source 844 is constantly drawing a vacuum, thereby creating a vacuum in the trap 845. When the tube assemblies of the present invention are up (out of the collection vial(s)), atmospheric air flows between first and second tubes of each tube assembly into trap 845, then out of trap 845 through third tube 843 through vacuum source 844. When the needles of the tube assemblies are down into the interiors of the collection vials, the vacuum in trap 845 draws air (contents) out of the collection vials as previously described. If the needles of the tube assemblies remain in the interior of the collection vials too long, the vial(s) will overfill and filtered fluid will flow through the interstitial space between first and second tubes of the tube assemblies, through the tube connecting the tube assembly to the needle attached to trap 845 into the trap 845 where the filtered fluid will fall to the bottom of trap 845. This trapping of filtered fluid prevents fluid from being drawn into vacuum source 844.
Using the system and method of the present invention, small volume ultrafiltrate samples may be collected in small collection vials, making the fluid samples easier to extract and allows a greater proportion of valuable sample to be extracted from the collection vial for processing and analysis. The ability to collect small samples is important because sometimes the analyte in solution is very dilute and sample volumes are limited when small animals are used. The greater the sample that can be removed to the collection vial, the easier it is to quantitate the analyte.
Sealed manifold 845 may comprise a standard vacutainer. Manifold 845 of this embodiment provides two functions. First, manifold 845 provides a trap for fluid if one of the collection vials 800 or 801 should overfill, thereby preventing fluid from entering vacuum source 844. Second, manifold 845 allows multiple tube assemblies, and therefore multiple ultrafiltration probes, to be connected to a single vacuum source, such as is illustrated in
It will be appreciated by one of skill in the art that the ultrafiltration collection system of
One skilled in the art will recognize that the collection vials used for ultrafiltrate according to the present invention do not have to be septum sealed. A septum is not required if the vacuum pump is sized properly to accommodate small air leaks into the vial and if the operator is confident that the vial will not over flow with sample. Also, the ultrafiltrate system and method do not require a trap. Instead, the vacuum source may be operatively connected to the tube assembly. However, the trap may be useful for support of multiple probes and to prevent filtered fluid from reaching the vacuum source.
It will be appreciated by those of skill in the art that the system and method for collecting ultrafiltrate samples according to the present invention resolves many of the shortcomings of the prior art. The present invention is suitable for use in drawing small volume samples as it permits for control of the vacuum, even if leakages exists in the system, and also permits for control of the flow of fluid from the probe.
One skilled in the art will also recognize that the system and method described for ultrafiltrate collection is not limited to ultrafiltration. The system and method may be used to pull other types of sample into a collection vial by use of the vacuum source. For example, blood could be collected from a small subject. Thus, the term “probe” as used herein and in the claims is not limited to an ultrafiltration probe, but may comprise a catheter or other tubing.
It will be further appreciated that the system and method of the present invention do not require human intervention for ultrafiltration collection of multiple samples. In addition, the present invention may be used manually or retrofitted into existing automated systems for ultrafiltration collection.
It will be still further appreciated that the tubing of the ultrafiltration collection system of the present invention addresses several shortcomings associated with some prior art systems. The tubing used in the system of the present invention is not of large volume, and therefore does not result in a large time lag for low flow rates. Also, the tubing is not of a type to contaminate the fluid washing through the tube, nor does the tubing of the present invention have changing flow characteristics. Therefore, the system and method of the present invention provide for consistent flow over time.
As used herein and in the claims, the term “tainted” describes some level of mixture, but is not intended to imply a mixture having a minimal amount of a particular constituent. For example, when rinsing according to the method of the present invention, the rinse solution is “tainted” by the biological waste fluid at a level of waste fluid much lower than the level the rinse fluid is “tainted” with continued flow of the rinse solution toward the waste container.
As used herein and in the claims, the “contents” of the collection vial or rinse vial is meant to cover any and all types of contents. For example, rinse vials usually initially contain rinse solution, perhaps with some air in the rinse vial. After some rinsing according to the present invention, the rinse vial will contain a combination of rinse solution and biological waste. Collection vials usually initially contain air. However, a collection vial could also contain chemicals, such as chemicals used to stabilize or affect the sample collected. An example of such chemicals is anticoagulants used for blood samples to inhibit coagulation of the blood sample. Often, such chemicals are in powder form at the bottom of the vial, but it is possible that the chemical could be in fluid form as well.
The above-described embodiments of the present invention are intended to be examples only. Alterations, modifications and variations to the invention by those of skill in the art may be effected to the particular embodiments without departing from the scope of the invention, which is defined solely by the claims appended hereto.
