WO1981003426A1

WO1981003426A1 - Arterial blood sampling device for blood gas analysis

Info

Publication number: WO1981003426A1
Application number: PCT/US1981/000735
Authority: WO
Inventors: C Hof; R Polak
Original assignee: C Hof; R Polak
Priority date: 1980-05-03
Filing date: 1981-06-01
Publication date: 1981-12-10
Also published as: EP0052656A1

Abstract

An apparatus for arterial blood sampling and blood gas analysis, comprising a standard tubular member (14) open on one end with a bore or fitting (24) on the other end to accept a standard taper hypodermic needle (80), and a closure (78) adapted to fit the tubular member, which closure provides (a) a low resistance air escape while the tubular member is filling with blood and (b) a high resistance to the flow of blood. The tubular member may be a hypodermic syringe barrel, such as a plastic 1-cc tuberculin syringe barrel. The syringe is preferably closed by one of the following: (a) a porous air-permeable membrane impermeable to blood (78); (b) a resilient rubber plug (92) having a narrow slit cut through it from front to back, with a removable venting means (such as a cuprophane hollow fiber) (90) inserted into it to allow the air to escape; and (c) two or more sheets of plastic film, e.g., PET, (110, 112) placed across the tubular member such that a tortuous passage is formed and the sheets act as a one-way valve. The apparatus minimizes gas contamination by allowing small samples to be taken and can be manufactured inexpensively.

Description

ARTERIAL BLOOD SAMPLING DEVICE FOR BLOOD GAS ANALYSIS

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to the field of blood sampling in general and, specifically, to arterial blood gas analysis. The invention also relates to the manufacture of disposable syringes and the apparatus associated therewith.

2. Description of the Prior Art and Other Information Blood gas analysis is one of the most important diagnostic procedures performed on critically ill, cardiovascular, and surgical patients.

Basic information obtained by blood gas analysis is the amount of oxygen (pO₂), carbon dioxide (pCO₂) and the acidity (pH) of arterial blood. Clinically, arterial blood provides very useful information since it directly reflects the ability of the human lung to transport oxygen from the inspired air into the bloodstream in order to make oxygen available to the tissues. The measure of carbon dioxide in arterial blood is an indicator of the ability of the lung to eliminate this metabolic waste product. Arterial blood should reflect the body's lowest CO₂ levels and any increases in arterial pCO₂ levels. Increases in arterial PCO ₂ not only indicate a possible respiratory problem, but also cause the acidity of the blood to increase, which could have serious metabolic implications, since the body can function normally only in a carefully controlled pH range. The measure of pO₂, pCO₂, and pH are important diagnostic indicators of respiratory and metabolic disorders.

Current arterial blood sampling practice generally involves: (1) Withdrawing an arterial blood sample from the radial, brachial, umbilical, or femoral artery, or from an indwelling arterial line; (2) Transporting the sample to a lab or some other hospital department; and

(3) Analyzing the sample in a blood gas analyzer.

In most cases, a sample is analyzed twice to minimize analyzed air. Normally, turnaround time for the results is fifteen minutes to three hours, although some operating rooms and respiratory therapy departments of modern hospitals have blood gas analyzers on site. The usual frequencies for arterial sampling are every ten minutes for cardiopulmonary resusitation, every twenty minutes for initiating or leading a patient on a ventilator, every thirty minutes for a patient undergoing cardiovascular surgery, and every one to two hours for patients in an intensive care unit.

Since blood gas analysis and acid-base analysis is critical to the evaluation of patient status and response to therapy, as many as thirty-five analyses per patient in an intensive care unit are considered normal. It is estimated that in the United States, eighteen to twenty million blood gas samples are taken annually from approximately one and one-half to two million patients; indeed, blood gas analysis is one of the most frequently performed of all hospital procedures. Among the techniques available to physicians for assessing the status of cardiovascular and respiratory systems, blood gas determinations rank in importance with blood pressure and ECG measurements.

The traditional and most frequently used methods for blood gas analysis are invasive; they require an arterial puncture. These procedures are painful for the patient, run the risk of infection, and represent blood gas values only at a single point in time. Procedures also need to be repeated often in critically ill patients. More recently, longer term indwelling catheters have been developed that allow continuous monitoring; however, they are very expensive and only provide information on a single patient. Typical prior art teachings are found in U.S. Pats. 3,908,657, 4,006,743, and 4,008,717 to Kowarski, disclosing a small, portable, constant withdrawal device connected to tubing, including a catheter, whose internal walls are coated with heparin (discussion, infra). See Figures 3-5 of each of the three related patents.

There are also non-invasive devices which have recently entered the U.S. market in the form of transeutaneous pO₂ sensors. These devices are considered unreliable on other than neonatal patients due to a number of factors - most notably the thickness of the skin of the adult patient. Further, they are not able to measure pCO₂ or pH.

In blood gas analysis, it is important that contaminants not be allowed to contact or mingle with the arterially collected blood sample. Typical contaminants which could introduce significant error in analysis include air, other gases or fluids, and possibly even solid materials. Microbiological life forms (e.g., bacteria, fungi, etc.) may also introduce significant errors since they may consume oxygen and/or generate carbon dioxide subsequent to sampling. It is also important that the arterially collected blood sample be prevented from clotting. To this end, it is typical to precondition the container into which the blood sample is received with an anticoagulant such as heparin solution. However, with such anticoagulant solutions, the dilutent of the solution may dilute the gases in the sample or cause contamination of the sample. An even greater problem in using liquid heparin is that such use increases the size of the syringe and eannula to be employed - with corresponding discomfort to the patient. In some cases, involving critically ill or anemic patients, or those having low blood pressures, the large size of the syringes and carnnulae present major problems to hospital personnel. Also, with premature infants and some neonates, who are typically maintained in oxygen-enriched atmospheres, and in whom high pO₂ may cause irreversible loss of sight and/or blindness, blood gas analysis should be performed routinely. Since these very small patients have small blood supplies (as little as one quart of blood or less), avoiding large, e.g., 3-5cc samples, is imperative.

Therefore, it is desirable in taking arterial blood samples for analysis to isolate the blood sample from extraneous gaseous materials and from the dilutent of the anticoagulant solution while leaving the anticoagulant itself to prevent coagulation of the blood prior to analysis.

An arterial blood sample is generally taken through a large (3 and generally 5cc) glass or plastic syringe. Clotting is prevented by using a solution of heparin which is taken into the syringe and then expelled to form a film over the walls by moving the plunger up and down a few times. Thus, air bubbles are eliminated and excess heparin is squirted out through the needle. The volume of heparin usually left in the dead space is reasonably constant and its effect on blood gas measurements in pH may usually be ignored for clinical purposes.

A blood sample should always be taken slowly to minimize the effect of temporary stimulation of ventilation resulting from insertion of the needle. Local anesthetics are sometimes employed to reduce the patient's response to the pain and trauma of arterial puncture. Changes in respiration rate, heart rate, etc, can introduce significant errors in pO₂, pCO₂, and pH measurements. The eannula employed should be large enough to allow free entry of blood to the syringe with minimal traction on the plunger. In most cases, the arterial pressure is utilized to fill the syringe to prevent contamination of the sample by air, which can leak between the syringe plunger and barrel if aspiration is applied.

There are several different devices used to collect an arterial sample of blood. These include non-disposable glass syringes, capillary tubes, disposable glass syringes, disposable plastic syringes, and devices such as the VACUTAINER^TM(Beeton-Dickinson & Co., Rutherford, New Jersey). Usually, a 5 ml. glass or special plastic syringe with a 20 gauge x 1 1/2" needle is utilized. This combination can be handled easily by most individuals because of its good balance. It fills quickly and has good visible pulsations to observe filling of the syringe.

Very recently, kits containing disposable arterial syringes have been introduced into the U.S. market. The advantages of the kits are many, especially for hospitals drawing sizable number of arterial bloods: they (1) provide surety of the avoidance of potential cross-contamination, (2) provide greater protection for patients and personnel, (3) take up less time in gathering components and are seemingly always available when needed, (4) provide in a convenient fashion everything necessary to obtain quickly blood samples for blood gas analysis, (5) provide easy storage capabilities and ease of storing supplies, (6) avoid the necessity of hospital sterilization, (7) in many instances, cost less than reusable apparatus of the traditional practice, and (8) offer the hospital standardized blood gas testing procedure from department to department. Examples of kits containing these disposable syringes are the (Concord Laboratories of Keene, New Hampshire) PULSATOR^R 3 cc syringe (prefilled with heparin); the (Medical Products Inc. of Englewood, California) OMNISΗK^TM/MINISTIK^TM 5cc syringe (precoated with crystalline sodium heparin); the (Bard-Parker division of Becton-Dickinson & Co. of Rutherford, New Jersey) U-MID^TM3cc or 5cc syringe (prefilled with sodium heparin solution); and the Becton-Dickinson "B-D" (logo) 3cc blood gas syringe.

One advanced blood gas syringe is an embodiment seen in Figures 1-3 of U.S. Pat. 4,133,304, which employs a heparin coated double-walled apparatus. This patent should be studied closely, as we believe it represents the state of the art and the most advanced syringe on the market. Apparatus 10 of U.S. Pat. 4,133,304, for use with a hypodermic needle 12 to collect an arterial blood sample, is shown in Figures 1-3 and comprises a syringe-like housing member 14 (plastic), a hollow capillary cartridge or tube 16, and a resilient element or scaling means 18 which is employed, in part, to locate and position the capillary tube 16 within the housing member.

The housing member 14 of '304, shown in Figures 1 and 2, may be an elongated tubular construction such as that of a conventional syringelike device. The housing member 14 comprises an elongated center chamber 20 having a cylindrical configuration and a circular cross section. The chamber 20 extends axially from an open end 22 of the housing member, and typical wing portions 23 extend from the open end 22 to facilitate handling and use of the syringe-like housing member 14. The opposite end of chamber 20 is terminated with a barrel portion end member 24. An axially extending and cylindrieally shaped outside surface (not shown) serves as one form of means for connecting the hypodermic needle 12 to the barrel portion end member 24. A bore extends axially through the barrel portion end member 24 and serves as one form of means adapted for providing fluid communication between the center chamber 20 and the connected hypodermic needle 12.

The capillary tube or cartridge 16 shown also in Figures 2 and 3 is received within chamber 20 of the housing member 14. The capillary tube 16 includes a fluid inlet nozzle 30, of radially inward and axially tapered configuration. The extreme end of nozzle 30 is of smaller configuration than the bore in the barrel portion end member 24 and can thus be received within the bore. The nozzle 30 serves as one form of means for inletting fluid or a blood sample into a hollow interior or blood sample repository 33 of the capillary tube 16. A fluid outlet means 32 is connected at the other end of the capillary tube 16 opposite the nozzle 30. The fluid outlet means 32 comprises a cap member 34 sealed to the end of the capillary tube. The cap member 34 has an opening 36 axially extending therethrough for receiving a resilient member 38. The resilient member 38 expands to receive at least one length or piece of fluid conductive fibrous material such as string or thread 40 which projects through the resilient member 38 to allow a small amount of fluid communication from the repository 33 of the capillary tube through the thread 40. U.S. Pat. 4,133,304 indicates at Col. 2, lines 11-13 that the fibrous material 40 can be removed so that the resilient member seals the cap member 34 of the capillary tube 16.

It is important to note that the '304 patent does not require thread or string 40 to be non-antigenic and inert, i.e., does not accelerate thrombogenesis.

Cap 34 is constructed of plastic material and scaled on capillary tube 16 by heat shrinking it to the end of the capillary tube at the cap hinge 35. The resilient member 38 may be constructed of silicone, rubber or other similar material and serves as one form of means for expanding to receive a portion of the thread 40 or other fibrous material extending through the resilient member 38 and as means for sealing the fluid outlet means 32 of the capillary tube upon removal of the fibrous material. The resilient characteristics of the member 38 close the opening through which the thread 40 was inserted upon removal of the thread. As repository 33 fills with blood, gas and air escapes through the fluid conductive fibrous material or thread 40. Once the blood sample completely fills the repository 33, a small amount of blood is conducted through the thread 40 to signal the user that the repository 33 of the capillary tube 16 is completely filled with the blood sample. Thus constructed, the fluid outlet means 32 serves to release or outlet fluid from the interior or repository 33 of the capillary tube. The scaling means or resilient sleeve member 18 shown in Figure 2 connects the fluid inlet nozzle 30 of the capillary tube 16 into the bore of the barrel portion end member 24, and establishes an air-tight and fluid conductive path through the connected hypodermic needle and into the capillary tube 16. The sleeve member 18 is received within the bore and comprises an opening (not shown) extending through the sleeve member coaxially with the bore. The sleeve member 18 also comprises a flange portion (not shown) adjacent the outer axial end of barrel portion end member 24. The nozzle end 30 of the capillary tube 16 is partially inserted into one end of the opening and compresses the resilient material of the sleeve member 18 against the interior wall of the bore, thus causing a fluid tight seal between the fluid inlet nozzle 30 and end portion of the opening of the sleeve member. The compressive forces of the resilient material of the sleeve member firmly holds the fluid inlet nozzle 30 of the capillary tube thus causing the sleeve member 18 to also serve as one form of means for positioning the capillary tube generally in an axially extending manner within the chamber 2 0 of the housing member 14 with the fluid inlet means or nozzle 30 oriented toward the bore.

The hypodermic needle 12 shown in Figure 2 is of a construction having an axially extending elongated hollow shaft (cannula) 50 terminated with a flesh piercing point 52. The hollow shaft 50 is received within a hub member 54, and a center tubular projection member 56 is sealed to and extends from the shaft 50 within the hub member 54. An axially extending opening 58 of the hub 54 receives the barrel portion of the end member 24 to attach the hypodermic needle 12 to the syringe-like housing member 14 with the surface of barrel portion serving as means for frictionally connecting the hypodermic needle 12 to the housing member 14. A reduced diameter end portion (not shown) of the tubular projection 56 extends into and mates with the opening in the sleeve member 18 adjacent the flange. Compression of the resilient material of the sleeve member 18 against the bore of the barrel portion end member 24 establishes a fluid tight seal and a fluid conductive path between the tubular projection 56 into the sleeve member 18. Consequently, once the hypodermic needle 12 is inserted on the apparatus 10, there is a fluid tight and conductive channel from the flesh piercing point 52 of the hypodermic needle 16 into and through the capillary tube 16.

Crystalline heparin 59 or other suitable anticoagulant is said to be deposited on the interior of the capillary tube 16 prior to use. The crystalline heparin 59 may be deposited by placing a drop of a solution of heparin into the interior of the capillary tube, and then allowing the dilutent to evaporate, thereby leaving only the solid heparin deposited on the walls of the repository 33. This process can be expedited by heating the capillary tube to hasten the evaporation. The crystalline heparin 59 or other suitable anticoagulant prevents the blood sample from coagulating in the capillary tube after it has been collected.

In the use of the apparatus 10 of U.S. Pat. 4,133,304, the capillary tube 16 of '304 is received within the housing member 14 with the nozzle 30 being sealed within the bore of the end member barrel portion 24 by the sleeve member 18. The user attaches the hypodermic needle 12 causing the end portion of the tubular projection 56 to be received within the opening through the sleeve member 18. The flesh piercing point is inserted in an artery of a person from whom the blood sample is collected. The blood pressure within the artery forces blood upward through the hollow shaft 50 and tubular projection 56, through the opening in the sleeve member 18 and into the fluid inlet nozzle 30 of the capillary tube 16. The hollow interior or repository 33 gradually fills because of the blood pressure in the artery and because the fibrous material or thread 40 of the fluid outlet means 32 expels air and other gases to allow the repository 33 to fill with blood. After all air and other gases in the interior of the capillary cartridge has been conducted from the capillary tube through thread 40, a small amount of the blood sample is conducted by the thread 40 through the resilient member 38 forming a drop on the top of the resilient member 38. The drop of blood signals the operator to remove the hypodermic needle from the artery, thereby terminating the blood sample collection. A cork or stopper (not shown) is immediately placed over the flesh piercing point 52 of the hypodermic needle to seal the hollow opening through the needle shaft 50. The portion of the thread 40 extending exteriorally of the resilient member 38 is grasped and the thread is pulled from the resilient member. The resilient member contracts, thereby sealing the hold which once received the thread 40 and seals the fluid outlet means of the capillary cartridge. In this manner, the collected blood sample is maintained in a protected and sealed environment within the capillary cartridge, essentially free of influence by air, gases or other potential contaminants until such time as the collected blood sample is analyzed. The crystalline heparin 59, which dissolves when the blood sample enters the repository 33 of capillary tube 16, prevents the blood sample from coagulating while in the repository.

The syringe of U.S. Pat. 4,133,304 is a state-of-the-art practical disposable arterial blood gas syringe and, because of its capillary construction, it permits one to avoid (1) taking large samples and use of liquid heparin, (2) employing large needles required to obtain the large samples, and (3) CO₂ dilution (a problem generally occurring because of the presence of aqueous heparin). Syringes made under U.S. Pat. 4,133,304 come in at least three sizes - to sample 0.3 cc, 0.6 cc, and 1.2 cc. Figure 4 discloses a plastic disposable single-use syringe now also commonly used in hospitals. The apparatus comprises an apparatus 10 comprising a tube 14 having wing or flange portions 23 for use with the hypodermic needle 80. The apparatus 10 is equipped with a plunger 17 that is adapted to slidably engage tube 10 by pressing or pulling plunger top 17a which is affixed by a shaft 17b narrower than that of tube 14. The shaft is affixed to a resilient rubber plug means 92 by balljoint 17c; the plug means that traverses and closes tube 10 to form a center chamber 95. A good example of such a state of the art device is the "B-D 1.Oce Sterile Single Use Tuberculin Syringe", Recorder No. 5602 by Becton-Dickinson & Co., Rutherford, New Jersey.

While the syringe of U.S. Pat. 4,133,304 has admirably satisfied the functions of obtaining a disposable syringe using powdered heparin (avoiding CO₂ dilution) that can take a small sample (thereby also eliminating the use of large needles) - which is of considerable efficiency for older and more anemic patients - its extraordinary complicated structure may result in considerable expense.

A need, therefore, arose in the art to perform the same functions as the syringe of U.S. Pat. 4,133,304 economically with simple construction, while at the same time providing a syringe easy to use and able to avoid contamination from atmospheric CO₂ and O₂.

SUMMARY OF THE INVENTION

A new and useful apparatus is disclosed for use with a hypodermic means to collect an animal fluid material (generally a blood or urine sample) having one or more predetermined gases or other clinically significant substances, consisting essentially of:

(a) means for storably receiving and housing a fluid material, comprising an elongated center chamber means open at a first end, and second member means terminating the center chamber means at a second end, the second end member means adapted to connectably and sealably receive hypodermic needle means thereto, and said second end member means further having bore means extending through the second member means, which bore means are adapted to communicate said fluid material between said center chamber means and said connectably received hypodermic needle means; and

(b) closure means adapted to fit the elongated center chamber means (for example, at the open end) to form a center chamber and for providing (1) low resistance escape means for air (which includes for our purposes all gases not entrained in the liquid) while the center chamber is filling with hquid, and (2) high resistance escape means to the flow of liquid. Low resistance escape means are to allow air to escape (without allowing liquid to escape) at pressure equal to or less than the pressure of the fluid material to be collected; high resistance escape means are to prevent liquid from escaping at pressures less than or equal to a predetermined pressure which is greater than or equal to the pressure of the fluid material to be collected.

Specifically, the new and useful apparatus comprises the following:

(a) means for storably receiving and housing a fluid material, comprising an elongated center chamber means open at a first end, and a second end member means terminating the center chamber means at a second end, the second end member means adapted to connectably and sealably receive hypodermic needle means thereto, and said second end member means further having bore means extending through the second end member means, which bore means are adapted to communicate said fluid material between said center chamber means and said connectably received hypodermic needle means; and (b) one of the following novel embodiments: (1) air-permeable membrane means for traversing said center chamber means to form a center chamber; which membrane means are impermeable to said fluid material in its liquid state; (2) flexible resilient plug means for traversing said center chamber means to form a center chamber between the plug and second end member for said fluid material, which plug means are inert to the fluid material, which plug means surround capillary tube means that (a) extend through the plug means to provide a passageway sufficient for air to escape from the center chamber to the open end of the center chamber means, and that (b) when removed from the plug means, said plug means seal the center chamber; or (3) one-way valve means for traversing said center chamber means to provide a center chamber between the one-way valve means and second end member means for said fluid material, which one-way valve means open to permit the escape of air from the center chamber in the event that a predetermined positive pressure is in the center chamber relative to that pressure outside the center chamber, and which seal the center chamber in the event that a positive pressure less than said predetermined pressure is in the center chamber relative to said pressure outside the center chamber.

With respect to the first or (b)(1) embodiment, preferably the air-permeable membrane seals the center chamber; also, it is preferred that the. membrane means be located at the first end. A preferred membrane is CELGARD^R 2400 by Celanese Plastics Co. (Newark, N.J.), or any airpermeable, non-water wettable membrane inert to the fluid to be collected. For blood, a membrane having air flux characteristics of π =

0.185ΔP ( π = air flux, cc/(cm² . sec) x 10² ; Δ P = pressure drop, inches

H₂O). Another suitable membrane is the ACCUREL^R microporous polymer membrane by Armak Co., Chicago, Illinois. The means (a) for all three embodiments are preferably made of plastic, most preferably polypropylene, which is coated with a suitable anticoagulant, such as solid heparin.

With respect to the second embodiment, it is preferred that the opening of the capillary tube extending through the plug means is flush with the surface of the plug means bordering the center chamber to minimize entrapment of air. The plug means is preferably made of resilient rubber. The type of plug is selected and constructed so that it can be moved to any predetermined position along the center chamber with an application of a predetermined force which is greater than the surface area of the plug times the pressure of the incoming fluid material. The capillary tube means is preferably comprised of one or more flexible plastic hollow fibers, most preferably cuprophane (most preferably having an internal diameter of about 200 to about 250 microns and a wall thickness of from 9 to about 16 microns). We prefer the use of one fiber, possibly coaxial with the plug and tube.

With respect to the third (b)(3) embodiment of the invention, preferably the one-way valve means comprise two or more overlapping membranes or impermeable film layers, each of which substantially traverse the center chamber means, so that the layers form a tortuous path for the air to escape in the event of a positive pressure in the center chamber. Most preferably, the one-way valve means comprises two or more sheets of plastic film impermeable to the fluid material to be collected. An excellent plastic film where blood is the fluid to be collected is polyethylene terephthalate.

In all three embodiments, it is preferred that a heavy, solid sphere, such as metal, be employed to mix the liquid material in the center chamber.

In the event that a blood sample is collected, and a membrane is employed, the membrane materials should be non-water wettable, non-antigenic, inert and impermeable to the blood sample. Accordingly, it is an object of the invention to provide an arterial blood gas syringe which need take only a small sample, in order to minimize chances of CO₂/O₂ contamination and the use of large needles.

It is also the object of this invention to provide a simple arterial blood syringe capable of being manufactured inexpensively.

It is also an object of the invention to provide a new and improved apparatus to collect at least one arterial blood sample and to effectively isolate the blood sample in an ordinary syringe after collection while preventing and avoiding contamination of the collected blood sample from gases and other foreign material.

Other objects of the invention are to provide a new and improved apparatus to collect at least one arterial blood sample in which the apparatus allows use of the blood sample during an analysis, significantly reduces the probabihty for error in the analysis results by eliminating or reducing the probability that contaminants may enter the blood sample, effectively avoids or prevents leakage of the blood sample after collection, and is easily and conveniently constructed and used.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 is a perspective view of one embodiment of the state of the art syringe of U.S. Pat. 4,133,304 in use with an attached hypodermic needle.

Figure 2 is an enlarged section view taken along line 2-2 of Figure 1.

Figure 3 is an enlarged fragmentary section view taken along line 3-3 of Figure 2 also illustrating a layer of anticoagulant deposited in the interior of one of the elements of the apparatus of the '304 patent.

Figure 4 is a perspective view of a prior art disposable syringe with plunger commonly sold in industry. Figure 5 is an enlarged sectional view of one aspect of the first illustrated embodiment of the invention, that using a porous air-permeable membrane.

Figure 6 is an enlarged sectional view of one aspect of the second illustrated embodiment of the invention, that using a resilient rubber plug.

Figure 6a is a cross-sectional view of Figure 6 from the vertical.

Figure 7 is an enlarged sectional view of one aspect of the third illustrated embodiment of the invention, that using a one-way valve comprising two sheets of polyethylene terephthalate.

Figure 8 is a plot of the air flux characteristics of a preferred material used as a membrane in the first embodiment of the invention.

Figure 9 depicts apparatus used in Example I for the testing of several embodiments of the invention.

Figure 10 is a cross-sectional view of Figure 7 from the vertical.

A more complete understanding of the invention, as well as other objects and advantages, can be obtained from the following brief description of the drawings, description of the preferred embodiments, Examples, and appended claims.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Figures 5-7 show three preferred embodiments of the invention. In Figure 5, apparatus 10 is shown for use with a hypodermic needle 80 to collect and storably receive a fluid material such as a blood sample or urine, etc By "blood sample", we mean whole blood, blood plasma, or any fraction of blood. The apparatus 10 comprises generally a tubular syringe-type housing member 14, an air-permeable membrane 78, a second end member means commencing with fluid inlet nozzle 30 and terminating with a barrel portion end member means or bore 2 4 that is adapted to connectably and sealably receive hypodermic needle J30_ to form a center chamber 95. Preferably the nozzl 30 and hypodermic needle 80 are made of plastic, so that the taper of bore 24 is so constructed to have its wall 81 fit snugly in sealing engagement with the wall 82 of needle 80 to form a fluid tight and conductive channel from flesh piercing point 52 (infra) to center chamber 95. Of course, other arrangements not shown are possible, such as a male-female bolt/nut construction. Needle 80 contains tip 74 which is molded to receive a hollow cannula or needle 50 which comprises a hollow (generally metal) shaft having flesh piercing point 52.

The apparatus 10 preferably has flanges or wing portions 23 terminating at open end 22 of the housing member 14. The flanges can extend completely around the periphery of open end 22 to form a circular disk and can be molded of a different piece of material than housing member 14 or can be part of member H. Air-permeable membrane 78 traverses the housing member 14 to form a center chamber 95 bordered by the second member means ending in bore 24 adapted to fit a hypodermic syringe 80. The membrane 78 is either self-adhesive or is sealed by adhesive means 76_ to flange 23 and the periphery of open end 22 If a blood sample is to be collected, the inside 20 of tubular member 14 is coated with a suitable anticoagulant 59, preferably solid heparin consisting of a coating or particles.

In order to take advantage of the invention, a small syringe tube should be employed of 1.2 cc or less (of course, as one skilled in the art may appreciate, a sleeve tightly fitting inside a syringe may be employed to reduce the volume of fluid material collected, to a predetermined amount). We use the tube 14. of apparatus 10 shown in Figure 4— a "B-D 1.0 cc Tuberculin Syringe, Recorder No. 5602, Single Use Plastipak" by Becton- Diekinson & Co., Rutherford, N.J. 07070. This single-use, disposable tube is made of plastic, although, as one skilled in the art will understand, certainly a glass or other tube (preferably transparent) could be employed. The apparatus 10 preferably has a luer taper molding or fitting wall 81 at the end of the barrel 14 which is adapted to fit a "luer lock" needle. An example of a good "luer lock" family of needles are the "B-D Yale Hypodermic Luer-Lok" disposable stainless steel needles by Becton-Dickinson & Co., supra. We find for a 1.0 cc Becton-Dickinson No. 3602 tube that the 23g 1 and 25g 7/8 eannulae are excellent. Even with extremely low blood pressure in a patient (about 50mm Hg, typical of critical or anemic patients), the l.0cc syringe fills completely (1.2-1.3ce) in about 58 seconds with a 23g 1 needle. Of course, as will be recognized by those in the art, the filling rate is a function of the air flux of the membrane, the internal diameter of the cannula, the barrel 14 volume, and the pressure drop (AP) from the patient to ambient. By "air", we mean not only air in the traditional sense, but gases comprising the ambient - present while the device of the invention is in operation, as well as non-entrained gases vis-a-vis the liquid present in the center chamber 95.

It is preferred to employ a tube having flanges 23 to provide a better, e.g., larger surface for adhesive 76 to join the membrane 78 to the apparatus 10. If the 1.0cc B-D syringe is used, we employ for blood samples an adhesive which is compatible with and inert to blood, i.e., non-antigenic and inert, preferably Stock C707 by Arno Tape Co., Michigan City, Indiana 46360. This tape is double-sided, fabric-based, and pressure sensitive, employing purified natural rubber, and, of course, is well adapted to receive membrane 78. Preferably, membrane 78 seals as well as traverses tube 14.

If a blood sample is to be taken, the membrane should be impermeable to blood or blood plasma, have sufficient air-flux characteristies to pass air reasonably quickly under 50-150mm Hg pressure (less than about two minutes, preferably about one minute or less) experienced with most patients, be non-antigenic, inert, and withstand at least about 200-250mm Hg (about 3-4 psig) without bursting. The membrane is preferably non-water wettable. An excellent membrane is CELGARD ^R 2400 (microporous polypropylene) by Celanese Fibers Marketing Co., Box 32414, Charlotte, N.C., 28232. Tapes capable of being applied to flanges 23 by thermosetting are also satisfactory if all the other parameters stated are met. See Figure 8 showing a. flux rate of ir = 0.185ΔP ( π is flux rate, cc/(cm² . sec) x 10 ,Δ P is a pressure drop in inches, H₂O) obtained by testing for CELGARD^R 2400.

It is understood that membrane 78 need not be located at the terminal end of tube 14, but may be located anywhere along the axis of tube 14 so that predetermined volume of sample in the center chamber 95 can be received. The membrane 78 is preferably located at the end of tube 14.

The tube 14 is coated with a suitable anti-coagulant 59, preferably solid heparin. Several methods for coating solid heparin to tubes (as well as the use of heparin) are known in the art. The diameter of the tubular member 14 should be small (e.g., 3-4 mm) to prevent the blood from flowing down the side of the partially filled device when the closed end traversing tube 14 is below the level of the needle end. A coating of silicone may be applied to the inside of the tube to aid in this aspect. The heparin coating may be applied to the inside walls of the tubular member, for example, by swabbing a glass tube 14 with aqueous solution of heparin and drying, or by applying to a glass or plastic tube 14 a thin film of finely ground heparin particles dispersed in a non-solvent such as petroleum ether and drying. Suitable alternate technology for applying the heparin coating as known to those skilled in the art may be used. See Examples II-V and R. D. Falb, R. I. Leininger, G. Grode and J. Crowley, "Surface-Bonded Heparin" at 365-374, and Vincent L. Gott, "Wall-Bonded Heparin - Historical Background and Current Clinical Applications" at 351-363, both articles in HEPARIN-STRUCTURE, FUNCTION and CLINCIAL IMPLICATIONS, Edited by Ralph A. Bradshaw and Stanford Wersler, Plenum Press (New York and London, 1975), summarizing proceedings of the International Symposium on Heparin, May 13-15, 1974, in St. Louis, Mo. These articles are incorporated herein by reference.

Another embodiment is shown in Figure 6. Here the same apparatus 10 is employed, again with the same hypodermic needle 80 (and its constituent parts, the molded tip 74, cannula 50 with flesh piercing point 52) which has its construction preferably designed so that its wall 82 fits snugly to the wall 81 of bore 24 of tube 1 4 and fluid inlet nozzle 30 of the second end member means. Again, the apparatus 10 is so designed that preferably flanges 23 terminating at open end 22 of tube 14.

In this embodiment, however, a flexible resilient plug 92 traverses the tube 14 to form a center chamber 95 between the plug 92 and bore 24 and fluid inlet nozzle 30. The plug 92 surrounds one or more capillary tubes 90 that extend down through the plug 92 to provide a passageway sufficient for air to escape from the center chamber 95 to the open end 22 of tube 14 The materials of plug 92 and tubes 90 are so selected and constructed so that when all tubes 90 are removed from the plug 92, the plug 92 seals the upper end center chamber.

As shown in Figures 6 and 6a, preferably the opening 102 of the capillary tube(s) 90 is flush with the base or lower rim 96 of plug 92, so that the opening 102 is just exposed to the center chamber. The plug need not be solid, but can have its base 96 connected by connecting means 98 to a ceiling 94 (which traverses the tube 14) as long as it is constructed of sufficient thickness and mass 100 to withstand a predetermined pressure (selected to be greater than the pressure of the liquid to be received) from being moved or dislodged from the tube 14 during operation.

Again, a suitable anti-coagulant 59 is bonded to the tube 14 in the center chamber 95.

In practice, if a blood sample is to be taken, we employ the same "B-D 1.0cc Tuberculin Syringe, Recorder No. 5602" of Figure 4 and the first embodiment. Here, however, we remove plug 92 in Figure 4 from the apparatus, dislodge it from ball joint 17c of plunger 17, and invert it in the cylinder so that the conical surface forms a ceiling 94 and base 96 for the plug. This plug 92 of the "B-D 1.0cc Tuberculin Syringe" is made of a flexible, resilient rubber, inert to blood and non-antigenic (if this were not so, we would treat the rubber to make it non-antigenic and inert). The plug is so constructed that while it can be moved to any predetermined position down the axis of tube 14, it cannot be displaced from a given position by 200mm Hg pressure - significantly higher than the maximum blood pressure found typically in humans. We use preferably only one capillary tube. The plug 92 is sliced with a bevel cut (such as that of a standing sewing machine needle, razor blade, surgical knife, or, preferably, 18 guage cannula needle) to insert the capillary tube. Preferably, we insert an 18 guage cannula through the plug, and then insert a euprophane hollow fiber in the needle. The euprophane hollow fibers are available in a variety of sizes from Enka A.G., Wuppertal-Elberfeld, Federal Republic of Germany. We preferably employ an Enka A.G. stock CUM, stock D2JM, or stock F11M fiber (each , having from 200-250 micron internal diameter, but varying (9-16) micron wall thicknesses). After insertion of the hollow fiber through the needle which has been inserted through the plug, the needle is removed, leaving the fiber traversing the plug and having extra length on both sides. The fiber is cut flush with the plug 92 at the plug's lower base 96 so that the opening 102 of the fiber is just exposed. The length of fiber 90 coming from ceiling 94 of plug 92 is cut to length. The plug is then inserted at and moved to a predetermined position in the tube 14. In practice, upon insertion of the hypodermic needle 80 in the patient, the center chamber 95 fills up with fluid, air escaping through opening 102 of the fiber 90; afterwards, blood can be seen to commence rising in the fiber 90. The fiber is removed by pulling and the plug 92 seals completely the upper end of the outer chamber 95.

Again, if a blood sample is to be taken, solid heparin 59 coats the wall of the tube 14.

We wish to bring to the attention of the reader Figure 3 of Bailey, U.S. Pat. 4,133,304. Bailey teaches that "fibrous material" (e.g., string or thread) projects through resilient member 38. Note resilient member 38 of Bailey is held in one position by cap 34 (probably needed to keep from pulling plug 38 out when the string 40 was removed from the plug 38 by the string's high frietional resistance). The second mode of our invention eliminates cap 34 of Bailey, provides a movable plug that can be located in a predetermined position in tube 14 (to synergistically eliminate (1) the necessity for capillary tube 16 and (2) the necessity of having different syringes for different volumns of blood to be taken). Moreover, the string 40 of Bailey is unacceptable for our use because it is not guaranteed to be (1) non-antigenic and (2) inert to the blood to be sampled. Hence, the use of a hollow fiber for the resilient member is truly synergistic in that (a) it provides a movable assembly for the plug (eliminates the necessity of different size syringes for different volumes), (b) is non-antigenic and inert for safety and efficacy, and (c) is removed easily.

A preferred third embodiment of our invention is shown in Figure 7. Again, we employ the same "B-D 1.0cc Tuberculin Syringe, Recorder No. 5602" of Figure 4, and the same hypodermic needle. Here, however, we employ one-way valve means to provide a center chamber 95 between the one-way valve means and the second end member means. The one-way valve means open to permit the escape of air in the center chamber 95 relative to that pressure outside the center chamber, i.e., at a predetermined pressure difference, and which seals the center chamber 95 in the event of a pressure less than said predetermined pressure in the center chamber relative to said pressure outside the center chamber 95. Preferably, the one-way valve comprises two (it can comprise, of course, more than two) overlapping membranes or impermeable film layers, each of which substantially traverses the center chamber means (tube 14), so that the layers form a tortuous path 114 and path 116 for the air to escape in the event of a positive pressure in the center chamber 95. In Figures 7 and 10, the one-way valve comprises two sheets 110 and 112 of plastic (preferably polyethylene terephthalate) located at the first or open end 22 of the tube 14, preferably across flanges 23. They are bonded to flange 23 by adhesive 76. The two sheets 110 and 112 overlap and are in tight- fitting engagement, only allowing air from center chamber 95 to pass through tortuous path 114 and escape through path 116 in the event that some positve predetermined minimum pressure differential is reached between the inside and outside of tube 14. In the case a blood sample is taken, again, tube 14 is provided with a coating 59 of suitable anti-coagulant, preferably solid heparin. In the event that a blood sample is taken, the membrane or plastic sheets are non-antigenic and inert. In the event membranes are used, they preferably are non-water wettable, as with the first embodiment of Figure 5. Polypropylene is a suitable alternative preferred embodiment to polyethylene terephthalate. It is to be noted that with all three embodiments, a heavy sphere (not shown, and preferaby stainless steel) can be placed in the center chamber 95 to help mix the fluid material collected.

A few remarks concerning the overall aspect of the invention can now be made.

As can be seen from the three specific embodiments, one primary result of the closure in each of the embodiments of Figures 5, 6, 6a, 7 and 10 is providing low resistance air escape means while the means for storably receiving and housing the fluid is filling with fluid. Another primary result is providing a very high resistance to the flow of fluids, such as blood. This allows the tubular means to fill with fluid freely while expelling the air originally in the tube and stopping the flow of sample when the liquid reaches the closure. In the case of the embodiment of Figure 6, the stopping function is accomplished by removing the venting means from the resilient plug.

Another function of the closure is to prevent contamination of the sample by O₂ and CO₂. In the cases of the embodiment of Figures 5 and 7, this is accomplished by applying a layer of pressure-sensitive adhesive coated barrier film over the end of the device once the tubular means, i.e., the center chamber 95, is filled.

The volume of sample taken by the device is generally dependent upon the volume of the tubular means 14. In the case of the alternate closure of the embodiment of Figure 6, the resilient plug may be positioned at suitable locations along the length of the tubular means 14 to obtain varying sample size volumes. This, of course, will require that the venting means be provided with sufficient length so that it extends beyond the open end of the tubular means 14 in all cases. The operation of the device of the invention is as follows for blood sampling. An appropriately sized syringe needle 80 is placed on the tapered bore 24 of the tubular means 14. An appropriate arterial puncture is made with the flesh piercing tip 52 of cannula 50 and under the force of normal blood pressure (generally about 50-150mm Hg), the patient's blood is forced through the needle and into the tubular means. When the level of blood within the tubular means reaches the closure, sample-taking is stopped. In the case of the alternate embodiment of Figure 5, because of the high resistance to liquid passage of the membrane sealing the tube, the flow of the sample ceases automatically. A plug of resilient material (not shown) is stabbed with the needle end to seal it. A pressure-sensitive adhesive tape is applied over the membrane closure end to seal it. In the case of the alternate embodiment of Figure 6, when the blood reaches the closure means, i.e., the plug, blood will begin to flow up the venting means, i.e., the capillary tube. At this point, the venting means is pulled out of the closure plug, thus sealing the closure plug opening. The alternate closure of Figure 7 is used in the same manner as the alternate of Figure 5.

The blood sample can be ejected from the sampling device as follows. In the cases of the alternates of Figures 5 and 7, the closure membrane or film is peeled away and an appropriately sized syringe plunger is inserted into the tubular means. After removing the resilient plug from the syringe needle, or the syringe needle itself, the sample can be expelled. In the alternate, the membrane 78 can be peeled away or punctured and the sample aspirated by a blood gas analysis machine, or by forcibly discharging the sample with air pressure, as with a pressure bulb pump. In the case of the alternate of Figure 6, following removal of the syringe needle, a shaft or rod is inserted into the open end of the tube 14. Pressing the rod against the resilient closure plug will cause the contents of the tubular means to be expelled. The sample may also be aspirated from the tube 14 by plunger means such as shown in Figure 4 (17). We believe that a device so constructed will incorporate all of the advantages of a small sample size device in that no contamination or dilution of the blood samples is allowed. This aspect provides for a small sample size, and a small gauge syringe needle. Further, we believe that a device so constructed according to one of our embodiments will be much less complicated and expensive than the small size blood gas analysis sampler, represented by Figures 1-4, 10-12 of U.S. Pat, 4,133,304. Along with reduced complexity, we believe that a much less costly device will result.

Embodiments of the present invention have been shown and described with a degree of particularity to enable a complete and full understanding of those embodiments. It should be understood that the present invention involves the inventive concepts taught above and defined in the appended claims, and these inventive concepts are not intended to be limited by the Examples and drawings. Moreover, it is understood that the following Examples merely typify a few of the teachings above, and can be modified by the average artisan without falling outside the intended teachings, the scope of the invention, or the appended claims.

EXAMPLE I

Experimental apparatus as shown in Figure 9 was set up to test the various embodiments of the invention. In Figure 9, a sturdy 500cc aspirator bottle 120, e.g., Pyrex "F-8" Aspirator (with outlet for tubing) No.

1220, 500ml, Corning Glass Co., Corning, New York, was affixed to a 3/8 inch (I.D.) rubber hose 126 by clamp .m ("tyton SNAPPER ") No. SNP-6 by

Tyton Corporation, 7930 N. Faulkner Road, Milwaukee, Wis. 53223 - see U.S.

Pat. 3,605,200). The other end of the hose was blocked off by a standard polycarbonate tubing clamp 127 so that blood could flow from aspirator bottle 120 down tube 126 to clamp 127. For clamp 127, we used Tubing Clamp Stock No. 11-4650 from ACE Scientific Co., 1420 East Linden Avenue, Linden, N.J. 07036. Stopper 123 was firmly affixed in bottle 120 as the cork was in sealing engagement with rim 122 of the bottle 120. The stopper had two holes 122a and I22b, adapted to fit hollow glass tubes 137a and 137b in sealing engagement to form an air-tight channel. Glass tube 137a was affixed to 1/4 inch (I.D.) rubber tube 131 to a common aspirator bulb 130. In the center of the length of the tube, a three-way stop cock 132 was employed (3-way stopcock of borosilieate glass by Corning Glass Co. - Stock 'No. 7380 having stopper bore 4mm, side arms 10mm) to release pressure in bottle 120 if desired. Glass tube 137b was affixed to a 100cm U- tube manometer (provided by SCA Scientific Supply Inc., Bloomfield, N.J.) 135 by 3/8 inch rubber tube 136 through clamp 129, the manometer containing mercury 134. The manometer was provided with stand 133.

About 250 ml of outdated whole human blood (obtained from North Jersey Blood Center, West Orange, New Jersey) 121 was placed in bottle 120. The aspirator 130 was pumped until a predetermined differential pressure was observed on manometer 135. The following Table shows the time to fill various syringes, including those of the invention.

Examples 2-6 demonstrate some methods for coating tubes with heparin. The amount of heparin to be deposited in each sampler or syringe barrel will be about 50 to 70 units of heparin. This is equivalent to approximately 0.5 mg of sodium heparin. An effective amount of heparin to prevent thrombogensis for 20 minutes at room temperature in a 1cc sample of blood is about one unit of heparin. Using 50 to 70 times the effective amount will help by reducing the amount of sampling and testing required to achieve an enormously high confidence level that an effective amount of heparin is present. Also, it will be extremely likely that a means for mixing blood samples within the sampling syringe will not be required if this large excess of heparin is present. Other sampling devices in the field also use about 50 units of heparin.

EXAMPLE II 350mg of sodium heparin are ground with a mortar and pestal and are dispersed in a non-solvent such as CH₂Cl₂ which wets the polypropylene tube 14 of the invention. 140 ml CH₂Cl₂ was employed. The polypropylene tube is wet by the dispersed solution and the CH₂Cl₂ is allowed to evaporate, leaving a fine white powdered dust coating of sodium heparin on the tube. Sodium heparin is available from:

Eastman Kodak Co.

Stock No. 11754, "Heparin Sodium"

Rochester, N.Y. 14650 and

Diosynth, Inc.

3432 West Henderson Street

Chicago, 111. 60618

EXAMPLE III

350mg Heparinic acid is dissolved in a 140ml organic solvent (chloroform) which wets polypropylene. Proceed in the same manner to coat tube 14 as in Example II. EXAMPLE IV To a concentrated solution of sodium heparin in water was added dropwide a volumn of aqueous solution of dodecyltrim ethyl ammonium chloride to form a precipitate of a heparin dodecyltrimethyl ammonium chloride. This was collected and washed with excess water and dried at ambient temperature under 1mm Hg vacuum. 160mg of the heparin/quarternary ammonium complex, to-wit, dodecyltrimethyl ammonium chloride is dissolved in sufficient

isopropyl alcohol solvent to form a concentration of 2.5 mg/ec of heparin/quarternary ammonium complex. The solution is loaded into a 1.0cc plastic syringe. After evaporation, a film coating of heparin/quarternary complex was left on the tube.

EXAMPLE V

A new approach is disclosed in which a concentrated aqueous solution of sodium heparin is prepared to which an alcohol, e.g., methanol, ethanol or 2-propanol, is added at a 1:1 or 2:1 ratio to the volume of the aqueous heparin solution. The sodium heparin will form a colloid and the alcohol will aid in wetting the hydrophobic polypropylene surface. An evaluation of the suitability of this approach was undertaken, and it was found that with an isopropanol to water ratio of about 30:1 to about 50:1, a stable dispersion was possible and good wetting of polypropylene was also achieved.

Specifically, a concentrated aqueous solution of sodium heparin was formed by mixing 250mg sodium heparin in lcc water. 20cc of isopropanol was added to the volume, after which the solution was again diluted with isopropanol to 100cc A tube 14 was wetted with the solution and the solution allowed to evaporate. Small particles of heparin could be seen on the tube. The colloid may be dried by shaking with a sufficient quantity of 3A or 4A molecular sieve (Linde Division of Union Carbide Co., Terrytown, New York). The removal of substantially all water from the coUoid will aid in wetting the tube and will make the coating smoother and more uniform for coating after evaporation.

Another experiment was performed similar to that above, except that enough isopropanol was added (200cc) to dilute the sodium heparin to 1.25 mg/cc The syringes were again loaded, and again small particles of heparin could be seen on the tubes.

EXAMPLE VI Sample devices using the CELGARD ^R 2400 membrane were prepared using the heparin powder dispersion approach of Example I, the quart ernary heparin complex of Example IV, and the heparin alcohol colloid of Example V. The heparin alcohol colloid was used to dose syringe barrels at the concentration of 2.5 mg per cc of alcohol and 1.25 mg per cc of alcohol. The other two heparin forms were both dosed at 2.5 mg per cc. The dosing procedure involved filling the syringe barrel and allowing the solution to drain from the inside through the luer taper end. The samples were dried under vacuum after complete draining of the contents. Half of the devices of each type of heparin dose form were prepared with a small steel mixing ball inside the syringe barrel Results indicated all of the devices had adequate anti-thrombogenic capacity.

Claims

WHAT IS CLAIMED IS:

1. Apparatus for use with hypodermic needle means to collect animal fluid material, consisting essentially of:

(a) means for storably receiving and housing a fluid material, comprising an elongated center chamber means open at a first end, and a second end member means terminating the center chamber means at a second end, the second end member means adapted to connectably and sealably receive hypodermic needle means thereto, and said second end member means further having bore means extending'through the second end member means, which bore means are adapted to communicate said fluid material between said center chamber means and said connectably received hypodermic needle means; and

(b) closure means adapted to fit the elongated center chamber means to form a center chamber and for providing (1) low resistance escape means for air while the center chamber is being filled with said liquid material, and (2) high resistance escape means to the flow of hquid.

2. Apparatus for use with hypodermic needle means to collect animal fluid material, comprising:

(a) means for storably receiving and housing a fluid material, comprising an elongated center chamber means open at a first end, and a second end member means terminating the center chamber means at a second end, the second end member means adapted to connectably and sealably receive hypodermic needle means thereto, and said second end member means further having bore means extending through the second end member means, which bore means are adapted to communicate said fluid material between said center chamber means and said connectably received hypodermic needle means; and (b) air-permeable membrane means for traversing said center chamber means to form a center chamber, which membrane means is impermeable to said fluid material.

3. The apparatus of Claim 2, wherein the air-permeable membrane seals the center chamber.

4. Apparatus for use with hypodermic needle means to collect at least one animal blood sample, comprising:

(a) means for storably receiving and housing a blood sample, comprising an elongated center chamber means open at a first end, and a second end member means terminating the center chamber means at a second end, the second end member means adapted to connectably and sealably receive hypodermic needle means thereto, and said second end member means further having bore means, extending through the second end member means, which bore means are adapted to communicate said blood sample between said center chamber means and said connectably received hypodermic needle means; and

(b) air-permeable, non-water wettable membrane means for traversing and seahng said center chamber means to form a center chamber, which membrane means are non-antigenic, inert, and impermeable to said blood sample.

5. The apparatus of Claim 1, 2, 3 or 4, where the membrane means is located at the first end.

6. The apparatus of Claim 1, 2, 3 or 4, where the means (a) is plastic.

7. The apparatus of Claim 4 where the membrane is microporous polypropylene.

8. The apparatus of Claim 7, where the membrane has an air flux rate of about:

whereimr = air flux, cc/(cm² . sec) x 10² and

ΔP = pressure drop across membrane in inches, H₂O.

9. Syringe tube for use with a hypodermic needle to collect at least one animal blood sample, comprising:

(a) barrel means for storably receiving and housing a blood sample, comprising an elongated cylindrical tube open at a first end, and a bore terminating tube at a second end, the bore adapted to sealably receive a hypodermic needle, said bore also adapted to communicate said blood sample between the tube and the hypodermic needle; and

(b) an air-permeable non-water wettable membrane for traversing and sealing said tube to form a center chamber, which membrane is non-antigenic, inert, and impermeable to said blood sample.

10. The syringe of Claim 9, where the membrane is at the first end of the tube and the tube is coated with a suitable anticoagulant.

11. Apparatus for use with hypodermic needle means to collect animal fluid material, comprising:

(a) means for storably receiving and housing a fluid material, comprising an elongated center chamber means open at a first end, and a second end member means terminating the center chamber means at a second end, the second end member means adapted to connectably and sealably receive hypodermic needle means thereto, and said second end member means further having bore means extending through the second end member means, which bore means are adapted to communicate said fluid material between said center chamber means and said connectably received hypodermic needle means; and

(b) flexible resilient plug means for traversing said center chamber means to form a center chamber between the plug and second end member for said fluid means material, which plug means are inert to the fluid material and surround capillary tube means that (1) extend through the plug means to provide a passageway sufficient for air to escape from the center chamber to the open end of the center chamber means, and that (2) when removed from the plug means seal the center chamber.

12. The apparatus of Claim 11, where the opening of the capillary tube extending through the plug means is flush with the surface of the plug means bordering the center chamber.

13. The apparatus of Claim 11, wherein the plug means are resilient rubber.

14. The apparatus of Claim 11 or Claim 12, wherein the capillary tube means comprise a flexible plastic hollow fiber.

15. The apparatus of Claim 14, wherein the plastic is euprophane.

16. The apparatus of Claim 11, wherein the fluid material comprises a blood sample.

17. The apparatus of Claim 16, wherein the capillary tube means comprise one or more euprophane hollow fibers.

18. The apparatus of Claim 17, wherein each fiber has an internal diameter of about 200 to about 250 microns and a wall thickness of from 9 to about 16 microns.

19. The apparatus of Claim 4 or Claim 16, wherein the means for storably receiving and housing the blood sample is coated with solid heparin or other suitable anticoagulant.

20. The apparatus of Claim 1 or Claim 2 or Claim 11, wherein the means for housing a fluid material further comprise laterally extending wing portions external to the elongated center chamber means.

21. Syringe tube for use with a hypodermic needle to collect at least one animal blood sample, comprising:

(a) barrel means for storably receiving and housing a blood sample, comprising an elongated cylindrical tube open at a first end, and a bore terminating the tube at a second end, the bore adapted to sealably receive a hypodermic needle, said bore also adapted to communicate said blood sample between the tube and the hypodermic needle, and

(b) a flexible resilient plug traversing the tube to provide a center chamber between the plug and tube bore, which plug surrounds one or more capillary tubes inert to the blood sample, each of which (1) extends through the plug to provide a passage-way sufficient for air to escape from the center chamber to the open end of the tube, and (2) when removed from the plug seals the center chamber.

22. The syringe tube of Claim 21, wherein the plug is adapted to slidably move along the axis of the tube and to rest at a predetermined position along the axis of the tube so that a predetermined amount of blood can be- received from the hypodermic syringe.

23. The syringe tube of Claim 21, where each capillary tube is a euprophane hollow fiber.

24. Apparatus for use with hypodermic needle means to collect animal fluid material, comprising:

(a) means for storably receiving and housing a fluid material, comprising an elongated center chamber means open at a first end, and a second end member means terminating the center chamber means at a second end, the second end member means adapted to connectably and sealably receive hypodermic needle means thereto, and said second end member means further having bore means extending through the second end member means, which bore means are adapted to communicate said fluid material between said center chamber means and said connectably received hypodermic means; and

(b) one-way valve means for traversing said center chamber means to provide a center chamber between the one-way valve means and second end member means for said fluid material, which one-way valve means open to permit the escape of air from the center chamber in the event a predetermined positive pressure in the center chamber relative to that pressure outside the center chamber, and which seal the center chamber in the event of a pressure less than said predetermined pressure in the center chamber relative to said pressure outside the center chamber.

25. The apparatus of Claim 24, wherein the one-way valve means comprise two or more overlapping membranes or impermeable film layers, each of which substantially traverses the center chamber means, so that the layers form a tortuous path for the air to escape in the event of a positive pressure in the center chamber.

26. The apparatus of Claim 24, wherein the one-way valve means comprise two or more sheets of plastic film impermeable to the fluid material to be collected.

27. The apparatus of Claim 26, wherein the plastic is polyethylene terephthalate.

28. The apparatus of Claim 24, wherein the one-way valve means is located at the first end of the elongated center chamber means.

29. Apparatus for use with hypodermic needle means to collect at least one animal blood sample, comprising:

(a) means for storably receiving and housing a blood sample, comprising an elongated center chamber means, open at a first end, and a second end member means terminating the center chamber means at a second end, the second end member means adapted to connectably and sealably reeeive hypodermic needle means thereto, and said second end member means further having bore means extending through the second end member means, which bore means are adapted to communicate said blood sample between said center chamber means and said connectably received hypodermic needle means; and

(b) one-way valve means for traversing said center chamber means to provide a center chamber betwen the one-way valve means and second end member means for said blood sample, which one-way valve means opens to permit the escape of air from the center chamber in the event of a predetermined positive pressure in the center chamber relative to the pressure outside the center chamber, and which seal the center chamber in the event of a pressure less than said predetermined pressure in the center chamber relative to that pressure outside the center chamber.

30. The apparatus of Claim 29, wherein the one-way valve means comprise two or more sheets of polyethylene terephthalate.

31. The apparatus of Claim 29, wherein the one-way valve means comprise two or more membrane sheets, each of which are non-water wettable, non-antigenic, inert, and are impermeable to said blood sample.

32. Syringe tube for use with a hypodermic needle to collect at least one animal blood sample, comprising:

(a) barrel means for storably receiving and housing a blood sample, comprising an elongated cylindrical tube open at a first end, and a bore terminating the tube at a second end, the bore adapted to sealably receive a hypodermic needle, said bore also adapted to communicate said blood sample between the tube and the hypodermic needle; and (b) a one-way valve means, comprising two or more overlapping membranes or impermeable film layers, each of which substantially traverse the center chamber, so that the layers form a tortuous path for the air to escape in the event of a predetermined positive pressure in the center chamber, and which seal the center chamber in the event of a pressure less than said predetermined pressure in the center chamber relative to said pressure outside the center chamber.

33. The apparatus of any of Claims 1, 2, 4, 9, 11, 21, 24, 29, or 32 in which the center chamber contains solid spherical means for mixing the fluid material.