Methods and devices for collecting, handling and processing mammary fluid samples for evaluating breast diseases, including cancer

• US 6,689,073 B2
• Filed: 11/13/2001
• Issued: 02/10/2004
• Est. Priority Date: 11/13/2000
• Status: Expired due to Term

• Current Assignee: Atossa Therapeutics, Inc.
• Original Assignee: Atossa Healthcare, Inc. (Adhera Therapeutics, Inc.)
• Inventors: Quay, Steven C.
• Primary Examiner(s): MARMOR II, CHARLES ALAN
• Application Number:
  US10/001,041
• Publication Number:
  US 20020127580A1
• Time in Patent Office: 819 Days
• Field of Search: 600/573, 604/73-76, 604/319, 604/320, 604/346, 422/100, 422/102, 422/104, 422/99, 435/6, 435/7, 435/7.1, 435/7.2, 435/7.21, 435/7.23, 435/24, 435/29, 435/30, 435/296, 435/810, 435/975, 436/64, 436/161, 436/162, 436/177, 436/178, 436/807, 436/808, 436/810, 436/813, 436/510, 436/574, 436/576, 436/523-531, 215/232, 215/380, 215/385, 220/661
• US Class Current: 600/573
• CPC Class Codes: A61B 10/0041 Detection of breast cancer mammography by transillumination A61B5/0091, by X-rays A61B6/502, by ultrasonic means A61B8/0825
• CPC Class Codes: A61B 10/0045 Devices for taking samples of body liquids devices for taking blood samples A61B5/15
• CPC Class Codes: A61B 10/0096 Casings for storing test samples A61B10/0038 and A61B10/0045 take precedence; preservation of living parts of the human or animal body A01N1/02; containers for retaining a material to be analysed B01L3/50; containers for enzymology or microbiology C12M1/16; swab-sampler being part of enzymology or microbiology container C12M1/30
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61M 1/06 Milking pumps
• CPC Class Codes: A61M 1/064 Suction cups
• CPC Class Codes: A61M 1/066 Inserts therefor
• CPC Class Codes: A61M 1/0697 having means for massaging the breast
• CPC Class Codes: A61M 2205/075 Bulb type
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574

Abstract

Biological samples of mammary fluid or components thereof are obtained using a breast pump device coupled with a solid phase sample collection medium, alternatively facilitated by administering oxytocin to the subject. The breast pump device stimulates expression of mammary fluid and provides for collection of diagnostic samples to evaluate breast disease, including cancer. The biological sample may include whole cells or cellular components, purified or bulk proteins, glycoproteins, peptides, nucleotides or other desired constituents comprising a breast disease marker. Methods, kits and adapter devices relating to the breast pump device are also provided. Yet additional methods, devices, accessories, and materials are provided for laboratory handling and processing of breast fluid samples and for related diagnostic methods.

Claims

1. A mammary fluid collection reservoir for collection, handling and processing biological samples of mammary fluid comprising:

a rigid tube or vial adapted for removable, sealable engagement in a mammary fluid collection device to establish a gaseous and fluid connection between a breast engaging member of the collection device and an inner lumen of the rigid tube or vial, said rigid tube or vial having a top end defining a primary opening for collecting and accessing the mammary fluid sample and a cylindrical outer wall defining a reservoir lumen closed at a bottom end thereof, said outer wall defining one or more air ports that communicate between the outer wall and the lumen of the rigid tube or vial, further comprising closure means for sealably closing the tube or vial after the mammary fluid is introduced therein and the tube or vial is disengaged from the mammary fluid collection device, to seal the tube or vial and prevent sample contamination and spillage during handling and processing of the biological sample.

2. The mammary fluid collection reservoir of claim 1, wherein the reservoir comprises a removable fluid reservoir member of a sample collection housing of a mammary fluid collection device.

3. The mammary fluid collection reservoir of claim 2, wherein the rigid sample collection tube or vial removably connected with an outer casing member of the sample collection housing of the mammary fluid collection device.

4. The mammary fluid collection reservoir of claim 3, wherein the reservoir is adapted for removable, sealable connection with said outer casing member of the housing, to form an airtight coupling therewith.

5. The mammary fluid collection reservoir of claim 4, wherein the reservoir is a cytology vial sealably connectable with the outer casing member to form the airtight coupling.

6. The mammary fluid collection reservoir of claim 2, wherein the reservoir is adapted to be removably nested within an outer casing member of the sample collection housing to form a substantially airtight contact between an inner wall of the casing member and an outer wall or top or bottom end of the reservoir member.

7. The mammary fluid collection reservoir of claim 2, wherein the outer wall of the reservoir is provided with a circumferential ridge, fin or O-ring.

8. The mammary fluid collection reservoir of claim 1, wherein said closure means comprises a cap adapted to sealably engage a top end of the fluid-retaining reservoir.

9. The mammary fluid collection reservoir of claim 8, wherein a top end of the tube or vial is provided with complementary threads to receive a conventional cap that is complementarily threaded to sealably engage the top end of the tube or vial.

10. The mammary fluid collection reservoir of claim 8, wherein said closure means includes secondary closure means for closing said one or more air ports.

11. The mammary fluid collection reservoir of claim 10, wherein said secondary closure means includes a secondary closure device selected from a plug, cap or adhesive cover sized and constructed to engage or adhere to the outer wall of the reservoir at or surrounding the one or more air port openings to form a secondary closure.

12. The mammary fluid collection reservoir of claim 10, wherein said secondary closure means comprise a combined closure and labeling device which functions as a secondary closure mechanism to seal the one or more air ports of the reservoir and as a labeling template to provide a writing surface for sample labeling.

13. The mammary fluid collection reservoir of claim 12, wherein said combined closure and labeling device is a labeling tab or sticker for application to the outer wall of the reservoir to seal the one or more air ports after the sample is collected.

14. The mammary fluid collection reservoir of claim 13, wherein said tab or sticker has a first, closure-forming surface for application over the one or more air ports to form a seal by juxtaposition or adhesive contact with the outer wall of the reservoir, and a second, labeling surface opposite the closure-forming surface made of a blank template material for imprinting written information thereon.

15. The mammary fluid collection reservoir of claim 12, wherein said secondary closure means is pre-attached to the reservoir member in a first, open configuration and is adapted to be manually repositioned or otherwise manipulated after sample collection to a second, closed configuration to form a seal or closure against the one or more air ports and provide an and exposed writing surface for sample labeling.

28. The method according to claim 1, wherein the fluid-retaining reservoir is a modified cytology vial.

29. The method according to claim 1, wherein the fluid-retaining reservoir comprises a removable fluid reservoir member of a sample collection housing of a mammary fluid collection device.

30. The method according to claim 29, wherein the rigid tube or vial is removably connected with an outer casing member of the sample collection housing of said collection device.

31. The method according to claim 30, wherein the fluid-retaining reservoir is adapted for removable, sealable connection with said outer casing member of said housing to form an airtight coupling therewith.

32. The method according to claim 31, wherein the fluid-retaining reservoir is a cytology vial sealably connectable with said outer casing member to form an airtight coupling therewith.

33. The method according to claim 32, wherein the fluid-retaining reservoir is adapted to be removably nested within said casing member to form a substantially airtight contact between an inner wall of the casing member and an outer wall, or a top or bottom end, of the reservoir member.

34. The method according to claim 1, wherein an outer wall of the fluid-retaining reservoir bears a circumferential ridge, fin or O-ring.

35. The method according to claim 34, wherein the fluid-retaining reservoir comprises a removable fluid reservoir member of a sample collection housing of a mammary fluid collection device and the circumferential ridge, fin or O-ring is adapted to engage and make a circumferential airtight seal against an inner wall of a casing member of a sample collection housing of said device.

36. The method according to claim 1, wherein said mammary fluid sample or component thereof includes whole cells or cell fragments.

37. The method according to claim 1, further comprising the step of accessing said sample within said reservoir to transfer or process the sample for detection or quantification of said breast disease marker.

38. The method according to claim 31, further comprising the step of transferring said sample to a second reservoir or other sample container or template for processing the sample to detect or quantify said breast disease marker.

39. The method according to claim 38, wherein said step of processing said sample to detect or quantify said breast disease marker comprises staining cells or cell fragments from said sample with a cytological stain to detect a cytological marker.

40. The method according to claim 31, further comprising the step of processing said sample to detect or quantify said breast disease marker by microscopic examination of stained cells or cell fragments from said sample.

41. The method according to claim 1, wherein said biological sample includes one or more components selected from the group consisting of whole mammary fluid, whole cells, cell fragments, cell membranes, purified proteins, bulk proteins, glycoproteins, peptides and polynucleotide components of a primary mammary fluid sample.

42. The method according to claim 1,wherein the breast disease marker is a breast cancer marker.

43. The method according to claim 1, wherein the breast disease marker is selected from the group consisting of a protein, a peptide, a glycoprotein, a lipid, a DNA polynucleotide and an RNA polynucleotide.

44. The method according to claim 1, wherein the breast disease marker is selected from the group consisting of Ki67 Growth Factor, Cyclin D1, Proliferating Cell Nuclear Antigen, Transforming Growth Factor Tissue Plasminogen Activator, Insulin Growth Factor Receptors, Collagenase Type IV, Laminin Receptor, Integrins, p53, rb, nm23, ras, c-myc, Heat Shock Proteins, Prolactin, Neuron-Specific Enolase, IR-14, KA 1, KA 14, Alpha-Lactalbumin and Actin.

45. The method according to claim 1,wherein the breast disease marker is selected from the group consisting of CEA, HMFG, MCA, vasopressin and cathepsin.

46. The method according to claim 1, further comprising the step of detecting or quantifying said breast disease marker by ELISA immunoassay, immunoprecipitation assay, or solid phase immunoassay.

47. The method according to claim 1, wherein said biological sample comprises an oxytocin-induced sample of mammary fluid or a component thereof.

48. The method according to claim 47, wherein said biological sample comprises whole cells or cell fragments from said oxytocin-induced sample of mammary fluid.

16. A method for handling or processing a biological sample of mammary fluid or a component thereof for use in a diagnostic assay to detect or quantify a breast disease marker in said sample comprising the step of:

providing or obtaining said biological sample of mammary fluid or component thereof in a fluid-retaining reservoir having a top end defining a primary opening for access to the sample and an outer reservoir wall defining one or more air ports that communicate between the outer wall and an inner lumen of the reservoir, said reservoir comprising a rigid tube or vial adapted for removable, sealable engagement in a mammary fluid collection device to establish a gaseous and fluid connection between a breast engaging member of the collection device and an inner lumen of the rigid tube or vial, said reservoir further comprising closure means for sealably closing the tube or vial after the mammary fluid is introduced therein and the tube or vial is disengaged from the mammary fluid collection device, to seal the tube or vial and prevent sample contamination and spillage during handling and processing of the biological sample.

17. The method according to claim 16, wherein the closure means comprises a cap adapted to sealably engage a top end of the fluid-retaining reservoir.

18. The method according to claim 17, wherein a top end of the tube or vial is provided with complementary threads to receive a conventional cap that is complementarily threaded to sealably engage the top end of the tube or vial.

19. The method according to claim 17, wherein the closure means further comprises secondary closure means for sealably closing the one or more air ports after said sample is introduced into said reservoir.

20. The method according to claim 19, wherein said secondary closure means comprise an adhesive seal or sticker sized and constructed to adhere to an outer wall of the reservoir surrounding an air port opening.

21. The method according to claim 19, wherein said secondary closure means comprises a combined closure and labeling device which functions as a secondary closure mechanism to seal the one or more air ports of the fluid-retaining reservoir and as a labeling template to provide a writing surface for sample labeling.

22. The method according to claim 19, wherein said secondary closure means comprises a combined closure and labeling tab or sticker which is adapted to be directly applied to seal the one or more air ports after sample collection having a first, closure-forming surface for application over the air port to form a seal by juxtaposition or adhesive contact with an outer wall of the fluid-retaining reservoir, and a second, labeling surface opposite the closure-forming surface made of a blank template material suitable for receiving a stable, ink or graphite imprint thereon.

23. The method according to claim 22, wherein said first, closure-forming surface bears an adhesive coating resistant to disruption by contact with aqueous solutions.

24. The method according to claim 19, wherein said secondary closure means comprises a combined closure and labeling tab or sticker which is pre-attached to the fluid-retaining reservoir in a first, open configuration and is adapted to be manually repositioned or otherwise manipulated after sample collection to a second, closed configuration to form a seal or closure against the one or more air ports.

25. The method according to claim 24, wherein said secondary closure means comprises an adhesive tab or strip folded in the open configuration to form an inner layer affixed to the reservoir proximate to the one or more air ports and an outer layer folded over the inner layer, said outer layer providing a first, closure-forming surface and a second, labeling surface, wherein the outer layer can be unfolded away from the inner layer and wrapped around the reservoir so that the closure-forming surface covers the one or more air ports to form a fluid-resistant closure and the labeling surface faces outward for recordation of sample data.

26. The method according to claim 25, wherein the outer layer is optionally secured in a folded-back position against the inner layer by adhesive engagement of the labeling surface with the inner layer.

27. The method according to claim 26, wherein said first, closure-forming surface bears an adhesive coating that is protected in the open configuration by folding of an end segment of the outer layer bearing the adhesive coating back, so that the closure forming surface provides a protective surface to shield the adhesive prior to closure, whereby the end segment is adapted to be lifted and pulled outward to unfold the end segment to separate the adhesive coating on the closure-forming surface from the protective surface and to release the outer layer from the inner layer for closing of the one or more air ports.