Liquid specimen container and attachable testing modules

Abstract

A biological fluid collection container comprising a cup member, a lid assembly removably mounted to the cup member comprising a housing with a downwardly extending cylindrical skirt, a luer lock with a throughgoing bore extending from one side of the lid housing. A hollow tube extends from the other side of the lid housing adjacent the luer lock and is axially aligned with the throughgoing bore of the luer lock. The hollow tube is provided with a plurality of throughgoing holes leading into its lumen along its surface to provide for a sampling along various liquid level layers of the biological fluid specimen collected in the cup member so that when the biological fluid specimen is removed from the cup member a representative sampling is obtained.

Description

This application is a divisional of application Ser. No. 08/340,884 filed on Nov. 15, 1994, now abandoned, which is incorporated entirely herein by reference, and a continuation79 101 of stepped end 78. The base 91 is provided with a threaded luer lock 99 on its exterior surface and defines a throughgoing bore 97 with a frusto conical proximal end which leads to membrane 84 and chamber 80. As previously noted, nipple 88 of the cytology/microbiology container is fitted with a threaded projection which is adapted to fit onto the luer lock 62 of a 30 cc syringe 64, manufactured by Becton Dickinson & Co. It should be noted that any pump type device could be used in place of the syringe 64 as for example an autovial spunglass filter manufactured by Genex Corporation. The syringe 64 has a barrel 66 with associated luer lock 62, piston 68 and piston head 69. While the cytology/microbiology container 70 can be used for any body fluid it is primarily designed for use with concentrated dialysis fluid and urine and for collecting associated sediments and/or bacteria for use in testing for various kinds of disease.

The male member 74 of the cytology/microbiology container 70 can contain a nitrocellulose membrane filter 84a with a filter size of 13 mm diameter and a porosity of approximately 0.45 microns for bacteria entrapment as shown in FIG. 11 or in the case of cell cytology, a polycarbonate filter 84, as shown in FIG. 10. The polycarbonate filter 84 has a five-micron pore size to trap the polymorph-nuclear leukocytes or even lymphocytes which are seven and one half microns in size.

It should be noted that various composition filters can be used and interchanged. One membrane filter that can be used for fluid screening is LEUCOSORE, a leucocyte retention medium manufactured by Pall BioSupport Division of Pall Corporation. Other membranes manufactured and sold by the Pall Corporation are BIODYNE A, an unmodified nylon with surface chemistry 50% amine and 50% carboxyl group with an isoelectric point of pH 6.5; BIODYNE B, a surface-modified nylon with surface chemistry characterized by a high density of strong cationic quarternary groups (the zeta potential is positive to pH>10); BIODYNE C, a surface-modified nylon with surface chemistry characterized by a high density of anionic carboxyl groups (the zeta potential is negative to pH>3; and LOPRODYNE, a low protein binding nylon 66 membrane with a tightly controlled microporous structure with high voids volume for rapid, efficient throughput of liquids and absolute retention of microparticles designed for cell separation and bacterial cell immunoassays. Fifty milliliters of dialysate will be pulled from container 10 through the desired filter membrane 84 or 84a depending upon the analysis into syringe 64. After the requisite amount of dialysate has been passed through the filter membrane, the cytology/microbiology container 70 and associated filter membrane is removed. The polycarbonate membrane 84 is placed on a glass slide 120 as shown in FIG. 10 and stained with a modified Wrights stain for cytologic determination.

Thus, the method of transferring cells to a slide is that of membrane filtration (filtration of fluid specimens through membrane filters to increase cell recovery). This particular technique provides the critical feature that the cells are evenly deposited over the slide with minimal overlap as this will allow clear observation and optimal diagnostic accuracy.

It should be noted that the process of transferring or collecting cells onto a slide or membrane is largely affected by preserving or fixing the cytology specimen in the body fluid, secretions or smears.

Currently, body fluid samples are collected for cytological examinations using special containers. These containers usually contain a preservation solution for preserving the cytology specimen during shipment from the collection site to the cytology laboratory. Furthermore, cytology specimens collected from the body cavities using a swab, smear, flush or brush are also preserved in special containers with fixatives prior to transferring cells onto the slide or membrane for staining or examination.

It has been found by the present inventor that the recovery (yield) as well as the quality of the cytology preparations from fresh body fluid specimens is superior when compared to routine cytology preparations that were prepared when the same samples were preserved. This is probably due to the fact that fresh cells stick better to glass and/or membranes than those preserved in alcohol or other preservatives.

The inventive apparatus also allows for isolation and collection of fresh cells and/or microorganisms from the body fluids to perform DNA probing and chromosomal analysis once the cells are hemolysed by the proper buffer.

The most widely used stain for visualization of cellular changes in cytology is the Papanicolaou staining procedure. This stain, which is used for both gynecologic and non-gynecologic applications, is basically composed of blue nuclear and orange, red and green cytoplasmic counterstains. The nuclear stain demonstrates the chromatin patterns associated with normal and abnormal cells, while the cytoplasmic stains help to indicate cell origin. The success of this procedure can be attributed to the ability to observe a number of factors, including definition of nuclear detail and cell differentiation. This staining procedure also results in a multicolor preparation that is very pleasing to the eye, possibly reducing eye strain.

Since cellular detail is dependent on fixation, it is extremely important that cells be fixed immediately after being deposited on the slide. Too long a delay between preparation and fixation exposes the cells to air drying, which is detrimental to the cellular structure. Moreover, air drying artifact can adversely affect the subsequent staining results. (An exception is when the cells are stained with Wright-Giemsa, where air drying is used as the fixation step.)

New methodologies such as immunocytochemistry and image analysis require preparations that are reproducible, fast, biohazard-free and inexpensive. Different cell preparation techniques of the present invention address the issues of non-uniform cell densities, uneven cell distribution and air drying artifact. These preparations have resulted in an even distribution of cells that have superior morphology, which has improved light microscopic visualization and has allowed for the use of image cytometry instruments.

The effectiveness of transferring the cells from the filter to the slide has proved to be very high without differential cell loss. (Microscopic examination showed that the cell distribution was the same on the slide as on the filter).

This procedure has many advantages for conventional cytology. The cells are in a predetermined area allowing for significant timesaving when screening the slide. Such problems as cells lying outside the coverslip or on the frosted end are eliminated. Because cells are lying in a single layer, they are almost always in a one focal plane when using a 10× objective—the objective most often used for the lower power screening of a slide. Even with a 40× objective, most cells are in focus. This eliminates frequent refocusing and saves time.

The minimal cell overlap achieved in this process ensures that all cells and cell groups can easily be examined with little chance for diagnostic cells to be obscured by clumps of overlapping cells or debris. Moreover, because the process takes place in the cytology laboratory, slide preparation and fixation are controlled by laboratory personnel and quality assurance is easily implemented.

Multiple specimens can be made from a single patient sample. Additional slides for other stain applications can be easily prepared. Human papilloma virus testing, for example, by newer methods such as immunocytochemistry or in-situ hybridization can be performed on the additional slides. As oncogene products or other immunocytochemical tests are developed, more slides may be necessary. The different fixations that these tests may need can easily be incorporated into the procedure since the preparation does not require the slides to be fixed in only one way.

This same slide preparation procedure can be used for virtually all forms of cytology. Furthermore, the use of completely contained disposable components addresses bio-hazard concerns. Ultimately, the enhanced presentation of cells, yielding improved cytologic interpretation, may expand the role of cytology by providing more consistent and reliable patient diagnosis.

In bacteria testing the filter 84a while shown in FIG. 11 to be elated and cultured in a standard petri dish 130 is preferably used for culturing with a Qualture device not shown readily obtainable to determine the presence of specific bacteria colonies. The Qualture device is a plastic capsule containing a filter membrane and four nutrient pads of dehydrated, selected media.

The Qualture technique is more sensitive than the agar plate method and more rapid in determining a presumptive diagnosis. The device screens, isolates and presumptively diagnoses bacterial isolates in one step most often in 4-6 hours. Tests have demonstrated that recovery from fifty milliliters of fluid is excellent and sensitive.

Thus is can be seen that the collection cup 10, syringe 64, antigen capture capsule 40 and cytology/microbiology container can be provided in kit form for easy use by the testing person in the desired mix and match combination.

In the foregoing description, the invention has been described with reference to a particular preferred embodiment, although it is to be understood that specific details shown are merely illustrative, and the invention may be carried out in other ways without departing from the true spirit and scope of the following claims:

Claims

1. An apparatus comprising:

a plurality of specimen collection containers defining a fluid flow path, intermediate ones of the containers along the fluid flow path each having an inlet and an outlet, and at least one container having chromatographic bed material for capturing particulate matter and cells.

2. The apparatus of claim 1, further comprising:

at least one specimen collection container having a membrane for capturing cells.

3. The apparatus of claim 1, wherein the container having said chromatographic bed material for capturing particulate matter includes chromatographic bed material for determining the presence of a specific analyte.

4. The apparatus of claim 1, wherein the container having said chromatographic bed material for capturing particulate matter includes chromatographic bed material for determining the presence of a multiple analyte.

5. The apparatus of claim 1, wherein one of said intermediate containers has a filter membrane disposed between its inlet and its outlet for capturing cells.

6. The apparatus of claim 5, wherein one said specimen collection containers along the flow path is a specimen cup, said specimen cup communicating with the inlet of said intermediate container having said filter membrane, the outlet of said intermediate container having said filter membrane communicating with the inlet of another one of said intermediate containers, and the outlet of said another intermediate container communicating with a pump; and wherein said pump is one of said specimen collection containers along the flow path.

7. The apparatus of claim 5, wherein cells captured by the membrane are captured in a single layer.

8. The apparatus of claim 1, wherein the container having said chromatographic bed material is an intermediate container and includes a membrane; and wherein said chromatographic bed material can pass freely through the outlet of said intermediate container.

9. The apparatus of claim 8, wherein the container having chromatographic bed material is an intermediate container and includes a membrane for preventing the chromatographic bed material from passing through its inlet.

10. The apparatus of claim 1, further comprising:

a pump communicating with a final one of the outlets along the fluid flow path.

11. The apparatus of claim 1, further comprising:

a specimen cup communicating with an initial one of the inlets along the fluid flow path.

12. The apparatus of claim 11, wherein the specimen cup includes a lid having a tube extending into the specimen cup, said tube having at least two perforations at different longitudinal points along its length.

13. An apparatus comprising:

a first housing having a first inlet and a first outlet, said first housing defining a first portion of a fluid flow path and having a filter membrane disposed between the first inlet and the first outlet for capturing cells in the fluid flow path; and

a second housing having a second inlet and a second outlet, said second housing defining a second portion of the fluid flow path and having a chromatography element disposed between the second inlet and the second outlet.

14. The apparatus of claim 13, further comprising:

a specimen cup for communicating with the first inlet along the fluid flow path.

15. The apparatus of claim 14, wherein the specimen cup includes a lid having a tube extending into the specimen cup, said tube having at least two perforations at different longitudinal points along its length.

16. The apparatus of claim 14, wherein the specimen cup is removable from the apparatus.

17. The apparatus of claim 13, further comprising:

a pump for communicating with the first outlet along the fluid flow path.

18. The apparatus of claim 13, further comprising:

a specimen cup for communicating with the second inlet along the fluid flow path.

19. The apparatus of claim 13, further comprising:

a pump for communicating with the second outlet along the fluid flow path.

20. The apparatus of claim 13, wherein the second housing includes a membrane; and wherein said chromatography element can pass freely through the second outlet.

21. An apparatus comprising:

a first housing having a first inlet and a first outlet, said first housing also having a filter membrane disposed between the first inlet and the first outlet for capturing cells;

a second housing having a second inlet and a second outlet, said second housing having chromatographic bed material disposed between the second inlet and the second outlet; and

a specimen container having a lid suitable for fluid communication with the first inlet or the second inlet, said lid having a tube extending into the specimen container, said tube having at least two perforations at different longitudinal points along its length;

wherein the lid is in direct fluid communication with the first inlet or the second inlet, and the first outlet is in direct fluid communication with the second inlet or the second outlet is in direct fluid communication with the first inlet, respectively.

22. An apparatus comprising:

a plurality of specimen collection containers defining a fluid flow path, intermediate ones of said plurality of specimen containers each having an inlet and an outlet, wherein at least one of said plurality of specimen containers has chromatographic bed material for capturing at least one analyte.

23. The apparatus of claim 22, wherein a first of said intermediate containers has a filter disposed between its inlet and its outlet.

24. The apparatus of claim 23, wherein one of said specimen collection containers is a specimen cup, wherein said specimen cup is in fluid communication with the inlet of said first of said intermediate containers, wherein the outlet of said first of said intermediate containers is in fluid communication with the inlet of a second of said intermediate containers, and wherein the outlet of said second of said intermediate containers is in fluid communication with a pump.

25. The apparatus of claim 24, wherein the pump is a syringe.

26. The apparatus of claim 22, wherein the container having chromatographic bed material is one of said intermediate containers, and wherein said chromatographic bed material can pass freely through the outlet of said intermediate container.

27. The apparatus of claim 26, wherein said container having chromatographic bed material includes a filter, wherein the filter of said container having chromatographic bed material is positioned at the inlet of said container having chromatographic bed material, and wherein said filter prevents said chromatographic bed material from passing through the inlet of said container having said chromatographic bed material.

28. The apparatus of claim 26, wherein said chromatographic bed material is a plurality of beads.

29. The apparatus of claim 22, wherein one of said specimen collection containers is a pump, and wherein said pump is in fluid communication with the outlet of a final of said intermediate containers.

30. The apparatus of claim 29, wherein said pump is a syringe.

31. An apparatus comprising:

a plurality of specimen collection containers defining a fluid flow path, intermediate containers of said plurality of specimen containers each having an inlet and an outlet; wherein at least one of said plurality of specimen containers has a filter for capturing cells, and wherein said plurality of specimen containers includes a pump which is in fluid communication with the outlet of a final of said intermediate containers.

32. The apparatus of claim 31, wherein one of said specimen collection containers is a specimen cup, wherein said specimen cup is in fluid communication with the inlet of a first of said intermediate containers, wherein the outlet of said first of said intermediate containers is in fluid communication with the inlet of said final of said intermediate containers.

33. The apparatus of claim 32, wherein the pump is a syringe.

34. The apparatus of claim 32, wherein the at least one of said specimen containers having a filter for capturing cells is the first of said intermediate containers.

35. The apparatus of claim 34, further comprising:

a slide, wherein the filter of said at least one of said specimen containers having a filter for capturing cells can be removed from said at least one of said specimen containers having a filter and positioned on the slide.

36. The apparatus of claim 32, further comprising:

a lid removably secured to said specimen cup; and

a luer lock, wherein said first of said intermediate containers is affixed to the lid, wherein the outlet of said first of said intermediate containers is connected to the inlet of the final of said intermediate containers by said luer lock.

37. An apparatus comprising:

a first housing having a first inlet and a first outlet, said first housing defining a first portion of a fluid flow path and having a filter disposed between the first inlet and the first outlet; and

a second housing having a second inlet and a second outlet, said second housing defining a second portion of the fluid path and having chromatographic bed material disposed between the second inlet and the second outlet.

38. The apparatus of claim 37, further comprising:

a specimen cup in fluid communication with the first inlet.

39. The apparatus of claim 38, wherein the specimen cup includes a lid through which the first inlet communicates with the specimen cup via a tube which extends into the specimen cup, and wherein said tube has at least two perforations at different longitudinal points along its length.

40. The apparatus of claim 39, wherein the specimen cup is removable from the apparatus.

41. The apparatus of claim 37, further comprising:

a pump in fluid communication with the second outlet.

42. The apparatus of claim 41, wherein the pump is a syringe.

43. The apparatus of claim 37, further comprising:

a filter,