Automated blood sampling apparatus

• US 20010031932A1
• Filed: 03/14/2001
• Published: 10/18/2001
• Est. Priority Date: 04/12/2000
• Status: Active Grant

• Current Assignee: Merck & Co., Inc.
• Original Assignee: Merck & Co., Inc.
• Inventors: Clarke, Glenn A., Blake, Kevin R., Cheng, Kang, Kath, Gary S., King, Gregory W., Wu, Tsuei-Ju
• Granted Patent: US 6,736,783 B2
• Time in Patent Office: Days
• US Class Current: 600/573
• CPC Class Codes: A61B 5/15003 for venous or arterial blood
• CPC Class Codes: A61B 5/150221 Valves
• CPC Class Codes: A61B 5/150229 Pumps for assisting the blood sampling
• CPC Class Codes: A61B 5/150389 Hollow piercing elements, e.g. canulas, needles, for piercing the skin
• CPC Class Codes: A61B 5/150503 Single-ended needles hollow piercing element tip design A61B5/150396, needle sets for catheters A61M25/06, needles for bringing media into the body A61M5/32
• CPC Class Codes: A61B 5/150992 Blood sampling from a fluid line external to a patient, such as a catheter line, combined with an infusion line; blood sampling from indwelling needle sets, e.g. sealable ports, luer couplings, valves tubing connectors and couplings A61M39/00
• CPC Class Codes: A61B 5/153 Devices specially adapted for taking samples of venous or arterial blood, e.g. with syringes
• CPC Class Codes: A61B 5/155 Devices specially adapted for continuous or multiple sampling, e.g. at predetermined intervals devices loaded with multiple lancets simultaneously A61B5/15146

Abstract

An apparatus and process for automatically, repetitively sampling blood from conscious animals. The apparatus can simultaneously extract blood from a number of conscious, catherized animals at programmable time intervals. The apparatus is characterized as a system of computer controlled valves and pumps connected by tubing filled with saline solution to a catherized animal. Blood samples are collected via a cannula from the animal and placed in a fraction collector for analyses.

Claims

1. An apparatus for automatically, repetitively sampling blood from a conscious animal, comprising:

a) means for confining a conscious, catheterized animal;

b) a cannula having first and second ends, said first end connected to the catheterized animal, said cannula being suitable for sampling blood from the animal;

c) a cannula valve having first and second ends, said first end connected to the cannula, said cannula valve opening and closing being computer controlled;

d) a cannula T-fitting having first, second and third ends, said first end connected to the second end of the cannula valve;

e) an outlet valve having first and second ends, said first end connected, via tubing, to the second end of the cannula T-fitting, said outlet valve opening and closing being computer controlled;

f) a dispensing tip having first and second ends, said first end connected to the second end of the outlet valve, said second end being suitable for discharging blood into a sample, collection vial;

g) means for horizontal and vertical movement of the dispensing tip, said means for movement being computer controlled;

h) an air T-fitting having first, second and third ends, said first end connected to the third end of the cannula T-fitting;

i) an air valve having first and second ends, said first end connected to the second end of the cannula T-fitting, said second end connected to a check valve;

j) a syringe pump suitable for transferring blood and saline solution through the apparatus, said pump having first and second ends, said first end connected, via tubing, to the third end of the air T-fitting, said pump being computer controlled;

k) a rotary, programmable valve having four ports for receiving and discharging fluids, wherein the ports open and close by computer control, said first port being connected, via tubing, to the second end of the syringe pump;

l) a heparinized saline source comprising a saline solution, said saline source being connected to the second port of the programmable valve;

m) a fraction collector, comprising;

i) a base having two horizontally opposed, parallel tracks, and a single track horizontally positioned above and perpendicular to the horizontally opposed, parallel tracks,

ii) a temperature controlled rack in slidable contact with the horizontally opposed, parallel tracks,

iii) means for sliding the rack along the tracks, said means being computer controlled, and

iv) a plurality of sample, collection vials removably located in the rack, said vials being suitable for receiving samples from the dispensing tip; and

n) computer means for accepting timing commands for collecting samples from the animal in coordination with the opening and closing of valves, sliding of the temperature controlled rack, pumping of the syringe pump, and dispensing samples into the collection vials,

wherein samples can be collected at predetermined time intervals.

2. The apparatus according to

claim 1

, wherein a water source is connected to the third port of the multi-port valve.

3. The apparatus according to

claim 2

, wherein an acid wash source is connected to the third port of the multi-port valve.

4. The apparatus according to

claim 3

, wherein the saline source comprises a heparinized saline solution.

5. The apparatus according to

claim 4

, wherein the acid source comprises from about 0.1 to about 1.0 weight percent of a hydrochloric acid solution, based on 100 weight percent total.

6. The apparatus according to

claim 5

, wherein the computer means further comprises an input/out interface card for operation of the cannula, outlet and air valves, and fraction collector.

7. The apparatus according to

claim 6

, wherein a swivel is connected between the cannula and the cannula valve.

24. A process for automatically, repetitively sampling blood of a conscious animal, utilizing the apparatus according to

claim 1

, comprising the steps of:

a) closing the cannula and air valves, opening the outlet valve, and the first and second ports of the programmable valve to the saline source;

b) filling the tubing with heparinized, saline solution from the saline source utilizing the syringe pump to push the solution into the tubing;

c) attaching a catheterized animal to the cannula, wherein the cannula is pre-filled with saline solution;

d) closing the outlet valve, opening the cannula valve and aspiring the saline solution from the cannula through the cannula T-fitting into the tubing in a direction towards the syringe pump until the saline in the cannula is in the tubing and a blood sample form the animal is drawn into the cannula;

e) closing the cannula valve, opening the outlet valve, and purging the tubing, through the dispensing tip of pre-filled saline solution, while filling the tubing with fresh, saline solution form the saline source;

f) closing the outlet valve, opening the air valve, and aspiring a first air bubble into the tubing at the air T-fitting;

g) closing the air valve, opening the outlet valve, and pushing the air bubble through the tubing towards the cannula T-fitting;

h) closing the outlet valve, opening the air valve, and aspiring a second air bubble into the tubing followed by closing the air valve, wherein an air-saline-air phase is formed within the tubing, wherein the volume of saline between the air bubbles is equal to the volume of saline desired to dilute the sample;

i) closing the air valve, opening the outlet valve, and pushing the air-saline-air phase through the tubing, towards the cannula T-fitting so that the saline-portion of the phase is over the cannula T-fitting, wherein the tubing is filled with additional saline solution;

j) opening the cannula valve and activating the syringe pump to introducing an amount of blood sample into the saline-portion of the air-saline-air phase, wherein an air-saline-blood-saline-air phase is formed in the tubing;

k) closing the cannula valve, and pushing the air-saline-blood-saline-air phase through the tubing to the dispensing tip;

l) discharging the air-saline-blood-saline-air phase through the dispensing tip, into a vial of the fraction collector, wherein the tubing is filled with additional saline solution;

m) closing the outlet valve, opening the air valve, and aspiring an air bubble into the tubing at the air T-fitting;

n) closing the air valve, opening the outlet valve, and pushing the air bubble through the tubing proximal to the cannula T-fitting to form an air-saline phase adjacent to the cannula T-fitting, wherein a volume of saline in the tubing between the air bubble and the end of the cannula T-fitting connected to the cannula valve is equal to the volume of blood withdrawn from the animal; and

o) closing the outlet valve, opening the cannula valve, said cannula being filled with blood, and pushing the air-saline phase and blood through the cannula into the animal, via the syringe pump, until the blood and saline are in the animal and the air bubble is adjacent to the outside of the animal;

wherein during collection of subsequent blood samples, steps a) through o) are repeated, wherein prior to repeating the steps, the air bubble adjacent to the animal and blood are raised to the cannula T-fitting and purged from the tubing with saline solution, and wherein the opening and closing of the valves, operation of the syringe pump and programmable valve are performed via computer control means.

25. The process according to

claim 24

, wherein the blood sample comprises an air-saline-blood-saline-air phase.

26. The apparatus according to

claim 25

, wherein the saline-blood-saline portion of the sample is diffused.

8. An apparatus for automatically, repetitively sampling blood from a plurality of conscious animals, comprising:

a) means for individually confining a plurality of conscious, catheterized animals;

b) a plurality of cannulae, each cannula having first and second ends, said first end connected to the catheterized animal;

c) a plurality of cannula valves, each valve having first and second ends, said first end being connected to each cannula, said cannula valves'"'"' opening and closing being computer controlled;

d) a plurality of cannula T-fittings, each valve having first, second and third ends, said first end being connected to the second end of each cannula valve;

e) a plurality of outlet valves, each valve having first and second ends, said first end being connected to the second end of each cannula T-fitting, said outlet valves'"'"' opening and closing being computer controlled;

f) a plurality of dispensing tips, each tube having first and second ends, said first end being connected to the second end of each outlet valve, said second end being suitable for discharging blood into a sample, collection vial;

g) means for horizontal and vertical movement of the dispensing tip in and out of the collection vial, said means for movement being computer controlled;

h) a plurality of air T-fittings, each valve having first, second and third ends, said first end being connected to the third end of the cannula T-fitting;

i) a plurality of air valves, each valve having first and second ends, said first end being connected to the second end of each air T-fitting, said air T-fittings'"'"' opening and closing being computer controlled;

j) a plurality of syringe pumps, each pump having first and second ends, said first end being connected to the third end of each air T-fitting, wherein the pumps are suitable for pumping blood and saline through the apparatus, said pumps being computer controlled, wherein each series of a) through j) components, comprise a separate sampling channel within the apparatus;

k) a rotary, multi-port, programmable valve, each port suitable for receiving and discharging fluids, said first port being connected to the second end of the syringe pump, optionally the second end of a plurality of syringe pumps connected to a first end of a common manifold having first and second ends, and the second end of the manifold connected to the first port of the programmable valve, each port'"'"'s opening and closing being computer controlled;

l) a saline solution source connected to the second port of the programmable valve;

m) a fraction collector, comprising;

i) a base having two horizontally opposed, parallel tracks, and a single track horizontally located above and perpendicular to the horizontally opposed, parallel tracks,

ii) a temperature controlled rack in slidable contact with the horizontally opposed, parallel tracks,

iii) means for sliding the rack along the tracks, said means for sliding the rack being computer controlled, and

iv) a plurality of sample, collection vials removably arranged in the rack, said collection vials being suitable for receiving a sample from the dispensing tip; and

n) computer control means for programming and coordinating the operation of the collector, valves and pumps to collect blood samples at desired intervals,

wherein the valves, syringe pump, and fraction collector functions are coordinated and controlled by the computer means to withdraw samples from the animal at repetitive, programmable intervals and discharge the samples in collection vials.

9. The apparatus according to

claim 8

, wherein a water source is connected to the third port of the programmable valve.

10. The apparatus according to

claim 9

, wherein an acid wash source is connected to the fourth port of the programmable valve.

11. The apparatus according to

claim 10

, wherein a swivel is connected between the cannula and the cannula valve, said swivel being for pivotal movement of the cannel.

12. The apparatus according to

claim 11

, wherein a waste removal system is incorporated into the apparatus, said waste removal system comprising a dispensing tip manifold for receiving the dispensing tips, a waste collection trap connected to said manifold, a safety trap connected to said waste collection trap, and a vacuum means connected to said safety trap, said vacuum means for removing waste fluids from the dispensing tip.

13. The apparatus according to

claim 12

, wherein the dispensing tip manifold comprises a base having a plurality of vertical holes therethrough, each hole for receiving a dispensing tip, and a single hole horizontal hole intersecting with each vertical hole, said vertical hole for the passage of air associated with the vacuum means.

14. The apparatus according to

claim 13

, wherein the cannula, outlet and air valves are selected from the group consisting of pinch and check valves.

15. The apparatus according to

claim 14

, wherein cannula, outlet and air valves are interfaced with an input/output controller prior to connecting to the computer means.

16. The apparatus according to

claim 15

, wherein the slidable, fraction collector is interfaced with an input/output controller prior to connecting to the computer means.

17. The apparatus according to

claim 16

, wherein the saline source comprises a heparinized saline solution.

18. The apparatus according to

claim 17

, wherein a water source is connected to the third port of the programmable valve.

19. The apparatus according to

claim 18

, wherein an acid wash source is connected to the fourth port of the programmable valve.

20. The apparatus according to

claim 19

, wherein the acid wash source comprises from about 0.1 to about 1.0 weight percent of a hydrochloric acid solution, based on 100 weight percent total.

21. The apparatus according to

claim 20

, wherein an air-saline-blood-saline-air phase is generated in the apparatus.

22. The apparatus according to

claim 21

, wherein the air-saline-blood-saline-air phase is the blood sample.

23. The apparatus according to

claim 22

, wherein the saline-blood-saline portion of the sample is diffused.