Blood coagulation and separation

• US 4,189,382 A
• Filed: 04/03/1978
• Issued: 02/19/1980
• Est. Priority Date: 11/07/1974
• Status: Expired due to Term

• Current Assignee: Sherwood Medical Company (Medtronic Plc)
• Original Assignee: Sherwood Medical Industries Inc. (Medtronic Plc)
• Inventors: Zine, Anthony R. Jr.
• Primary Examiner(s): Spitzer, Robert H.
• Application Number:
  US05/892,992
• Time in Patent Office: 687 Days
• Field of Search: 210/46, 210/51, 210/59, 210/83, 210/84, 210/209, 210/DIG. 23, 210/516-518, 128/214 R, 128/272, 23/230 B
• US Class Current: 210/714
• CPC Class Codes: G01N 33/491 by separating the blood components G01N15/05 takes precedence

Abstract

Methods and apparatus for separating blood which utilize suspendable contact-activating particles to initiate blood clotting generally throughout the volume of blood are disclosed herein. The contact-activating particles are deposited in a vessel; and when whole blood is supplied to the vessel, the particles are suspended throughout the volume of the blood and remain so suspended, without mechanical agitation, during at least the initial stages of coagulation. The particles are precipitated from the serum portion of the blood during a subsequent centrifugal separation. Also, a process for making appropriately sized contact-activating particles is disclosed.

Claims

1. An improved method of collecting a sample of whole blood within a vessel having a sidewall terminating at first and second ends, coagulating the blood to form intermixed serum and red cell phases, and simultaneously separating said phases and partitioning said phases with a quantity of thixotropic material having a density intermediate the densities of said phases, including the steps of initially positioning the thixotropic material within the vessel adjacent the first end thereof, partially submerging energizer means for directing the flow of said thixotropic material within said thixotropic material, introducing the sample of blood into said vessel through the second end thereof, activating the clotting factors of said blood at inner surface portions of said vessel to form intermixed serum and clotted red cell phases, and applying centrifugal force to said sample of blood, thixotropic material and energizer means to simultaneously separate said phases, move said energizer means into said thixotropic material, and to move said thixotropic material from said first vessel end to a position partitioning said phases, wherein the improvement comprises the steps of:

removably applying to said energizer means a quantity of particles made from material which promotes the clotting of blood, each of said particles having a density and size sufficient to be suspended in said sample of whole blood as said sample is supplied to the vessel and to be sedimented from said serum phase during the application of centrifugal force to separate said sample into said serum and red cell phases;

simultaneously with said step of supplying said sample of blood to said vessel, suspending said particles in said sample, to establish a plurality of sites for the contact activation of clotting of blood throughout said blood sample whereby the time for complete coagulation is substantially reduced; and

,

concurrently with the step of applying centrifugal force to separate said serum and red cell phases, centrifugally forcing said particles into said red cell phase, whereby said separated serum is free from said powdered means.

2. The improved method of claim 1 further comprising the steps of evacuating said vessel, inserting a needle-pierceable stopper in said second end of said vessel to form a removable sealed relationship therewith, and siphoning blood through said stopper with a needle.

15. The apparatus of claim 1 wherein said means for directing said gel-like means comprises a member having a density greater than said gel-like means and which applies a force to said gel-like means moving it away from its initial location during centrifugation.

3. A method of collecting blood, coagulating the blood and centrifugally separating the blood into a serum phase and a red cell phase comprising the steps of:

(a) providing a vessel with contact-activating particles, said particles having a density greater than the serum phase of blood and being of a size sufficient to facilitate their initial and continued suspension in a body of blood as said body of blood is supplied to said vessel means and to also facilitate their precipitation from the serum phase of said body of blood during the centrifugal separation of said serum phase from said body of blood;

(b) evacuating the vessel, and sealing an open end of the vessel with a closure;

(c) siphoning blood through the closure to supply the vessel with a body of blood, and simultaneously with such flow of blood initially suspending a substantial portion of the contact-activating particles generally uniformly throughout the body of blood;

(d) activating clotting factors within the blood generally uniformly throughout the body of the blood concurrently at the inner surface of the vessel and at the surfaces of said suspended contact-activating particles;

(e) maintaining in suspension said initially suspended particles throughout the body of blood, and continuing said activation of clotting throughout the body of blood to substantially complete coagulation of the blood, this step being performed substantially without agitating the vessel; and

(f) centrifuging the body of blood to separate the blood into a lighter phase consisting essentially of serum and a heavier phase consisting essentially of cellular and fibrillar matter and the contact-activating particles.

4. A method of separating a serum phase from blood comprising the steps of:

providing a vessel with a preselected quantity of gel-like material having a density intermediate the densities of a lighter phase of blood consisting essentially of serum and a heavier phase of blood consisting essentially of cellular and fibrillar matter;

partially submerging an energizer member in the gel-like material;

removably applying a preselected amount of contact-activating particles to the energizer member, said particles having a density greater than said lighter phase of blood and being of a size sufficient to facilitate their initial suspension in a body of blood as the body of blood is supplied to the vessel and to also facilitate their precipitation from said lighter phase during the centrifugal separation of said lighter phase from the body of blood;

supplying the vessel with a body of blood and simultaneously initially suspending a substantial portion of the contact-activating particles generally uniformly throughout the body of blood;

activating clotting factors within the blood generally uniformly throughout the body of the blood concurrently at the inner surface of the vessel and at the surfaces of said suspended contact-activating particles;

continuing to suspend said initially suspended particles and maintaining said activation of clotting throughout the body of blood to substantially complete coagulation of the blood; and

after the substantially complete coagulation of the blood, centrifugally forcing the body of blood to separate into a lighter phase consisting essentially of serum and a heavier phase consisting essentially of cellular and fibrillar matter and the contact-activating particles, and centrifugally forcing the gel-like material to a position intermediate the lighter phase consisting essentially of serum and the heavier phase consisting essentially of cellular and fibrillar matter and the contact-activating particles.

5. The method of claim 4 further including the steps of evacuating the vessel, sealing the open end of the vessel with a pierceable closure and supplying the blood to the vessel by siphoning the blood through the closure.

6. A method of separating a serum phase from whole blood comprising the steps of:

providing a vessel with a preselected quantity of gel-like material having a density intermediate the densities of a lighter phase of whole blood consisting essentially of serum and a heavier phase of whole blood consisting essentially of cellular and fibrillar matter;

providing the vessel with means for directing the gel-like material from its initial location toward its position intermediate said lighter phase and said heavier phase during centrifugation of the vessel means;

providing the interior of said vessel with a preselected amount of contact-activating particles, said particles having a density greater than said lighter phase of said whole blood and being of a size sufficient to facilitate their initial suspension in a body of whole blood as the body of blood is supplied to the vessel and to also facilitate their precipitation from said lighter phase during the centrifugal separation of said lighter phase from said body of blood;

supplying the vessel with a body of whole blood and simultaneously initially suspending a substantial portion of said contact-activating particles generally uniformly throughout the body of blood;

activating clotting factors within the blood generally uniformly throughout the body of the blood concurrently at the inner surface of the vessel and at the surfaces of said suspended contact-activating particles;

continuing to suspend said initially suspended particles and maintaining said activation of clotting throughout the body of blood to substantially complete coagulation of the blood; and

after the substantially complete coagulation of the blood, centrifugally forcing the body of blood to separate into a lighter phase consisting essentially of serum and a heavier phase consisting essentially of cellular and fibrillar matter and the contact-activating particles, and simultaneously centrifugally forcing the gel-like material to a position intermediate said lighter phase and said heavier phase.

7. The method of claim 6 wherein said means for directing the gel-like material includes a member having a density greater than that of the gel-like material and centrifugally urging the member against the gel-like material facilitating the movement thereof.

8. The method of claim 6 or 7 wherein the step of continuing to suspend said initially suspended particles is performed substantially without agitating the vessel.

9. An apparatus for centrifugally separating blood into serum and clotted red cell phases and for simultaneously partitioning the phases comprising:

partially evacuated vessel means for collecting a sample of fresh blood to be coagulated and thereafter separated into serum and clotted red cell phases under the influence of centrifugal force, said vessel means having first and second ends, with said first end having a needle-pierceable closure inserted therein in an air-tight sealed relationship therewith;

gel-like means for forming a partition between said blood phases simultaneously with their centrifugal separation, said gel-like means being chemically inert with respect to blood and having a density intermediate the serum and clotted red cell phases of blood, and said gel-like means being initially positioned within said second end of said vessel means;

energizer means, initially partially submerged within said gel-like means, for directing the flow of said gel-like means during the centrifugal separation of the phases;

powder means for establishing coagulation activation sites at a plurality of positions dispersed generally throughout the sample of whole blood as the blood is supplied to the vessel means, said powder means being initially removably applied to said energizer means; and

,

said powder means comprising a plurality of particles of material which promotes coagulation of whole blood, said particles having a density and a selected particle size sufficient to allow the particles to be initially suspended within said sample of blood as said sample is collected within said vessel means and to remain suspended therein during coagulation, and said particles having a density greater than the density of said serum phase and a minimum particle size sufficient to allow all of said particles to be separated from the serum phase of said blood sample into the clotted red cell phase simultaneously with the centrifugal separation of said phases.

10. The apparatus of claim 9 wherein said particles comprising said powder means have a minimum particle size and density which will precipitate from a mixture of said particles with water under the influence of centrifugal force approximating in magnitude the centrifugal force used to separate the serum phase from coagulated blood.

11. The apparatus of claim 10 wherein said particles comprising said powder means will precipitate from a mixture of the particles with water under the influence of centrifugal force of up to 1100 gravities.

12. The apparatus of claim 9 wherein said particles comprising said powder means are made from glass having a density of approximately 2.23 grams per cubic centimeter and have a minimum particle size of approximately 0.4 microns.

13. An apparatus for collecting blood and centrifugally separating the blood into a serum phase and a red cell phase comprising, vessel means for collecting a body of blood;

gel-like means for establishing a barrier between the separated serum and red cell phases, said gel-like means being thixotropic in nature and having a density between the densities of the serum and red cell phases;

energizer means having a density greater than the density of said gel-like means for initiating and directing the flow of said gel-like means, with said gel-like means being initially positioned adjacent one end of said vessel means and said energizer means being initially partially submerged in said gel-like means; and

powdered means within said vessel means for establishing blood clotting contact-activation sites throughout said body of collected blood, said powdered means comprising a plurality of particles made from a clot promoting material, each particle having a density greater than that of said serum phase and a size sufficient to allow both initial and extended suspension thereof within said body of blood as said body of blood is supplied to said vessel means, with said particles having a minimum particle size capable of being precipitated from said serum phase during centrifugal separation of said blood into said phases, whereby the establishment of activation sites throughout the blood assures complete coagulation before centrifugal separation and said minimum particle size assures complete precipitation of said powdered means during centrifugal separation, thereby providing a separated serum phase which is completely free from latently formed fibrin and from suspended powdered means.

14. Apparatus for collecting whole blood and centrifugally separating the blood into a serum phase and a red cell phase comprising, vessel means for collecting a body of whole blood, gel-like means for establishing a barrier in a position between the separated serum and red cell phases, said gel-like means being thixotropic in nature and having a density between the densities of the serum and red cell phases, said gel-like means being disposed in an initial location in said vessel means and movable during centrifugation from said initial location in said position;

means in said vessel means for directing said gel-like means from said initial location to said position between separated serum and red cell phases; and

powder means within said vessel means for establishing blood clotting contact-activation sites throughout said body of collected blood, said powder means comprising a plurality of particles made from a clot-promoting material, said particles having a density greater than that of said serum phase and a size sufficient to allow both initial and extended suspension thereof within said body of blood as said body of blood is supplied to said vessel means, said particles having a minimum particle size capable of being precipitated from said serum phase during centrifugal separation of said blood into said phases; and

said powder, through the establishment of activation sites throughout the blood, providing means for complete coagulation of the blood before the centrifugal separation thereof, with said minimum particle size providing means for complete precipitation of said powder during the centrifugal separation of the blood, thereby providing a separated serum phase which is completely free from latently formed fibrin and from suspended powder means.