JP2025536237A - Gas filling of vacutainer tubes and packaging for improved blood gas and shelf life performance - Google Patents

Abstract

A biological liquid collection device comprising: a collection module for receiving a biological liquid sample; a vacuum vessel having an open end and a closed end, the vacuum vessel containing the collection module therein; and a closure for closing the open end of the vacuum vessel, the vacuum vessel containing a gas composition having a selected partial pressure of a target gas that is substantially greater than the partial pressure of the target gas in the atmosphere outside an internal cavity of the vacuum vessel.

Description

The present disclosure relates generally to balanced fluid collection apparatus and methods for collecting biological fluid samples, and more particularly to blood sample collection devices integrated with evacuated blood collection tubes for use in connection with blood gas analysis, and even more particularly to blood sample collection devices designed to collect blood using an "atmospheric pressure balanced vacuum" to ensure that the blood is exposed to sample atmospheric pressure oxygen and partial pressure carbon dioxide levels similar to those found in standard arterial blood gas (ABG) syringes.

CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims priority to both U.S. Provisional Patent Application No. 63/413,013, entitled "Gas-Filling Vacutainer Tubes to Reduce the Rate of Extractable Loss and Improve Shelf Life Performance," filed on October 4, 2022, and U.S. Provisional Patent Application No. 63/510,476, entitled "Gas-Filling Vacutainer Tubes to Reduce the Rate of Extractable Loss and Improve Shelf Life Performance," filed on June 27, 2023, the entirety of both applications being incorporated herein by reference in their entirety.

1 ml to 3 ml syringe-based platforms are commonly accepted for blood gas testing. Current blood gas devices fall into two categories based on the filling method employed: (1) plunger-user-assisted and (2) ventilated-pressure-assisted. These syringe configurations typically require users to follow protocols that include air purging, capping/sealing, and anticoagulant mixing steps to ensure the quality of the blood sample is not compromised for analysis on diagnostic equipment. In addition to complex multi-step workflows, traditional blood collection syringes significantly increase the safety risk of blood exposure during air burp and capping procedures.

A recent blood collection device for collecting a small blood sample and dispensing a portion of the sample to a device intended or designed to analyze the sample, such as a point-of-care or near-patient testing device, is disclosed in U.S. Patent No. 6,273,625, the entire contents of which are incorporated herein by reference. The blood sample collection device disclosed therein is integrated into an evacuated container, such as a BD Vacutainer® blood collection tube, owned by the assignee of the present invention, Becton, Dickinson, and Company. Use of this device enables blood sample collection and dispensing for point-of-care applications that incorporate traditional automated blood collection and include novel controlled sample dispensing capabilities while minimizing exposure risks. When blood fills a traditional Vacutainer® tube, gas components dissolved and bound to hemoglobin in the blood (O ₂ , N ₂ , CO ₂ ) are exposed to the gas mixture in the tube, with each gas mixture component having its own partial pressure. The total pressure within the tube is the sum of the partial pressures of each individual gas (Ptube = _PO2 + _PCO2 + _PN2 ), as indicated by Dalton's law of partial pressures. This fundamental property of gases dictates a conventional tube vacuum pressure of 300 mmHg. However, the internal pressure of the tube is defined by the internal volume of the tube and the desired draw volume of the tube (e.g., 1 mL, 2 mL, etc.). In contrast, normal atmospheric gas composition has an oxygen partial pressure of 160 mmHg at atmospheric pressure and 760 mmHg at sea level. This standard vacuum process creates an environment that exposes the blood to a larger partial pressure gradient (ΔP) for both oxygen and carbon dioxide within a conventional Vacutainer® tube compared to a syringe, which in turn can result in blood gas bias. As a result, gas can come out of solution (blood) as determined by the equilibrium between the undissolved gas within the evacuated tube and the gas dissolved in the blood.

Air is a mixture of approximately 80% nitrogen and 20% oxygen, but the two gases permeate the vacuum tube independently. Oxygen permeates approximately 10 times faster than nitrogen, and accounts for the majority of the tube's suction loss over the vacuum vessel's shelf life.

There is a need in the art for an atmospherically balanced evacuated tube architecture that reduces blood gas bias and enables stable blood gas levels during blood vacuum aspiration using conventional blood collection devices. There is also a need in the art for an atmospherically balanced evacuated tube architecture that provides superior vacuum shelf life by reducing gas permeability through plastic tubing. There is a further need in the art for atmospherically balanced conventional specimen collection containers, such as evacuated blood collection tubes, that provide superior vacuum shelf life by reducing gas permeability through plastic materials.

U.S. Pat. No. 9,649,061

A key advantage of the disclosed arterial blood gas (ABG) atmospherically balanced evacuated tube is the reduction of both blood collection workflow steps and blood exposure associated with conventional (ABG) syringe blood collection sets. The disclosed device uses vacuum aspiration to uniformly mix anticoagulant into a fixed, air-free maximum blood sample, providing a simplified user workflow. A plug element is located in a fixed position within the tip cap. This plug element is air-permeable and liquid-impermeable, allowing air to be purged when the device is filled and then sealed upon blood contact. The disclosed atmospherically balanced vacuum design allows for the removal of the dispenser component from the evacuated tube, thereby allowing a controlled sample to be dispensed into a diagnostic cartridge or aspirated by/through a probe in a blood gas diagnostic port.

According to one aspect, a biological liquid collection device may include a collection module for receiving a biological liquid sample, a vacuum vessel having an open end and a closed end, the vacuum vessel containing the collection module therein, and a closure for closing the open end of the vacuum vessel, and the vacuum vessel may contain a gas composition having a selected partial pressure of a target gas that is substantially greater than the partial pressure of the target gas in an atmosphere outside an internal cavity of the vacuum vessel.

According to another aspect, a vacuum vessel may contain a gas composition having a selected partial pressure of a target gas greater than the partial pressure of the target gas in the atmosphere outside the vacuum vessel. The gas composition in the vacuum vessel may include oxygen, carbon dioxide, and nitrogen. The oxygen in the gas composition located in the vacuum vessel may have a partial pressure greater than the partial pressure of atmospheric oxygen outside the vacuum vessel. The carbon dioxide in the gas composition located in the vacuum vessel may have a partial pressure substantially equal to the partial pressure of carbon dioxide in the atmosphere outside the vacuum vessel. The gas composition may include approximately 75% oxygen, approximately 23% nitrogen, and approximately 0.1% carbon dioxide. The vacuum vessel may have a total pressure of 300 mmHg, and the oxygen in the gas composition in the vacuum vessel has a partial pressure of approximately 160 mmHg. The vacuum vessel may have a total pressure of 300 mmHg, and the carbon dioxide in the gas composition in the vacuum vessel has a partial pressure of approximately 0.3 mmHg. The oxygen in the ambient gas composition may have a partial pressure of about 160 mmHg, and the carbon dioxide in the ambient gas composition may have a partial pressure of about 0.3 mmHg. The collection module may include a first end having a sample introduction opening, a second end having a sample distribution opening, a passageway extending between the sample introduction opening and the sample distribution opening, and a porous plug covering the second end of the housing. The closure may be configured to close the sample introduction opening in the collection module, the closure comprising a pierceable self-sealing stopper. The porous plug may be adapted to allow air to pass from the passageway of the collection module while preventing a biological liquid sample from passing therethrough. When the evacuated container is one of a 1 mL 13x75 tube, a 2 mL 13x75 tube, a 2.5 mL 13x75 tube, a 3.5 mL 13x75 tube, and a 4 mL 13x75 tube, the evacuated container may have a shelf life of at least 10 months, 24 months, 24 months, 12 months, and 21 months, respectively. The gas composition within the evacuated container may include argon. The gas composition within the evacuated container may include oxygen, nitrogen, and a third gas, such as argon, that has a permeability similar to that of nitrogen. The oxygen in the gas composition located within the evacuated container may have a partial pressure equal to the partial pressure of oxygen in the atmosphere outside the evacuated container, and the argon in the gas composition located within the evacuated container may have a partial pressure greater than the partial pressure of argon in the atmosphere outside the evacuated container. The evacuated container may be a partial suction tube.

According to one aspect, a biological fluid collection device may include a collection module for receiving a biological fluid sample, a vacuum vessel containing the collection module therein, and a closure for closing an open end of the vacuum vessel, wherein the vacuum vessel contains a gas composition having an enriched oxygen content with a partial pressure substantially greater than the partial pressure of oxygen in air at 760 mmHg at atmospheric pressure outside an interior cavity of the vacuum vessel.

According to one embodiment, the vacuum vessel may have a partial pressure of approximately 300 mmHg, and the partial pressure of oxygen within the vacuum vessel may be approximately 160 mmHg. The gas composition may include carbon dioxide and nitrogen, and the partial pressure of carbon dioxide within the vacuum vessel may be approximately 0.3 mmHg, and the partial pressure of nitrogen within the vacuum vessel may be approximately 140 mmHg. The vacuum vessel may have a partial pressure of approximately 300 mmHg, and the partial pressure of oxygen within the vacuum vessel may be greater than 160 mmHg. The gas composition may include approximately 75% oxygen. The gas composition may include approximately 23% nitrogen and approximately 0.1% carbon dioxide.

According to one aspect, a method of making an atmospherically balanced fluid collection device may include providing a container having an open end and a closed end, the container defining a chamber; drawing a vacuum within the container to remove at least some gas from within the chamber; filling the chamber with a gas composition having a proportion greater than the gas composition of the atmosphere outside the evacuated container, where the filling of the chamber occurs until a predetermined vacuum pressure is reached within the container; filling the chamber; drawing a further vacuum within the container to remove at least some gas from within the chamber; filling the chamber with a further gas composition having a proportion greater than the atmospheric composition outside the evacuated container, where the filling of the chamber occurs until a predetermined vacuum pressure is reached within the container; and closing the open end of the container.

According to one aspect, the predetermined vacuum pressure within the container can be 300 mmHg, and the gas composition can include approximately 75% oxygen with a partial pressure of approximately 160 mmHg. The method can further include disposing a fluid collection module within the container, the fluid collection module including a first end having a sample introduction opening, a second end having a sample dispensing opening, a passageway extending between the sample introduction opening and the sample dispensing opening, and a porous plug covering the second end of the housing, the porous plug adapted to allow air to pass through the passageway of the collection module while preventing a biological fluid sample from passing therethrough. When the vacuum container is one of a 1 mL 13x75 tube, a 2 mL 13x75 tube, a 2.5 mL 13x75 tube, a 3.5 mL 13x75 tube, and a 4 mL 13x75 tube, the vacuum container can have a shelf life of at least 10 months, 24 months, 24 months, 12 months, and 21 months, respectively.

According to one aspect, a biological fluid collection device assembly may include an evacuated tube for receiving a biological fluid sample and barrier packaging, the barrier packaging including the evacuated tube therein, the barrier packaging including a gas composition having a selected partial pressure of a target gas that is substantially greater than the partial pressure of the target gas in the atmosphere external to the barrier packaging. The evacuated tube may also include a gas composition having a selected partial pressure of a target gas that is substantially greater than the partial pressure of the target gas in the atmosphere external to the barrier packaging.

The present invention is also disclosed in the following clauses:

Clause 1: A biological liquid collection device comprising: a collection module for receiving a biological liquid sample; a vacuum vessel having an open end and a closed end, the vacuum vessel containing the collection module therein; and a closure for closing the open end of the vacuum vessel, the vacuum vessel containing a gas composition having a selected partial pressure of a target gas that is substantially greater than the partial pressure of the target gas in the atmosphere outside an internal cavity of the vacuum vessel.

Clause 2: The biological fluid collection device described in Clause 1, wherein the vacuum vessel contains the gas composition having a selected partial pressure of a target gas that is greater than the partial pressure of the target gas in the atmosphere outside the vacuum vessel.

Clause 3: The biological fluid collection device described in Clause 1 or 2, wherein the gas composition in the vacuum vessel comprises oxygen, carbon dioxide, and nitrogen.

Clause 4: The biological fluid collection device described in Clause 3, wherein the oxygen in the gas composition located within the evacuated vessel has a partial pressure greater than the partial pressure of oxygen in the atmosphere outside the evacuated vessel.

Clause 5: A biological fluid collection device described in Clause 3 or 4, wherein the carbon dioxide in the gas composition located within the vacuum vessel has a partial pressure substantially equal to the partial pressure of carbon dioxide in the atmosphere outside the vacuum vessel.

Clause 6: The biological fluid collection device described in any one of clauses 3 to 5, wherein the gas composition comprises approximately 75% oxygen, approximately 23% nitrogen, and approximately 0.1% carbon dioxide.

Clause 7: The biological fluid collection device described in Clause 6, wherein the evacuated vessel has a total pressure of 300 mmHg and the oxygen in the gas composition within the evacuated vessel has a partial pressure of approximately 160 mmHg.

Clause 8: The biological fluid collection device described in Clause 7, wherein the evacuated vessel has a total pressure of 300 mmHg and the carbon dioxide in the gas composition within the evacuated vessel has a partial pressure of approximately 0.3 mmHg.

Clause 9: The biological fluid collection device described in Clause 8, wherein the oxygen in the ambient air gas composition has a partial pressure of approximately 160 mmHg and the carbon dioxide in the ambient air gas composition has a partial pressure of approximately 0.3 mmHg.

Clause 10: The biological fluid collection device of any one of clauses 1 to 9, wherein the collection module includes a first end having a sample introduction opening, a second end having a sample dispensing opening, a passage extending between the sample introduction opening and the sample dispensing opening, and a porous plug covering the second end of the housing.

Clause 11: The biological fluid collection device described in Clause 10, wherein a closure is configured to close the sample introduction opening in the collection module, the closure comprising a pierceable self-sealing stopper.

Clause 12: The biological fluid collection device of clause 10 or clause 11, wherein the porous plug is adapted to allow air to pass through the passage of the collection module while preventing the biological fluid sample from passing through.

Clause 13: The biological fluid collection device described in any one of clauses 1 to 12, wherein when the vacuum container is one of a 1 mL 13X75 tube, a 2 mL 13X75 tube, a 2.5 mL 13X75 tube, a 3.5 mL 13X75 tube, and a 4 mL 13X75 tube, the vacuum container has a shelf life of at least 10 months, 24 months, 24 months, 12 months, and 21 months, respectively.

Clause 14: The biological fluid collection device described in any one of clauses 1 to 13, wherein the gas composition in the vacuum vessel further comprises argon.

Clause 15: The biological fluid collection device described in any one of clauses 1 to 14, wherein the gas composition in the vacuum vessel comprises oxygen, nitrogen, and a third gas, such as argon, having a permeation rate similar to that of nitrogen.

Clause 16: The biological fluid collection device described in Clause 15, wherein the oxygen in the gas composition located within the vacuum vessel has a partial pressure equal to the partial pressure of oxygen in the atmosphere outside the vacuum vessel, and the argon in the gas composition located within the vacuum vessel has a partial pressure greater than the partial pressure of argon in the atmosphere outside the vacuum vessel.

Clause 17: The biological fluid collection device described in Clause 1, wherein the vacuum container is a partial suction tube.

Clause 18: A biological fluid collection device comprising: a collection module for receiving a biological fluid sample; an evacuated vessel containing the collection module therein; and a closure for closing an open end of the evacuated vessel, wherein the evacuated vessel contains a gas composition having an enriched oxygen content with a partial pressure substantially greater than the partial pressure of oxygen in air at an atmospheric pressure of 760 mmHg outside an interior cavity of the evacuated vessel.

Clause 19: The biological fluid collection device described in Clause 18, wherein the vacuum container has a partial pressure of approximately 300 mmHg and the partial pressure of oxygen within the vacuum container is approximately 160 mmHg.

Clause 20: The biological fluid collection device described in Clause 19, wherein the gas composition comprises carbon dioxide and nitrogen, the partial pressure of carbon dioxide within the evacuated vessel is approximately 0.3 mmHg, and the partial pressure of nitrogen within the evacuated vessel is approximately 140 mmHg.

Clause 21: The biological fluid collection device described in any one of clauses 18 to 20, wherein the vacuum vessel has a partial pressure of approximately 300 mmHg, and the partial pressure of oxygen within the vacuum vessel exceeds 160 mmHg.

Clause 22: The biological fluid collection device described in any one of clauses 18 to 21, wherein the gas composition comprises approximately 75% oxygen.

Clause 23: The biological fluid collection device described in Clause 22, wherein the gas composition further comprises approximately 23% nitrogen and approximately 0.1% carbon dioxide.

Clause 24: A method for manufacturing an atmospherically balanced fluid collection device, comprising: providing a container having an open end and a closed end, the container defining a chamber; drawing a vacuum within the container to remove at least some gas from within the chamber; filling the chamber with a gas composition that is greater than the gas composition of the atmosphere outside the vacuum container, the filling of the chamber occurring until a predetermined vacuum pressure is reached within the container; drawing a further vacuum within the container to remove at least some of the gas from within the chamber; further filling the chamber with a gas composition that is greater than the gas composition of the atmosphere outside the vacuum container, the filling of the chamber occurring until a predetermined vacuum pressure is reached within the container; and closing the open end of the container.

Clause 25: The method of clause 24, wherein the predetermined vacuum pressure within the container is 300 mmHg and the gas composition comprises approximately 75% oxygen having a partial pressure of approximately 160 mmHg.

Clause 26: The method of clause 24 or clause 25, further comprising disposing a fluid collection module within the container, the fluid collection module including a first end having a sample introduction opening, a second end having a sample dispensing opening, a passage extending between the sample introduction opening and the sample dispensing opening, and a porous plug covering the second end of the housing, the porous plug adapted to allow air to pass from the passage of the collection module while preventing the biological liquid sample from passing therethrough.

Clause 27: The method of any one of clauses 24 to 26, wherein when the vacuum container is one of a 1 mL 13X75 tube, a 2 mL 13X75 tube, a 2.5 mL 13X75 tube, a 3.5 mL 13X75 tube, and a 4 mL 13X75 tube, the vacuum container has a shelf life of at least 10 months, 24 months, 24 months, 12 months, and 21 months, respectively.

Clause 28: A biological fluid collection device assembly comprising: an evacuated tube for receiving a biological fluid sample; and barrier packaging containing the evacuated tube therein, the barrier packaging comprising a gas composition having a selected partial pressure of a target gas that is substantially greater than the partial pressure of the target gas in the atmosphere external to the barrier packaging.

Clause 29: The biological fluid collection device assembly of Clause 28, wherein the evacuated tube also contains a gas composition having a selected partial pressure of a target gas that is substantially greater than the partial pressure of the target gas in the atmosphere outside the barrier packaging.

The above and other features and advantages of the present disclosure, as well as the manner in which they are achieved, will become more apparent, and the disclosure itself will be better understood, by reference to the following description of embodiments of the disclosure taken in conjunction with the accompanying drawings.
FIG. 1 is a front perspective view of a biological fluid collection device having a collection module disposed within an outer housing according to aspects of the present disclosure. 2 is a partial cross-sectional side view of the biological fluid collection device of FIG. 1 according to aspects of the present disclosure. FIG. 3A is an enlarged, partial cross-sectional side view of FIGS. 1 and 2 illustrating a porous plug closing a liquid collection chamber according to an aspect of the present disclosure. FIG. 3B is an enlarged, partial cross-sectional side view of FIGS. 1 and 2 illustrating a porous plug closing a liquid collection chamber according to an aspect of the present disclosure. FIG. 4A is a schematic diagram illustrating blood gas vacuum biasing using a standard vacuum process in a conventional Vacutainer® tube, according to principles known in the art. FIG. 4B is a schematic diagram illustrating blood gas vacuum biasing using a standard vacuum process in a conventional Vacutainer® tube, according to principles known in the art. FIG. 5 is a schematic diagram of regulating pressure within a vessel according to one aspect of the present disclosure. FIG. 6 is a schematic diagram illustrating oxygen flow to a container of the present disclosure. FIG. 7 is a graph showing tubing pressure versus time for oxygen-filled non-gelling tubing as well as unfilled tubing in accordance with the disclosed invention. FIG. 8 is a graph showing tube pressure versus time for an oxygen-filled gelling tube according to the disclosed invention as well as an unfilled tube. FIG. 9 is a schematic diagram illustrating the flow of oxygen and argon to a vessel of the present disclosure. FIG. 10 is a schematic diagram of an evacuated tube with barrier packaging according to one non-limiting embodiment or aspect of the present disclosure.

Corresponding reference characters indicate corresponding parts throughout the several views. The examples set forth herein illustrate exemplary embodiments of the present disclosure, and such examples should not be construed as limiting the scope of the present disclosure in any way.

The following description is provided to enable any person skilled in the art to make and use the described embodiments intended to practice the invention. However, various modifications, equivalents, variations, and alternatives will be readily apparent to those skilled in the art. Any and all such modifications, variations, equivalents, and alternatives are intended to be within the spirit and scope of the present invention.

Hereinafter, for purposes of explanation, the terms "upper," "lower," "right," "left," "vertical," "horizontal," "top," "bottom," "lateral," "longitudinal," and their derivatives shall refer to the present invention as oriented in the drawings. However, it will be understood that the present invention may assume various alternative modifications unless expressly specified to the contrary. It should also be understood that the specific devices and processes illustrated in the accompanying drawings, and described in the following specification, are merely exemplary embodiments of the present invention. Hence, specific dimensions and other physical characteristics relating to the embodiments disclosed herein are not to be considered limiting.

1 and 2, a biological fluid collection device, generally designated 1, is shown having a collection module 10 disposed within an outer housing or vacuum vessel 34 in accordance with aspects of the present disclosure. The collection module 10 is adapted to receive a biological fluid sample, such as a blood sample, and includes a housing 12, a closure 14, a mixing chamber 16, a holding chamber 18, a cap 26 (shown in FIG. 2), and an activation member 22.

In one embodiment, the housing 12 includes a first end 24, a second end 26, and a passageway 28 extending therebetween that provides fluid communication between the first end 24 and the second end 26 of the housing 12. The passageway 28 has a sample introduction opening 30 at the first end 24 of the housing 12 and a sample dispensing opening 32 at the second end 26 of the housing 12. The mixing chamber 16 and the holding chamber 18 are provided in fluid communication with the passageway 28. The mixing chamber 16 and the holding chamber 18 are positioned such that a biological fluid sample, such as a blood sample, introduced into the sample introduction opening 30 of the passageway 28 passes first through the mixing chamber 16 and then through the holding chamber 18 before reaching the sample dispensing opening 32 of the passageway 28. In this manner, the blood sample can be mixed with an anticoagulant or other additive provided in the mixing chamber 16 before a stabilized sample is received and stored in the holding chamber 18.

The mixing chamber 16 allows the blood sample to passively mix with another additive, such as an anticoagulant or blood stabilizer, as the blood sample flows through the passageway 28. The interior portion of the mixing chamber 16 may have any suitable structure or configuration, so long as it allows the blood sample to mix with the anticoagulant or another additive as the blood sample passes through the passageway 28. The mixing chamber 16 may include a dry anticoagulant, such as heparin or EDTA, deposited on or within the mixing chamber 16. The mixing chamber 16 may, for example, include an open-cell foam with a dry anticoagulant dispersed within the cells of the open-cell foam to promote flow-through mixing and the effectiveness of anticoagulant uptake.

After passing through the mixing chamber 16, the blood sample may be directed to the holding chamber 18. The holding chamber 18 may take any suitable shape and size to store a sufficient amount of blood for the desired test, e.g., 500 μl or less. In the embodiment shown in FIGS. 1 and 2, the holding chamber 18 is defined by a portion of the housing 12 in combination with an elastic sleeve 40 secured around the outside of the housing 12. The elastic sleeve 40 may be made of any material that is flexible, deformable, and capable of providing a fluid-tight seal with the housing 12, including, but not limited to, natural or synthetic rubber and other suitable elastomeric materials.

Continuing with reference to FIGS. 1 and 2, and with further reference to FIGS. 3A and 3B, a porous or vent plug 44 is positioned at the second end 26 of the housing 12 and plugs the sample dispensing opening 32 of the passageway 28. The structure of the vent plug 44 allows air to pass therethrough and exit the collection module 10 while preventing the blood sample from passing therethrough, and may include a hydrophobic filter. The vent plug 44 has a selective airflow resistance that can be used to finely control the fill rate of the passageway 28. By varying the porosity of the plug, the rate at which air exits the plug 44, and therefore the rate at which the blood sample enters the collection module 10, can be controlled. If the blood sample flows too quickly into the collection module 10, hemolysis may occur. If the blood sample flows too slowly into the collection module 10, sample collection times may be excessive.

The closure 14 engages the first end 24 of the housing 12 to seal the passageway 28. The closure 14 allows a blood sample to be introduced into the passageway 28 of the housing 12 and may include a pierceable self-sealing stopper 36 with an outer shield 38, such as a Hemoguard® cap available from Becton, Dickinson and Company. The closure 14 is also secured to an outer housing or vacuum receptacle 34. It will be appreciated that the vacuum receptacle 34 may be a well-known vacuum-containing blood collection tube, such as a Vacutainer® blood collection tube available from Becton, Dickinson and Company.

4A and 4B, which schematically illustrate blood gas vacuum biasing using a standard vacuum process in a conventional or prior art evacuated vessel 200, such as a Vacutainer® vessel, according to principles known in the art. As blood fills the conventional evacuated vessel 200, the gas components dissolved and bound to hemoglobin in the blood ( _O2 , _N2 , _CO2 ) are exposed to the gas mixture within the tube, with each gas mixture component having its own partial pressure. The total pressure (P) within the vessel 200 is the sum of the partial pressures (P) of each individual gas ( _Ptube = _PO2 + _PCO2 + _PN2 ), as indicated by Dalton's law of partial pressures. This fundamental property of gas dictates a conventional tube vacuum pressure of 300 mmHg using atmospheric gas composition (21% O ₂ , 0.04% CO ₂ , and 78% N ₂ ), resulting in partial pressures of 63, 12, and 237 mmHg, respectively. The internal pressure of the tube is defined by the internal volume of the tube and the desired draw volume of the tube (e.g., 1 mL, 2 mL, etc.). In contrast, typical atmospheric gas composition has an oxygen partial pressure of 160 mmHg at atmospheric pressure and 760 mmHg at sea level. As shown by graph 160 and FIG. 4B , the standard vacuum process creates an environment that exposes the blood to a larger partial pressure gradient (ΔP) for both oxygen and carbon dioxide within the conventional vacuum vessel 200 compared to a syringe, which can then result in blood gas bias. Henry's Law states that the amount of dissolved gas is proportional to its partial pressure in the gas phase. This equilibrium constant indicates that the partial pressure of blood gases is directly proportional to the partial pressure of the gas within the tube. As a result, as discussed above and shown in FIG. 4A, gas within the conventional vessel 200 comes out of solution (blood) as determined by the equilibrium between the undissolved gas within the evacuated vessel and the gas dissolved in the blood.

Referring now to FIG. 5 , which schematically illustrates a liquid vacuum vessel 34 and a method for preparing the vacuum tube 34 according to the present disclosure, the vacuum vessel 34, including the collection module 10, contains a gas composition having a pressure greater than that of the atmospheric gas composition outside the vacuum vessel 34. In one non-limiting embodiment or aspect of the present disclosure, the term “external” may be understood to mean an area or location outside the interior cavity of the vacuum vessel 34. In another example, the gas composition has a pressure equal to or matching that of the atmospheric gas composition outside the vacuum vessel 34 (approximately 160 mmHg). The proposed device adjusts the basic partial pressure composition of oxygen, O ₂ , and carbon dioxide, CO ₂ , within the vacuum chamber relative to that of atmospheric conditions to provide a blood gas sample equivalent to a standard arterial blood gas (ABG) syringe (the current standard of care). In one non-limiting embodiment or aspect of the present disclosure, O ₂ may be considered the target gas because the partial pressure of O ₂ is adjusted relative to that of the atmospheric O ₂ outside the interior cavity of the vacuum vessel 34. In other embodiments of the present disclosure, the target gas may be different from or in addition to _O2 , such as argon gas, described below. In one embodiment or aspect, a target gas is understood to be a particular gas of a gas composition that is adjusted to reduce or eliminate the same target gas from permeating into the vacuum vessel 34 from outside _the vacuum vessel 34. This was accomplished by developing a vacuum assembly procedure in which a high vacuum is drawn and then oxygen, _O2 , and carbon dioxide, _CO2 , are charged into the chamber until the desired final vacuum level and partial pressures of _O2 and _CO2 are achieved.

5 and 6, the device and method of the present disclosure provides for the collection of a blood sample in a vacuum chamber or vacuum vessel 34, where the blood is exposed to increased pressure compared to atmospheric pressure and the oxygen ( _PO2 ) and carbon dioxide ( _PCO2 ) levels and their respective _PO2 and _PCO2 levels found in a standard arterial blood gas syringe that exposes the blood sample to normal atmosphere, as shown in the graph of FIG. 4B. With continued reference to FIG. ₅ , the method for obtaining the pressure regulated vessel 34 of the present disclosure is accomplished by starting with a vessel at atmospheric pressure of 760 mmHg with approximately 21% oxygen, _O2 , and a partial pressure of nitrogen ( _PN2 ) of approximately 160 mmHg, and a partial pressure of oxygen _PO2 of approximately 600 mmHg. Next, a high vacuum is pulled from within the tube where most of the gas is removed from chamber 135, so that the tube has a total pressure of about 20 mmHg and the composition of the tube is about 21% oxygen, _O2 having a partial pressure _PO2 of about 37 mmHg, nitrogen about 79%, and _N2 having a partial pressure _PN2 of about 140 mmHg. In the next step, another high vacuum is pulled from within the tube where most of the gas is again removed from chamber 135. In the final step, the tube is re-purged with a deliberately proportioned gas composition of O ₂ , N ₂ , and CO ₂ until a desired vacuum level of approximately 300 mmHg above atmospheric pressure of O ₂ and CO ₂ is reached, forming the pressure-regulated vacuum tube 34 of the present disclosure, as shown in FIG. 5 , where the tube composition is approximately 30%-100% oxygen and up to 70% nitrogen, with a partial pressure of oxygen PO ₂ of approximately 160 mmHg, a partial pressure of nitrogen PN ₂ of approximately 140 mmHg, and a partial pressure of carbon dioxide PCO ₂ of approximately 0.3 mmHg. In one example of the present disclosure, the tube composition is greater than 50% oxygen and less than 50% nitrogen. In another example of the present disclosure, the tube composition may be 100% oxygen. It will be appreciated that the tube can be filled such that the partial pressure of oxygen within the vacuum vessel exceeds 160 mmHg. In another example, an oxygen barrier may be provided in the body of the vacuum tube to help prevent gas permeation.

In another embodiment or aspect of the present disclosure, the _PO2 (or other gas) within the tube may be intentionally greater than the atmospheric _PO2 (or other gas) (e.g., supersaturation within the tube). This can also be used to increase the suction volume over time, if desired. This is potentially useful in tubes with higher internal pressure/internal volume ratios (e.g., partial suction tubes). Use of this embodiment further extends the shelf life of the product (beyond that already discussed). In one non-limiting embodiment or aspect of the present disclosure, a partial suction tube is understood to be a blood collection tube that is smaller (e.g., about 3.0 mL or less) than a standard suction tube (e.g., about 4.5 mL). In some situations, partial suction tubes are used when small amounts of blood are required for testing and analysis. Partial suction tubes can be used for a variety of applications, including blood donor screening and infectious disease testing, plasma measurements, serum measurements, hematology measurements, immunohematology measurements, and routine coagulation tests.

By increasing the oxygen content in the tube, the atmospheric oxygen gradient is reduced, slowing or eliminating oxygen permeation through the tube. As the oxygen content in the tube increases, the oxygen content in the tube blocks this permeation, significantly reducing or preventing atmospheric oxygen from permeating into the tube.

The pressure-regulated partial pressure _PO2 and _PCO2 evacuated tube architecture allows for stable blood gas levels during blood vacuum aspiration using conventional blood collection sets based on typical evacuated container systems.

The loss of vacuum shelf life in prior art vacuum vessels 134 is due to gas permeation through the plastic tubing, driven by atmospheric pressure and vacuum partial pressure gradients across the plastic barrier. Nitrogen contributes least to vacuum loss because the permeability coefficient of oxygen is several orders of magnitude higher in polyethylene terephthalate (PET), the plastic primarily used in typical vacuum tubing. The pressure-regulated vacuum tubing architecture described above provides superior vacuum shelf life because the increased _PO2 and _PCO2 gradients within the tubing are less susceptible to gas permeation. This is due to the fact that the design increases the difference in _PO2 and _PCO2 pressures inside and outside the prior art vessel 134. For example, if the total atmospheric pressure outside the vacuum vessel is 760 mmHg, oxygen in the ambient gas composition has a partial pressure of approximately 160 mmHg, and carbon dioxide in the ambient gas composition has a partial pressure of approximately 0.3 mmHg. In the pressure-regulated vacuum tube 34 of the present disclosure, oxygen in the gas composition within the tube also has a partial pressure of approximately 160 mmHg, and carbon dioxide in the gas composition within the tube has a partial pressure of approximately 0.3 mmHg, but the composition within the tube has an increased percentage of oxygen. Because the oxygen percentage of the composition increases within the tube, there is no pressure exchange and no resulting vacuum loss from _O2 and _CO2 . The difference in partial pressure of nitrogen (N2 ₎ within the tube and outside the tube can be significant; i.e., the partial pressure of nitrogen (PN2 ₎ within the tube is approximately 140 mmHg, while the partial pressure of nitrogen (PN2 ₎ in the atmosphere outside the tube is approximately 593 mmHg. This partial pressure difference can result in a slight increase in vacuum pressure within the tube due to nitrogen (N2 ₎ permeation into the tube, as nitrogen has approximately 10 times lower permeability than oxygen. It is noted herein that pressure-regulated compositions as described may be useful for extending the shelf life of any conventional specimen collection container. For example, this pressure regulation technique may be useful for extending the shelf life of plastic blood collection containers, including any type of evacuated tube. While the present application has particular applicability to arterial blood gas applications, the pressure regulation methodology described herein may be utilized with any evacuated plastic container. Furthermore, it is contemplated herein that the pressure regulation methodology identified herein may be suitably used in venous or other blood collection applications.

Figures 7 and 8 show different graphs of the volume drawn as a function of time due to the permeability of the tested tubes. As shown in each plot, the O2 _- filled tubes were found to take significantly longer to reach a threshold (e.g., a critical 20% threshold, referred to herein as "shelf life") than the corresponding unfilled tubes. Consequently, this corresponds to a significant improvement in the shelf life of the _O2- filled tubes. Figure 6 shows the validation results achieved with 13 x 75 mL non-gelling tubes. Figure 7 shows the validation results achieved with 13 x 75 mL gelling tubes. Specifically, when the evacuated container is one of a 1 mL 13x75 tube, a 2 mL 13x75 mL tube, a 2.5 mL 13x75 tube, a 3.5 mL 13x75 tube, and a 4 mL 13x75 tube, the evacuated container has a shelf life of at least 10 months, 24 months, 24 months, 12 months, and 21 months, respectively. These results indicate that this oxygen pressure adjustment method extends the shelf life of the container by at least 6 months.

It can be appreciated that patients exposed to hyperoxia for extended periods of time can experience higher-than-normal oxygen partial pressures, which can exceed 500 mmHg. Under these conditions, gases are forced to dissolve in the blood plasma in an unbound state, although a small fraction still binds to hemoglobin. During blood gas analysis, these samples can exhibit higher bias levels within a typical 15-minute turnaround time due to the high dissolved gas exchange rate of oxygen in plasma combined with the partial pressure gradient when blood is exposed to ambient air. High oxygen (compared to ambient air _PO2 and _PCO2 ) _PO2 and _PCO2 levels can be used with evacuated tube architectures to further improve blood gas stability in oxygen therapy products that are less susceptible to extreme bias. This is feasible in ABG applications because the device design does not have sufficient surface area required to actively bias blood gas levels, which is not possible with conventional ABG syringes.

As shown in FIG. 8, according to another embodiment or example of the present disclosure, the method of adjusting the composition in the tube may also include introducing a third gas, in addition to oxygen and nitrogen, to provide the evacuated tube with the potential for an even longer shelf life. By using this method, the pressure in the tube is maintained at a nearly constant level for a significant portion of the tube's shelf life. Using this method, the oxygen in the tube is matched to the oxygen content in the atmosphere, effectively eliminating oxygen permeation. A third gas is also introduced into the evacuated tube to counteract nitrogen permeation from the atmosphere into the tube. In one example of the present disclosure, the third gas may be argon. Argon has a similar permeation rate to nitrogen, nearly balancing the permeation of nitrogen from the atmosphere into the tube. It should also be understood that there are scenarios in which intentional and deliberate gas combinations of three or more gases (e.g., volatile gases/gases coming from components in a vacuum space, intentional chemical reactions to release gases/gases, or others) can be used to achieve the same desired result (e.g., a gaseous substance at an intentional partial pressure with permeability similar to nitrogen).

According to one non-limiting embodiment or aspect of the present disclosure, a method for controlling the vacuum composition of an evacuated blood collection container can be used to improve blood gas testing performance of a device. In this example, the evacuated tube can have a vacuum with a controlled and optimized oxygen pressure ( _pO2 ) to improve blood gas testing performance of the device. The controlled vacuum composition can be achieved by creating a vacuum within the tube and filling the tube with a gas mixture during the tube evacuation process. In one example, the controlled vacuum composition can include a tube oxygen pressure _pO2 of approximately 70 mmHg. It should be understood that 70 mmHg is just one pressure measurement that can be used to optimize device oxygen pressure to improve blood gas testing performance. The optimized device oxygen pressure can be greater or less than 70 mmHg as needed based on the type of device being used. In one example, the gas mixture filled into the tube can include at least one of nitrogen, oxygen, or a combination of nitrogen and oxygen. Using this method, several advantages are realized. In particular, vacuum-based devices such as vacutainers are generally not recommended for blood gas testing due to the headspace after blood sample collection. Headspace (or air bubbles) can cause erroneous results due to oxygen exchange with the blood sample. However, the optimized oxygen pressure in the tubing described above significantly improves oxygen pressure ( _pO2 ) blood gas performance and extends the _pO2 test range. However, the controlled vacuum composition as a fresh product should be maintained throughout the product's shelf life. In one example, the tubing O2 _pressure can be controlled to be lower than atmospheric pressure (pO2 ₎ but still higher than that of a typical vacuum tube. This control provides a balanced O2 pressure _in the device headspace after sample collection compared to the _pO2 in the blood sample , thereby reducing _O2 transfer from the headspace to the sample and vice versa during the turnaround time before testing the blood sample.

10 , according to a non-limiting embodiment or aspect of the present disclosure, barrier packaging 100 having a controlled oxygen pressure can be used to extend the product shelf life of the evacuated tube 102. In this example, the packaging 100 can have a controlled oxygen pressure that matches the controlled oxygen pressure of the evacuated tube 102. In some examples, the packaging 100 can be a foil pouch, a blister pack, a foil film shelf pack, an oxygen barrier shrink wrap, or any other packaging used to store the evacuated tube 102 or a fluid container. By matching the controlled oxygen pressure of the packaging 100 to the controlled oxygen pressure of the evacuated tube 102, oxygen transmission from the evacuated tube 102 is reduced, extending the product shelf life of the evacuated tube 102. The oxygen pressure of the packaging 100 can be controlled during the packaging process by drawing a vacuum and/or filling the packaging with a gas, such as nitrogen or oxygen, to match the oxygen pressure of the evacuated tube 102. Consistent oxygen pressure within the packaging 100 reduces oxygen transmission and extends the shelf life of the evacuated tube 102.

Evacuated blood collection tubes typically have a much lower oxygen pressure (e.g., approximately 0-20 mmHg) compared to atmospheric air (approximately 160 mmHg). This pressure difference creates oxygen permeation through the tube wall of the blood collection tube, inducing vacuum loss and limiting the product shelf life of the blood collection tube. Oxygen barrier packaging 100 with controlled oxygen pressure can extend the product shelf life by reducing oxygen permeation without changing the tube design and/or materials. The controlled oxygen pressure within the packaging 100 can accommodate semi-barrier packaging materials.

In one non-limiting embodiment or aspect of the present disclosure, the evacuated tube can have a vacuum with a controlled and optimized oxygen tension ( _pO2 ) to improve the blood gas performance of the device. The controlled vacuum composition can be achieved by drawing a vacuum within the tube and filling the tube with a gas mixture during the tube evacuation process. In addition to the controlled vacuum composition, the barrier packaging for the evacuated tube can have a controlled oxygen pressure that matches the controlled oxygen pressure of the evacuated tube. Thus, using this process, the shelf life of the evacuated tube is extended and oxygen permeation of the evacuated tube is reduced by using a combination of a controlled vacuum composition within the evacuated tube and barrier packaging with controlled oxygen pressure.

While this disclosure has been described as having exemplary structures, the disclosure can be further modified within the spirit and scope of the disclosure. This application is therefore intended to cover any variations, uses, or adaptations of the disclosure using its general principles. Further, this application is intended to cover such departures from the disclosure as are known or customarily practiced in the art to which this disclosure pertains and which fall within the scope of the appended claims.

Claims (32)

1. A biological fluid collection device comprising:
a collection module for receiving the biological fluid sample;
a vacuum vessel having an open end and a closed end, the vacuum vessel containing the collection module therein;
a closure for enclosing the open end of the vacuum vessel, the vacuum vessel containing a gas composition having a selected partial pressure of a target gas that is substantially greater than the partial pressure of the target gas in the atmosphere outside an interior cavity of the vacuum vessel; and
A biological fluid collection device comprising: The biological fluid collection device of claim 1, wherein the vacuum vessel comprises the gas composition having a selected partial pressure of a target gas that is greater than the partial pressure of the target gas in the atmosphere outside the vacuum vessel. The biological fluid collection device of claim 1, wherein the gas composition within the vacuum vessel comprises oxygen, carbon dioxide, and nitrogen. The biological fluid collection device of claim 3, wherein the oxygen in the gas composition located within the evacuated vessel has a partial pressure greater than the partial pressure of oxygen in the atmosphere outside the evacuated vessel. The biological fluid collection device of claim 3, wherein the carbon dioxide in the gas composition located within the evacuated vessel has a partial pressure substantially equal to the partial pressure of carbon dioxide in the atmosphere outside the evacuated vessel. The biological fluid collection device of claim 3, wherein the gas composition comprises approximately 75% oxygen, approximately 23% nitrogen, and approximately 0.1% carbon dioxide. The biological fluid collection device of claim 6, wherein the evacuated vessel has a total pressure of 300 mmHg and the oxygen in the gas composition within the evacuated vessel has a partial pressure of approximately 160 mmHg. The biological fluid collection device of claim 7, wherein the evacuated vessel has a total pressure of 300 mmHg and the carbon dioxide in the gas composition within the evacuated vessel has a partial pressure of approximately 0.3 mmHg. The biological fluid collection device of claim 8, wherein the oxygen in the gas composition of ambient air has a partial pressure of approximately 160 mmHg and the carbon dioxide in the gas composition of ambient air has a partial pressure of approximately 0.3 mmHg. The biological fluid collection device of claim 1, wherein the collection module includes a first end having a sample introduction opening, a second end having a sample dispensing opening, a passage extending between the sample introduction opening and the sample dispensing opening, and a porous plug covering the second end of the housing. The biological fluid collection device of claim 10, wherein a closure is configured to close the sample introduction opening in the collection module, the closure comprising a pierceable self-sealing stopper. The biological fluid collection device of claim 10, wherein the porous plug is adapted to allow air to pass through the passage of the collection module while preventing the biological fluid sample from passing through. The biological fluid collection device of claim 1, wherein when the vacuum container is one of a 1 mL 13x75 tube, a 2 mL 13x75 tube, a 2.5 mL 13x75 tube, a 3.5 mL 13x75 tube, and a 4 mL 13x75 tube, the vacuum container has a shelf life of at least 10 months, 24 months, 24 months, 12 months, and 21 months, respectively. The biological fluid collection device of claim 1, wherein the gas composition in the vacuum vessel further comprises argon. The biological fluid collection device of claim 1, wherein the gas composition within the vacuum vessel comprises oxygen, nitrogen, and a third gas, such as argon, that has a permeability similar to that of nitrogen. The biological fluid collection device of claim 15, wherein the oxygen in the gas composition located within the evacuated vessel has a partial pressure equal to the partial pressure of oxygen in the atmosphere outside the evacuated vessel, and the argon in the gas composition located within the evacuated vessel has a partial pressure greater than the partial pressure of argon in the atmosphere outside the evacuated vessel. The biological fluid collection device of claim 1, wherein the vacuum container is a partial suction tube. The biological fluid collection device of claim 3, wherein the oxygen in the gas composition located within the evacuated vessel has a partial pressure that is lower than the partial pressure of oxygen in the atmosphere outside the evacuated vessel. 1. A biological fluid collection device comprising:
a collection module for receiving the biological fluid sample;
a vacuum vessel containing the collection module therein;
a closure for enclosing an open end of the vacuum vessel, the vacuum vessel containing a gas composition having an enriched oxygen content with a partial pressure substantially greater than the partial pressure of oxygen in an atmosphere of 760 mm Hg at atmospheric pressure outside an interior cavity of the vacuum vessel;
A biological fluid collection device comprising: The biological fluid collection device of claim 19, wherein the evacuated vessel has a partial pressure of approximately 300 mmHg, and the partial pressure of oxygen within the evacuated vessel is approximately 160 mmHg. The biological fluid collection device of claim 20, wherein the gas composition comprises carbon dioxide and nitrogen, the partial pressure of carbon dioxide within the evacuated vessel is approximately 0.3 mmHg, and the partial pressure of nitrogen within the evacuated vessel is approximately 140 mmHg. The biological fluid collection device of claim 19, wherein the evacuated vessel has a partial pressure of approximately 300 mmHg, and the partial pressure of oxygen within the evacuated vessel exceeds 160 mmHg. 20. The biological fluid collection device of claim 19, wherein the gas composition comprises approximately 75% oxygen. The biological fluid collection device of claim 23, wherein the gas composition further comprises approximately 23% nitrogen and approximately 0.1% carbon dioxide. 1. A method for manufacturing an atmospherically balanced fluid collection device, comprising:
providing a container having an open end and a closed end, said container defining a chamber;
drawing a vacuum within the vessel to remove at least some gas from within the chamber;
filling the chamber with a gas composition that is greater than the gas composition of the atmosphere outside the vacuum vessel, the filling of the chamber occurring until a predetermined vacuum pressure is reached within the vessel;
drawing a further vacuum within the vessel to remove at least some of the gas from within the chamber;
filling the chamber with a further gas composition in a proportion greater than the gas composition of the atmosphere outside the vacuum vessel, the filling of the chamber occurring until the predetermined vacuum pressure within the vessel is reached;
and closing the open end of the container. 26. The method of claim 25, wherein the predetermined vacuum pressure within the container is 300 mmHg and the gas composition comprises approximately 75% oxygen having a partial pressure of approximately 160 mmHg. 26. The method of claim 25, further comprising disposing a fluid collection module within the container, the fluid collection module including a first end having a sample introduction opening, a second end having a sample dispensing opening, a passage extending between the sample introduction opening and the sample dispensing opening, and a porous plug covering the second end of the housing, the porous plug adapted to allow air to pass from the passage of the collection module while preventing the biological liquid sample from passing therethrough. The method of claim 25, wherein when the vacuum container is one of a 1 mL 13x75 tube, a 2 mL 13x75 tube, a 2.5 mL 13x75 tube, a 3.5 mL 13x75 tube, and a 4 mL 13x75 tube, the vacuum container has a shelf life of at least 10 months, 24 months, 24 months, 12 months, and 21 months, respectively. 1. A biological fluid collection device assembly comprising:
an evacuated tube for receiving a biological fluid sample;
barrier packaging, the barrier packaging containing the vacuum tube therein;
Equipped with
A biological fluid collection device assembly, wherein the barrier packaging contains a gas composition having a selected partial pressure of a target gas that is substantially greater than the partial pressure of the target gas in the atmosphere external to the barrier packaging. The biological fluid collection device assembly of claim 29, wherein the evacuated tube also contains a gas composition having a selected partial pressure of a target gas that is substantially greater than the partial pressure of the target gas in the atmosphere outside the barrier packaging. The biological fluid collection device assembly of claim 29, wherein the vacuum tube also contains a gas composition having a selected partial pressure of a target gas that is substantially less than the partial pressure of the target gas in the atmosphere outside the barrier packaging. The biological fluid collection device assembly of claim 29, wherein the evacuated tube also contains a gas composition having a selected partial pressure of a target gas substantially equal to the partial pressure of the target gas in the atmosphere outside the barrier packaging.