Disposable cartridge for investigating physical properties of blood

Abstract

A disposable cartridge for measuring the physical properties of blood is disclosed. A waste compartment supports a platform having first and second syringe fittings. First and second syringes containing blood samples to be measured are positioned within the fittings. At least one testing station is located on the platform for subjecting blood flowing from one of the syringes to a test station, and the testing station is connected at a second end to the waste compartment. Tests on blood running through each of the blood channels may be conducted by inducing various platelet activation conditions, such as piercing a channel, or putting a platelet activating substance within a test channel. The cartridge interfaces with a test stand which will measure pressure changes within each of the test channels.

Description

The present invention relates to disposable devices for making measurements of the physical properties of blood. Specifically, a cartridge has been designed which is especially useful in conducting experiments on native, non-anticoagulated blood.

In the treatment of various blood disorders, it has been necessary to make measurements on whole, native blood to assess the formation of platelets and the adequacy of haemostatic functions of the blood before embarking on specific medical procedures for patients having these disorders. Further, other disorders such as myocardial infarction, stroke, thrombolysis or blood dissolution properties, must be monitored and assessed repeatedly following recovery to prevent recurrence of a blood clot.

Techniques for measuring the physical attributes of platelet activation, all of which is related to the foregoing disorders, have been the subject of numerous investigations. The difficulty in making such measurements lies in the difficulty to collect native whole blood which has not been anticoagulated and conduct experiments which do not induce any platelet activation except under very controlled circumstances. In investigating the behavior of native whole blood, a device for performing in vitro haemostasis on native whole blood, is described in EPO Application No. 129425. This patent describes a laboratory technique which is capable of simulating bleeding. A fresh supply of native blood is connected to a polyethylene tube. A flow of blood is started through the tube and bleeding is simulated by establishing a hole in the tubing of a known diameter. The bleeding which occurs through the hole is monitored, both optically and through a pressure measurement of the flow of blood.

A further improvement of this technique is described in a later International Patent Application PCT/GB87/00633, having an international filing date of Sep. 10, 1987. In this patent, multiple channels of blood flow were established, and concurrent measurements of haemostasis were made in each of the blood flow channels. This permitted a control channel having blood drawn at the same time, thus having substantially the same chemical composition to be measured and compared to each other.

The laboratory technique set forth in the above-referenced patent documents requires a fairly high level of skill on the part of the personnel conducting such tests. Further, as blood is known to carry viruses, including the deadly HIV virus, it is necessary that personnel always take precautions to avoid contact with the blood.

A disposable blood-handling cassette is described in U.S. Pat. No. 5,047,211 which will permit such tests to be carried on in accordance with the preceding patent documents, while isolating medical personnel from coming in contact with the blood under test. The device, which is completely self-contained, includes multiple reservoirs which receive a blood sample for carrying out the experiments and investigation of blood, as set forth in the previously identified patent documents.

Further investigation of these techniques have demonstrated how the handling of blood, even in a disposable cartridge can result in platelet activation before any testing begins. The process of extracting blood from a human donor in itself can activate platelets which interfere with the investigation of blood under controlled conditions.

It has also been found that further control over punching holes in a blood-carrying tubing is necessary in order to provide for repeatability between tests of succeeding samples of blood.

SUMMARY OF THE INVENTION

It is an object of this invention to provide for a disposable cartridge which can be used to carry out tests on blood.

It is a more specific object of this invention to provide for a disposable cassette which may be used in haemostasis and thrombolysis measurements, and which effectively isolates infected blood samples from users of these devices.

It is yet a more specific object of this invention to provide a device which is designed to avoid inadvertent platelet activation in a sample of blood under test.

These and other objects of the invention are provided by a disposable cartridge which is capable of conducting tests on whole blood. The cartridge is designed to introduce a minimum amount of disturbance to the blood's physical properties, and specifically to avoid platelet activation through handling of the blood samples. The cartridge creates an in vitro environment which models the circulatory system with regard to temperature and flow. In doing so, shear force experienced by the blood is accurately controlled. In this way, platelet activation is maintained under control until tests are performed on the blood. The device therefore permits the simulation of normal circulatory blood conditions, as well as simulating a disease environment or injury during testing.

In carrying out the invention, the disposable cartridge incorporates a totally isolated compartment for tested blood which will preclude any inadvertent contact with medical personnel. The compartment supports a platform which includes at least one receptacle for receiving a blood sample vessel such as a syringe. The use of the syringe as the blood sample 13or hydraulic couplings 36. The end of the receptacles 36 which receives the front tip 22 of each of the syringes 20 has a luer fitting taper to provide a force fit, tight against any blood or pressurizing fluid leakage.

The stud 24 for each of the test channels includes a fluidic factor coupling member 37, which may be an elastomeric substance which is pierced by an injection needle or pointed cannula from the test stand 10. Displacing fluid is received through the coupling member 37 and supplies the immiscible displacing fluid through the standpipes 38 into the body of the syringes 20.

Each of the pressure chambers 51 extends through the platform and have domed portions 69 which are connected to the outlet tubes 53 which provide an orifice. Displacing fluid for the pressure chambers 51 is received through the couplings 54, which also may be of an elastomeric insert, pierced by a needle or pointed cannula supplying the displacing fluid. A similar fluid coupling is provided at 50 for injecting a saline solution into the bleeding chamber 42.

Each of the blood-carrying tubes 40 for each test channel is supported on a surface 39. Surface 39 is positioned so that in use it touches the heater 29, thereby maintaining constant the temperature of the blood-carrying tubes 40. The receptacles 36 and studs 24 are also positioned such that each of the syringe bodies 20 is located within the heater 21.

The blood carrying tubes 40 have a routing path which is initially straight down, and then routed upward. A collagen substance 61 is shown introduced in one of the blood carrying tubes which is by the radius of the blood carrying tube.

A top cover 67 is fixed to the platform 64 62 and includes a pair of guide holes 20 which support the syringes 20 in alignment with the receptacles or hydraulic couplings 36. Guides 70 position the syringes tangential to the rear edge of the cartridge so that the syringes can be located against a common heating surface. The cover 67 also includes a hole 66 which receives the ram 68. Ram 68 is advanced by the linear actuator 45 towards the punching mechanism 43 at a controlled speed to control the shape of the hole being formed.

The section view of FIG. 5 illustrates the test channels. The test channels include the bleeding chamber 42, as well as the platelet-activating substance 61. Also shown is an outlet 72 for the saline solution which enters via the coupling 50 to fill the bleeding chamber 42.

Details of the cartridge punching station 43 are shown more particularly in FIGS. 6 and 7. The punching station includes a plunger 80 which slides within a sleeve 77. A guide 75 having a forked end positioned over the blood-carrying tube 40 is connected to the sleeve 77. A centrally-located needle 76 is connected to move with the plunger 80 when the ram 62 68 is accelerated against the surface 83. The end of the needle 76 is located within a through-hole in the forked end. The forked end positions the needle tip in line with the inner diameter of the blood-carrying tube 40.

The plunger 80 moves inside the sleeve 77, pushing the needle through the hole in the guide 75, and pierces opposite sides of the blood-carrying tube. A detent on the plunger 80 moves between a first notch 79 and second notch 81 in the sleeve 77. As the ram 82 pushes plunger 80 against the force of a spring 82 when the ram is retracted, the spring 82 withdraws the plunger 80, the needle 76 and guide 75. The result is a pair of holes in the blood-carrying tube 40, which permits bleeding to occur in the bleeding chamber 42. The elastomeric material 83 at the top of the plunger seals the cartridge against leakage.

The blood profusing from the hole drains via the tapered section 71 with the saline solution into the waste compartment 63, where it is captured. Other waste material from the pressure chambers 51 also exit via the drain tubes 53 to the waste compartment 63. The level of saline in the bleeding chamber 42 is controlled by the rate at which saline is introduced, and the height of the exit port 73. The level of saline is maintained at a level which insures washing of the holes punched in the blood-carrying tubes.

The foregoing structure of the cartridge provides for a minimum disturbance to blood samples which are to be tested under very controlled test conditions. By using the syringes as the reservoir, the inadvertent activation of platelets in the test sample are kept to a minimum. Further, the entire cartridge is designed such that the blood sample throughout the test channel can be maintained at a constant temperature, thus minimizing the effects of temperature differentials on each test being conducted. Once the test is completed, the motor 17 of FIG. 1 can be reversed and by grasping the handle 74 of the cartridge, the entire cartridge with connected syringes may be disposed of without risk of contamination to any of the testing personnel.

As the cartridge can be made from any suitable plastic material, the costs can be maintained at a minimum, while insuring safety to those carrying out such tests.

Thus, there has been described with respect to one embodiment, an example of the invention. Those skilled in the art will recognize yet other embodiments defined more particularly by the claims which follow.

Claims

1. A disposable cartridge for measuring the properties of blood comprising:

a waste compartment for receiving blood samples which have been subject to measuring;

a platform supported on said waste compartment including first and second fluidic couplings, which receive the front tips of first and second syringes which contain blood samples, connecting wherein said fluidic couplings connect said platform and syringes together, forming to form a leak-proof assembly, said fluidic couplings providing a pressurizing fluid to said syringes and each having an outlet for delivering pressurized blood;

first guide means for supporting said syringes in alignment with said fluidic couplings;

first and second blood-carrying tubes mounted along a routing path on a surface, connected to each of said outlets;

a punching mechanism comprising:

a ram operated punching needle, said needle being positioned during a punching operation by a second guide means to punch an opening in said first blood carrying tube, permitting blood to exit through said opening;

a first domed chamber receiving the an end of said first blood-carrying tube, and receiving a first pressurizing fluid from a first source of pressurizing fluid for, said receipt of said first pressurizing fluid displacing air through a restricted orifice, and for said first source of pressurizing fluid providing a pressure transducer connection which measures changes in blood pressure occurring during a flow of blood through said first blood-carrying tube into said first domed chamber, said flow of blood displacing first pressurizing fluid through said restrictive orifice into said waste compartment; and

a second domed chamber receiving the a distal end of said second blood carrying tube, and receiving a second pressurizing fluid for from a second source of pressurizing fluid said receipt of said second pressurizing fluid displacing air through a restricted orifice in said second domed chamber, as well as said second source of pressurizing fluid providing a connection to a pressure transducer for measuring changes in blood pressure in said second blood-carrying tube from blood flowing through said second domed chamber, said blood flow displacing said second pressurizing fluid through said restrictive orifice into said waste compartment.

2. The disposable cartridge of claim 1 wherein said second blood-carrying tube contains a platelet-induced body.

3. The disposable cartridge of claim 1 further comprising a vertically extending conduit connected to said fluidic couplings which is received in said syringes, and supplies said pressurizing fluid to said syringes.

4. The disposable cartridges of claim 3 wherein said guide means position said syringes to be tangential to a rear edge of said cartridge so that said syringes can be located against a common heating surface.

5. The disposable cartridge of claim 1 further comprising a tapered chamber having an axis aligned with said punching needle, said chamber tapered to receive an optical sensor for detecting blood exiting from a punched hole in said first blood-carrying tube.

6. The disposable cartridge of claim 5 wherein said tapered chamber includes an inlet for receiving a saline solution which washes blood from said hole punched in said first blood-carrying tube.

7. The disposable cartridge of claim 1 wherein each of said first and second blood-carrying tubes are supported in a common plane to permit said tubes to be heated by a heating surface.

8. An apparatus for measuring the properties of blood comprising:

a disposable cartridge including first and second supports for vertically supporting two blood-filled syringes, in first and second fluidic couplings forming a sealed assembly therewith, said couplings having inlets for receiving a pressurized fluid, and outlets for supplying blood and, and said disposable cartridge further including first and second testing channels for carrying blood from said outlets, and a waste receptacle for receiving tested blood from said first and second testing channels; and,

a test stand for receiving said cartridge, said test stand having a heater for maintaining said blood-filled syringes at a constant temperature, and including means for maintaining plungers associated with said syringes in a fixed position when said disposable cartridge is receiving a pressurizing fluid, and a ram which operates a punching needle at a constant speed for punching a hole having a precise diameter in one of said testing channels.

9. The apparatus of claim 8 wherein said test stand further comprises a second heater for maintaining said first and second testing channels at a constant temperature.

10. The apparatus of claim 9 further comprising an optical sensor support for maintaining an optical sensor positioned with respect to a bleeding chamber in one of said testing channels.

11. The apparatus of claim 9, wherein said test stand further provides a connection between a bleeding chamber centrally positioned with respect to said channel hole punching needle and a source of saline solution.

12. The apparatus of claim 8, wherein said test stand includes a source of pressurizing fluid coupled to said fluidic coupling inlets when said cartridge is received in said test stand.

13. The apparatus of claim 12, wherein said test stand includes first and second pressure transducers which measure the blood pressure in said first and second testing chambers.

14. A disposable cartridge for measuring physical properties of blood comprising:

a waste compartment supporting a platform, said platform having at least one fluidic coupling, and having

a guide for positioning at least one syringe holding a blood sample into said fluidic coupling which forms a sealed assembly therewith with said syringe;

at least one testing station, located on said platform, for subjecting blood flowing from said syringe to a testing condition, and connected to said waste compartment to discharge tested blood in to said waste compartment; and

conduit means connecting said at least one syringe to said testing station.

15. A disposable cartridge according to claim 14, wherein said testing station comprises means for creating a precise opening in said conduit means to simulate bleeding.

16. A disposable cartridge according to claim 14 further comprising a second syringe having a blood sample, said second syringe forming a sealed assembly with said cartridge, and a second testing station which includes a flow channel connected to said second syringe having a blood sample which includes, said flow channel including a blood platelet activating substance.

17. The disposable apparatus cartridge of claim 14 further comprising a conduit extending through said fluidic coupling along an axis of said syringe, and connected to receive a pressurizing media.

18. The disposable cartridge of claim 14, wherein said test station further comprises a columnar pressure chamber having a volume of fluid immiscible with blood which is displaced by said blood, and which is connectable to a pressure transducer for monitoring pressure resulting from blood flowing into said columnar pressure chamber.

19. The disposable cartridge of claim 14 wherein said testing station includes means for introducing a shear force to blood flowing in said channel, thereby activating blood platelets.