MXPA99006331A - Method of pcr testing of pooled blood samples - Google Patents

Abstract

Systems, processes, and devices are provided which are useful for testing blood or plasma donations to detect those specific donations which are contaminated by a virus above a predetermined level. An apparatus and process is described which forms individual, separately sealed and connected sample containers from a flexible hollow tubing segment connected to a fluid donation container. The tubing segment is sealed at spaced-apart intervals along its length, with tubing segment portions in the intervals between the seals defining containers, each of which holds a portion of a plasma sample. The contents of the containers are formed into pools which are subsequentlytested for virus contamination by a high-sensitivity test such as PCR. The pools are tested in accordance with an algorithm by which a sample from each donation is mapped to each element of an N-dimensional matrix or grid. Each element of the matrix is identified by a matrix identifier, Xrcs, where rcs defines the dimensional index. An aliquot is taken from each sample, and subpools are formed, each subpool comprising aliquots of samples in which one dimensional index is fixed. All of the subpools are tested in one PCR test cycle. The dimensional indicia of each positive subpool is evaluated mathematically in accordance with a reduction by the method of minors, thereby unambiguously identifying a unique element in the grid, thereby unambiguously identifying a uniquely positive blood or plasma donation.

Description

METHOD OF REACTION IN CHAIN OF THE POLYMERASE TO ANALYZE COLLECTED BLOOD SAMPLES FIELD OF THE INVENTION The present invention is refers, in general, to systems and processes to prepare and analyze samples taken from plasma donations to uniquely identify donations that are contaminated by viruses. In particular, the invention relates to an apparatus and process for forming individual containers, sealed separately, and connected, containing samples of the same plasma that is found. in the donation. The invention also relates to an apparatus and process for forming, from containers, initial collections for the analysis by selective classification, and analyzing the collections regarding the presence of a virus, in accordance with an algorithm to identify contaminated individual donations, in the least number of analysis cycles.

Ref .: 30746 BACKGROUND OF THE INVENTION Blood, plasma, and biological fluid donation programs are the first essential steps in the manufacture of blood and pharmaceutical products that improve the quality of life and are used to save lives in a variety of traumatic situations. These products are used for the treatment of immunological disorders, for the treatment of hemophilia, and are also used to maintain and re-establish blood volume in surgical procedures and in other treatment protocols. The therapeutic uses of blood, plasma, and biological fluids, require that donations of these materials be, as much as possible, free of viral contamination. Typically, a sample for serological analysis, of each individual blood, plasma, or other fluid donation, is analyzed for several antibodies that are produced in response to specific viruses, such as that of hepatitis C (HCV) and two forms of the human immunode fi ciency virus (HIV-1 and HIV-2). In addition, the sample for analysis Serology can be analyzed for antigens designated for specific viruses such as hepatitis B (HBV), as well as for antibodies produced in response to those viruses. If the sample is positively positive for the presence of any of those specific antibodies or antigens, the donation is excluded from further use. Although it is believed that an analysis of antigens for certain viruses, such as that of hepatitis B, is closely correlated with the degree of infection, antibody assays are not. It has long been known that a blood plasma donor can, in fact, be infected with a virus and present a negative result and negative for the antibodies related to that virus. For example, there is a period between the time in which a donor can become infected with a virus and the appearance of antibodies produced in response to that virus in the donor system. The period between the first appearance of a virus in the blood and the presence of detectable antibodies, produced in response to that virus, it is known as the "window period". In the case of HIV, the average window period is approximately 22 days, while for HCV, the average window period has been estimated at approximately 98 days. Therefore, analyzes focused on the detection of antibodies can provide a false indication for an infected donor, if carried out during the window period, that is, the period between the viral infection and the production of antibodies. In addition, although conventional analysis for HBV includes analyzes for both antibodies and antigens, analysis through more sensitive methods has confirmed the presence of HBV in samples that were negative in the analysis of antigens for HBV. A method for the analysis of donations, which have passed the analyzes available for antibodies and antigens, in order to further ensure that they are free from incipient viral contamination, involves analyzing the donations through a polymerase chain reaction method ( RCP). RCP is a highly sensitive method to detect the presence of specific DNA or RNA sequences related to a virus of interest, in a biological material, through the amplification of the viral genome. Because the PCR analysis is focused on detecting the presence of an essential component of the virus itself, its presence in a donor can be found almost immediately after the infection. Therefore, theoretically there is no window period during which an analysis can provide a false indication of absence of inf ectivity. An appropriate description of the methodology and practical application of the PCR analysis is contained in US Pat. No. 5,176,995 the description of which is expressly incorporated herein by reference. However, the RCP analysis is very expensive and given that the general population of donors includes a relatively small number of positive donors to the RCP, the individual analysis of each donation is not cost effective or economically feasible. Hence, an efficient and effective cost method is required for the analysis of a large number of donations of blood or plasma, to eliminate units that have a viral contamination above a predetermined level. One method to analyze a large number of plasma donations is to collect a certain number of individual plasma donations. Then, the volume collected by RCP is analyzed and the individual donations that comprise the collection are stored or discarded depending on the results of the PCR analysis. Although the number of PCR analyzes, and the costs associated with them, are reduced, this method results in substantial disposal of a significant portion of virus-free donations. Given that a single donation with a viral contamination above a predetermined level will cause a collection to be positive to the RCP, the remaining donations that contribute to a collection can be, individually, perfectly negative to the RCP. This result is very likely given that there is a relatively small number of positive donors in the general population of donors. In the conventional collection approach, all The donations that comprise the collection, are discarded if the result of a CPR is positive, including those donations that individually are negative to the RCP. In addition, plasma donations are often frozen soon after they are received. When samples of individual plasma donations need to be mixed, each donation can be thawed, an aliquot of blood or plasma must be removed from the donation, and then the donation must be frozen again for its conservation. Multiple freeze-thaw cycles can adversely affect the recovery of the RNA or DNA of interest, as well as the proteins contained within the plasma, and thus adversely affect the integrity of the PCR analysis. In addition, each time an aliquot of individual plasma donations is withdrawn, to form a collection, the donation is subject to contamination, both from the surrounding environment and from the device used to withdraw the aliquot. In addition, if the donation contains a virus it can contaminate other donations. To avoid introducing viral contaminants to another donation without a virus, the apparatus for taking samples must be sterilized after each individual use, or used to take only a single aliquot of a single individual donation and use a new device to take samples, to take an aliquot of a subsequent individual donation. Any of these methods involves considerable expense and are quite late. Therefore, there is a need for a process and system to obtain multiple samples of blood or plasma, from individual donations, in such a way that particular samples can be collected without contaminating the remaining samples. It is also desirable that the process, and system, be capable of forming those collections, in a fast and efficient manner, without contaminating a technical technician who will carry out the clinical analyzes or the analytical laboratory environment. In addition, it is desirable that the process and system provide an efficient and effective cost analysis of blood or plasma donations to uniquely identify positive donations to the patient.

CPR, in the smallest possible number of analisys cycles.

BRIEF DESCRIPTION OF THE INVENTION Therefore, in the practice of this invention, there exists an efficient and effective process regarding costs, to prepare and analyze samples from a multiplicity of blood or plasma donations, in order to uniquely identify donations that are infected with viruses. , as well as systems and devices to carry out the process. The process of the present invention results in blood and plasma products that are substantially safer because virus contamination in the blood or plasma supply can be readily analyzed directly. He . cost effective, highly sensitive analysis can be done immediately, and identify contaminated donations, without considering a period of inf ectivity window.

In one embodiment of the practice of the present invention, the process comprises the steps of providing a blood or plasma donation in a collection container. A flexible collection segment is connected to the container and is open inside the container. The collection segment is filled with blood or plasma from the collection container, and a portion of the collection segment is sealed at both ends. The sealed portion of the collection segment is removed from the container and, either before or after the sealed portion of the collection segment is removed, a plurality of separate seals are provided at intervals along the length of the collection segment between sealed ends. Segment portions in the intervals, between adjacent seals, define the containers, wherein each container contains a plasma or blood sample, and wherein the intervals between the seals provide a sufficient volume in each container for the planned analysis.

In a more detailed embodiment of the present invention, individual plasma donations are collected in a plasma collection bottle having an analysis vessel connected thereto through a hollow, flexible tubular segment. After being filled with the plasma of a donor, the plasma bottle is inclined to transfer the sma to the analysis vessel and to the flexible tubular segment, thereby filling the tubular segment. The tubular segment is sealed by separate intervals, along its length, the portions of the tubular segment that are in the intervals between the seals, define pockets each of which contains a sample of the plasma donation. The tubular segment, which has been converted into a series of bags, is then disconnected from the bottle for plasma collection, and frozen until it is needed for analysis. In a further aspect of the present invention, the hollow tubular segment comprises a series of Y-shaped sites attached to one another, including a site for injection provided in a leg of the Y, and wherein each branch leg of a particular Y site, which does not include a site for injection, is connected to the base. from the next site in Y of the chain, through a tubular segment of flexible plastic. Separate thermal seals are formed, along the length of each flexible plastic tubular segment that separates the sites in, Y. In a further aspect of the present invention, a device for providing multiple thermal seals along the length of the segment tubular filled with the blood or plasma donation, comprises a first and a second seal plates, opposite. Each seal plate includes a plurality of separate and elevated portions, along its length, alternating with recess portions. The portions of enhancement and recesses that are on the first stage coincide with portions of enhancement and recesses, corresponding, that are on the second stage. The opposing sealing plates move together on a plastic tubular segment filled with the blood or plasma donation to form seals thermic over those portions of the tubular segment, which are compressed between the enhancement portions, and to form chambers defined by the opposing recess portions. The thermal seals define a plurality of individual and sequential, intermediate pockets, and each chamber, defined by each closed pair of recess portions, is configured to house a bag. In particular, a device for providing multiple thermal seals along the length of the tubular segment filled with blood or plasma donation, is configured to be mounted on a commercially available heat sealing apparatus, as a modification after purchased. Still in a further embodiment of the invention, a system for collecting and preparing plasma samples for analysis comprises a plasma collection vessel and a hollow plastic tube connected to the vessel, each of which is constructed of plastic and each of which contains coded marks, molded into the plastic. The coded marks are placed at the along the main axis of the tubular segment and the code is repeated at separate intervals such that the tubular segment can be provided with a plurality of seals spaced along its length, thereby defining pockets between the seals. The code intervals of the marks correspond to the intervals of the bags, so that each or 1 s_a will contain at least one cycle of the code. To initiate the analysis process of the present invention, a first bag is removed from each of the groups of tubular segments corresponding to a plurality of separate plasma donations. A portion of the contents of each of the first bags is removed and the contents are collected in a collection, in a container. In an exemplary embodiment of the present invention, the first collection is analyzed with respect to the viral indication. When the first collection is positive for a viral indication, a next or second sequential bag is removed from each of the tubular segments that were used to form the first collection. The second ones bags are divided into two approximately equal subgroups, and the content of one of the subgroups is analyzed for the presence of a specific virus. When the collection of the subgroup analyzed is negative for the virus, an additional sequential bag is removed from the corresponding tubular segments used to form the non-analyzed subgroup. The bags are divided into two subgroups of the next generation, approximately equal, and the contents of the bags of the subgroups are collected. One of the subgroups of the next generation is analyzed, with respect to the viral indication. When the collection of the analyzed subgroups is positive for that viral clue, a bag is removed from the corresponding tubular segments used to form the subgroup analyzed. The process is iterated, and each positive collection is further subdivided into successively smaller subgroups, where each of the successive subgroups comprises a fraction of the samples of the preceding positive subgroup, until the bag is identified. final that corresponds to an individual donation of plasma. In a further embodiment of the present invention, an additional process for analyzing a multiplicity of plasma donations, to uniquely identify donations that have a positive viral clue in a single cycle of PCR analysis, includes the steps of defining a grid n-dimension that defines internal elements in the intersections of each of the n dimensions of the grid. A map is drawn of a sample of each number of plasma donations, for a corresponding element of the grid, and each sample is defined by a matrix notation, Xres, where the matrix element notation subscript defines dimensional indexes of the grid. Aliquots are taken from each sample of each of the plasma donations and are collected in secondary collections. Each secondary collection includes an aliquot of all plasma donation samples in which one of the dimensional indices is fixed. Secondary collections are analyzed all at Once, in a single cycle of PCR analysis, and the dimensional marks of each secondary collection that are positive, they are evaluated in accordance with a reduction by the sub-termination method, thereby identifying, unambiguously, a single element defined by the dimensional marks of each secondary collection, positive, and unambiguously identifying a positive, singular sample.

BRIEF DESCRIPTION OF THE DRAWINGS These and other features, aspects, and sales of the present invention will be more fully understood when they do consider with respect to the following detailed description, appended claims, and accompanying drawings, wherein: Figure 1 is a perspective, burnable view, of an example of a bottle for plasma donation and a sample container attached to a tubular segment, useful in the practice of the present invention; Figure 2 is a perspective view, emysquematica, of a tubular segment connected between a plasma donation bottle and a sample container, and divided into bags, in accordance with the present invention; Figure 2a is a perspective view, only one of a tubular segment, connected between a plasma donation bottle and a sample container, and which includes a series of Y-shaped sites joined together, in accordance with the present invention; Figure 3a is a top view, of the enlarged upper portion, of a portion of the tubular segment shown in Figure 2, showing additional details of the seals separating the bags; Figure 3b is a cross-sectional view, shattered, of a seal of the tubular segment; Figure 4 is an exploded perspective view of a device providing in accordance with the practice of the present invention, to seal a tube in individual bags; Figure 4a is a perspective, semi-quest view, of a top and bottom plates, of the thermal sealing device, provided in accordance with the practice of the present invention, for mounting on a commercially available thermal sealant; Figure 5 is a perspective view, burned first, of a sampling plate and cover provided in accordance with the present invention; Figure 6 is a partial cross-sectional, semi-chemi- cal view of a plasma bag contained in a sample well, of a sampling plate, provided in accordance with the present invention; Figure 7 is a perspective view, only one of a device provided in accordance with the present invention, for compressing sample bags and squeezing the container of the fluid samples found therein, in a harvest; Figure 8 is a semi-schematic cross-sectional view of a compression cylinder of the device of Figure 7; Figure 9a is a partial cross-sectional, semi-schematic view of a filter plate against which the packages containing the samples are compressed; Figure 9b is a top view, chemi- cal hemisphere, of a filter plate showing channels for the emptying of fluids, radial and concentric, to collect the sample fluid from the sample containers, tablets; Figure 10 is a partial cross-sectional view, s emi is quemate, of a compression piston, of the device of Figure 7; Figure 11 is a flow diagram representing the methodology of analysis according to the invention, to determine positive donors to the RCP, from a donation collection; Figure 12 is a flowchart representing a sequence of analysis according to the invention, to identify a single positive donation to the PCR from a collection of 512 donations; Figure 13 is a flowchart representing a second methodology of analysis according to the invention, to determine positive donors to the PCR, from a donation claim; Y Figure 14 is a representation of a three-dimensional grid, in accordance with the invention, which shows the definition of the indices r, c, and s.

DESCRIPTION OF ALLADA OF THE INVENTION The present invention relates to systems, processes and devices useful for the analysis of blood or plasma donations, to detect those specific donations that have a viral contamination above a predetermined level. These contaminated donations are then discarded to prevent their incorporation into the flow of raw materials of pharmaceutical products or to prevent their transfusion to human patients. The viral detection assays used in accordance with the practice of the present invention can be of any type that directly detects a virus instead of the antibodies produced in response to the virus. Analyzes include analyzes by polymerase chain reaction (PCR) and other assays that are sensitive enough to directly detect a virus even after mixing samples from multiple donations. In one embodiment of the practice of the present invention, a plurality of separate blood or plasma donations are provided. A blood or plasma sample is removed from each donation and sent to a corresponding hollow, flexible tubular segment. A plurality of separate seals are provided, at intervals along the length of the tubular segment, so that the segment portions, at intervals between the seals, define pockets, wherein each bag contains a sample of blood * 'or plasma. As discussed in more detail below, a unique methodology is provided, in accordance with the present invention, for analyzing plasma samples from the bags, after which the samples are formed in collections to detect and thereby isolate them. efficient and effective, any of those donations of blood or plasma that is contaminated with a virus. Focusing on Figure 1 shows an exemplary mode of a system provided in accordance with the practice of the present invention, to effect the sampling process. The system includes a standard container 20 for plasma donation, constructed of a non-reactive material such as polyvinyl chloride (PVC). The donation container 20 includes a lid 22 having two hollow elbow-shaped fittings 23 and 24, respectively, attached to the upper surface thereof. The accessories communicate with the interior of the donation bottle through holes provided in the lid 22 for that purpose. A flexible, hollow, filling tube 26 constructed of a biologically neutral material, such as PVC plastic, is connected at one end to the elbow fitting 23 and connected at the other end, for example, to a needle which is inserted into a donor to procure a donation. In the illustrated embodiment, an analysis vessel 28 is also provided, to collect a sample of the donation to be analyzed serologically. The test vessel 28 is generally in the form of a test tube and is also constructed of a material biologically unreactive The analysis vessel 28 includes an integral lid member 30 through which holes are provided for communicating with the interior of the analyzer vessel. A tubular, hollow, flexible segment 32 constructed of a biologically unreactive plastic material is connected between the cap member 30 of the analysis vessel 28 and the hollow elbow fitting 24 of the lid of the plasma donation vessel. . The tubular segment 32 is connected to the cap member 30 in such a way that the fluid passing through the tubular segment, will enter the analysis vessel 28 through a. hole provided in the cap member 30 for that purpose. The tubular segment 32 can be adjusted to friction within the hole, it can be welded thereto with sound energy, or otherwise bonded in a coaxial relationship with the hole, through techniques well understood by those skilled in the art. A second hole may also be provided in the cap member 30, at which connects a vent tube 34, in a manner similar to the tubular segment 32. The vent tube 34 typically has a length no greater than 2.54 cm (1 inch) to 5.08 cm (2 inches), and typically ends in a filter 36 for the exclusion of bacteria, inserted and adjusted by friction. In an exemplary embodiment, a donation of plasma from a donor is withdrawn and collected in container 20 for plasma donation, for subsequent storage until needed. In the case of a plasma donation, the blood is typically withdrawn from a donor and passed through a continuous centrifugation apparatus, where the red blood cells are centrifuged out of the supporting plasma fluid and returned to the donor. . Then the asthma is collected. After a donation of plasma from a donor is taken, and the donation container 20 is full, the donation container is tilted so that the fluid level is raised above the elbow fitting 24 connected to the tubular segment 32 The plasma enters the tubular segment, flows through the tubular segment, and fills the test vessel 28. During filling, the air trapped inside the analysis vessel 28 escapes through the vent tube 34, allowing the test vessel to fill completely . The filter 36 for the exclusion of bacteria filters and retains any bacteria present in the return air, thus preventing contamination of the sample by the surrounding environment. After the test vessel is filled, the donation plasma is filled in to the tubular segment 32. Focusing now on Figure 2, after the plasma sample from the donation is drawn into the segment tubular 32, the tubular segment is sealed by a heat seal 38 or by another suitable sealed means such as a sonic weld, in a location proximate the connection of the tubular segment to the plasma donation vessel. An additional thermal seal 40 is applied to the tubular segment, in a location near the connection of the segment, to the test vessel 28. Of this In this manner a hollow and elongated tube, closed at both ends, and containing an amount of the plasma donation is provided. The filled portion of the tubular segment 32 is removed from the plasma donation and from the test vessels by cutting the tubular segment through the center of the seals, 38 and 40. The separate plasma donor vessel is then removed for freezing and storage, while the separate analysis vessel is removed and sent to a laboratory for serological analysis. Typically, the content is analyzed for several antibodies that are produced in response to specific viruses such as hepatitis C (HCV), or HIV-1 and HIV-2. Additional seals 42 are also provided, at spaced intervals, along the length of the tubular segment, to define individual and connected bags, sequentially, each of which suitably comprises a hollow, tubular segment portion 44. Each one of those portions 44 contains a particular amount of blood or plasma, necessary for specific collection of generation, which will be formed. For example, for bags that are going to be formed for PCR analysis, they can be sealed from 0.02 to 0.5 ml of blood or plasma from the host donation. The tubular segment is sealed in such a way as to provide from 5 to 15 individual and connected bags. The seal, to define the bags, can be made, either after the tubular segment has been removed from the location between the plasma donation container and the serological analysis vessel, or is preferably performed while the tubular segment is located. still attached to the vessel for plasma donation, to avoid the formation of hydrostatic pressure. Sealing can be done through any known method, such as sealing by thermocompr is ion (heat sealing), sonic sealing or the like, as long as the length of the compressed and sealed region is sufficient to allow connected bags are separated from each other by cutting through the center of the seal, without violating the integrity of the bag by both sides, as indicated more clearly in Figures 3a and 3b. A second embodiment of the tubular segment adapted to be subdivided into portions of aliquots containing blood or plasma samples, is shown in Figure 2a, which is a semi-schematic, perspective view of a tubular collection segment modality, connected between a plasma donation bottle 20 and a sample container 28, and divided into portions containing aliquots, in accordance with the present invention. The collecting tubular segment 50 is connected between the lid member 30 of the analytical container 28 and the elbow fitting, hollow, 24, of the lid of the plasma donation container. The tubular segment 50 suitably comprises a plurality of Y-sites 51 connected in series by tubular, medical grade, hollow, flexible plastic segments. Sites Y 51 are of the type commonly adapted for connection to a device for intravenous infusion and include a cylindrical body portion 53 with a defined flow path through the same, having an exit 54 at one end of the flow path and an access site 55 at the other end. An orifice 56 is provided in the shunt, along the body 53 of the Y-site, and includes a path for the fluid, which is in communication with the fluid path, through the body 53. A Y-site is connects to the next one through the solvent connection of a plastic, hollow, flexible medical grade tube between the exit hole 54 that lies on the bottom of a Y-site, to the orifice 56 of the bypass, of the next site in Y, in the series. An initial inlet tube, hollow, 57, is attached with solvent, to the orifice of the derivation, of the initial Y-site, in the series. The initial inlet tube 57 is connected, in turn, to the elbow fitting 24 of the lid of the plasma donation container. The connection can be made by adjusting by friction, the initial inlet tube 57 on the elbow fitting 24, welding, with sonic energy, the tube thereto, or otherwise joining the tube in a coaxial relationship with the fitting, through techniques well understood by those experienced in the countryside. In addition, the initial inlet tube 57 may terminate in a standard luer-type fitting 58 that would allow the Y-sites, connected in series, to be removably connected to the donation vessel provided with a luer-type coupling connector, at the end of the elbow 24. Similarly, the Y-terminal site is fitted with a flexible, hollow, terminal outlet tube, s59, which binds with solvents to the Y-terminal site at its outlet orifice. This tubing can also be connected to a standard luer fitting, at its distal end. In a manner similar to that described in relation to the first embodiment, after a donation of plasma from a donor is taken, and after the recipient 20 is filled for donations, the recipient for donations is tilted in such a way as to raise the level of the fluid above the elbow fitting 24 connected to the inlet tubular segment 57. The plasma enters the tubular segment and flows through the Y-sites connected in series, enters each of the Y-sites through its orifice 56 of the shunt and flows to the next Y-site from the outlet hole 54 of the preceding Y-site. The plasma is decanted until the analytical vessel 28 is full. After the analytical vessel is filled, the donation is further decanted until the Y-connected sites in series comprising the tubular segment 50 are also filled. that the plasma sample from the donation is withdrawn towards the tubular segment 50, the terminal tubular exit segment 59 is closed through a thermal seal or a solder 40a or through another suitable sealing means such as through a sonic weld, at a suitable site along its length, close to the connection, from the tubular outlet, terminal segment, to the analysis vessel 28. The filled tubular segment 50 is removed from the vessel analysis by cutting the tubular, outlet, terminal segment, 59, of the analysis vessel, through the center of the seal 40a. Alternatively, if the tubular segment 50 terminates in a luer-type connector, the tubular segment 50 is removed from the analysis vessel 28 by disconnecting the luer. A second thermal seal 38a is applied to the initial input tubular segment, 57, at a site along its length, close to the connection of the initial segment, to the recipient 20 for donations. The filled portion of the tubular segment 50 is removed from the plasma donation, by cutting the initial entry segment 57 through the center of the seal 38a, or by disconnecting the luer-type fitting 58 if it is provided. In this way an elongated, hollow articulated tube is provided, closed at both ends and comprising a plurality of Y-sites joined together in series. Each of the Y-shaped sites, linked together, contains an aliquot of the blood or plasma donation. As will be described in more detail below, the tubular segments connecting the outlet hole of the preceding Y-site to a bypass orifice of the subsequent Y-site are also provided with thermal seals 42a to define aliquots of samples, is, individual, and connected, each of which suitably comprises a site in and individual. Each of these Y-sites contains a particular amount of blood or plasma, necessary for a specific generation collection to be formed. The seal for isolating each Y-site can be made either after the tubular segment 50 has been removed from the container for plasma donation or can be performed while the tubular segment is still attached. Preferably the seal for isolating the Y-sites is made while the tubular segment 50 is still attached to the vessel for plasma donation, so that the reduction in volume caused by the crushing of a portion of the tube during the process of sealing, does not cause the formation of an internal hydrostatic pressure of the sample. When the tubular segment 50 remains connected to the • container for plasma donation, the excess fluid created by the reduction in the volume of the tube created by the thermal seals is allowed to compress back into the recipient for donations. Excessive hydrostatic pressure, which can leading to a dangerous jet ejection, during the extraction of the sample, is thus safely relieved. Sealing can be done through any known method, such as thermocompression sealing (heat sealing), sonic sealing or the like, as long as the length of the region that is compressed and sealed is sufficient to allow the sites in Y, connected, be sated from one another by cutting through the center of the seal, without violating the integrity of the tubular segment on each side of the seal. Now focusing on Figures 3a and 3b, in a preferred embodiment, the seal between the bags (42 in Figure 2) and / or the Y-sites (51 in Figure 2a) includes a flat area 46 which includes a central narrow portion 47 through which the seal is cut or torn, to sate the connected bags. The cut is made through the central region to ensure that each sate bag remains sealed in the 48 compressed-fin portions 48 at each end, after sation. The length of the seal piece It can be manufactured larger or smaller, depending on the sation method selected. The sation can be done by the use of a scalpel, a guillotine cutter, or a simple cutter. Focusing on Figure 4, there is shown an exemplary embodiment of a sealing device 60, useful for providing bags of specific desired sizes, to easily sate the bags and identify their sequential number along a segment. The sealing devices suitably comprise first and second opposing plates 61 and 62, respectively, each of which includes a plurality of raised sealing head portions 63, arranged in a spaced relation on the opposite surfaces of the plate. The sealing device 60 is preferably constructed in such a way that the sealing head relief portions 63 are movable along their respective platens, such that the spacing of a sealing head enhancement portion, a another, it can be varied. The heads high, sealing, 63 can be accommodated along the stage, in such a way that the distance between successive sealing heads becomes progressively smaller, so that the sealing is carried out along the length of a segment tubular, at separate intervals that are progressively shorter. In this way, pockets can be formed for samples of a progressively more sticky size, and therefore of a volumetric content also progressively smaller, by moving pairs of sealing heads along their respective platens, to a desired location. To form multiple heat seals along the tubular segment of plastic filled with a plasma or blood sample, the tubular segment is placed within a sealing device 60 between the sealed, upper and lower sealing plates, 61 and 62, respectively. The opposing plates approach each other, compressing and sealing the tubular segments. As shown in Figure 4, the plurality of sealing head portions 63, spaced apart, extended or high, along the length of each stage, alternate with the recess portions 64. As the opposing platens move together to form thermal seals on those portions of a plastic tubular segment, filled with a blood sample or plasma, compressed between the sealing head enhancing portions 63, chambers are formed by the opposing recess portions 64. The chambers are provided to accommodate those portions of the tubular segment that are not to be compressed but that effectively , they will be converted into bags. Each chamber defined by each closed pair of recess portions is configured to receive a bag. A heater 65 is configured to heat each of the sealing head portions of the platen, so that the opposing enhancement portions form a thermal seal on the tubular segment when the sealing device is closed. The heater 65 can be any of the well-known types of heaters, such as radiant heaters, heaters induction or resistance, or similar. The heater 65 is preferably directly to each of the raised sealing heads 63 for heating the enhancement portions without unduly heating the recesses. If desired, insulation can be provided to reduce heat transfer between the "enhancement" and the "recess" portions In an exemplary fashion, a cooling device 66, such as radiating or cooling fins, can be connected to the sealing device 60. , a mobile air flow, or a cold finger.The cooling device 66 is directly connected to each of the recess portions 64 such that the chambers defined when the opposite recess portions are moved together are maintained at In this way, the blood or plasma samples contained in the bags formed inside the chamber during the sealing process are not damaged by the high temperature of the thermal seal.The narrow area (47 in Figure 3b) ), approximately through the center of the seal, is formed by a flange structure, elongated, 67, provided below the center of the sealing head portion, extended, 64, of the sealing plates. As the tubular segment is tightened between the upper and lower sealing heads, the flange 67 forces an indentation that lies on the upper surface and the bottom, of the seal portion. The indentation narrows the plastic material that contains the center of the seal, making it easy to separate. In one embodiment of the invention, the flange 67 can be sawed to provide perforations positioned in a direction orthogonal to the main axis of the tubular segments. The perforations allow the individual and connected bags to be removed from each other, without the inherent damage that exists when cutting with a pointed object since the integrity of a bag can be violated, by inadvertently cutting the area containing the sample . the perforations are preferably provided during the sealing process, by providing serrations to the sealing heads. Alternatively, perforations may be provided slightly later, by using a separate punch or drilling template. Means 68 for opening and closing the sealing device 60 is also provided to compress the sealing plates with one another, and thus form seals along the length of the tubular segment. Such means are well known in the art and can conveniently comprise a manual opening and closing apparatus, such as a lever handle, attached to a support structure and moving the structure, for example, against a hinge. Other suitable arrangements may include vertical guides, springs, or piston presses that operate hydraulically, or other common mechanical, electrical, or hydraulic presses. Now focusing on Figure 4a, a specific embodiment of a sealing device 70, useful for providing thermal seals by thermocompression, at separate, uniform intervals to form bags is shown in a perspective view. of specific sizes, desired, or to isolate sites in Y, united, in individual aliquots that contain samples. The sealing device 70 conveniently comprises the top and bottom platens, 71 and 72, respectively, adapted to be mounted along the pressure lever and the sealing band, respectively, of a commercially available pulse sealer, such as one of the pulse sealers of the ALIÑE M series, manufactured and sold by ALIÑE Company of Santa Fe Springs, California. The specific embodiment shown in Figure 4a is a two-part sealing head, adapted to be attached to a pulse thermal sealant, ALI E MC-15, as a modification after being acquired, and allows the MC-15 to produce bags pre-filled plasma, for further processing, in accordance with the system and method of the present invention. The backing plate 72 of the heat sealing head 70 is constructed of a rigid, suitable, tempered tent material, such as laminated Klevar ™, manufactured and sold by the DuPont Company. In the illustrated embodiment the bottom platen 72 preferably has a length of approximately 30.10 cm (15 inches) to fit the mounting surface of the MC-15 pulse thermal sealant. The bottom platen 72 includes a longitudinal groove 72 which is centrally located and extends along the entire length of the bottom platen 72. The width of the longitudinal groove 73 is approximately 0.51 cm (0.2 inches) to accommodate standard medical tubing, which typically has a diameter of approximately 0.48 cm (0.1875 (3/16) inches), mounted in series along the length of the groove. A plurality of transverse grooves 74 are provided, at spaced intervals, along the length of the bottom plate 72, which are positioned in a direction orthogonal to that of the central groove 73. The transverse grooves 74 have a width of approximately 1.27 cm (0.5 inches) and are located on centers of 2.86 cm (1.125 (1-1 / 8) inches). Therefore each transverse groove is separated from its neighboring grooves, by a residual block of platen material, divided centrally by a groove longitudinal, central, 73, which has a width of approximately 1.6 cm (0.625 (5/8) inches). Both grooves, longitudinal and transverse, 73 and 74, respectively, are cut only partially through the material of the bottom platen 72, thus forming a substantially flat bed 75 defining the bottom surface of both grooves, longitudinal and transverse . When the apparatus is used to form thermal seals, a standard medical tubing is mounted in series, in a position along the longitudinal groove 73 and rests on the bed 75 of the bottom platen, which functions as a support surface during The sealing process. A heating element 76, such as a nickel-chromium (NiCr) resistive wire, with a sinuous pattern, from groove to groove, is provided and is positioned along each transverse groove comprising the bottom stage, approximately at the center of the stage. Where the heating element 76 crosses the center of the cross grooves 74, the NiCr wire is protected from contact with thermosensitive plastic tubing, covering the wire, for example, with a piece of Teflon ™ tape. The blood or plasma samples, contained in the bags formed within the sealing device, during the sealing process, are thus not damaged by the high temperatures of the thermal seal. The top plate 71 is also approximately 38.10 cm (15 inches) in length, and is suspended on the bottom plate 72 by the pressure lever of the MC-15 heat sealer. The upper plate 71 is constructed of a synthetic plastic material such as the carved LexanHR or Klevar ™, and comprises a set of teeth, generally rectangular, equally spaced, protruding from its bottom surface, and they extend in a direction towards the bottom stage. The teeth 77 have a length of approximately 1.27 cm (0.5 inches) and are spaced over centers of 2.9 cm (1.125 (1-1 / 8 inches)). Accordingly, it can be seen that each of the teeth 77 is sized to fit within the cavity defined by the transverse grooves 74 of the plate 72. Each of the teeth 72 of the bottom platen 71 is positioned to be suspended above a corresponding intersection of a transverse groove 74 and the longitudinal groove 73 of the platen of the bottom 72. Thus, each tooth 77 is configured to be accommodated within the cavity thus defined when the heat sealing plates are closed with each other by the removal operation of the MC-15 device. After a flexible tubular segment is placed within the longitudinal groove 73, the top plate 72 is pushed to contact the bottom platen 72, lowering the lid of the heat sealing apparatus MC-15. When the lid is lowered, the teeth 77 of the top plate 71 enter the cavity defined by the transverse grooves 74 of the bottom plate 72 and make contact with that portion of the tubular segment that is exposed on the bed 75 at the intersection of each transverse groove 74 with the longitudinal, central groove, 73. Current is supplied to the heating wire, resistive, made of nickel- chrome, which causes the plastic material of the tubular segment to soften. At the same time, the top plate 71 is compressed on the bottom plate, thus applying pressure "to the plastic material that is being softened by the heating element 76. After sealing, the tubular segment is marked or labeled, at least on one end, with a unique identifier that corresponds to the donation of original plasma.This can be achieved, for example, by applying, with glue, a label on the segment or by printing a bar code emblem directly on the material of the A properly prepared recess 78 is provided on the heat sealer 70 to hold and align a pre-printed barcode label to the label, which is formed of a material such as the labile, The tubular segment, which includes the cells containing the sample, is thermally sealed to the tubular segment in the first position of the seal for identification purposes. ra, is then frozen for preservation.

Focusing on Figure 2, it is important to be able to unambiguously identify all parts of the system comprising an individual plasma donation. In this way, unique identifiers such as coded threads, coded points, or other structure coded with the unique identifier can be placed and placed in the physical structure of the plasma collection system. For example, in one embodiment, a coded thread 37 is molded in the donation container 20, a coded thread 39 is molded along the edge of the bottle cap 22, a coded thread 41 is molded along the side of the analysis vessel 28, and a coded thread 43 is molded into the tubular segments, at spaced intervals. The unique identifier in the tubular segment extends along the length of the tubular segments and the code is repeated to allow segmentation of the tubular segments while maintaining the identification integrity of each segment thus prepared. In addition, each portion of the donation system is identified with the same code, so such that the identity of the donation is maintained, for all parts of the system. Focusing now on Figures 3a, 3b, and 4, it may also be desirable to have identified, each individual bag that is along the segment, through an alphabetic or numeric code, equal to the position of the bag throughout of the linear length of the original tubular segment. That code can be printed, for example, on the compressed portion of the stamp piece located between adjacent bags, by the use of a stamping die. That stamping die may comprise an integral part of the sealing device, such as illustrated in Figures 4 and 4a, such that the seal, which forms bags of varying sizes, the provision of narrow or perforated areas for easy separation , as well as identification numbers, can all be achieved in one efficient step. Alternatively, the alphabetical or numerical identifier could comprise part of a drilling template or a die. Stamping dies are known which include means for advancing the alphabetic or numerical character towards a sequential next, so that the sequential bags that are in a tubular segment are identified, each one, through a sequential, corresponding string of alphabetic characters (a, b, c, .. .) or numeric (1, 2, 3, ...). Therefore, if a first collection is prepared for analysis, from bags of several donations, a verification of the quality control can be carried out, confirming that all the bags that are to be collected from each tubular segment, have the same location code, for example, number 1. Similarly, when a second collection is prepared for analysis, from samples of the same donations, a verification of quality control can be carried out, confirming that all the Bags to be collected from each tubular segment have, for example, the number 2 printed on the same spot on the compressed portion of the bag. To perform an efficient RCP analysis of a donation, the sample for the serological analysis, taken from each donation individual in the analysis vessel 28, is analyzed against several antigens and / or antibodies, known, which are designated for specific viruses. If a sample is positive for one or more known antigen or antibody assays, the individual donation and its corresponding tubular segment are excluded from further analysis and both can be discarded in an appropriate manner. The tubular segments that correspond to the rest of the negative donations, are divided into identified groups, each of which comprises a selected number of donations. As will be further described below, the number of donations per group is determined through the sensitivity of the highly sensitive specific analyzes, such as the PCR analysis, the anticipated concentration of RNA or viral DNA of interest in the plasma sample, and the anticipated frequency of a positive sample to the RCP, which occurs within the general population of donors. For example, for the detection of hepatitis C virus, which contains the RNA of interest, in a population of donors for plasmapheres is repeating, it is appropriate to collect samples of between 100 and 700 individual donations. For a population in which viral contamination occurs more often, smaller collections, ranging from 50 to 100 individual donations, may be appropriate. Now, one will describe, with reference to Figures 5 and 6, one embodiment of a process for preparing a collection or mixture for PCR analysis, in accordance with the present invention. A sampling plate 80, generally similar in application, is provided to a titration plate, but configured in accordance with the practice of the present invention. The sampling plate 80 is configured to contain wells 81 for samples, in general, half-way, placed horizontally on the plate, with an arrangement, in general, regular. A suitable sampling plate, used to carry out the method of the invention, has 64 of these sample wells, accommodated in rectangular 8x8, columns / f i 1 as. A cover plate 82 is also provided which has approximately the same outer dimensions as the sampling plate 80. The cover plate 82 is adapted to cover the surface of the sampling plate 80 in a tight and closed connection. On the cover plate the passage holes 83 are arranged, with the same arrangement or arrangement as that of the sample wells, of the sampling plate 80. When the cover 82 is placed on the surface of the sampling plate 80 , the passage holes 83 are vertically aligned above the sample wells 81, thereby allowing communication with the sample wells, through the through holes. The diameter of the through holes is substantially smaller than the surface area of the bags with samples for analysis and that of the corresponding sample wells. However, the diameter of the through holes is large enough to allow a needle, or other cannula-like object, to pass through the holes and enter the sample wells, which are below.

As shown in relation to Figure 6, a terminal bag (first generation, "number 1") 84, of each tubular segment that has been identified as belonging to a particular group to be analyzed by PCR is removed. Each terminal bag 84 is washed, but not opened, and placed in a well 81 for corresponding samples of plate 80 for samples. The cover plate 82 is secured above the top of the sampling plate 80, and the plate, the cover, and the bags are defrosted at an appropriate temperature. An equal volume, between about 0.02 to 0.5 ml of plasma, is removed from each bag and collected in a container for analysis. A needle 85 or other device similar to a cannula is inserted through the through hole in the cover plate and into the sample well of the sampling plate directly below, thereby piercing the tubular material of the sample. lateral wall of the bag and gaining access to the plasma sample within it. In an exemplary embodiment, the needle is connected to a device that provides a vacuum or continuous suction to extract all the blood or plasma contained in the bag and minimizes any leakage of fluid to the surrounding tray. The needle can be held in a device that allows the needle to move through the through hole and the upper wall of the bag, but to restrict its progress downward, so as to prevent the needle from touching or piercing the needle. wall of the bottom of the bag, when the bag sits in the well for samples. When the cannula is removed after extracting a sample, the material 86 of the cover plate, which surrounds the through-hole, prevents accidental removal of the bag together with the cannula, as shown in Figure 6. Although the method to prepare a collection for analysis by PCR has been described in terms of the manual extraction of a sample, inserting a cannula individually into each well for samples, the method can be implemented, likewise, using an automated process. The sampling plate, which contains bags in each well, can be maintained for allowing an arrangement of cannulas, accommodated in a manner corresponding to the arrangement of the through holes in the cover plate, to be pressed onto the sampling plate, thereby allowing all sample bags to be punctured, and that the samples are extracted from them at the same time. Alternatively, a single cannula, or a device for attaching cannulae, can be automated or programmed to successively perforate and withdraw fluid from each bag. To prevent remaining contamination, a clean cannula is used to extract samples from each collection. In addition, it will be apparent to a person skilled in the art, that the combination of sampling plate, sample wells, cover, passage holes, and cannula, described at the same time in relation to the extraction of a sample fluid, from a sample pack, is equally applicable to the extraction of sample fluid from sample containers, with Y-sites, of Figure 2a. The configuration of the wells for samples of Figures 5 and 6 are determined by the shape of the container containing the fluid, and only minor modifications are required to reconfigure them for the Y-sites. For example, sample wells may comprise an elongated, vertically oriented cylinder, into which each site is inserted into. Y. A notch may be caused at a certain appropriate location, around the upper periphery of each sample well, which functions as a retainer within which the Y-site derivation hole may be located. This would also work to orient each site in Y and provide additional position security. In the same manner described in relation to Figures 5 and 6, fluid can be extracted from each Y-site, by inserting a cannula through each access hole 'to the Y-site, and in fluid communication with the sample. When the cannula is removed from the access hole, the material of the cover plate surrounding each through hole acts as a retainer and prevents the Y-site from being withdrawn from the sample well. It will also be evident, for a person who has experience in the technique, that this The configuration is equally convenient for the practice of the invention, using an automated process. An arrangement of cannulas can be accommodated in a manner corresponding to the arrangement of the through holes found in the cover plate, thereby allowing all access holes of the Y-sites to be perforated, and the samples. after they are removed from them, at the same time. Alternatively, a single cannula or cannula attachment device can be automated or programmed to successively drill each access hole and withdraw fluid from each Y-site. A further embodiment of a suitable apparatus and method will now be described for preparing a collection for PCR analysis, in accordance with the present invention, in relation to Figures 7, 8, 9a, 9b, and 10. Focusing first on Figure 7, a plasma donation collection or mixture, comprising compressed fluids and withdrawn from a multiplicity of plasma samples, is prepared from a number of sample packages of plasma donations, in a press hydraulically activated 90. The hydraulic press 90 suitably comprises a pressure cylinder 91 in which packages of the samples are placed, and a hydraulically operating piston 92 which compresses the sample packages. The samples contained within the packages are compressed in the pressure cylinder 91 by a suitable compressed gas, such as air or nitrogen, compressed, and collected in a collection container, as a mixture. Initially, a generation bag (for example bag # 1) is removed from each tubular segment that has been identified as belonging to a particular group that is to be analyzed per RCP. Each generation group is washed, but not opened, and placed inside the pressurizing cylinder 91 of the press 90. The loading of the pressing cylinder is done within the environment of a bell for biological safety, class II, handling a flow pattern of air to avoid inadvertent contamination of the surrounding environment, for a package that has lost its structural integrity. In a way that will be described with In greater detail subsequently, the pressure piston 92 is firmly seated within the open throat 91a of the pressure cylinder 91, in such a manner as to ensure containment of the contents of the pressure cylinder 91, and that the combination of cylinder 91 and piston 92 encloses completely sample packages. The manner in which the pressure piston 92 engages the pressure cylinder 91 is designed to ensure that the exterior environment of the cylinder 91 is protected from contamination by any harmful virus that may be present in any of the samples contained by the sample packages. . The pressing cylinder 91 is then mounted on the seat 93 of a cylinder, which aligns the cylinder in the correct position on the hydraulic press 9 0 and which further allows a hydraulic shaft 94, functionally connected to the hydraulic cylinder 95, to be aligned and engaged. with the plunger piston 92. In a manner that will be described in greater detail below, the plunger piston 92 is connected, so that it can be released, to the hydraulic shaft 94, so that the piston 92 can be made, both ascending and descending, by operation of the hydraulic cylinder 95. After the cylinder 91 and the piston 92 have been properly aligned on the cylinder seat 93, and have been connected to the hydraulic cylinder 95 through the shaft 94, a control valve 96 is operated to cause the hydraulic cylinder to exert a force on the shaft 94 and the piston 92, which in turn presses the sample packs that are located inside the pressure cylinder 91. The hydraulic cylinder 95 operates in conjunction with an electric motor 97 of four horsepower, at 240 volts alternating current (AC), which operates a reciprocating hydraulic pump 98 that pumps fluid, together with a fluid reservoir 99, in order to operate the cylinder 95. Approximately 1.818.2 kilograms force (4,000 pounds force) are applied punctually to the hydraulic ee 94 which d It develops a pressure of approximately 56.25 to 63.28 kg / cm2 (from approximately 800 to 900 psi), force that is applied by the piston 92 to the sample packages. After the sample packages have been pressed, the fluid donation samples, contained therein, are pressed into the pressure cylinder 91 through a supply of compressed gas, by, for example, a cylinder of compressed air 100. which is connected through a pressure regulator 101 to a direct acting valve 102 provided in the pressure piston 92. To allow the direct acting valve to work correctly, the piston 92 is first raised slightly from its fully extended pressing position. Compressed air is vented to cylinder 91 through pressure regulator 101 until the threshold pressure of the direct acting valve is reached. The valve 102 is then opened, allowing the compressed gas to pressurize the inside of the cylinder which forces the plasma collection out of the pressure cylinder 91 and through the collection hole 103 provided at the bottom of the cylinder. The plasma collection is then collected in a collection vessel connected to collection hole 103 by a line or compression tube, as the fluid is forced out of the cylinder, by compressed air. The compressed air is expelled in a bell for class II biological safety, after passing through a purification trap. Now focusing on Figure 8, a partially cut-away cross-sectional view of a pressure cylinder 91 constructed in accordance with the principles of the invention is shown. The pressing cylinder 91 conveniently comprises a base plate 105, generally circular, having a top and bottom surface, and a circumferential lip 106 extending in an upward direction, from the top surface, with carved threads within its inside face A cylindrical wall 107 of the cylinder, open at both ends, is threaded on the outer face of its bottom end. A recess or groove 108 is machined within the inner face of the end of the bottom of the wall 107 of the cylinder, in order to define an annular lip 109 which is placed in position. parallel to the upper surface of the base plate 105 and has a face opposite thereto. As the cylinder wall 107 is screwed into the base plate 105, a filter plate 110 placed on the surface of the base plate 105 is engaged by the annular lip 109 of the cylinder wall 107, and is compressed between the lip annular 109 and the upper surface of the base plate. Focusing now on Figures 9a and 9b, the filter plate 110 is a disc-shaped plate, generally circular, against which the packages containing samples are forced, when pressed by the pressure piston 92. As shown in Figure 9b, the plate filter 110 includes fluid drain channels, comprising radial grooves 11 and concentric circular grooves 112, all having a width of about 0.08 cm (1/32 inch), which are cut into the upper surface of the filter plate. The radial grooves 111 are cut with an angle that slopes towards the center of the filter plate 110 where they end in an axially located drain or sump 113, the which drains through a drain pipe 114 of 0.64 cm (1/4 in.) (best observed in Figure 8) drilled through the base plate 105. Now focusing on Figure 8, a seal is formed between the wall 107 of the cylinder, and the filter plate 110, engaging and compressing an "O" ring 115, provided in a duct 116 recorded in the base plate 105 for that purpose. The channel 116 of the seal is located on the base plate, such that the "O" ring 115 is below the vertical intersection of the filter plate 110 and the cylinder wall 107. A step 117 is worked on the base plate 105, and a coupling slit 108 is engraved on the filter plate, such that a positive retainer is able to precisely locate the filter plate on the base plate, for its proper alignment with the "O" ring, such that the wall 107 of the cylinder will properly engage the filter plate, and its intersection will properly engage the ring at "0" 115.

Now focusing on Figure 10, a partially cut-away cross-sectional view of a pressure piston 92 provided in accordance with the principles of the invention is shown. The pressing piston 92 comprises a piston head 120, generally cylindrical, having a centrally located and axially extending cup 121 projecting therefrom, the cup 121 having walls of generally cylindrical shape, and an open end for defining with it a sleeve 123 for receiving a shaft 94 of the hydraulic cylinder, of generally cylindrical shape. An annular rim 122 surrounding the open mouth of the cup is provided around the circumference of the cylindrical cup 121. The outer surface of the flange 122 is bevelled, such that the beveled surface increases its diameter in the direction towards most of the body of the head 120 of the piston. When the hydraulic shaft 94 is advanced within the sleeve 123, a pair of clips or fasteners 124 with springs are advanced above the surface of the annular flange 122 until they stop at its end. position and hold the lower side of the annular flange. To be accommodated in engagement with the sleeve 123, each retaining clip 124 includes a bevelled tooth 125 that moves along the beveled surface of the annular retainer ring 122 of the piston head, whereby the jaws are separated and opened. of spring retaining clips 124. As the hydraulic shaft 94 continues to advance, the beveled teeth 125 of the retaining clips 124 are eventually advanced past the bevelled surface of the annular retainer ring 122. The action of the springs on the retaining clips forces the beveled teeth to come into contact with the outer surface of the side wall of the cup. The teeth of the retaining clips 124 thus engage the lower surface of the annular retaining collar 122, gripping the pressing piston 92 and providing a means for causing the piston to move in both directions. In addition, it will be evident to a person who has experience in the technique that the spring retention fasteners 124 can be easily uncoupled from the annular retaining ring 122 by pressing together the ends of the fasteners, opposite the beveled retention teeth 125. Accordingly, it will be noted that the piston head 120, the axially mounted cylindrical cup 121, the annular retaining ring 122 and the retaining clips or fasteners 124, in combination, provide means for quick and easy disengagement of the hydraulic shaft 94 from the pressure piston 92. This quick disconnect feature allows the piston combination 92 and cylinder 91 is easily removed from the seat 93 of the cylinder, from the hydraulic pressure 110 for cleaning, sterilization, filling with additional sample packs, and similar actions. As shown in Figure 10, the pressure piston 92 further includes several "0" rings 126 positioned in raceways 178 for seals, provided around the periphery of the head 120 of the piston. The "O" rings are provided to form a pressure seal, between the surface circumferential, outer, of the head 120 of the piston, and the circumferential, inner surface, of the cylindrical wall 107 of the pressurizing cylinder 91. Multiple O-ring seals provide a measure of safety to ensure the containment of a sample fluid, potentially contaminated, within the confines of the cylinder 91. Although in the embodiment illustrated in Figure 10 there are three "O" rings 126, it will be evident that according to the invention a greater or lesser number of seals can be provided. O-rings All that is required is that a seal be formed between the pressure plunger 92 and the pressure cylinder 91 to ensure the containment of potentially contaminated fluid within the cylinder. Now focusing on Figure 8, the side wall of the presser cylinder includes a beveled step 130 of 0.050 cm (0.020 in) which is machined on the inner surface of the side wall. Approximately the first 2.54 cm (1.0 inch), from the top, of the side wall 107 of the cylinder, are machined to have a inner diameter (DI) approximately 0.10 cm (0.040 in) greater than the ID of the remaining portion of the side wall 107 of the cylinder, which extends downwards, towards the filter plate 110 and towards the base 105. The interface between the step and the remaining sidewall portion is beveled to provide a smooth transition, at an angle, from the slightly larger upper DI to the lower, slightly lower DI. The step on the side wall 107 of the cylinder is provided such that the pressing piston 92 can be manually inserted into the open throat of the pressing cylinder 91 by making only slight contact between the "0" rings (126 in the Figure). 10) and the cylinder ID surface. Once the manually assembled piston-cylinder combination is placed on the seat (93 in Figure 7) of the cylinder, the hydraulic shaft 94 is advanced to engage with the piston sleeve 123 and extends until the loops or retaining clips 124 stop against the bottom surface of the retaining collar, annular, 122, of the piston head. The hydraulic shaft 94 is then further advanced, to further push the piston in the cylinder, thereby pushing the "0" rings past the step 130 on the ID of the cylinder wall. When pushed past the step, the "O" rings are fully compressed between the ID of the side wall 107 of the cylinder and the piston seal channels 127, thereby forming a seal. In operation, the pressure piston 92 develops a pressure from about 56.25 to 63.28 kg / cm2 (from about 800 to 900 psi) (1,812.2 kilograms force (4,000 pounds force) applied punctually to the hydraulic shaft) which is a pressure sufficient to press the Sample packs contained inside the cylinder. The fluid from the blood or plasma samples flows along the channels for the emptying of the fluid, which are found in the filter plate, towards the central drain, where it is collected and where it is allowed to flow towards the extraction hole and towards the collection container. After the compression operation, the hydraulic cylinder 95 is operated to raise the pressure piston 92 a small distance (approximately 1.27 cm to 2.54 cm (from 1 in. To 1 in.) Above the mass of the sample packages, Pressurized, whereby a chamber is created inside the cylinder A compressed gas, such as compressed air, is forced into the chamber and through a direct acting valve 102 in the piston 92. Pressurization of the valve causes any remnant blood or plasma sample fluid to be compressed and expelled out of the cylinder, through the outlet hole 103 and into the collection container, once the pressing and collection operation is complete, the compression line connected to the outlet hole 103 is clamped to prevent any additional sample of fluid from leaving the cylinder.The compression line is placed inside a container with b lanqueador, and it causes that the hydraulic cylinder 95 e l eves the piston, additionally, in the cylinder, creating with it a suction that extracts, by siphon effect, bleach from the container, and takes it towards the cylinder. Preferably, the bleach compression and extraction steps, by siphoning effect, are repeated two additional times, to ensure that any amount of fluid, from the plasma or blood sample, that returns abruptly, is completely expelled from the pressure cylinder 91. -and that the bleach have ample opportunity to fill the interior volume of the pressure chamber, thereby reducing any strong viral contamination that may be inside. Afterwards, the clamps are manipulated quick release and the combination of pi s ton / ci lindro, of the. hydraulic press 90 and subjected to sterilization procedures, for example, in an autoclave. The piston and the cylinder can be cleaned, subsequently, chemically, rinsing them in a 10% bleach solution, for fifteen minutes, followed by a rinse cycle with H20. DSS (sodium dodecyl sulphate) surfactant IB ** »1%, and H20 again, before introducing them to autoclave. If there is enough time for autoclave sterilization, chemical cleaning can conclude with a sterile solution of H20 and ETOH at 70%. ' If additional chemical cleaning is desired, it is carried out under a biological safety hood, class II, which expels the vapors through a HEPA filter. While under the hood, the pressing cylinder is loaded with a next group of sample packages to be pressed, and the pressure piston 92 is manually inserted into the open mouth of the pressure cylinder 91 and forced down until the rings in? Or "of the piston make contact with the bevelled step formed in the side wall of the cylinder.The new cylinder / piston combination, reloaded, is now ready to be placed on the seat 93 of the cylinder, of the pressurizer 90. The hydraulic cylinder 95 is operated to cause the hydraulic shaft 94 to descend on the piston 92 in such a way that the quick-release clamps engage the annular retaining ring on the piston.The crushing, compression, and cleaning with bleach.

From the foregoing, it will be evident to a person having experience in the art, that the hydraulic press (the pusher) that operates electrically, 90, allows the collection -of blood and plasma samples, of a large number of packages of samples, in a minimum time. The number of sample packages that can be crushed or compressed by that apparatus is limited mainly by the scale of the device and by the pressure capable of being developed by the pressing piston, against the mass of the sample packages contained in the cylinder. The pressure of 56.25 to 63.28 kg / cm2 (800 to 900 psi) developed by the hydraulic press, of the illustrated embodiment, is sufficient to completely crush up to 64 packages containing samples, of the type described in relation to Figure 2. Consequently, collections on a larger scale, comprising up to 512 samples, can be formed through 8 cycles of operation of the crushing device of the present invention. This would provide a significant reduction of the time for the formation of the harvest, with respect to a method in which 512 sample packages were individually accessed through a cannula to collect samples from the same. Furthermore, it will be apparent to a person skilled in the art that a single large-scale collection, comprising up to 512 samples or more, can be formed with the use of a crushing apparatus, manufactured large enough to accommodate the largest number of sample packages in the cylinder. The size of the hydraulic press portion could also be increased to provide greater crush power and overcome the increased resistance of the increased number of bags. As mentioned above, the size of the collection should be limited only by the desired scale for the crushing device. Referring now to the Figure 11, a flow diagram of a PCR analysis methodology is shown, according to the invention, which allows the identification of a positive donation to the PCR analysis, unique, with the least number of additional analyzes. The process begins in block 200 with the definition of an initial, appropriate collection size, which in turn depends on several factors such as the frequency of the occurrence of the virus of interest in the general population of donors, the probable final concentration of viral DNA or RNA after dilution in the collection, and imí lar factors. Although PCR analysis is highly sensitive and capable of detecting a single virus in a contaminated sample, it must necessarily be found-a virus is present in the sample for PCR analysis to yield a positive result. For example, if a sample from a contaminated donation, which has a relatively low virus concentration, is mixed together with a large number of uncontaminated samples, the concentration of virus in the resulting mixture may be so low that the statistical probability that the virus is not present in a sample taken from the collection for analysis by RCP These collections or mixtures can, in effect, be deceptively negative in the test for viral contamination. For example, if a 0.02 ml sample was prepared from a donation of plasma contaminated with virus, at a concentration of 500 viruses per ml of sample, the 0.02 ml sample would contain, on average, 10 viruses. If this contaminated sample, 0.02 ml, were mixed with approximately 500 samples of 0.02 ml of uncontaminated donations, the resulting 10 ml mixture would contain virus at a concentration of 1 virus per ml. Therefore, if 1 ml samples were taken from the collection, to perform the PCR analysis, there is a statistically significant probability that the sample for the PCR analysis will not contain viruses. These low concentrations of virus contamination represent very little threat to products produced from plasma, because several methods are available to inactivate viruses present in those donations with these low concentrations of viruses. Those methods of viral inactivation they include the use of solvent / detergent, or heating to a temperature above 60 ° C for an appropriate time, or similar method. These methods are generally described as being able to reduce the concentration of virus by a number of "logarithmic units". For example, the solvent and detergent method is capable of reducing viral contamination of hepatitis C by at least 107 per ml or "logarithmic units". Thus, plasma products, such as factor VIII, factor IX or the prothrombin complex, can be prepared from plasma donations treated in the routine form, for example, with the solvent and detergent method, after having negative results to the analysis by RCP. For blood products, routinely transfused directly into a container, there is still some risk of viral contamination at low concentration, after those donations have been negative for PCR analysis. In the modality illustrated in relation to Figure 11, the factors discussed above are evaluated, such as the frequency of occurrence of the virus of interest, in the donor population, and the probable concentration of the virus, after dilution. It is first designated, a collection for the analysis by RCP, of a first level and of an appropriate size, which minimizes the statistical probability that there are no detected viruses that are present in low concentrations. The collection or mixing is prepared in block 201 by collecting the contents of identified tubular section end bags, in the manner described above. In block 202, a PCR analysis is performed in the first level collection for the PCR analysis. Block 203 represents a decision point in the methodology of the invention, which depends on the results of the PCR analysis, performed in block 202. In the event that a negative result is obtained in the analysis, it is presumed that all the donations that correspond to samples used to elaborate the first level collection for the PCR analysis, are free of viral contination and are released for further processing for the manufacture of pharmaceutical products. The methodology ends then upon receiving a negative result in the analysis by RCP. When CPR analysis produces a positive indication, this indicates that viral contamination is present in one, or more than one, of the donations that were part of the first level collection for CPR analysis. In block 204, an additional bag, the bag next to which it was first removed, is removed from the tubular segments corresponding to donations containing the original first-level collections for PCR analysis. These additional sample bags are divided into two roughly equal subgroups, designated herein as A and B, for the purposes of privacy. These subgroups are then collected separately using a separate, clean cannula to form each collection or mixture of the subgroup, in the same manner as described above, and only one of the subgroup collections is analyzed by PCR, as indicated in block 205. It is insubstantial, for purposes of the invention, which of the two groups is analyzed. In block 205, subgroup A is identified as the subgroup to be analyzed, but subgroup B could have been designated without disturbing the methodology of the invention. In block 206, a decision is made, depending on the result of the analysis by _RCP, of the collection of subgroup A. In the case that the collection of subgroup A is negative for viral indication by PCR analysis, it is not performed an additional analysis in the samples of the donations that comprised the subgroup A. On the contrary, as it is indicated in the blog 207, the next bags of samples are taken, in sequence, of the tubular segments that comprised the subgroup B, which in turn are divided into two approximately equal subgroups, A 'and B'. Each subgroup comprises, in this step, approximately half of the number of samples that those that comprised the immediately preceding subgroup. The contents of the sample bags of the subgroups are collected again separately, in the same way as described above. In the case that subgroup A is positive for PCR analysis, indicating that at least one of its component donations was contaminated, it is now analyzed, by RCP, in blog 108, the other subgroup not analyzed (subgroup B in the example of Figure 11), to confirm that it is also not positive for PCR analysis. Subgroup A now becomes the subgroup further subdivided into two approximately equal subgroups (A 'and B'), as indicated in block 209. In block 210, PCR analysis is performed in only one of the collections of subgroups Af and B ', defined in the previous step 207 or 209. The method is "iterated now and returns to block 206, where the decision step is applied to the results of the PCR analysis, performed in block 210 Again, if the analysis by PCR is negative for the subgroup analyzed, the subgroup not analyzed should be subdivided, in addition, into two approximately equal subgroups, each of which contains approximately half of the samples of the preceding subgroup.

If the analyzed subgroup produces a positive result for the analysis by PCR, the subgroup analyzed should be subdivided further into two approximately equal subgroups, each of which would comprise half of the samples of the preceding subgroup. In this case, the subgroup not analyzed would be analyzed again by means of PCR, to confirm that it was not positive to the analysis by PCR. The analysis methodology continues to perform iterations from block 206 to block 210, until it is determined that the analysis has finished. The finalization of the analysis is defined as the moment in which the division of a subgroup results in the creation of two subgroups, each of which contains only one sample bag, which corresponds to a single donation. One of the samples is analyzed by PCR, in block 210 and, if the results of the analysis are negative, the other sample is identified as belonging to a donation of virally contaminated plasma. If the analyzed sample produces a positive result, the remaining sample is also analyzed by PCR. confirm that the CPR analysis is not positive either. At the end of all the analyzes, the methodology of the invention ends in block 211. It should be clear, from the flow chart of Figure 11, that the analysis methodology of the invention requires only that two PCR analyzes be performed. , _ at each level of analysis, when the collection analyzed is positive first: An initial analysis for one of the two subgroups, and a subsequent analysis to confirm that the collection initially not analyzed, corresponding, is effectively negative. The analysis methodology requires only a single PCR analysis at each level of analysis, when the collection analyzed initially is negative. The application of the system and method for the analysis of samples of the invention will now be described, in relation to a particular collection size, for the PCR analysis, as shown in Figure 12. In Figure 12 the terminal bags of 512 individual donations meet in one initial collection for PCR analysis, in 212. For purposes of illustration, it will be assumed that only one of the 512 samples was taken from a donation that was contaminated by a virus of interest. The tubular segment shown in Figure 12 comprising 10 individual and connected bags, represents the tubular segments originally connected to, and taken from, the contaminated plasma donation container. The initial collection of 512 samples is analyzed by PCR and due to the presence of the contaminated sample, it produces a positive viral indication. In step 213, two collections of 256 donations (256A and 256B) are prepared from the next sequential bags taken from segments that formed the previous positive collection. The 256B collection is now analyzed by PCR and as shown in Figure 12, it produces a negative viral indication, indicating that the 256A collection contains a sample of the contaminated donation. In step 21--, two collections of 128 donations are prepared, starting with the next sequential bags of the tubular segments that formed the 256A collection. Thus, according to the invention, the 256A collection has been subdivided without having been analyzed by RCP. In step 203, the collection 128A is now analyzed by PCR and, since it produces a negative viral indication, it is now known that the collection 128B includes a sample bag of the contaminated donation. Collection 128B is then subdivided into two collections of -64 donations (64A and 64B) eliminating the next sequential bag of those tubular segments whose previous bags formed the 128B collection. Then, the 64B collection is analyzed by PCR and, in the example of Figure 12, it produces a positive viral indication. In this case, the PCR analysis is performed in the 64A collection to verify that it is, in effect, negative, and that no additional contaminated samples are present, more than those found in the 64B collection. In step 216, the 64B collection is further subdivided into two collections of 32 donations, 32A and 32B, eliminating the next Sequential bag of the tubular segments used to form the preceding collection 64B. Collection 32B is analyzed by PCR, produces a negative viral indication, as indicated, and therefore collection 32A is subdivided, additionally, into two collections of 16 donations, 16A and 16B. Again, the collections of 16 donations are prepared by eliminating, the next sequential sample bag, the tubular segments that formed the preceding positive collection, 32A. In step 217, collection 16B is analyzed by PCR, and produces a positive viral indication. Therefore, collection 16A is analyzed by PCR to confirm that it is negative, and that all contaminated samples are present in collection 16B. In 218, collection 16B is subdivided into two collections of 8 donations, 8A and 8B, eliminating the next sequential sample bag from the tubular segments that formed the preceding positive collection, 16B. The 8B collection is then analyzed by PCR and, as illustrated, produces a viral indication negative, indicating that collection 8A contains a sample of a contaminated donation. Collection 8A is further subdivided into two collections of 4 donations, 4A and 4B, in step 219. The PCR analysis is performed in collection 4B, which produces a negative indication, thus indicating that collection 4A contains a sample of a contaminated donation. Harvesting 4A is then subdivided, at 220, into collections 2A and 2B in the same manner as described above. When performing PCR analysis, collection 2A produces a negative viral indication, indicating that one of the two samples comprising group 2B was taken from a tubular segment of a corresponding contaminated donation. In step 221, individual donations are analyzed by eliminating the final bag of tubular segments that formed group 2B. The final donations, individual, are analyzed by RCP, to identify positive, specific donation, which is eliminated after storage and disposed of properly. The 511 donations without viruses, The rest are kept for further processing in the manufacture of products and appliances. In the previous example, a single contaminated donation has been uniquely identified from a group of 512 of those donations, making only 13 separate PCR analyzes, including the primary PCR analysis, in the original 512 collection donations The method of the invention allows to skip or avoid an analysis by PCR, in a secondary, particular collection, as long as the corresponding secondary collection, analyzed, produces a negative viral indication. By avoiding performing certain PCR analyzes, the method of the invention reduces the number of PCR analyzes that must be performed to identify a positive, specific donation, without sacrificing the resolution of the PCR analysis methodology. Under the method of the invention, all positive donations will be identified without requiring that all donations be analyzed. From the exemplary mode of Figure 12, it will be clear that one of the subgroups successively smaller can be analyzed by CPR and that the arbitrary position of the positive sample can be varied. Thus, if a positive donation sample were present in each secondary collection initially submitted for analysis, 18 analyzes would have been required to uniquely identify the positive donation (an initial analysis that produces a positive result, and an additional analysis to ensure that the collection corresponding is negative). For the same indication, if each secondary collection, subjected to the analysis initially, produces a negative indication, 10 analyzes would have been required to identify the positive donation. In practice, the positive and negative results in secondary collections would have tended to be distributed equally, thus, 14 analyzes would have been required on average to identify a singularly positive donation, starting with an initial donation collection, for 512 units. Therefore, it is clear, from the foregoing, that the system and method of present invention, including the provision of tubular segments comprising individual and connected bags, each of which contains a sample of a donation plasma, is advantageous in providing a multiplicity of collections for PCR analysis. Unlike the conventional preparation of collections or mixtures, in which. A sequence of initial and subsequent collections is formed from a single sample of each donation, at the same time, this invention allows the formation of a collection for analysis, immediately before the analysis. This way of training "just in time" collections allows the construction of collections for analysis, from individual bags, only if necessary. The possibility of contamination is eliminated since the collections are constructed at different times, each one with sealed sample bags. In addition, the sample bags remain frozen until a collection for analysis needs to be developed. Avoid freezing and thawing cycles that can affect adversely recovering the DNA or RNA of interest, thus ensuring the integrity of the PCR analysis. Although the method described above is effective in identifying a virally positive donation, with the least number of relatively expensive PCR tests, other methods for identifying positive, individual donations are also provided in accordance with the practice of the present invention. In particular, one of these methods has the property of being able to identify positive, individual donations, with a number of two to three cycles of analysis by PCR, meaning a reduction of the amount of administrative time required to analyze a large number of donations For example, in the method described above, once a secondary collection has been identified, a technician must identify those donations that contributed to the mixtures to form that particular collection. These donations must then be analyzed again and an additional sample-pack of each tubular segment must be collected, correspondent. Two next-generation secondary collections should then be formed, and the PCR analysis is repeated. This collection, formation of the collection of the subgroup, and PCR analysis process, is repeated for smaller and smaller generation secondary collections, until the method identifies, singularly, the donation vira.lmente contaminated. However, in each cycle of PCR analysis, a significant amount of time is consumed (collection, formation of subgroup collection, and PCR analysis). Taking as an example the first collection or mixture, of generation, of 512 samples, it will be evident that at least 10 cycles of PCR analysis will be required to identify a virally contaminated, unique donation. Although it is extremely cost-effective, the method described above can present challenges for a PCR analysis laboratory, when time is of the essence. A methodology to identify, in a singular way, plasma or blood donations, positively positive, through the minor number of PCR analysis cycles will now be described in relation to Figures 13 and 14. Now focusing on Figure 13, a flow diagram of a PCR analysis methodology according to the invention is shown to detect efficiently a positive individual donation to the analysis by PCR, in a collection or mixture, with the minimum number of cycles of analysis by PCR. As was the case with the previously described PCR analysis method, the method in Figure 13 assumes that the PCR analysis has sufficient sensitivity to detect the presence of a positive sample in a collection of an appropriate size. For illustration purposes only, the initial grouping has been selected to represent 512 plasma or blood donations. Those of ordinary skill in the art will understand that the size of the initial pool may be larger or smaller, depending on the corresponding genome marker, to be evaluated, depending on the sensitivity of the PCR analysis procedure, used, of the expected value of the concentration of the genome marker within an aliquot of a sample, and the size of the aliquot of the sample. The method starts in block 301, defining a matrix or grid of samples, N-dimension. The matrix can be of any size and can comprise any number of dimensions, from 2 to N, but preferably is a regular three-dimensional array, organized as a square. An example of that matrix is presented in Figure 14, which is a graphic illustration of a square matrix, characterized by three-dimensional indices; row, column, and layers (r, c, s (for its acronym in English)). In the exemplary matrix of Figure 14, there are 3 rows, 3 columns, and 3 layers, so that 27 elements are finished. In the exemplary mode, it is considered that a row comprises all the defined elements, taking a vertical, imary section, through the regular, square matrix. In the embodiment of Figure 14, the elements comprising, for example, row 3 of the matrix, are identified by the letter r3 is the fronts of his girls. Likewise, a column comprises all the elements of the matrix, taking a second vertical section through the matrix, in a direction orthogonal to the direction of a row. In the exemplary embodiment of Figure 14, the elements comprising, for example, column 1 have the letter c, on the fronts of their column. A layer or slice is defined as all elements comprising a horizontal section taken through the exemplary matrix of Figure 14. Similarly to the definition of row and column, the elements comprising the layer or slice 1 are identified with the letter Si on the fronts of its layers. It can be observed, therefore, that each of the 27 elements that are in the matrix of Figure 14 belongs, in a unique way, to 1 of the 3 rows, to 1 of the 3 columns, and to 1 of the 3 layers . Maternally this can be expressed by the relation Xr c s r where X denotes an element, and res is a dimensional index, where each of the indices can take a value from 1 to 3. specific element X113 can be identified as the element at the intersection of row 1, column 1, and layer 3. From the foregoing, it will be apparent that although the exemplary matrix of Figure 14 is a 3 x matrix 3 x 3, the principles of matrix definition and element formation will be maintained for arrays of much larger numbers of rows, columns, and layers. In particular, an 8-row, 8-column, and 8-layer matrix can still be represented mathematically as XrCs where rc and s can now take values from 1 to 8. Thus, a three-dimensional matrix, 8 x 8 x 8, It is capable of accommodating identifiers for 512 elements. Focusing now on the method of the flow diagram of Figure 13, following the definition of a sample matrix, N-dimensional, the samples of donation, blood or plasma, particulars, are removed in each one of the elements defined by the matrix. In a three-dimensional, exemplary matrix of 8 x 8 x8, a sample of each of 512 individual donations is associated with an element of the matrix, and is identified by its corresponding, unique Xres indicator. Then, an aliquot of each sample is taken, and a multiplicity of collections is formed in minor sugbrupos. Each smaller collection includes the aliquots of all the samples (XIOS) in which 1 of the dimensional indexes is fixed. In other words, in accordance with the exemplary matrix described above, all samples (Xrcs) having r = 1, without considering the value of the column or layer, are formed in a smaller collection; in the same way for r = 2, r = 3 ... r = N; in the same way for c = l, without considering the value of the row or layer, c = 2, ... c = N; in the same way, for s = l, without considering the value of the row or column, s = 2 ... s = N. Each minor collection thus represents each row, each column, layer, or other dimensional index, so that if an N-dimension matrix has been defined, there will be N-dimension ions of times (the total number of samples). / n of minor collections For the exemplary three-dimensional matrix, 8 8 x8, which contains 512 samples, there will be 24 collections of minor subgroups (8 collections of 8 rows, 8 collections of 8 columns, and 8 collections of 8 layers). The creation of minor collections, according to the invention, can be seen as something similar to the method of reducing a determinant by the method of minors. In the same way, it will be understood that each sample is represented in N minor collections, 1 for each dimension of the matrix. In addition to forming smaller collections, an aliquot of each of the smaller collections is combined to form a unique master collection that contains a sample of all 512 donations that comprise the present donation space. After all collections have been formed, remnant samples and minor collections and master collection can be frozen and stored until CPR analysis is desired. When it is desired to carry out the PCR analysis, the PCR analysis is first performed in the master collection, which represents an aliquot of each sample comprising the matrix. If the results for the master collection are negative, at least at the sensitivity level of the PCR analysis, no virally positive donation, represented by the samples, is forming the matrix. Donations of blood or plasma, which have contributed to the matrix samples, may be released for further use. However, if PCR analysis of the master collection is positive for a particular genome marker, a cycle of PCR analysis is introduced, in step 300, in which each of the minor collections is now analyzed. In a manner similar to that described above, the sizes for the main collections are selected such that the statistical probability of their at least one positive sample, in the master collection (the 512 samples) is small, preferably less than 1 to 2%. This can be done through the evaluation of the frequency of the appearance of the virus of interest in the general population of donors, with a confidence level of 98% to 99%. For example, if it is determined that only one donor, one General population of 1,000 donors, is contaminated with the virus of interest, at a confidence level of 98%, there is a 2% chance of finding more than 1 contaminated donor in the next 1,000 donors evaluated. This ensures that the algorithm will be able, in general, to identify reactive, singular units, in a collection or mixture of appropriate size, within the PCR analysis cycle. In accordance with the invention, given a positive individual sample, within the matrix, 3 of the minor collections will contain an aliquot of the positive donation, 1 in each dimension. In the exemplary mode (the matrix of 512 samples) there are 8 smaller collections in rows, 8 smaller collections in rows, and 8 smaller collections in layers. If the result of the analysis of the master harvest is positive, then a 1-row, 1-column, and 1-layer harvest will be positive during the second cycle of PCR analysis, as shown in block 307. The intersection of the index of the element of the row, the column, and the layer, identifies, unambiguously, Reactive donation, as shown in block 309. As an example, if a map of the reactive sample has been drawn on element X? 13, the minor collection of row 1 will produce a positive result in the analysis by PCR, while the smaller collections of row 2, and the subsequent rows will see a negative result to the test. In addition, the minor collection of column 1 will produce a positive result to the analysis, while the collections of column 2 and subsequent columns will give a negative result. Similarly, minor collections of layer 1 and 2 will produce a negative result, the collection of -the. Layer- 3 will give a positive result to the analysis, and smaller collections of the subsequent layers will give a negative result to the analysis. . The 3 positive minor collections (row 1, column 1, and layer 3), have only one element in common, XH3- Thus, the positive donation is uniquely identified, as represented by the map raised from the sample for the element Xll3 - If there is more than one reactive donation in the matrix, the reactive donations can still be unambiguously identified through the method of the invention, performing no more than one cycle of analysis per CPR, additional. It is observed that more than 1 minor collection of a single dimensional index produces a positive analysis result, while only a single minor collection that represents each of the remaining dimensional indices produces a positive analysis result, and the most of 1 positive donations can be identified in an unambiguous way through the mathematical evaluation of the results of analyzes are the need for a third cycle of analysis by CPR. For example, if a smaller collection of row 1, and no other collection, is positive; a smaller collection of column 1, and no other, is positive; and a smaller collection of layer 1 and a smaller collection of layer 3, both are positive, there are only two positive donations that comprise the matrix, and are able to be unambiguously identified as Xin and x113- 'Not required of the additional analysis to arrive at this result.

If, on the other hand, it is observed that multiple minor collections are positive in the analysis and their identities indicate changes along 2 dimensional indexes, as shown in 310, it will be apparent that there will be z elements identified as potentially mapped for a positive donation. , where z is the actual number of positive donations that compose the grid. For example, if the minor collection of row 1, and no other, is positive, the smaller collections of column 1 and column 3 are positive, and the smaller collections of layer 1 and layer 3 are positive, this suggests that the potentially active candidate elements are Xi i ± r x131 'Y x133- Since there is a multiple of only two of the dimensional indices (column and layer), and for candidate elements, it will be observed that there are only two real positive donations that the matrix comprises. In this circumstance all 4 donations can be found arbitrarily as positive, and discarded or, alternatively, an aliquot of each of the 4 candidate elements can be taken and analyze individually by CPR during a third cycle of analysis by CPR, in 311, to identify in a unique way that 2 of the 4 include real positive donations. In the same way, it is mathematically -evident that if there are more than 2 positive donations in the matrix and their identifiers vary in more than 2 dimensions, there will be at most, zn elem.entos candidates, potentially positive, identified, where z is the actual number of positive donations , and where n is the number of dimensions that vary. In this circumstance, aliquots of all suspicious elements are taken in the matrix and analyzed directly. Thus, it can be observed that the method of the invention allows unambiguous identification of donations that are reactive for a particular genome marker within a single PCR analysis cycle, for an initially positive master collection, in 2 analysis cycles. by PCR, for all matrices that contain a single reactive donation or a multiplicity of reactive reactions that vary along with only a single dimensional index, and in 3 cycles of analysis by CPR for any other situation.

Accordingly, the practice of the present invention results in the delivery of blood, and blood or plasma products prepared therefrom, which are substantially safer by virtue of being free, as much as possible, from viral contamination. Advantageously, the high sensitivity analysis, effective with respect to cost, is easily carried out to analyze the presence of a virus directly. Thus, false indications of virus contamination usually associated with antibody analysis during the window period of infectivity are avoided. In addition, the present invention allows the use, effective against cost, of high sensitivity analyzes that are capable of detecting the presence of a single virus in the test sample, thus helping to ensure the lack of incipient viral contamination of the blood supply. Those skilled in the art will appreciate that the foregoing examples and descriptions of various preferred embodiments of the present invention are merely illustrative of the invention as a whole, and that variations in the shape, size, and number of various embodiments can be made. components of the present invention, as well as in the types of analysis implemented, within the spirit and scope of the invention. For example, it will be clear to a person skilled in the art that the length of the individual and connected bags, and therefore their volumetric content, can be progressively increased along the length of the tubular segment. How secondary collections are made for the successive analysis, from smaller and smaller sample numbers, the volume of plasma that includes the collection necessarily decreases. It should be clear that in order to maintain a sufficient volume of plasma in each successive secondary collection, the bags of successive samples may contain a larger volume to accommodate a desired final collection volume. To accommodate collections ranging in size from about 1 ml to about 10 ml, it will be clear that the volumes of successive sample bags will increase from about 0.02 ml to 0.5 ml, in incremental steps. In an exemplary embodiment, the volume of the bag is 0.02 ml in the first bag that is going to be used, in the largest collection, and 0.2 in the final bag. It will also be clear to those skilled in the art that the system of the invention is not limited to the exemplary container for plasma collection and an associated tubular segment. Blood bags or other containers for biological fluids can be used with equal ease and can be attached to the same suitable tubular segments, both before the fluid is collected and after the end of the collection thereof. All that is required is that quantities of biological fluid samples are transferred to a tubular segment which then takes the form of bags, in accordance with the practice of the invention. Accordingly, the present invention is not limited to the specific embodiments described therein but, on the contrary, is defined by the scope of the appended claims.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention. Having described the invention as above, property is claimed as contained in the following:

Claims (19)

1. A method for identifying, in a singular or original way, donations of biological fluids, virally positive, in the least number of cycles of analysis by the Polymerase Chain Reaction (PCR), the method is characterized in that it comprises: providing a multiplicity of donations of biological fluids; define an n-dimensional matrix, where n is an integer, the matrix also comprises a multiplicity of internal elements, each element is defined by an intersection of n dimensions of the matrix, each individual element is identified by a respective matrix notation, matrix notation comprises at least one index for each dimension of the array; take a sample of each of the multiplicity of donations of biological fluids; erect a map of each sample for each particular element, respective, of the matrix, and each individual sample is identified by its respective matrix notation of the corresponding element; take aliquots of each sample, and the number of aliquots taken from each sample is defined by the number of dimensions that characterize the matrix; form secondary collections of the aliquots of each sample, each secondary collection contains an aliquot of all the samples identified by a matrix notation in which a dimensional index is fixed, and each respective secondary collection is identified by that fixed dimensional index; provide secondary collections to a facility for analysis by RCP, where all the secondary collections are analyzed with respect to viral signs, in a single cycle of analysis by PCR; determine the fixed, respective dimensional indices of the secondary collections that produce a positive viral indication; and combining the fixed dimensional indexes in a matrix notation, identifying with it a non-ambiguous single matrix element, defined by matrix notation, thus unambiguously identifying a virally positive, unique sample.

2. The method according to claim 1, characterized in that the matrix is constructed as a regular array, and each of the n dimensions of the array is characterized by an integer, equal number of elements.

3. The method according to claim 2, characterized in that the regular array comprises a three-dimensional array, and the array is further divided into two rows, columns, and layers, wherein each element is characterized by a matrix notation Xrcs, wherein the indexes Dimensions, r, c, and s, respectively, identify elements that comprise a row, a column, and an array layer.

4. The method according to claim 3, characterized in that the step of forming the secondary collection further comprises: form secondary collections of aliquots, from samples identified by identical indices "r" but by different cys indices, form secondary collections of aliquots, from samples identified by identical c indices but different indexes, form secondary collections of aliquots, from of samples identified by identical indices but with different r and c indices, and evaluating each of the secondary collections related to the r, c, and s indices, for a virally positive indication produced by the PCR analysis.

5. The method according to claim 4, characterized in that it further comprises the steps of: determining the entire index of each secondary collection r that produces a positive viral indication; determine the entire index of each secondary collection c that produces a positive viral indication; Y determine the entire index of each secondary collection that produces a positive viral indication.

6. The method according to claim 5, characterized in that it also comprises the step of substituting the entire indices of each of the secondary recollections r, c, and s, which produce a positive viral indication for the dimensional indices r, c and s of the matrix notation. , identifying with it a single matrix element defined by matrix notation, thus uniquely identifying the corresponding virally positive sample.

7. The method according to claim 6, characterized in that the three-dimensional array comprises a regular array of 8 x 8 x8, wherein the dimensional indices r, c, and s each take integer values from 1 to 8.

8. The method according to claim 7, characterized in that three aliquots are taken from each respective sample of the donations of biological fluids.

9. The method according to claim 8, characterized in that it further comprises the steps of: forming eight secondary collections in rows, each secondary collection in a row is singularly identified by an integer from 1 to 8, each secondary collection in a row is formed of aliquots of 64 samples; forming 8 secondary collections in columns, and each secondary collection in column is uniquely identified by an integer from 1 to 8, and each secondary collection in column is made up of aliquots of 64 samples; and forming 8 secondary collections in layers, and each secondary collection in layers is uniquely identified by an integer from 1 to 8, and each secondary collection in layer is made up of aliquots of 64 samples.

10. A method to ident in a singular or original way, donations of viral positive biological fluids, in the least number of cycle of analysis by the Polymerase Chain Reaction (PCR), and the method is characterized because it comprises: provide a multiplicity of donations of biological fluids; defining an n-dimensional matrix, where n is an integer, the matrix also comprises a multiplicity of internal elements, each element is defined by an intersection of n-dimensions of the matrix, where each individual element is identified by a notation respective matrices i ... N 'where the matrix notation subscript defines the dimensional index of the array; take N aliquots of each sample from each multiplicity of donations of biological fluids, the number of aliquots taken from each sample is defined by the number of dimensional indices that comprise the array; form secondary collections of the aliquots of each sample, each secondary collection includes an aliquot of all the samples identified by a matrix notation in which a dimensional index is fixed; provide secondary collections to a facility for PCR analysis, where all secondary collections they are analyzed with respect to viral signs in a first cycle of analysis by PCR; and evaluate the dimensional indices of each secondary collection that produce a positive viral indication, in the first cycle of analysis by PCR, in accordance with a reduction by the juvenile method, the evaluation identifies a single element defined by the dimensional indices of each, positive secondary collection if only a single secondary collection, representing each dimensional index, produces a positive viral indication, thus unambiguously identng a virally positive sample.

11- The method according to claim 10, characterized in that the matrix is constructed as a three-dimensional, regular array, and the array is further subdivided into rows, columns, and layers, wherein each element is characterized by a matrix notation Xrcs, where the dimensional indices r, c, and s, respectively, identelements that comprise a row, a column and an array layer.

12. The method according to claim 1, characterized in that the evaluation of the dimensional indexes identifies a multiplicity of elements defined by the dimensional indices of each positive secondary collection, if more than one secondary collection of a particular dimensional index produces a viral indication positive whereas only a secondary, singular collection, which represents each of the remaining dimensional indices, produces a positive viral indication, thus identng unambiguously more than one of the virally positive samples, unique.

13. The method according to claim 12, characterized in that the evaluation of the dimensional indices identifies • Potentially positive viral candidate elements, if multiple secondary collections representing each dimensional index produce a positive viral indication, where z represents the actual number of virally positive samples and where n represents the number of viral samples. dimensions that has multiple positive secondary collections.

14. The method according to claim 13, characterized in that it further comprises the step of taking an additional aliquot of each sample identified for each of the zn candidate, virally positive elements; provide the aliquots to an installation for the analysis by RCP, where all the aliquots are analyzed with respect to viral indications in a second cycle of analysis by PCR; and identify, unambiguously, all virally positive samples.

15. The method according to claim 11, characterized in that the step of forming a secondary collection, further comprises: forming secondary collections of aliquots from samples identified by identical r-indexes but with different c and s indices; form secondary collections of aliquots, from samples identified by identical c indices but by different r and s indices; form secondary collections of aliquots, from samples identified by identical indices but different indices r and c; And evaluate each of the secondary collections r, c, and s with respect to the virally positive indication produced by the PCR analysis.

16. The method according to claim 15, characterized in that it further comprises the steps of: determining the entire index of each secondary collection r that produces a positive viral indication; determine the entire index of each secondary collection c that produces a positive viral indication; and determine the entire index of each secondary collection that produces a positive viral indication.

17. The method according to claim 16, characterized in that it also comprises the step of substituting the entire indices of each secondary collection r, c, and s, which produce a positive viral indication for the dimensional indices r, c, and s of the matrix notation, identifying therefore a single matrix element defined by the matrix notation, thus identifying in a singular or original way the corresponding virally positive sample.

18. The method according to claim 17, characterized in that the three-dimensional array comprises a regular array of 8 x 8 x 8, wherein the dimensional indices r, c, and s each take integer values from 1 to 8.

19. The method according to claim 18, characterized in that it further comprises the steps of: forming eight secondary collections in rows, each secondary collection in a row is singularly identified by a whole number of 1 to 8, each secondary collection in a row is made up of aliquots of 64 samples; forming eight secondary column collections, each secondary collection column is uniquely identified by an integer from 1 to 8, each secondary column collection is made up of aliquots of 64 samples; and forming eight secondary collections in layers, each secondary collection in layers is uniquely identified by an integer from 1 to 8, and each secondary collection in layer is formed by aliquots of 64 samples. SUMMARY OF THE INVENTION The present invention provides systems, methods and devices which are useful for analyzing blood or plasma donations, to detect those specific donations which are contaminated by a virus above a predetermined level. An apparatus and a process are described which form sample containers connected and sealed separately, individual, from a hollow, flexible tubular segment, connected to a container for the donation of fluid. The tubular segment is sealed at spaced intervals, along its length, with tubular segment portions in the intervals between the seals defining the containers, each of which holds a portion of a plasma sample. The contents of the containers are formed in blood collections which are subsequently tested for contamination by viruses through a high sensitivity analysis such as the Polymerase Chain Reaction (PCR), the blood collections are analyzed according to with an algorithm by which a sample of each donation is explored or represented for each element of an N-dimension matrix or grid. Each element of the matrix is identified by a matrix identifier, Xrcs, where res defines the dimensional index. An aliquot is taken from each sample, and secondary blood collections are formed, each secondary blood collection comprising aliquots of samples in which it is fixed, a dimensional index. All secondary blood collections are tested in a cycle of PCR analysis. The dimensional index of each secondary collection of positive blood is evaluated mathematically according to a reduction by the minor determinant method, for this reason a single element in the grid is clearly identified, for which a donation is unambiguously identified of plasma or positive blood, in a singular or original way.