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CA-3067372-C - SYSTEM AND PROCEDURE FOR STABILIZING, STORING AND RECOVERING BLOOD SAMPLES

CA3067372CCA 3067372 CCA3067372 CCA 3067372CCA-3067372-C

Abstract

Blood samples are maintained in a modified atmosphere sealed environment, where moisture is reduced using a desiccant and oxygen is removed using a deoxygenation compound, thus resulting in the preservation of numerous blood analytes, for delayed (e.g., 14 days from collection) blood testing, such as for enzymatic activity, concentration of protein and measurement of other blood components in human and veterinary blood test applications.

Inventors

  • Randy Ringold
  • KYLE WILSON
  • Tyson Ringold
  • Ekaterina PESHEROV

Assignees

  • VETERINARY DIAGNOSTICS INSTITUTE, INC.

Dates

Publication Date
20260505
Application Date
20180613
Priority Date
20170613

Claims (19)

  1. 90993914 31 Claims 1. A system for stabilizing analytes in blood samples, and for delayed extraction of the blood samples from dried blood spots resulting in near neat-level blood samples for use in tests in human and veterinary applications, said system comprising: 5 a device for holding a blood sample; and a sealable centrifuge tube having an elevator.
  2. 2. The system of claim 1, further comprising a sealable container for holding there within, in a sealed environment, said device for holding said blood sample, a 10 desiccant compound and a deoxygenation compound.
  3. 3. The system of claim 1, wherein said sealable centrifuge tube is a sealable micro-centrifuge tube. 15
  4. 4. The system of claim 1 further comprising a buffer solution.
  5. 5. The system of claim 3, wherein said elevator has an elongated shape a first end of which rests against a bottom of said sealable micro-centrifuge tube, and has a middle portion a cross section profile of which matches an inner section profile of said 20 sealable micro-centrifuge tube.
  6. 6. The system of claim 5, wherein said elevator further has a second end that rests against a lid of said sealable micro-centrifuge tube. 25
  7. 7. The system of claim 1 further comprising at least one strip of absorbent paper obtained from said device for holding said blood sample.
  8. 8. The system of claim 7, wherein said at least one strip of absorbent paper further comprises at least one paper punch.
  9. 9. The system of claim 7, wherein said at least one strip of absorbent paper further comprises at least one paper rectangle. 90993914 32
  10. 10. The system of claim 1, wherein said device for holding said blood sample further comprises an enclosure comprised of a first region for holding an absorbent medium and a second region for holding a desiccant compound, wherein said enclosure allows for free air circulation between said first region and said second region, wherein 5 said absorbent medium further comprises cellulose-based paper.
  11. 11. The system of claim 1, wherein said device for holding said blood sample further comprises an enclosure comprised of a first region for holding an absorbent medium and a second region for holding a desiccant compound, wherein said enclosure 10 allows for free air circulation between said first region and said second region, wherein said absorbent medium further comprises synthetic paper.
  12. 12. A method for stabilizing analytes in blood samples, and for delayed extraction of blood samples from dried blood spots resulting in near neat-level blood 15 samples for use in tests in human and veterinary applications, said method comprising the steps of: obtaining a blood sample from a subject, placing said blood sample in a device for holding said blood sample, wherein said device comprises an absorbent medium; placing a test tube elevator in a sealable centrifuge tube and a buffer solution in 20 said sealable centrifuge tube; obtaining at least one strip of absorbent paper from a dried blood holding device and placing said at least one strip in said sealable centrifuge tube on top of said test tube elevator; incubating said absorbent medium in said buffer solution inside by holding said 25 sealable centrifuge tube flipped upside-down; and centrifuging said sealable centrifuge tube while directing a centrifugal force toward a bottom of said sealable centrifuge tube to push said buffer solution toward the bottom of said sealable centrifuge tube, while said absorbent medium remains held by said test tube elevator close to the top of said sealable centrifuge tube.
  13. 13. The method of claim 12, wherein said step of placing said test tube elevator in said sealable centrifuge tube further comprises placing said test tube elevator in a sealable micro-centrifuge tube. 90993914 33
  14. 14. The method of claim 12 further comprises placing a sealable container within a parcel for shipping via a postal service.
  15. 15. The method of claim 12, wherein said step of placing said blood sample in 5 said device for holding said blood sample further comprises placing a plurality of fixed quantities of said blood sample on said absorbent medium contained within a dried blood spot card.
  16. 16. The method of claim 12, wherein said obtaining said at least one strip 10 further comprises obtaining paper punches.
  17. 17. The method of claim 12, wherein said obtaining said at least one strip further comprises obtaining paper rectangles. 15
  18. 18. The method of claim 12, wherein said obtaining said at least one strip further comprises obtaining paper wedges.
  19. 19. The method of claim 12 further comprising the steps of: placing said device for holding said blood sample into a sealable container; and 20 providing a modified atmosphere environment within said sealable container by placing, into said sealable container, a desiccant compound to remove residual moisture and a deoxygenation compound to remove residual oxygen and sealing said sealable container to prevent fluid exchange between an interior and an exterior of said sealable container.

Description

SYSTEM AND PROCEDURE FOR STABILIZING, STORING AND RECOVERING BLOOD SAMPLES FIELD OF THE INVENTION The invention relates to a method, apparatus, devices and system for handling blood samples, more specifically, the invention comprises a system and procedure for stabilizing, 10 extracting and testing blood samples. BACKGROUND OF THE INVENTION Clinical laboratory testing typically involves liquid whole blood and/or liquid plasma, or serum. It is thus critical to preserve the integrity of blood samples from the location and 15 time they are drawn to the location and time they are used. Special preservatives and/or transportation procedures to preserve specimen integrity are required as proteolytic enzymes, naturally occurring in blood, plasma or serum, can degrade proteins. Routine commercial laboratories have set up extensive logistical 20 networks to rapidly transport specimens. This includes, for example, shipping the specimens in insulated containers with cold packs or dry ice and/or tubes with special preservatives. In the 1960s, dried whole blood testing was launched for neonatal testing of Phenylketonuria (PKU). Using special cellulose based paper, dried blood spot cards were 1 Date rei;ue/Date received 2023-06-12 WO 2018/231960 PCT/0S2018/037302 used to collect blood samples for PKU testing. The specimens, once dried, assisted in the preservation of this analyte. The DBS cards could be stored and transported at ambient temperature for up to two weeks, which allows for transportation by common letter mail service, thus reducing cost of transportation. Upon receipt by the laboratory, blood in the 5 specimen is extracted and tested for PKU. Since that time, the use of dried blood spot collection and testing has expanded to test for other analytes, provided that certain requirements are met, which include, for example, that the analyte must be in relatively high concentration; the analyte must be very stable under adverse conditions and the analyte must not require a high degree of analytical 10 precision to be useful. Further, other manufacturers have developed similar devices using cellulose based paper and synthetic based papers for dried blood, serum, plasma testing, herein referred to dried blood specimen (DBS), however still suffer from the same limitations. The prior art methods and devices meet the above limitations only for those 15 applications that can be satisfied with low precision (e.g., genetic DNA testing). However the use of DBS for routine chemistries, enzymes, or high precision and/or high sensitivity work fails to meet the required specifications. In tests that measure enzyme activity, for example, enzymes often become inactive after being dried i.e. the enzymes do not convert substrate to product. In tests that use antibodies to measure protein mass (ELISA), drying 20 specimens causes epitopes to become hidden or 3-dimensional conformation is lost i.e. antibodies fail to bind to the target protein. In tests that require a high degree of precision or sensitivity, consistent concentration of the DBS to near neat blood levels is not achieved i.e. unable to measure low concentration of a target analyte with satisfactory precision. The fundamental problems to be solved are: 25 • how to stabilize the specimen so enzymes would properly function • how to maintain protein structure so immunoassays would properly recognize epitopes • how to consistently concentrate the specimen to maintain precision and sensitivity Alternative materials, other than cellulose, have been developed. Synthetic materials 30 have advantages over cellulose in greater recovery due to low non-specific binding. However due to the impact of specimen drying and prolonged storage (up to two weeks) at 2 WO 2018/231960 PCT/0S2018/037302 ambient temperature the inherent limitations of DBS still remain. Another process that dries and stabilizes biological samples is lyophilization. Invented in the early 1900's, it was derived from a similar method used by the natives of the Andes. Lyophilization is a process of water removal by sublimation. Under a vacuum, liquid water 5 is quickly frozen and the water is instantly turned into a gas and removed. The process is also known as freeze-drying. Lyophilization is well known for its ability to preserve a wide range of biological samples. Pharmaceuticals, diagnostic reagents and calibrators, bacterial cultures, are frequently lyophilized. The end result is a dry sample that is under vacuum that can be 10 stored. Studies performed since the nineteen sixties have shown that higher vacuum conditions result in longer storage time, presumably due to lower oxygen levels (Dewald, 1966). Because of the required logistics and the prohibitive cost, even as lyophilization is effective at sample preservation, the process is impracticable to implement as a routine use in blood sample preservation and diagnostics. 15 On other hand, DBS eliminates the time-sensitive nature of blood testing. It removes t