Gas backfill of vacuum blood collection tubes and packages to improve blood gas and shelf life performance

Abstract

A biological liquid collection device comprises: a collection module for receiving a biological liquid sample; the vacuumized container is provided with an open end and a closed end, and the vacuumized container contains the acquisition module therein; and a closure for closing the open end of the evacuated vessel, where the evacuated vessel includes a gas composition having a selected partial pressure of a target gas substantially greater than a target gas partial pressure of the atmosphere outside the interior cavity of the evacuated vessel.

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 63 / 413,013, filed on October 4, 2022, entitled "Gas Backfill of Vacutainer Tubes to Decrease Rate of Draw Volume Loss and Improve Shelf Life Performance", and U.S. Provisional Patent Application No. 63 / 510,476, filed on June 27, 2023, entitled "Gas Backfill of Vacutainer Tubes to Decrease Rate of Draw Volume Loss and Improve Shelf Life Performance", the entire contents of both of which are incorporated herein by reference. Background of the Invention

[0004] Field of the Invention

[0005] The present disclosure generally relates to a collection device for collecting a biological fluid sample and a method of manufacturing a balanced fluid collection device for collecting a biological fluid sample, and more particularly, to a blood sample collection device integrated with a vacuum blood collection tube for use in conjunction with blood gas analysis, and even more particularly, to a blood sample collection device designed to draw blood using "atmospheric equilibrium vacuum" to ensure that the blood is exposed to the sample partial pressure of oxygen and partial pressure of carbon dioxide levels of the sample atmosphere as found in a standard arterial blood gas (ABG) syringe, thereby achieving blood gas sample stability during collection.

[0006] Background of the Related Art

[0007] Platforms based on 1 mL to 3 mL syringes are generally accepted for blood gas laboratory testing. Based on the filling method employed, current blood gas devices are divided into two categories: (1) plunger-user assisted and (2) vented-blood pressure assisted. These syringe configurations typically require the user to follow protocols involving air purging, capping / sealing, and anticoagulant mixing steps to ensure that the quality of the blood sample is not compromised by the analysis in the diagnostic instrument. In addition to the complex multi-step workflow, conventional blood collection syringes significantly increase the safety risk of blood exposure during air expulsion and capping.

[0008] U.S. Patent 9,649,061 discloses a state-of-the-art device for blood collection that is configured to collect a small volume of blood sample and dispense a portion of the sample into a device intended or designed to analyze the sample (e.g., a point-of-care testing device or a near-patient testing device), the entire content of which is incorporated herein by reference. The blood sample collection device disclosed in that patent is integrated within a evacuated container, such as a BD blood collection tube owned by the assignee of the present invention, Becton, Dickinson, and Company. The use of this device allows for blood sample collection and dispensing for point-of-care applications, which includes conventional automated blood draw and includes novel controlled sample dispensing capabilities while minimizing exposure risks. When blood fills a conventional tube, the gas components (O2, N2, CO2) of hemoglobin that are dissolved and bound to the blood are exposed to the gas mixture within the tube, where each respective gas mixture component has its own partial pressure. The total pressure within the tube is the sum of the partial pressures of each individual gas (P 管 = PO2 + PCO2 + PN2), as demonstrated by Dalton's law of partial pressure. This fundamental property of gases dictates that the vacuum pressure of a conventional tube is 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, the partial pressure of oxygen in normal atmospheric gas composition is 160 mmHg at atmospheric pressure and 760 mmHg at sea level. Compared to syringes that may cause blood gas biasing as a result, this standard vacuum process creates an environment within a conventional tube that exposes the blood to a greater partial pressure gradient (ΔP) for both oxygen and carbon dioxide. As a result, gas can come out of solution (blood), which is determined by the equilibrium between the undissolved gas in the evacuated tube and the gas dissolved in the blood.

[0009] Although air is a mixture of approximately 80% nitrogen and approximately 20% oxygen, these two gases will independently permeate into the evacuated tube. The permeation rate of oxygen is approximately ten times that of nitrogen and is the cause of most of the tube draw volume loss during the shelf-life of the evacuated container.

[0010] There is a need in the art for an atmospheric equilibrium vacuum tube architecture that reduces blood gas bias and achieves stable blood gas levels during blood vacuum draw using conventional blood collection devices. There is also a need in the art for an atmospheric equilibrium vacuum tube architecture that provides an excellent vacuum shelf-life by reducing the gas permeability through plastic tubing. There is also a need in the art for an atmospheric equilibrium conventional sample collection container (e.g., evacuated blood collection tube) that provides an excellent vacuum shelf-life by reducing the gas permeability through plastic materials. Summary of the Invention

[0011] A key advantage of the disclosed arterial blood gas (ABG) atmospheric equilibrium vacuum tube is the reduction in blood collection workflow steps and blood exposure associated with conventional (ABG) syringe blood collection kits. The disclosed device provides a simplified user workflow as it uses a vacuum draw method to uniformly mix an anticoagulant in a fixed maximum air-free blood sample. The stopper element is in a fixed position within the end cap. The stopper element is air-permeable but liquid-impermeable to allow purging of air during filling of the device and then to seal upon blood contact. This atmospheric equilibrium vacuum design of the disclosure allows removal of the dispenser component from the evacuated tube, which allows controlled sample dispensing into a diagnostic instrument cassette or aspiration via a probe in a blood gas diagnostic port.

[0012] According to one aspect, a biological fluid collection device may include: a collection module for receiving a biological fluid sample; an evacuated container having an open end and a closed end, the evacuated container containing the collection module therein; and a closure for closing the open end of the evacuated container, wherein the evacuated container includes a gas composition having a selected partial pressure of a target gas, the selected partial pressure being substantially greater than the partial pressure of the target gas in the atmosphere outside the inner cavity of the evacuated container.

[0013] According to another aspect, the selected partial pressure of the target gas of the gas component in the evacuated container can be greater than the partial pressure of the target gas in the atmosphere outside the evacuated container. The gas component in the evacuated container can include oxygen, carbon dioxide, and nitrogen. The partial pressure of oxygen in the gas component located in the evacuated container can be greater than the partial pressure of atmospheric oxygen outside the evacuated container. The partial pressure of carbon dioxide in the gas component located in the evacuated container can be substantially equal to the partial pressure of atmospheric carbon dioxide outside the evacuated container. The gas component can include approximately 75% oxygen, approximately 23% nitrogen, and approximately 0.1% carbon dioxide. The total pressure of the evacuated container can be 300 mmHg, and among them, the partial pressure of oxygen in the gas component in the evacuated container is approximately 160 mmHg. The total pressure of the evacuated container can be 300 mmHg, and among them, the partial pressure of carbon dioxide in the gas component in the evacuated container is approximately 0.3 mmHg. The partial pressure of oxygen in the gas component of the external air can be approximately 160 mmHg, and the partial pressure of carbon dioxide in the gas component of the external air can be approximately 0.3 mmHg. The collection module can include a first end having a sample introduction opening, a second end having a sample dispensing opening, a channel extending between the sample introduction opening and the sample dispensing opening, and a porous plug covering the second end of the housing. The closure can be configured to close the sample introduction opening in the collection module, and among them, the closure includes a pierceable self-sealing stopper. The porous plug can be adapted to allow air to pass through the channel of the collection module while preventing the biological liquid sample from passing through the channel of the collection module. When the evacuated container is one of a 1 mL 13×75 tube, a 2 mL 13×75 mL tube, a 2.5 mL 13×75 tube, a 3.5 mL 13×75 tube, and a 4 mL 13×75 tube, the shelf life of the evacuated container can be at least 10 months, 24 months, 24 months, 12 months, and 21 months respectively. The gas component in the evacuated container can further include argon. The gas component in the evacuated container can include oxygen, nitrogen, and a third gas having a permeability similar to that of nitrogen, such as argon. The partial pressure of oxygen in the gas component located in the evacuated container can be equal to the partial pressure of atmospheric oxygen outside the evacuated container, and the partial pressure of argon in the gas component located in the evacuated container can be greater than the partial pressure of atmospheric argon outside the evacuated container. The evacuated container can be a partial draw tube.

[0014] According to one aspect, a biological fluid collection device may include: a collection module configured to receive a biological fluid sample; a vacuum container that contains the collection module therein; and a closure configured to seal an open end of the vacuum container, wherein the vacuum container includes a gas composition having an oxygen-rich inclusion, and a partial pressure of the oxygen-rich inclusion is substantially greater than a partial pressure of oxygen in air at an atmospheric pressure of 760 mmHg outside the inner cavity of the vacuum container.

[0015] According to one aspect, the partial pressure of the vacuum container may be approximately 300 mmHg, and wherein the partial pressure of oxygen in the vacuum container is approximately 160 mmHg. The gas composition may include carbon dioxide and nitrogen, and wherein the partial pressure of carbon dioxide in the vacuum container may be approximately 0.3 mmHg, and the partial pressure of nitrogen in the vacuum container may be approximately 140 mmHg. The partial pressure of the vacuum container may be approximately 300 mmHg, and wherein the partial pressure of oxygen in the vacuum container is 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.

[0016] According to one aspect, a method of manufacturing an atmospheric equilibrium fluid collection device may include: providing a container having an open end and a closed end, the container defining a chamber; evacuating the container to remove at least some gas from the chamber; back purging the chamber with a gas composition having a proportion greater than a proportion of a gas composition outside the evacuated container, wherein the chamber is back purged until a predetermined vacuum pressure is reached within the container; further evacuating the container to remove at least some gas from the chamber; back purging the chamber with another gas composition having a proportion greater than a proportion of a gas composition outside the evacuated container, wherein the chamber is back purged until the predetermined vacuum pressure is reached within the container; and sealing the open end of the container.

[0017] 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 the oxygen being approximately 160 mmHg. The method can further include placing a fluid collection module within the container, wherein the fluid collection module includes a first end having a sample introduction opening, a second end having a sample dispensing opening, a channel 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 being adapted to allow air to pass through the channel of the collection module while preventing a biological liquid sample from passing through the channel of the collection module. When the evacuated container is one of a 1 mL 13×75 tube, a 2 mL 13×75 mL tube, a 2.5 mL 13×75 tube, a 3.5 mL 13×75 tube, and a 4 mL 13×75 tube, the shelf life of the evacuated container can be at least 10 months, 24 months, 24 months, 12 months, and 21 months, respectively.

[0018] According to one aspect, a biological liquid collection device assembly can include: an evacuated tube for receiving a biological liquid sample; and a barrier packaging containing the evacuated tube therein, wherein the barrier packaging includes a gas composition having a selected partial pressure of a target gas, the selected partial pressure being substantially greater than the partial pressure of the target gas in the atmosphere outside the barrier packaging. The evacuated tube can also include a gas composition having a selected partial pressure of a target gas, the selected partial pressure being substantially greater than the partial pressure of the target gas in the atmosphere outside the barrier packaging.

[0019] The present invention is also disclosed in the following clauses:

[0020] Clause 1: A biological liquid collection device, comprising: a collection module for receiving a biological liquid sample; an evacuated container having an open end and a closed end, the evacuated container containing the collection module therein; and a closure for closing the open end of the evacuated container, wherein the evacuated container includes a gas composition having a selected partial pressure of a target gas, the selected partial pressure being substantially greater than the partial pressure of the target gas in the atmosphere outside the inner cavity of the evacuated container.

[0021] Clause 2: The biological liquid collection device according to Clause 1, wherein the selected partial pressure of the target gas of the gas composition of the evacuated container is greater than the partial pressure of the target gas in the atmosphere outside the evacuated container.

[0022] Clause 3: The biological liquid collection device according to Clause 1 or Clause 2, wherein the gas composition within the evacuated container includes oxygen, carbon dioxide, and nitrogen.

[0023] Article 4: The biological fluid collection device according to Article 3, wherein the partial pressure of oxygen in the gas component located within the evacuated container is greater than the partial pressure of atmospheric oxygen outside the evacuated container.

[0024] Article 5: The biological fluid collection device according to Article 3 or 4, wherein the partial pressure of carbon dioxide in the gas component located within the evacuated container is substantially equal to the partial pressure of atmospheric carbon dioxide outside the evacuated container.

[0025] Article 6: The biological fluid collection device according to any one of Articles 3 to 5, wherein the gas component comprises approximately 75% oxygen, approximately 23% nitrogen, and approximately 0.1% carbon dioxide.

[0026] Article 7: The biological fluid collection device according to Article 6, wherein the total pressure of the evacuated container is 300 mmHg, and wherein the partial pressure of oxygen in the gas component within the evacuated container is approximately 160 mmHg.

[0027] Article 8: The biological fluid collection device according to Article 7, wherein the total pressure of the evacuated container is 300 mmHg, and wherein the partial pressure of carbon dioxide in the gas component within the evacuated container is approximately 0.3 mmHg.

[0028] Article 9: The biological fluid collection device according to Article 8, wherein the partial pressure of oxygen in the gas component of the external air is approximately 160 mmHg, and the partial pressure of carbon dioxide in the gas component of the external air is approximately 0.3 mmHg.

[0029] Article 10: The biological fluid collection device according to any one of Articles 1 to 9, wherein the collection module comprises a first end having a sample introduction opening, a second end having a sample dispensing opening, a channel extending between the sample introduction opening and the sample dispensing opening, and a porous plug covering the second end of the housing.

[0030] Article 11: The biological fluid collection device according to Article 10, wherein the closure is configured to close the sample introduction opening in the collection module, and wherein the closure comprises a pierceable self-sealing stopper.

[0031] Article 12: The biological fluid collection device according to Article 10 or 11, wherein the porous plug is adapted to allow air to pass through the channel of the collection module while preventing the biological fluid sample from passing through the channel of the collection module.

[0032] Article 13: For the biological fluid collection device described in any one of Articles 1 to 12, when the evacuated container is one of a 13×75 tube of 1 mL, a 13×75 mL tube of 2 mL, a 13×75 tube of 2.5 mL, a 13×75 tube of 3.5 mL, and a 13×75 tube of 4 mL, the storage periods of the evacuated container are at least 10 months, 24 months, 24 months, 12 months, and 21 months respectively.

[0033] Article 14: For the biological fluid collection device described in any one of Articles 1 to 13, wherein the gas component in the evacuated container further includes argon.

[0034] Article 15: For the biological fluid collection device described in any one of Articles 1 to 14, wherein the gas component in the evacuated container includes oxygen, nitrogen, and a third gas with a permeability similar to that of nitrogen, and the third gas is, for example, argon.

[0035] Article 16: For the biological fluid collection device described in Article 15, wherein the partial pressure of oxygen in the gas component located in the evacuated container is equal to the partial pressure of atmospheric oxygen outside the evacuated container, and the partial pressure of argon in the gas component located in the evacuated container is greater than the partial pressure of atmospheric argon outside the evacuated container.

[0036] Article 17: For the biological fluid collection device described in Article 1, wherein the evacuated container is a partially evacuated tube.

[0037] Article 18: A biological fluid collection device, comprising: a collection module for receiving a biological fluid sample; an evacuated container containing the collection module therein; and a closure for closing the open end of the evacuated container, wherein the evacuated container includes a gas component having an oxygen-rich inclusion, and the partial pressure of the oxygen-rich inclusion is substantially greater than the partial pressure of oxygen in the air at an atmospheric pressure of 760 mmHg outside the inner cavity of the evacuated container.

[0038] Article 19: For the biological fluid collection device described in Article 18, wherein the partial pressure of the evacuated container is approximately 300 mmHg, and wherein the partial pressure of oxygen in the evacuated container is approximately 160 mmHg.

[0039] Article 20: For the biological fluid collection device described in Article 19, wherein the gas component includes carbon dioxide and nitrogen, and wherein the partial pressure of carbon dioxide in the evacuated container is approximately 0.3 mmHg, and the partial pressure of nitrogen in the evacuated container is approximately 140 mmHg.

[0040] Article 21: The biological fluid collection device according to any one of Articles 18 to 20, wherein the partial pressure of the evacuated container is approximately 300 mmHg, and wherein the partial pressure of oxygen in the evacuated container is greater than 160 mmHg.

[0041] Article 22: The biological fluid collection device according to any one of Articles 18 to 21, wherein the gas composition comprises approximately 75% oxygen.

[0042] Article 23: The biological fluid collection device according to Article 22, wherein the gas composition further comprises approximately 23% nitrogen and approximately 0.1% carbon dioxide.

[0043] Article 24: A method of manufacturing an atmospheric equilibrium fluid collection device, the method comprising: providing a container having an open end and a closed end, the container defining a chamber; evacuating the container to remove at least some gas from the chamber; backflushing the chamber with a gas composition having a proportion greater than the proportion of the gas composition of the atmosphere outside the evacuated container, wherein the chamber is backflushed until a predetermined vacuum pressure is reached within the container; further evacuating the container to remove at least some gas from the chamber; backflushing the chamber with another gas composition having a proportion greater than the proportion of the gas composition of the atmosphere outside the evacuated container, wherein the chamber is backflushed until the predetermined vacuum pressure is reached within the container; and closing the open end of the container.

[0044] Article 25: The method according to Article 24, wherein the predetermined vacuum pressure within the container is 300 mmHg, and the gas composition comprises approximately 75% oxygen, and the partial pressure of the oxygen is approximately 160 mmHg.

[0045] Article 26: The method according to Article 24 or 25, the method further comprising placing a fluid collection module within the container, wherein the fluid collection module comprises a first end having a sample introduction opening, a second end having a sample dispensing opening, a channel 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 channel of the collection module while preventing a biological fluid sample from passing through the channel of the collection module.

[0046] Article 27: The method according to any one of Articles 24 to 26, wherein when the evacuated container is one of a 1 mL 13×75 tube, a 2 mL 13×75 mL tube, a 2.5 mL 13×75 tube, a 3.5 mL 13×75 tube, and a 4 mL 13×75 tube, the shelf life of the evacuated container is at least 10 months, 24 months, 24 months, 12 months, and 21 months, respectively.

[0047] Article 28: A biological fluid collection device assembly, comprising: a vacuum tube for receiving a biological fluid sample; and a barrier package containing the vacuum tube therein, wherein the barrier package includes a gas component having a selected partial pressure of a target gas, the selected partial pressure being substantially greater than the partial pressure of the target gas in the atmosphere outside the barrier package.

[0048] Article 29: The biological fluid collection device assembly according to Article 28, wherein the vacuum tube also includes a gas component having a selected partial pressure of a target gas, the selected partial pressure being substantially greater than the partial pressure of the target gas in the atmosphere outside the barrier package. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] The above and other features, advantages, and ways of achieving these features and advantages of the present disclosure will become more apparent and the present disclosure itself will be better understood by reference to the following description of embodiments of the present disclosure in conjunction with the accompanying drawings, in which:

[0050] Figure 1 is a front perspective view of a biological fluid collection device having a collection module disposed within a housing according to one aspect of the present disclosure;

[0051] Figure 2 is according to one aspect of the present disclosure Figure 1 partial cross-sectional side view of the biological fluid collection device;

[0052] Figure 3A and Figure 3B is according to one aspect of the present disclosure Figure 1 and Figure 2 enlarged partial cross-sectional side view showing a porous plug closing a liquid collection chamber;

[0053] FIGS. 4A and 4B are schematic diagrams showing blood gas vacuum biasing using a standard vacuum process in a conventional tube;

[0054] Figure 5 is a schematic diagram of adjusting the pressure within a container according to one aspect of the present disclosure;

[0055] Figure 6 is a schematic diagram depicting the flow of oxygen with respect to a container of the present disclosure;

[0056] Figure 7 is a graph showing the relationship between tube pressure and time for an oxygen backfill non-gelling tube and a non-backfill tube according to the invention of the present disclosure;

[0057] Figure 8 is a graph showing the relationship between the tube pressure and time of an oxygen-backfilled gel tube and a non-backfilled tube according to the present disclosure;

[0058] Figure 9 is a schematic diagram depicting the flow of oxygen and argon with respect to a container of the present disclosure; and

[0059] Figure 10 is a schematic diagram of an evacuated tube with a barrier package according to a non-limiting embodiment or aspect of the present disclosure.

[0060] In all of the several views, corresponding reference numerals represent corresponding components. The examples presented 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. Detailed Description

[0061] The following description is provided to enable a person skilled in the art to make and use the described embodiments contemplated for implementing the invention. However, various modifications, equivalents, variations, and alternatives will be apparent to a person skilled in the art. Any and all such modifications, variations, equivalents, and alternatives are intended to fall within the spirit and scope of the invention.

[0062] In the following, for purposes of description, the terms "upper", "lower", "right", "left", "vertical", "horizontal", "top", "bottom", "lateral", "longitudinal" and their derivatives shall relate to the invention as oriented in the drawings. However, it should be understood that the invention may adopt alternative variations and step sequences, unless expressly stated to the contrary. It should also be understood that the specific devices and processes shown in the drawings and described in the following specification are merely exemplary embodiments of the invention. Accordingly, the specific dimensions and other physical characteristics related to the embodiments disclosed herein should not be considered restrictive.

[0063] Reference Figure 1 and Figure 2 , Figure 1 and Figure 2 show a biological liquid collection device according to an aspect of the present disclosure, the biological liquid collection device generally designated as 1, having a collection module 10 disposed within an outer housing or evacuated container 34. The collection module 10 is adapted to receive a biological liquid sample (e.g., a blood sample), and includes a housing 12, a closure 14, a mixing chamber 16, a holding chamber 18, a cap 26 (as shown in Figure 2 ), and an activation member 22.

[0064] In one embodiment, the housing 12 includes a first end 24, a second end 26, and a channel 28 extending between the first end and the second end, which provides fluid communication between the first end 24 and the second end 26 of the housing 12. The channel 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 arranged to be in fluid communication with the channel 28. The mixing chamber 16 and the holding chamber 18 are positioned such that a biological fluid sample (e.g., a blood sample) introduced into the sample introduction opening 30 of the channel 28 will first pass through the mixing chamber 16, then enter the holding chamber 18, and then reach the sample dispensing opening 32 of the channel 28. In this way, the blood sample can be mixed with an anticoagulant or other additive provided in the mixing chamber 16 before the stable sample is received and stored within the holding chamber 18.

[0065] When the blood sample flows through the channel 28, the mixing chamber 16 allows the blood sample to be passively mixed with an anticoagulant or other additive (e.g., a blood stabilizer). The internal portion of the mixing chamber 16 can have any suitable structure or form as long as it can mix the blood sample with an anticoagulant or other additive when the blood sample passes through the channel 28. The mixing chamber 16 can include a dry anticoagulant deposited on or within the mixing chamber 16, such as heparin or EDTA. The mixing chamber 16 can, for example, include an open-cell foam that contains a dry anticoagulant dispersed within the pores of the open-cell foam to facilitate flow-through mixing and the effectiveness of anticoagulant absorption.

[0066] The blood sample can be directed to the holding chamber 18 after passing through the mixing chamber 16. The holding chamber 18 can have any suitable shape and size to store a sufficient amount (e.g., 500 μl or less) of blood for the desired test. In the embodiment shown in Figure 1 and Figure 2 , the holding chamber 18 is defined by a combination of a portion of the housing 12 and an elastic sleeve 40 fixed around the outside of the housing 12. The elastic sleeve 40 can be made of any flexible, deformable material that can provide a fluid-impermeable seal with the housing 12, including but not limited to natural rubber or synthetic rubber, and other suitable elastomeric materials.

[0067] Continuing to refer to Figure 1 and Figure 2 , and further referring to Figure 3A and Figure 3B, A porous or venting plug 44 is disposed at the second end 26 of the housing 12 and closes the sample dispensing opening 32 of the channel 28. The venting plug 44 is configured to allow air to pass through the venting plug and out of the collection module 10 while preventing the blood sample from passing through the venting plug, and may include a hydrophobic filter. The venting plug 44 has a selective air passage resistance, which can be used to finely control the filling rate of the channel 28. By changing the porosity of the plug, the rate of air flowing out of the plug 44 can be controlled, thereby controlling the rate of blood sample flowing into the collection module 10. If the flow rate of the blood sample into the collection module 10 is too fast, hemolysis may occur. If the flow rate of the blood sample into the collection module 10 is too slow, the sample collection time may be too long.

[0068] A closure 14 engages the first end 24 of the housing 12 to seal the channel 28. The closure 14 allows a blood sample to be introduced into the channel 28 of the housing 12 and may include a pierceable self-sealing stopper 36 having an outer shield 38, such as a Hemogard available commercially from Becton Dickinson and Company TM cap. The closure 14 is also fixed to the outer housing or evacuated container 34. It will be appreciated that the evacuated container 34 can be any well-known blood collection tube containing a vacuum, such as those available commercially from Becton Dickinson and Company blood collection tubes.

[0069] Now referring to FIGS. 4A and 4B, FIGS. 4A and 4B schematically illustrate the blood gas vacuum biasing using a standard vacuum process in a conventional or prior art evacuated container 200 (e.g., container). When the blood fills the conventional evacuated container 200, the gaseous components (O2, N2, CO2) of the hemoglobin dissolved and bound to the blood are exposed to the gas mixture inside the tube, where each respective gas mixture component has its own partial pressure. The total pressure (P) inside the container 200 is the sum of the partial pressures (P) of each individual gas (P 管=(PO2 + PCO2 + PN2), as demonstrated by Dalton's law of partial pressures. This fundamental property of gases determines the use of the atmospheric gas composition (21% O2, 0.04% CO2, and 78% N2) with a conventional tube vacuum pressure of 300 mmHg, which will produce partial pressures of 63 mmHg, 12 mmHg, 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, the partial pressure of oxygen in normal atmospheric gas composition is 160 mmHg at atmospheric pressure and 760 mmHg below sea level. As indicated by graph 160 and shown in FIG. 4B, this standard vacuum process creates an environment that exposes blood in a conventional evacuated container 200 to a greater partial pressure gradient (ΔP) for both oxygen and carbon dioxide compared to a syringe that may cause 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 proportional to the partial pressure of the gas in the tube. Therefore, the gas in the conventional container 200 as described above and shown in FIG. 4A will come out of solution (blood), which is determined by the equilibrium between the undissolved gas in the evacuated tube and the gas dissolved in the blood.

[0070] Now referring to Figure 5 , Figure 5 schematically shows a liquid evacuated container 34 according to the present disclosure and a method of preparing an evacuated tube 34, wherein the evacuated container 34 including the collection module 10 includes a gas composition having a pressure greater than the gas composition of the atmosphere outside the evacuated container 34. In one non-limiting embodiment or aspect of the present disclosure, the term "outside" may be understood as the region or location outside the inner cavity of the evacuated container 34. In another example, the pressure of the gas composition is equal to or matches the gas composition of the atmosphere outside the evacuated container 34 (about 160 mmHg). The proposed device adjusts the basic partial pressure composition of oxygen O2 and carbon dioxide CO2 in the vacuum chamber with respect to the atmospheric conditions to provide a blood gas sample equivalent to a standard arterial blood gas (ABG) syringe (current standard of care). In one non-limiting embodiment or aspect of the present disclosure, O2 may be considered the target gas because the partial pressure of O2 is adjusted with respect to the partial pressure of O2 in the atmosphere outside the inner cavity of the evacuated container 34. In other embodiments of the present disclosure, the target gas may be different from O2, or in addition to O 2There are other gases as well, such as argon gas discussed below. In one embodiment or aspect, the target gas is understood to be the specific gas in the gas composition that is to be regulated to reduce or eliminate the same target gas that leaks into the evacuated container 34 from outside the evacuated container 34. This is accomplished by developing a vacuum assembly procedure in which a high vacuum is first drawn and then oxygen O2 and carbon dioxide CO2 are backfilled into the chamber until the desired final vacuum level and the partial pressures of O2 and CO2 are reached.

[0071] Referring Figure 5 and Figure 6 , the presently disclosed devices and methods enable a blood sample to be collected into a vacuum chamber or evacuated container 34 in which the blood is exposed to a pressure that is higher than the partial pressure of oxygen (PO2) level and the partial pressure of carbon dioxide (PCO2) level found in a standard arterial blood gas syringe, which exposes the blood sample to normal atmospheric air and its corresponding PO2 level and PCO2 level, as shown in the graph of FIG. 4B. Continuing to refer Figure 5 , the method of the present disclosure for obtaining the pressure-regulated container 34 is implemented starting with a container at an atmospheric pressure of 760 mmHg that contains a composition of approximately 21% oxygen O2 and 79% nitrogen N2, having 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 drawn from within the tube to remove most of the gas from within the chamber 135 such that the total pressure of the tube is approximately 20 mmHg and the composition within the tube is approximately 21% oxygen O2 and approximately 79% nitrogen N2, with the partial pressure of O2, PO2, being approximately 37 mmHg and the partial pressure of N2, PN2, being approximately 140 mmHg. In a subsequent step, another high vacuum is drawn from within the tube to again remove most of the gas from the chamber 135. In a final step, the tube is backflushed with a deliberately proportioned gas composition of O2, N2, and CO2 until the desired vacuum level of approximately 300 mmHg (the desired vacuum level being greater than the atmospheric partial pressures of O2 and CO2) is reached, thereby forming the pressure-regulated evacuated tube 34 of the present disclosure, as Figure 5As shown, the composition of the tube is approximately 30% to 100% oxygen and up to 70% nitrogen, and the partial pressure of oxygen PO2 is approximately 160 mmHg, the partial pressure of nitrogen PN2 is approximately 140 mmHg, and the partial pressure of carbon dioxide PCO2 is approximately 0.3 mmHg. In one example of the present disclosure, the composition of the tube is approximately greater than 50% oxygen and less than 50% nitrogen. In another example of the present disclosure, the composition of the tube can be 100% oxygen. It can be understood that the tube can be backflushed so that the partial pressure of oxygen in the evacuated container is greater than 160 mmHg. In another example, an oxygen barrier can be provided in the body of the evacuated tube to assist in preventing gas permeation.

[0072] In another embodiment or aspect of the present disclosure, the PO2 (or another gas) in the tube can be intentionally higher than the PO2 (or another gas) in the atmosphere (e.g., supersaturated inside the tube). If desired, this can also be used to allow for an increase in the draw volume over time. This may be useful for tubes with a higher internal pressure / internal volume ratio (e.g., partial draw tubes). Using this embodiment further extends the product shelf life (beyond what has already been discussed). In a non-limiting embodiment or aspect of the present disclosure, a partial draw tube is understood to be a blood collection tube (in one example, approximately 3.0 mL or less) that is smaller than a standard draw tube (in one example, approximately 4.5 mL). In some cases, a partial draw tube is used when less blood is needed for testing and analysis. Partial draw tubes can be used for a variety of purposes, including donor screening and infectious disease testing, plasma determination, serum determination, hematology determination, immunohematology studies, and routine coagulation studies.

[0073] By increasing the oxygen content inside the tube, the oxygen gradient in the atmosphere is reduced to slow down or eliminate the penetration of oxygen into the tube. Since the oxygen content inside the tube increases, the atmospheric oxygen is greatly reduced or prevented from penetrating into the tube because the oxygen content inside the tube hinders this penetration.

[0074] The pressure-regulated partial pressure PO2 and PCO2 evacuated tube architecture enables stable blood gas levels to be achieved during blood vacuum draw using a conventional blood collection kit based on a typical evacuated container system.

[0075] The loss of vacuum shelf life in the prior art evacuated container 134 is due to gas permeation through the plastic tube, which is driven by the atmospheric and vacuum partial pressure gradients at the plastic barrier. Nitrogen contributes minimally to vacuum loss because the permeability coefficient of oxygen in polyethylene terephthalate (PET), a plastic mainly used in typical evacuated tubes, is an order of magnitude higher. The above-described pressure-regulated tube architecture provides excellent vacuum shelf life because the increased PO2 and PCO2 gradients inside the tube are less susceptible to gas permeation. This is due to the fact that, by design, the difference in PO2 and PCO2 pressures inside and outside the prior art container 134 increases. For example, when the total pressure of the atmospheric air outside the evacuated container is 760 mmHg, the partial pressure of oxygen in the gas composition of the outside air is approximately 160 mmHg, and the partial pressure of carbon dioxide in the gas composition of the outside air is approximately 0.3 mmHg. In the pressure-regulated evacuated tube 34 of the present disclosure, the partial pressure of oxygen in the gas composition inside the tube is also approximately 160 mmHg, and the partial pressure of carbon dioxide in the gas composition inside the tube is approximately 0.3 mmHg, but the percentage of oxygen in the composition inside the tube has increased. Since the percentage of oxygen in the composition inside the tube has increased, there is no pressure exchange due to O2 and CO2 and the resulting vacuum loss. The difference in the partial pressure of nitrogen N2 inside and outside the tube can be significant, i.e., the partial pressure of nitrogen PN2 inside the tube is approximately 140 mmHg, while the partial pressure of nitrogen PN2 in the atmosphere outside the tube is approximately 593 mmHg. Due to the permeation of nitrogen N2 into the tube, this partial pressure difference may cause a slight increase in the vacuum pressure inside the tube because the permeability of nitrogen is approximately one-tenth of the permeability of oxygen. It is noted herein that the pressure-regulated composition as described can be used to increase the shelf life of any conventional sample collection container. For example, this pressure regulation technique can be used to extend the shelf life of plastic blood collection containers, including any type of evacuated tube. Although this application is particularly applicable to arterial blood gas applications, the pressure regulation method described herein can be used for any evacuated plastic container. In addition, it is contemplated herein that the pressure regulation method determined herein can be suitably used for venous or other blood collection applications.

[0076] Figure 7 and Figure 8Shows different curves of the extraction volume varying with time due to the permeability of the tubes being tested. As shown in each curve, it has been found that, compared with the corresponding non-backfilled tubes, the O2-backfilled tubes take much longer to reach the threshold (e.g., the critical 20% threshold, where the tube can still extract within 20% of the volume it extracted when it was first evacuated, and this volume is referred to herein as the "shelf life"). Thus, this corresponds to a significant increase in the shelf life of the O2-backfilled tubes. Figure 6 Shows the verification results achieved using 13×75 mL non-gel tubes. Figure 7 Shows the verification results achieved using 13×75 mL gel tubes. Specifically, when the evacuated container is one of the 1 mL 13×75 tubes, 2 mL 13×75 mL tubes, 2.5 mL 13×75 tubes, 3.5 mL 13×75 tubes, and 4 mL 13×75 tubes, the shelf life of the evacuated containers is at least 10 months, 24 months, 24 months, 12 months, and 21 months respectively. These results indicate that this method of regulating the oxygen pressure increases the shelf life of the container by at least six months.

[0077] It can be understood that patients who are long-term exposed to high oxygen conditions may experience an oxygen partial pressure higher than normal, and this normal oxygen partial pressure may exceed 500 mmHg. Under these conditions, the gas is forced to dissolve in the plasma of the blood in an unbound state, while a small portion remains bound to hemoglobin. During blood gas analysis, since the oxygen in the plasma has a higher dissolved gas exchange rate combined with the partial pressure gradient when the blood is exposed to the atmosphere, these samples can exhibit a higher partial pressure level within a typical 15-minute turnaround time. The PO2 level and PCO2 level of hyperoxia (relative to atmospheric PO2 and PCO2) can be used for the vacuum tube structure to further improve the blood gas stability of oxygen therapy products, and such oxygen therapy products are not easily affected by partial pressure in extreme cases. This is feasible for ABG applications because the device design does not have a large enough surface area required for positive partial pressure blood gas levels. This would never be possible in a classic ABG syringe.

[0078] As Figure 8As shown, according to another embodiment or example of the present disclosure, the method of conditioning the components in the tube may further include introducing a third gas in addition to oxygen and nitrogen, thereby providing an advantage of a longer shelf life for the evacuated tube. By using this method, the pressure in the tube remains at an almost constant level for most of the shelf life of the tube. Using this method, the oxygen in the tube is matched to the oxygen content in the atmosphere to effectively eliminate oxygen permeation. A third gas is also introduced into the evacuated tube to counteract the permeation of nitrogen from the atmosphere into the tube. In one example of the present disclosure, the third gas may be argon. The permeation rate of argon is similar to that of nitrogen, and argon almost balances the permeation of nitrogen from the atmosphere into the tube. It should also be understood that there are cases where an intentional and purposeful combination of gases, i.e., a combination of more than three gases (e.g., one volatile gas / multiple volatile gases from one or more components within the evacuated space, an intentional chemical reaction releasing one gas / multiple gases, or others) can be used to achieve the same desired result (e.g., a gaseous substance at an intentional partial pressure with a permeation rate similar to that of nitrogen).

[0079] According to a non - limiting embodiment or aspect of the present disclosure, a method of controlling the vacuum composition of an evacuated blood collection container can be used to improve the device blood gas test performance. In this example, the evacuated tube can have a vacuum and a controlled and optimized oxygen pressure (pO2) to improve the device blood gas performance. A controlled vacuum composition can be achieved by evacuating the tube during the tube evacuation process and backfilling the tube with a gas mixture. 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 a pressure reading that can be used for the optimized device oxygen pressure to improve the blood gas test performance. Based on the type of device used, the optimized device oxygen pressure may be greater than or less than 70 mmHg as needed. In one example, the gas mixture backfilled into the tube can include at least one of the following: nitrogen, oxygen, or a combination of nitrogen and oxygen. Several advantages are achieved using this method. In particular, due to the headspace after blood sample collection, vacuum - based devices (e.g., vacuum blood collection tubes) are generally not recommended for blood gas testing. The headspace (or bubble) may cause erroneous results by exchanging oxygen with the blood sample. However, the optimized oxygen pressure inside the tube described above significantly improves the oxygen pressure (pO2) blood gas performance and extends the pO2 test range. However, as a new product, the controlled vacuum composition should be maintained within the shelf life of the product. In one example, The tube O2 pressure can be controlled to be below atmospheric pressure (pO2), but still higher than a conventional evacuated tube 。 With the blood sample Compared to the pO2 in this This control will Provide an equilibrium O2 pressure in the headspace of the device after sample collection reduce the O2 transfer from the headspace to the sample, or vice versa, during the turnaround time before testing the blood sample.

[0080] Reference Figure 10 According to non - limiting embodiments or aspects of the present disclosure, a barrier package 100 having a controlled oxygen pressure can be used to extend the product shelf life of a evacuated tube 102. In this example, the package 100 can have a controlled oxygen pressure that matches the controlled oxygen pressure of the evacuated tube 102. In some examples, the package 100 can be a foil bag, blister pack, foil film shelf pack, oxygen barrier shrink wrap, or any other package for storing the evacuated tube 102 or fluid container. By matching the controlled oxygen pressure of the package 100 with the controlled oxygen pressure of the evacuated tube 102, oxygen permeation of the evacuated tube 102 can be reduced and the product shelf life of the evacuated tube 102 can be extended. The oxygen pressure of the package 100 can be controlled by evacuating and / or backfilling the package with a gas (e.g., nitrogen or oxygen) during the packaging process to match the oxygen pressure of the evacuated tube 102. The matched oxygen pressure within the package 100 reduces oxygen permeation and extends the shelf life of the evacuated tube 102.

[0081] An evacuated blood collection tube typically has a much lower oxygen pressure (e.g., about 0 to 20 mmHg) than atmospheric pressure (about 160 mmHg). This pressure differential causes oxygen to permeate through the tube wall of the blood collection tube, which results in vacuum loss and limits the product shelf life of the blood collection tube. An oxygen barrier package 100 having a 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 in the package 100 can accommodate semi - barrier packaging materials.

[0082] In one non - limiting embodiment or aspect of the present disclosure, an evacuated tube can have a vacuum and a controlled and optimized oxygen pressure (pO2) to improve the device blood gas performance. A controlled vacuum composition can be achieved by evacuating the tube and backfilling the tube with a gas mixture during the tube evacuation process. In addition to the controlled vacuum composition, the barrier package of the evacuated tube can also 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 can be extended and the oxygen permeation of the evacuated tube can be reduced by using a combination of a controlled vacuum composition in the evacuated tube and a barrier package having a controlled oxygen pressure.

[0083] Although the present disclosure has been described as having an exemplary design, the present disclosure can be further modified within the spirit and scope of the present disclosure. Accordingly, this application is intended to cover any variations, uses, or adaptations of the present disclosure using its general principles. Additionally, this application is intended to cover such departures from the present disclosure as are known or customary in the art to which the present disclosure pertains and fall within the limits of the appended claims.

Claims

1. A biological liquid collection device, the biological liquid collection device comprising: A collection module for receiving a biological fluid sample; A vacuum container having an open end and a closed end, the vacuum container containing the collection module therein; and A closure for closing the open end of the vacuum container, wherein the vacuum container includes a gas composition having a selected partial pressure of a target gas, the selected partial pressure being substantially greater than the target gas partial pressure of the atmosphere outside the inner cavity of the vacuum container.

2. The biological liquid collection device according to claim 1, wherein, The selected partial pressure of the target gas of the gas composition of the vacuum container is greater than the target gas partial pressure of the atmosphere outside the vacuum container.

3. The biological liquid collection device according to claim 1, wherein, The gas composition within the vacuum container includes oxygen, carbon dioxide, and nitrogen.

4. The biological liquid collection device according to claim 3, wherein, The partial pressure of oxygen in the gas composition within the vacuum container is greater than the partial pressure of atmospheric oxygen outside the vacuum container.

5. The biological liquid collection device according to claim 3, wherein, The partial pressure of carbon dioxide in the gas composition within the vacuum container is substantially equal to the partial pressure of atmospheric carbon dioxide outside the vacuum container.

6. The biological liquid collection device according to claim 3, wherein, The gas composition includes approximately 75% oxygen, approximately 23% nitrogen, and approximately 0.1% carbon dioxide.

7. The biological liquid collection device according to claim 6, wherein, The total pressure of the vacuum container is 300 mmHg, and wherein the partial pressure of oxygen in the gas composition within the vacuum container is approximately 160 mmHg.

8. The biological liquid collection device according to claim 7, wherein, The total pressure of the vacuum container is 300 mmHg, and wherein the partial pressure of carbon dioxide in the gas composition within the vacuum container is approximately 0.3 mmHg.

9. The biological liquid collection device according to claim 8, wherein, The partial pressure of oxygen in the gas composition of the external air is approximately 160 mmHg, and the partial pressure of carbon dioxide in the gas composition of the external air is approximately 0.3 mmHg.

10. The biological liquid collection device according to claim 1, wherein, The collection module includes a first end having a sample introduction opening, a second end having a sample dispensing opening, a channel extending between the sample introduction opening and the sample dispensing opening, and a porous plug covering the second end of the housing.

11. The biological liquid collection device according to claim 10, wherein, The closure is configured to close the sample introduction opening in the collection module, and wherein the closure includes a pierceable self-sealing stopper.

12. The biological liquid collection device according to claim 10, wherein, The porous plug is adapted to allow air to pass through the channel of the collection module while preventing the biological fluid sample from passing through the channel of the collection module.

13. The biological liquid collection device according to claim 1, wherein, When the vacuum 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 shelf lives of the vacuum containers are at least 10 months, 24 months, 24 months, 12 months, and 21 months, respectively.

14. The biological liquid collection device according to claim 1, wherein, The gas composition in the vacuum container further includes argon.

15. The biological liquid collection device according to claim 1, wherein, The gas composition within the vacuum container includes oxygen, nitrogen, and a third gas having a permeability similar to that of nitrogen, such as argon.

16. The biological liquid collection device according to claim 15, wherein, The partial pressure of oxygen in the gas component within the evacuated container is equal to the partial pressure of atmospheric oxygen outside the evacuated container, and the partial pressure of argon in the gas component within the evacuated container is greater than the partial pressure of atmospheric argon outside the evacuated container.

17. The biological liquid collection device according to claim 1, wherein, The evacuated container is a partial extraction tube.

18. The biological liquid collection device according to claim 3, wherein, The partial pressure of oxygen in the gas component within the evacuated container is less than the partial pressure of atmospheric oxygen outside the evacuated container.

19. A biological liquid collection device, the biological liquid collection device comprising: A collection module, the collection module being adapted to receive a biological fluid sample; An evacuated container, the evacuated container containing the collection module therein; And A closure, the closure being adapted to seal the open end of the evacuated container, wherein the evacuated container includes a gas component having an oxygen-rich inclusion, and the partial pressure of the oxygen-rich inclusion is substantially greater than the partial pressure of oxygen in air at an atmospheric pressure of 760 mmHg outside the inner cavity of the evacuated container.

20. The biological liquid collection device according to claim 19, wherein, The partial pressure of the evacuated container is approximately 300 mmHg, and wherein the partial pressure of oxygen within the evacuated container is approximately 160 mmHg.

21. The biological liquid collection device according to claim 20, wherein, The gas component includes carbon dioxide and nitrogen, and wherein the partial pressure of carbon dioxide within the evacuated container is approximately 0.3 mmHg, and the partial pressure of nitrogen within the evacuated container is approximately 140 mmHg.

22. The biological liquid collection device according to claim 19, wherein, The partial pressure of the evacuated container is approximately 300 mmHg, and wherein the partial pressure of oxygen within the evacuated container is greater than 160 mmHg.

23. The biological liquid collection device according to claim 19, wherein, The gas component includes approximately 75% oxygen.

24. The biological liquid collection device according to claim 23, wherein, The gas component further includes approximately 23% nitrogen and approximately 0.1% carbon dioxide.

25. A method of manufacturing a fluid collection device for atmospheric balance, the method comprising: Provide a container having an open end and a closed end, the container defining a chamber; Evacuate the container to remove at least some gas from the chamber; Backflush the chamber with a gas component having a proportion greater than the proportion of the gas component in the atmosphere outside the evacuated container, wherein the chamber is backflushed until a predetermined vacuum pressure is reached within the container; Further evacuate the container to remove at least some gas from the chamber; Backflush the chamber with another gas component having a proportion greater than the proportion of the gas component in the atmosphere outside the evacuated container, wherein the chamber is backflushed until the predetermined vacuum pressure is reached within the container; and Seal the open end of the container.

26. The method according to claim 25, wherein, The predetermined vacuum pressure within the container is 300 mmHg, and the gas component includes approximately 75% oxygen, and the partial pressure of the oxygen is approximately 160 mmHg.

27. The method according to claim 25, the method further comprising placing a fluid collection module in the container, wherein, The fluid collection module includes a first end having a sample introduction opening, a second end having a sample dispensing opening, a channel 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 being adapted to allow air to pass through the channel of the collection module while preventing the biological fluid sample from passing through the channel of the collection module.

28. The method according to claim 25, wherein, 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 shelf lives of the evacuated containers are at least 10 months, 24 months, 24 months, 12 months, and 21 months, respectively.

29. A biological liquid collection device assembly, the biological liquid collection device assembly comprising: An evacuated tube for receiving a biological fluid sample; and a barrier package containing the evacuated tube therein, wherein the barrier package includes a gas composition having a selected partial pressure of a target gas, and the selected partial pressure is substantially greater than the partial pressure of the target gas in the atmosphere outside the barrier package.

30. The biological liquid collection device assembly according to claim 29, wherein, The evacuated tube also includes a gas composition, and the selected partial pressure of the target gas in the gas composition of the evacuated tube is substantially greater than the partial pressure of the target gas in the atmosphere outside the barrier package.

31. The biological liquid collection device assembly according to claim 29, wherein, The evacuated tube also includes a gas composition, and the selected partial pressure of the target gas in the gas composition of the evacuated tube is substantially lower than the partial pressure of the target gas in the atmosphere outside the barrier package.

32. The biological fluid collection device assembly according to claim 29, wherein, The evacuated tube also includes a gas composition, and the selected partial pressure of the target gas in the gas composition of the evacuated tube is substantially equal to the partial pressure of the target gas in the atmosphere outside the barrier package.

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