MXPA97006779A - Quick evaluation of thick-layer barrier coatings on large substrates, through transient action measures - Google Patents

Abstract

The present invention is directed to a method and apparatus for measuring the shelf life of vacuum-operated tubes, for the collection of blood samples, in which this method and apparatus perform in a rapid manner.

Description

QUICK EVALUATION OF THIN FILM BARRIER COATINGS ON THICK SUBSTRATES. FOR TRANSITIONAL RESPONSE MEASURES FIELD OF THE INVENTION This invention relates to the collection of blood and, more particularly, to tubes operated by a vacuum for the collection of blood samples and to a method and apparatus for measuring the shelf life of these tubes in a manner fast BACKGROUND OF THE INVENTION Blood samples are routinely taken in evacuated tubes, such as VACUTAINER® glass or plastic tubes (Becton Dickinson and Company). The end of a double-ended needle, next to a patient, is inserted into the vein of this patient. The patient's extreme end of the same needle then pierces the septum (septum) of the obturator of a blood collection tube. The elevated pressure of the patient's blood, in relation to the evacuated tube, forces this blood through the needle into the tube, until the pressure in the tube equals the pressure of the patient's vein. With the use of this technique, a plurality of samples can be taken in separate tubes with the use of a single needle puncture of the skin.

The exact volume of blood removed by a device varies, depending on the environmental atmospheric conditions and the storage conditions of the tube up to the time of use. Industrial standards specify a variation of ± 10% permissible from the extracted volume labeled, with standard atmospheric conditions. The volumetric accuracy is required for the precise control of the analytical chemical reactions carried out on the tube in freshly extracted samples. Shelf life regimens greater than two years are acceptable for evacuated blood collection tubes. To experimentally verify the shelf life of the blood collection tubes in less than two years, an "Accelerated Aging" process is conventionally used. By raising the temperature and storage pressure of the blood collection tubes, the aging process is accentuated. Based on the calibration experiments or a point-by-point comparison with the results of the control tube, an estimate of the shelf life of a tube stored at ambient temperature and pressure can be made based on the results of the measurement made under these accelerated aging conditions.

To make the measurement of the previous shelf life, the required number of tubes (30"test" tubes and 30 control tubes, for example), are evacuated and placed in a can under pressure (typically at 3 absolute atmospheres). ) inside an oven at high temperature (402C, for example). At specified points of time, 5-10 days apart, a representative sample of the "test" tubes and control tubes, usually 5 of each, are removed from the chamber. Each individual tube is weighed before and after filling with water. The mass of water introduced into each tube is recorded by the operator. The data from each time point are analyzed to make predictions of shelf life. This Accelerated Aging Method is a destructive test that typically consumes 60 tubes and requires 45 to 90 days to complete. Due to variations in reading at each time point, the longer the shelf life of a tube under test, the more time points are required to successfully complete this measurement to give a statistically significant result. Therefore, there is a need in the blood collection technique for a timely method, ie faster 45 to 90 days, to evaluate the shelf life of the evacuated blood collection tubes and, in particular, the shelf life of thermoplastic, coated, barrier blood collection tubes. SUMMARY OF THE INVENTION The present invention relates to a rapid method to estimate the shelf life of evacuated tubes to collect blood, and an apparatus to carry out this method. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 illustrates one embodiment of the apparatus of the present invention. Figure 2 illustrates the geometric distinction of the tube wall used for numerical molding purposes. Figure 3 is a graph showing the change in the flow of a coated tube, interior or exterior, over time. Figure 4 is a graph showing a comparison of the internal pressure rise with time in a control tube and an internally coated tube. Figure 5 is a graph showing the pressure differential over time for two different tubes tested in the apparatus of Figure 1. Figure 6 is a graph showing the pressure differential over time of a steel tube. stainless steel and the comparison of these results with the results of Figure 5, which uses a polyethylene terephthalate (PET) tube. Figure 7 is a graph showing the pressure differential over time for an unknown barrier tube in the apparatus of Figure 1. Figure 8 is a schematic representation of a tube used in an embodiment of the invention. DETAILED DESCRIPTION OF THE INVENTION The present invention is directed to a method for estimating the shelf life of evacuated blood collection tubes, and also refers to an apparatus by which the transport of gas within an evacuated blood collection tube it can be measured exactly, along with the physical interpretation of the results for the estimation of shelf life. The measurement can be performed with an apparatus which includes two measuring chambers, 10 and 15, which can be sealed, interconnected by a first valve and a differential pressure transducer. In one embodiment, the apparatus is indicated in Figure 1. After placing a sample tube 11 in the measurement chamber 10, the system is subjected to pressure at some value above ambient pressure. The rapid rise in external pressure causes permeation to start through the wall of the tube. The first valve 12 and a second valve 13 are sealed, resulting in two chambers at almost identical pressures, insulated from each other. From this point forward, any leakage of the gas within the test article from the measurement chamber 10 is detected as a change in the differential pressure relative to the reference chamber 15 and recorded. This reference chamber 15 remains empty and free of leaks. The rate of change of this pressure is directly proportional to the regime of gas transport in the test sample. The history of pressure is recorded by a computer and stored in a file for further processing. For thermoplastic blood collection tubes, the gas transport regime can be quantified in days, such as, for example, 10 to 12 days at 252C. A second aspect of this invention is the non-destructive nature of the test. The measurement in this apparatus requires raising the external pressure surrounding a tube. While this change does not mechanically damage the device, it can subsequently be subjected to a traditional process of accelerated aging and destructively tested for full volume. The traditional result can then be used as a system calibration method. In the conventional test, many tubes are required, usually 60 or more, as discussed above.

Each tube is finally filled with water to measure the extracted volume. In the proposed test, one tube is monitored for the entire test. When the test is completed, one can still use the tube for further testing or can perform, if desired, the destructive filling test. A third aspect of this invention is the ability to evaluate externally coated tubes with a barrier, at very early time points, for example in as little as 4 days. Thus, the non-barrier tubes take 10 days for evaluation, while the barrier tubes can take as little as 4 days. This is possible because the transient response of the barrier film is much shorter than the transient response of the thick polymer substrate (i.e., the tube wall itself). The tubes covered with external barrier are evaluated using the data of pressure vs. time recorded by the instrument, which adjusts to the curve with a slot or wedge. The first derivative of this curve is then projected against time. The value of the first derivative (slope of the pressure vs. time) converges to a value which will provide the evaluation. A fourth aspect of this invention is the ability to average the results in many tubes, enclosing these tubes in a single test chamber. By testing several tubes in a chamber, the average value can be determined quickly using a minimum of hardware (equipment). Such measurements will be useful for the process of control applications, where the average of many tubes is routinely measured. Rather than placing a tube in the sample chamber, an array of tubes is placed in the test chamber of this apparatus. The response of the instrument then presents the total transport in all the tubes that are tested. The average value can then be calculated for many tubes, using a single device, reducing the costs and labor associated with performing multiple measurements. A fifth aspect of this invention is the ability to isolate the barrier properties of the system tube from the enclosure. Testing a tube with a non-conductive seal, such as an aluminum seal with O-ring seals, only the contribution of the tube and barrier system will be measured. Yes, rather than sealing the mouth of an evacuated blood collection tube with an elastomeric obturator, a waterproof cap is placed in the mouth, as in Figure 8, then all the leakage can be attributed to the tube 20. This tube 20 has a ring seal 21 at 0 and an aluminum closure 22. This escape is not possible with a conventional measurement scheme that requires a cannula perforation in the closure to make the measurement.

Example l The following experiment demonstrates the physical principle on which all subsequent measurements will be based. A numerical representation of a blood collection tube, made of polyethylene terephthalate (PET) was created. This model includes a ring 0.5 mm high from the tube wall with a barrier coating on the outer surface. The barrier for this numerical model is a material that exhibits the transport characteristics of a thin film barrier coating of any type. The elements of 8 nodes were oriented highly towards the free surfaces to accommodate the high transient gradients expected. In the first experiment, a tube without barrier was subjected to an equilibrium stage to precondition the tube to environmental conditions. When molded, an initial definition of the state of all components in a system must be made. This is the equilibrium stage. Here, the tube was subjected to ambient temperature and pressure until it is in equilibrium with the surrounding gas (the oxygen for these simulations), which represents any tube removed from the shelf. Thus, oxygen diffusion was calculated until obtaining a stable state condition. In the next stage, the boundary condition on the inner surface was adjusted to that of an evacuated tube. The external boundary condition was adjusted to an oxygen pressure of three atmospheres. This change of stage in conditions was simulated through a stable state result. In numerical simulations, in regions of large response, such as on the inner and outer surface of the simulated tube, a very small mesh size was used. In regions of small response, a relatively large mesh size was used. This orientation of the mesh allows an exact solution over the whole computational domain without paying a great penalty for the refined mesh, as would be the case if a fine mesh was used on the whole model. An illustration of the oriented mesh is shown in Figure 2. For a second and third experiments, a barrier tube with approximately twice and approximately three times the oxygen barrier respectively, was subjected to exactly the same environmental conditions. The results of all three numerical experiments are depicted in Figure 3. The term "Cont" in Figure 3 refers to "Control" as in the control tube, a blood collection tube, PET coated without barrier. The different dashed lines for each of these tubes illustrates the mass transport on the inner surface of each tube, simulating the conventional method of measurement. From these results it was found that, before 50 hours, all three tubes responded identically to each other with the use of conventional test methods. In other words, considering the first 50 hours of data, one can not make any inference as to the quality of the barrier coating on the outside of the tube, or even if there is a barrier coating on the tube. Also, as the barrier improves, the distinction between two tubes becomes increasingly difficult, that is, the distinction between any two barrier tubes becomes smaller as the barrier in each tube increases. In Figure 3, the solid lines represent the results of stimulating the transport in the outer tube for each of the three tubes. Here, we can conclude that the non-barrier tubes again take hundreds of hours to converge into a stable state result. However, the results of the barrier tubes converge within 20% of the steady state values within hours, ie within 1 to 24 hours. These results do not include the effects of the shutter. Thus, the numerical simulation of transport during an experiment shows that most of the transient responses of a barrier tube take place an order of magnitude faster than the transient responses of a non-barrier tube, under the same conditions. Example II The following experiment demonstrates that the acceleration predicted in the measurements can be measured in an inner coated barrier tube, which uses a pressure transducer to record the pressure over a period of time. For this experiment, a PET tube, not a barrier tube, was evacuated and sealed with a conventional "red" seal. The septum of the closure was penetrated by a cannula equipped with an absolute pressure transducer to provide a continuous measurement of the internal pressure of the tube. The pressure was recorded manually as a function of time. The same test was also performed with an internally coated barrier tube, of unknown barrier quality. The results of both tests are presented in Figure 4. From this graphical display, it was concluded that the internal barrier tubes can be distinguished from the control tube within 20 hours of the start of the test, as predicted by the numerical simulation of Example I. Example III The following experiment demonstrates the use of the apparatus indicated in the present invention with a conventional blood collection tube, PET, without barrier, measured by the apparatus on the outside of the tube. The device was built to perform this measurement. A schematic representation of this apparatus is shown in Figure 1. Figure 1 illustrates the apparatus having an absolute pressure transducer, a differential pressure transducer, two valves, and a minimum of pipe fittings and connection. All connections were made with the use of ultra-low escape fittings VCR Caisson. The apparatus also has a test chamber, which conforms to the blood collection tube, made of PET, equipped with a shutter, also uses ultra-low escape fittings in all joints. The apparatus system was tested for leaks with a soap solution and subsequently for long duration pressure measurements, to ensure a leak-free system, before introducing a test specimen. To perform the test, a bleed collection tube, made of PET, and a conventional red, lubricated obturator, were equilibrated in an enclosure at 25SC, with 50% Relative Humidity, for 1 week. The tube was then evacuated to an absolute pressure of 50 Torr and the closure was inserted using standard procedures. The freshly evacuated tube was sealed in the test chamber of the apparatus. The pressure of the test chamber was then raised to 2250 Torr (approximately a pressure of 3 atmospheres) and valve one was sealed. Valve two was sealed immediately, isolating the test specimen (the tube) from the reference volume. The pressure difference between the two chambers was then monitored and the results recorded at regular intervals. These results were recorded at a rate of 20 samples per hour, with the use of a computer data acquisition system. Figure 5 graphically displays this data for two different tubes tested under identical conditions. These are two approximately identical tubes. Any discrepancy in the measurement showed a level of irreproducibility. In this case, after 10 hours, the curves were virtually identical, a very good sign. The results show that, in addition to the short initial transient period, the system behaves as predicted in the numerical experiment and can be repeated. Additionally, the results are consistent with those in the experiment of Example II. Example iv This example illustrates the contribution of the closure to the response of the previous experiment. This example also defines the lower limit of mass transfer for a perfect barrier tube using the conventional closure system. The experiment was performed exactly as the experiment of Example III, except that the test article is a stainless steel tube of identical dimension to the blood collection tube, PET, evacuated and sealed with the same closure style as before. The results were shown graphically in Figure 6. In addition, the results of the non-barrier PET tube of Example III are shown to compare these results with those of the steel tube. The results show that this experiment can be repeated and also that the results of the steel tube are significantly different from the PET control tube. The slope of the pressure curve vs. time represents the pipe leakage regime. By dividing the terminal slope of the two curves, an estimate was obtained that the shelf life of the steel tube will be 3.5 times greater than that of the PET tube. This estimate was made in 2 days, instead of the 45 days required by the conventional test methods. EXAMPLE V A barrier tube, with an unknown barrier, was tested in the same apparatus as that used in the above Examples III and IV. Identical experimental procedures were used. The results, shown in Figure 7, again indicate that the leak rate of the tube is below the values of a blood collection tube, made of PET. Secondly, while measuring the control tube took approximately 250 hours to converge on a final result, the barrier tube converges to a final result in 80 hours. This is in contrast to a minimum of 45 days for the evaluation of the leakage regime of a conventional tube, with the use of a conventional method.

Claims (9)

1. CLAIMS 1. A method to quickly estimate the shelf life of evacuated blood collection tubes, this method comprises: a) supplying an apparatus having a first and second chambers, which can be sealed; a first and second valves; a differential pressure transducer; and a gas supply; wherein the first chamber is interconnected with the second chamber by the first valve, and where the second valve is connected to the gas supply and where the first chamber can contain at least one tube, b) place at least one evacuated collection tube of blood in the first chamber that can be sealed; c) pressurizing the appliance to a value above ambient temperature; d) sealing the first valve and the second valve, so that the first and second chambers are at almost identical pressures, isolated from each other; e) detecting any leakage of the gas in the blood collection tube in the first chamber, as a change in the differential pressure relative to the second chamber; f) recording the rate of change of this pressure as directly proportional to the gas transport regime in the blood collection tube; and g) quantify gas transport in 2 to 10 days.
2. 2. The method of claim 1, wherein this method estimates the shelf life of the tubes in 2 to 10 days.
3. 3. The method of claim 1, wherein the first chamber can contain from one to ten tubes.
4. 4. The method of claim 1, wherein the tube placed in the first chamber is a barrier coated tube, and further in that the tube has a conventional lubricated obturator and a non-conductive seal.
5. 5. The method of claim 4, wherein the non-conductive seal is an aluminum seal with 0-ring seals.
6. 6. The method of claim 1, wherein the tube placed in the first chamber is a non-barrier coated tube, and further in that the tube has a conventional lubricated obturator and a non-conductive seal.
7. 7. The method of claim 1, wherein the results of the tubes are averaged, in order to quickly obtain an average value of shelf life.
8. 8. An apparatus for rapidly estimating the shelf life of evacuated blood collection tubes, this apparatus comprises: a first, resealable chamber, capable of containing at least one tube; • a second chamber, which can be sealed, which has a reference volume; a first valve, in which the first chamber, which can be sealed, is interconnected to the second chamber, which can be sealed, by the first valve; . a second valve, connected to a gas supply; Y • a differential pressure transducer.
9. 9. The apparatus of claim 8, wherein this apparatus contains from one to ten tubes.