Abstract:
The present invention provides a filtration assembly in the form of a disposable cartridge. A key feature of the invention is a filtration chamber having a porous membrane also referred to as a filter, a sample inlet to the filtration chamber, and an outlet for outflow of the fraction of sample that does not penetrate the membrane. The membrane can be used in any configuration, for example a hollow fiber. The fraction of sample that penetrates the membrane is referred to as the filtrate, and the fraction that does not penetrate the membrane is referred to as the retentate or concentrate. Some uses of the cartridge are to prepare plasma from blood, and to prepare a plasma ultra-filtrate from plasma, without the need for centrifugation. Many therapeutic drugs are highly protein bound, and a plasma ultra-filtrate is sometimes required to measure the unbound biologically active drugs.

Description:
RELATED APPLICATIONS 
       [0001]    This application is a Nonprovisional United States patent application, claiming the benefit of U.S. Provisional Patent Application No. 61/510,506, filed 22 Jul. 2011. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The invention relates to a filtration assembly that can be used to extract a filtrate from a sample or prepare a concentrate from the sample. 
       BACKGROUND OF THE INVENTION 
       [0003]    Many medical diagnostic tests are performed in a medical laboratory, on serum and plasma. Serum is the yellow liquid obtained from blood after the blood is allowed to clot, and the clot is removed by centrifugation; plasma is the yellow liquid obtained from blood by centrifugation of blood mixed with an anticoagulant, e.g. heparin. Whole blood comprises the formed elements (i.e., the cellular components and the cell-derived components), and plasma. Red blood cells are the most abundant formed elements in blood, and platelets are examples of cell-derived components. In the case of a blood sample, the filtrate usually refers to the blood plasma (or simply, plasma), depending on the size of the pores in the porous membrane, and the retentate or concentrate usually refers to blood with enriched concentration of cellular components. 
         [0004]    For Point-of-Care Testing (POCT), whole blood is usually used because the sample does not have to be processed before testing. If serum and plasma were as easily available as whole blood, the serum and plasma would be preferred because they are not as complex as blood, and therefore serum and plasma would produce more accurate test results. Plasma is usually preferred over serum because the blood needs to sit at room temperature for about half an hour in order to complete the clotting process, and then the serum is extracted by centrifugation of the sample; blood can be centrifuged immediately after the blood is collected in a tube containing an appropriate anticoagulant, in order to extract the plasma from the blood. 
         [0005]    The inventor was awarded U.S. Pat. Nos. 7,816,124 and 7,807,450 that disclose cartridges for rapidly extracting plasma from blood. These cartridges can be used to virtually collect plasma directly from a patient&#39;s blood vessel or from some other blood supply. The cartridges use negative pressure created by manually compressing flexible members of compression chambers, for creating blood flow, and for pulling plasma from whole blood across a membrane. U.S. Pat. Nos. 7,816,124 and 7,807,450 describe the use of the thumb and forefinger for compressing flexible members of blood and plasma compression chambers. U.S. Pat. Nos. 7,816,124 and 7,807,450 also described flexible members that possess physical properties that will allow the flexible members to rebound at desired speed. Nevertheless, there is still a need for an apparatus that extracts plasma from blood in a simpler and more efficient manner. Particularly, there is a need for a cartridge that can be used instead of an evacuated tube, whereby no centrifugation has to be performed in order to extract the plasma. 
         [0006]    There is also a need to extract an ultra-filtrate from a sample, for example serum or plasma, without the need for centrifugation. Many therapeutic drugs, ions and hormones are highly protein bound. Only the free therapeutic drugs, ions and hormones are available to cross vascular walls and biological membranes in order to interact with biologically important binding sites. Some examples of a therapeutic drug, an ion and hormone are phenytoin, calcium and thyroid hormones (T3 and T4) respectively. 
         [0007]    Phenytoin, for example, is a therapeutic drug used to treat epilepsy. In the blood, about 90% of the phenytoin is bound to plasma proteins. Only the portion of phenytoin that is unbound or “free” is pharmacologically or biologically active. A test for total phenytoin represents the sum of the bound and unbound phenytoin. Under normal conditions, the balance between bound and unbound phenytoin in the blood is relatively stable, so measuring the total phenytoin is appropriate for monitoring therapeutic levels of phenytoin. However, in certain conditions and disease states, that balance can be upset, causing the percentage of free or active phenytoin to increase. Consequently, a patient may experience symptoms of phenytoin toxicity even though the total phenytoin result falls within a therapeutic range. In such cases, doctors may order a free phenytoin test to more reliably monitor the patient&#39;s phenytoin levels, instead of a test for total phenytoin. 
         [0008]    One method used to measure free phenytoin in a patient&#39;s serum or plasma sample involves: 1) adding the patient&#39;s sample to the sample reservoir of an ultra-filtration device; 2) capping the sample reservoir; 3) placing the ultra-filtration device in a centrifuge and centrifuging for about 25 minutes; and 4) measuring total phenytoin in the ultra-filtrate of the serum or plasma. 
         [0009]    As in the case of extracting plasma from whole blood, there is a need to eliminate the step of centrifugation in order to measure free phenytoin. Because the size of the proteins that bind phenytoin is larger than the pore size of the membrane in the ultra-filtration device, the bound phenytoin cannot travel with the ultra-filtrate. 
         [0010]    In the case of a serum or plasma sample, the filtrate (or more appropriately, referred to as an ultra-filtrate) usually refers to the serum or plasma containing the smaller molecular weight substances like the free phenytoin, and the retentate usually refers to serum or plasma containing the higher molecular weight substances like the proteins that bind phenytoin. An example of such a protein is albumin, having a molecular weight of about 66 kilodaltons. In contrast, the molecular weight of phenytoin is about 0.25 kilodaltons. A person of ordinary skill in the art will appreciate that an ultra-filtrate is still a filtrate, and the term ultra-filtrate is only used for clarity when the starting sample is plasma, for example, which is already considered to be a filtrate of blood. 
         [0000]    By way of examples only, some embodiments of a cartridge or filtration assembly can be used to perform the following: extract plasma from whole blood; extract cell-free liquid from a non-blood sample comprising cells; extract a plasma ultra-filtrate containing a free drug/hormone from plasma; and concentrate the drug/hormone or cellular components of a sample. Some advantages of the embodiments of the present invention over U.S. Pat. Nos. 7,816,124 and 7,807,450 awarded to the inventor will be described. 
       SUMMARY OF THE INVENTION 
       [0011]    According to an aspect of an embodiment of the invention there is provided a filtration assembly for preparing a filtrate or a retentate from a liquid sample, the assembly comprising: a) a housing; b) an inlet in the housing for receiving the liquid sample; c) a filtration chamber comprising a membrane having a retentate side and a filtrate side; d) a retentate flow path in the housing comprising the retentate side of the membrane and a dead-end channel for trapping air; e) means for compressing and decompressing the air in the dead-end channel to facilitate filtration of the liquid sample across the membrane; and f) an outlet for removing at least one of the filtrate and the retentate from the housing. 
         [0012]    According to yet another aspect of an embodiment of the invention, there is provided a filtration assembly for preparing a filtrate or a retentate from a liquid sample, the assembly comprising: a) a housing; b) an inlet in the housing for receiving the liquid sample; c) a filtration chamber comprising a membrane having a retentate side and a filtrate side; d) a retentate flow path in the housing comprising the retentate side of the membrane; e) a filtrate flow path beginning at the filtrate side of the membrane and terminating at a manually operable filtrate compression chamber comprising a frictionally engaged plunger for modulating pressure inside the manually operable filtrate compression chamber; and f) an outlet for removing at least one of the filtrate and the retentate from the housing. 
         [0013]    According to yet another aspect of an embodiment of the invention, there is provided a filtration assembly for preparing a filtrate from a liquid sample, the assembly comprising: a) a housing; b) an inlet in the housing for receiving the liquid sample, the inlet having a pierceable septum; c) a filtration chamber comprising a membrane having a retentate side and a filtrate side; d) a retentate flow path in the housing comprising the retentate side of the membrane and a manually operable retentate compression chamber; and e) an outlet for removing the filtrate from the housing. 
         [0014]    Other aspects and features of the present invention will become apparent, to those ordinarily skilled in the art, upon review of the following description of the specific embodiments of the invention. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0015]    For a better understanding of the present invention, and to show more clearly how it may be carried into effect, reference will now be made, by way of example, to the accompanying drawings, which illustrate aspects of embodiments of the present invention and in which: 
           [0016]      FIG. 1A  is a schematic drawing showing details of a top view of double-ended needle assembly  20 , which may be used with some embodiments of the present invention; 
           [0017]      FIG. 1B  is a right side view of the double-ended needle assembly shown in  FIG. 1A ; 
           [0018]      FIG. 1C  is a cross-sectional view through the double-ended needle assembly shown in  FIG. 1A  along line C-C; 
           [0019]      FIG. 1D  is a detailed view of the detail D shown in  FIG. 1C ; 
           [0020]      FIG. 1E  is a perspective view of the double-ended needle assembly shown in  FIG. 1A ; 
           [0021]      FIG. 2A  is schematic drawing showing details a double-ended needle assembly  20  shown in  FIG. 1A , with an evacuated tube  26  inserted into the tube holder  10 ; 
           [0022]      FIG. 2B  is a right side view of the double-ended needle assembly and evacuated tube shown in  FIG. 2A ; 
           [0023]      FIG. 2C  is a cross-sectional view through the double-ended needle assembly and evacuated tube shown in  FIG. 2A  along line C-C; 
           [0024]      FIG. 2D  is a perspective view of the double-ended needle assembly and evacuated tube shown in  FIG. 2A ; 
           [0025]      FIG. 3A  is a schematic drawing showing details of a front view of a filtration assembly  30  suitable for extraction of a filtrate from a sample according to a first embodiment of the invention; 
           [0026]      FIG. 3B  is a top view of the assembly  30  shown in  FIG. 3A ; 
           [0027]      FIG. 3C  is a cross-sectional view through the assembly  30  shown in  FIG. 3A  along line C-C; 
           [0028]      FIG. 3D  is a detailed view of the detail D shown in  FIG. 3C , showing a schematic representation of the filtration chamber; 
           [0029]      FIG. 4A  is a schematic drawing showing details of a top view of the assembly  30  shown in  FIG. 3A  inserted into the tube holder  10  of the double-ended needle assembly  20  shown in  FIG. 1A ; 
           [0030]      FIG. 4B  is a first cross-sectional view through the filtration assembly  30  shown in  FIG. 4A  along line B-B; 
           [0031]      FIG. 4C  is a second cross-sectional view through the filtration assembly  30  and double-ended needle assembly  20  shown in  FIG. 4A  along line C-C; 
           [0032]      FIG. 4D  is a perspective view of the assemblies shown in  FIG. 4A ; 
           [0033]      FIG. 5A  is schematic drawing showing details of a hollow fiber membrane bundle  76   a  shown in  FIGS. 3C and 3D ; 
           [0034]      FIG. 5B  is a cross-sectional view through the hollow fiber membrane bundle  76   a  shown in  FIG. 5A  along line B-B; 
           [0035]      FIG. 5C  is a perspective view of the hollow fiber membrane bundle  76   a  shown in  FIG. 5A ; 
           [0036]      FIG. 5D  is a detailed view of detail D shown in  FIG. 5B  showing a schematic representation of the membrane  82 ; 
           [0037]      FIG. 6A  is a schematic drawing showing details of a front view of a filtration assembly  40  suitable for extraction of a filtrate from a sample according to a second embodiment of the invention; 
           [0038]      FIG. 6B  is a first cross-sectional view through the assembly  40  shown in  FIG. 6A  along line B-B; 
           [0039]      FIG. 6C  is a second cross-sectional view through the assembly  40  shown in  FIG. 6B  along line C-C; 
           [0040]      FIG. 7A  is a schematic drawing showing details of a front view of a filtration assembly  50  suitable for extraction of a filtrate from a sample according to a third embodiment of the invention, engaged with a hollow needle assembly  144 ; 
           [0041]      FIG. 7B  is a cross-sectional view through the assemblies shown in  FIG. 7A  along line B-B; 
           [0042]      FIG. 7C  is a perspective view of the assemblies shown in  FIG. 7A ; 
           [0043]      FIG. 8A  is a schematic drawing showing details of a front view of a filtration assembly  60  suitable for extraction of filtrate from a sample according to a forth embodiment of the invention; 
           [0044]      FIG. 8B  is a perspective view of the assembly  60  shown in  FIG. 8A ; 
           [0045]      FIG. 8C  is a cross-sectional view through the filtration assembly  60  shown in  FIG. 8A  along line C-C; 
           [0046]      FIG. 9  is a self-explanatory illustration of a plurality of positions of 3-way and 4-way valves, showing Type-T and Type-L; 
           [0047]      FIG. 10A  is a schematic drawing showing details of a front view of a filtration assembly  70  suitable for extraction of filtrate from a sample according to a fifth embodiment of the invention; 
           [0048]      FIG. 10B  is a first cross-sectional view through the filtration assembly  70  shown in  FIG. 10A  along line B-B; 
           [0049]      FIG. 10C  is a second cross-sectional view through the filtration assembly  70  shown in  FIG. 10B  along line C-C; 
           [0050]      FIG. 11A  is a schematic drawing showing details of a front view of a filtration assembly  80  suitable for extraction of filtrate from a sample according to a sixth embodiment of the invention; 
           [0051]      FIG. 11B  is a top view of the filtration assembly  80  shown in  FIG. 11A ; 
           [0052]      FIG. 11C  is cross-sectional view through the filtration assembly  80  shown in  FIG. 11A  along line C-C; 
           [0053]      FIG. 11D  is a perspective view of the filtration assembly  80  shown in  FIG. 11A ; 
           [0054]      FIG. 12A  is a schematic drawing showing details of a front view of a filtration assembly  90  suitable for extraction of filtrate from a sample according to a seventh embodiment of the invention; 
           [0055]      FIG. 12B  is a first perspective view of the filtration assembly  90  shown in  FIG. 12A   
           [0056]      FIG. 12C  is a cross-sectional view through the filtration assembly  90  shown in  FIG. 12A  along line C-C; 
           [0057]      FIG. 12D  is a second perspective view of the filtration assembly  90  shown in  FIG. 12A ; 
           [0058]      FIG. 13A  is a schematic drawing showing details of a perspective view of a filtration assembly  100  suitable for extraction of filtrate from a sample according to a eight embodiment of the invention, with a syringe  184  attached; 
           [0059]      FIG. 13B  is a front view of the filtration assembly  100  shown in  FIG. 13A , with a syringe  184  attached; 
           [0060]      FIG. 13C  is cross-sectional view through the filtration assembly  100  shown in  FIG. 13B  along line C-C, showing opening  54   b  absent syringe  184 ; 
           [0061]      FIG. 14A  is a schematic drawing showing details of a front view of a filtration assembly  110  suitable for extraction of filtrate from a sample according to a ninth embodiment of the invention; 
           [0062]      FIG. 14B  is a top view of the filtration assembly  110  shown in  FIG. 14A ; 
           [0063]      FIG. 14C  is a cross-sectional view through the filtration assembly  110  shown in  FIG. 14A  along line C-C; 
           [0064]      FIG. 14D  is a perspective view of the filtration assembly  110  shown in  FIG. 14A . 
           [0065]      FIG. 15A  is a schematic drawing showing details of a front view of a filtration assembly  120  suitable for extraction of filtrate from a sample according to a tenth embodiment of the invention, with a syringe  184   b  attached; 
           [0066]      FIG. 15B  is a cross-sectional view through the filtration assembly  120  shown in  FIG. 15A  along line B-B; 
           [0067]      FIG. 15C  is a perspective view of the filtration assembly  120  shown in  FIG. 15A , showing inlet opening  22   c  absent syringe  184   b;    
           [0068]      FIG. 15D  is a cross-sectional view through the filtration assembly  120  and syringe  184   b  shown in  FIG. 15B  along line D-D; 
           [0069]      FIG. 15E  is an enlarged perspective view of a pivotal frictionally engaged plunger  44   b  of the compression chamber  64  shown in  FIG. 15D . 
           [0070]      FIG. 16A  is a schematic drawing showing details of a front view of a filtration assembly  130  suitable for extraction of filtrate from a sample according to an eleventh embodiment of the invention; 
           [0071]      FIG. 16B  is a first cross-sectional view through the filtration assembly  130  shown in  FIG. 16A  along line B-B; 
           [0072]      FIG. 16C  is a top view of the filtration assembly  130  shown in  FIG. 16A ; 
           [0073]      FIG. 16D  is a second cross-sectional view through the filtration assembly  130  shown in  FIG. 16C  along line D-D; 
           [0074]      FIG. 16E  is a third cross-sectional view through the filtration assembly  130  shown in  FIG. 16C  along line E-E; 
           [0075]      FIG. 17A  is a schematic drawing showing details of a front view of a filtration assembly  140  suitable for extraction of filtrate or concentrate from a sample according to a twelfth embodiment of the invention; 
           [0076]      FIG. 17B  is a first cross-sectional view through the filtration assembly  140  shown in  FIG. 17A  along line B-B; 
           [0077]      FIG. 17C  is a second cross-sectional view through the filtration assembly  140  shown in  FIG. 17B  along line C-C; 
           [0078]      FIG. 17D  is a perspective view of the filtration assembly  140  shown in  FIG. 17A ; and 
           [0079]      FIG. 17E  is a perspective view of the filtration assembly  140  shown in  FIG. 17D , with all the parts hidden except the plungers  42   c  and  44   c , and the corresponding springs  92   a  and  92   b.    
       
    
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
       [0080]    Several embodiments of a filtration assembly and their advantages over the prior art are discussed. A basic filtration chamber comprises a sample inlet, a porous membrane (also referred to as a filter, a membrane or a membrane filter) of any configuration, a sample outlet for outflow of sample that does not penetrate the membrane (referred to as the retentate or concentrate), and an outlet for the sample that penetrates the membrane (referred to as the filtrate). The sample is usually a liquid, absent cellular components or comprising cellular components. An example of a liquid absent cellular components is plasma, and an example of a liquid that comprises cellular components is whole blood (also referred to as blood). The sample introduced at the inlet of the filtration assembly is referred to as the primary sample. 
         [0081]    Although blood is used as an example of a primary sample comprising cellular components, when describing some of the embodiments, one of ordinary skill in the art will appreciate that the invention is not limited to processing blood, serum or plasma. 
         [0082]    In order to illustrate most of the embodiments of the present invention clearly, reference is made to blood as the sample because blood was the sample and plasma extracted from the blood was the filtrate described in the prior art (U.S. Pat. Nos. 7,816,124 and 7,807,450), and because it easier to describe the invention using one or more than one blood flow path and one or more than one plasma flow path. 
         [0083]    In order to appreciate some aspects of the embodiments illustrated in the figures provided, and examples of usefulness, relevant prior art is provided in  FIGS. 1A-1D  and  2 A- 2 D. Prior to the invention of the double-ended needle, single ended needles attached to syringes were used to draw blood from a patient&#39;s blood vessel. A single ended needle refers to a hypodermic needle with a sharp open end for insertion into a patient&#39;s blood vessel, and a blunt open end for engagement with a syringe. By way of an example, a double-ended needle assembly is illustrated as assembly  20  shown collectively in  FIGS. 1A-1E . A double-ended needle assembly refers to an apparatus commonly used to draw blood from a patient, having a blood supply end and a collection end. Both ends are sharp and open. During use, the blood supply end is inserted in the patient&#39;s blood vessel. The collection end is used to pierce the septum or cap of an evacuated tube. The negative pressure in the evacuated tube causes blood to flow from the patient into the evacuated tube. The blood draw, i.e., the maximum amount of blood that is allowed to enter the tube, depends on the magnitude of the negative pressure in the tube. The blood supply end and the collection end in some double-ended needle assemblies are connected by a piece of tubing of any desired length. An example of a double-ended needle assembly is illustrated in  FIGS. 1A-1D . In this example, the double-ended needle is of rigid construction, showing the sharp portion  12  of the blood supply end, and the sharp portion  16  of the blood collection end. 
         [0084]      FIG. 1A  is a schematic drawing showing details of a top view of double-ended needle assembly, having an evacuated tube holder  10 .  FIG. 1B  is a right side view of the double-ended needle assembly shown in  FIG. 1A .  FIG. 1C  is a cross-sectional view through the double-ended needle assembly shown in  FIG. 1A  along line C-C.  FIG. 1D  is a detailed view of the detail D shown in  FIG. 1C . The detailed view of the collection end illustrated in  FIG. 1D  also shows the lumen  18  of the needle, which runs from the sharp end  16  to the sharp end  12 . The collection end  16  is covered with a pierceable and flexible sheath  14 , which acts as a valve to prevent blood flow after the sharp end  12  is inserted into the patient&#39;s blood vessel.  FIG. 1E  is a perspective view of the assembly  20 . 
         [0085]      FIG. 2A  is a schematic drawing showing details of a top view of an evacuated tube  26  engaged with the tube holder  10  illustrated in  FIG. 1A .  FIG. 2B  is a right side view of the evacuated tube  26  engaged with the tube holder  10 . The evacuated tube  26  is covered with a rubber septum  28 .  FIG. 2C  is a cross-sectional view through the double-ended needle and tube assembly shown in  FIG. 2A  along line C-C.  FIG. 2D  is a perspective view of the double-ended needle and tube assembly shown in  FIG. 2A . Although  FIG. 2C  does not show the needle unsheathed, unsheathing the collection end  16  of the needle occurs when the needle is pushed against the septum  28  of the tube  26 , allowing blood to flow into the tube. 
         [0086]    Referring collectively to  FIGS. 3A-3D , shown are schematic drawings illustrating details of a filtration assembly  30  suitable for, for example, extraction of plasma from a whole blood sample according to a first embodiment of the invention. A person of ordinary skill in the art will appreciate that blood is used for illustration only, and the present invention is not limited in any way to processing blood.  FIG. 3A  is a front view of the filtration assembly  30 .  FIG. 3B  is a top view of the assembly  30  shown in  FIG. 3A .  FIG. 3C  is a cross-sectional view through the apparatus  30  shown in  FIG. 3A  along line C-C.  FIG. 3D  is a detailed view of the detail D shown in  FIG. 3C , which is a schematic representation of the filtration chamber. 
         [0087]      FIG. 3C  is used to illustrate some features of the first embodiment of the filtration assembly  30 . A septum  48  is shown as a cap placed over the inlet opening  22   a  of the assembly  30 . A septum refers to a wall separating two compartments, preventing fluid communication between the two compartments except when the wall is pierced with, for example, the collection end  16  of a double-ended needle assembly shown in  FIG. 1D . A person of ordinary skill in the art will appreciate that although septum  48  is illustrated as a cap-like structure attached to the inlet opening  22   a , the septum in some embodiments is an integral part of the housing  32 . A feature of the septum  48  is that it temporarily closes the inlet opening  22   a  of assembly  30 , and that the septum  48  is pierceable. However, septum  48  of the present invention is optional, as illustrated in assembly  140 , for example, shown in  FIGS. 17B and 17D . By being pierceable, the sharp end of a hollow needle can pierce the septum, creating an opening via the lumen of the needle, for causing blood to flow from a blood supply into the blood flow path (defined later) of filtration assembly  30 . Therefore, in this embodiment of the invention, the septum is considered to be a component of the inlet of assembly  30 . The housing inlet in a filtration assembly refers to the general area around the inlet opening  22   a  as shown in  FIGS. 3B and 3C . A person of ordinary skill in the art will appreciate that the housing inlet also refers to the general area around inlet open  22   b  of assembly  40  shown in  FIGS. 6A and 6B , although the assembly  40  does not include a septum identified as  48  in  FIG. 3C . Non-limiting examples of a blood supply are: a patient&#39;s blood vessel, blood in a blood bag, blood in a syringe, and blood in an evacuated tube. An advantage of having a septum at the inlet of assembly  30 , over the prior art, is that assembly  30  can replace the evacuated tube  26  illustrated in  FIGS. 2A-2D , whereby plasma can be obtained without having to centrifuge the blood. Replacing an evacuated tube with assembly  30  is illustrated in  FIGS. 4A-4D . A person of ordinary skill in the art will appreciate that in other embodiments of the invention, the inlet opening can be configured as in assembly  140  shown collectively in  FIGS. 17A-17E , where the inlet opening is shown as  22   d  absent the septum  28 . The sample can be drawn into assembly  140  using a sipper (a piece of tubing) attached to inlet opening  22   d.    
         [0088]    Flow path refers to the path along which a fluid is free to travel, but the fluid does not necessarily have to travel the full length of the flow path. Using filtration assembly  30  as an example (see  FIG. 3D ), a person will appreciate that the blood flow path begins at an opening created by a hollow needle inserted into the septum  48 , and terminates at the blood compression chamber  62 , using blood as an example of the sample. In more general terms, the blood flow path of assembly  30  comprises inlet opening  22   a , blood flow channel  66 , chamber  74  of the filtration chamber illustrated in  FIG. 3D , valve  33 , blood flow channel  58 , and blood compression chamber  62 . A person of ordinary skill in the art will appreciate that channel  66  is a dead-end channel when the pierceable septum  48  is unpierced, which is the state of the septum after it is pierced by a hollow needle and then the hollow needle is removed. Dead-end channels are discussed in details later. Using filtration assembly  80  as another example (see  FIG. 11C ), a person of ordinary skill in the art will appreciate that the blood flow path begins at an opening created by a hollow needle inserted into the septum  48 , and terminates at the compression chamber  62 , and comprises channel  58 . One difference in the illustrations is that channel  58  in embodiment  30  appears to be short and straight, and channel  58  in assembly  80  is torturous and therefore longer. By torturous, it is implied that the channel is not straight, and contains any number of bends in order to increase the volume of the channel. It is easier for one to appreciate that although the flow paths in assembly  30  and assembly  80  begin at an opening in the septum  48  and terminate at the compression chamber  62 , blood is more likely to flow into the compression chamber  62  of assembly  30 , and blood is less likely to reach the compression chamber  62  in assembly  80  due to the long torturous channel  58  in assembly  80 . Therefore, although the blood in the blood flow path illustrated in FIG.  11 C may stop before entering the compression chamber  62 , the blood is free to enter compression chamber  62 , depending on factors like the length of the torturous channel  58 , and the extent to which the flexible member  42  (see  FIG. 11D ) of compression chamber  62  of assembly  80  is depressed. 
         [0089]    The blood compression chamber  62  comprises a flexible member  42  illustrated in  FIGS. 3A and 3B , but some embodiments of the filtration assembly have two flexible members, for example  42   a  and  42   b  shown in embodiment  100  illustrated collectively in  FIGS. 13A-13C . A person of ordinary skill in the art will appreciate that a compression chamber of the present invention is not limited to one flexible member, and more than one flexible member is within the scope of the invention. An advantage to having the flexible member on the top side of the assembly is so that the bottom side of the assembly is flat for placing the assembly on a flat surface, for ease of use. The volume of the compression chamber  62 , and the maximum depression of the flexible members  42 , determines the maximum volume of blood that could be drawn into the blood flow path. Also, the rigidity of the flexible member  42 , which contributes to the rate at which the members  42  is restored to its original shape after squeezing and releasing, i.e. the rebound of the flexible members  42 , determines the velocity of the blood in the blood flow path. An advantage over the prior art (U.S. Pat. Nos. 7,816,124 and 7,807,450) is the disposition of one or more than one valve at strategic locations in the assembly. Several embodiments are shown with valves disposed in different locations in the assembly, and there functions will be described along with the description of the embodiments. Other embodiments are described to illustrate that a compression chamber of the present invention is not limited to one or more than one flexible member, as will be later described for assembly  120  (illustrated collectively in  FIGS. 15A-15D ), assembly  130  (illustrated collectively in  FIGS. 16A-16E ) and assembly  140  (illustrated collectively in  FIGS. 17A-17E ). 
         [0090]    A valve is a device that regulates, directs or controls the flow of a fluid by opening, closing, partially obstructing passageways, or redirecting flow of a fluid. Some examples of fluids are: gases, liquids, fluidized solids and slurries. Valves are available in various designs, for example, globe valve, butterfly valve, pinch valve, needle valve, poppet valve, gate valve. Valves are classified by the number of ports they contain: a 2-port valve means that the valve stem contains two ports, but the ports could be aligned along a straight line (“straight” configuration) or in an “L” configuration; a S-port valve means that the valve stem contains three ports, and the ports are usually in a “T” configuration (see  FIG. 9 ). Valves are also classified by how they are actuated, for example manually operable, hydraulically operable, pneumatically operable, solenoid operable or motor operable. Valves are further classified by the operating positions, for example, 1-way valves, 2-way valves, 3-way valves and 4-way valves. Self-explanatory illustrations of valve operating positions for Type-T and Type-L valves are illustrated in  FIG. 9 . The Type-T and Type-L valves are also referred to as 3-way and 4-way valves or stopcocks. A 1-way valve is also referred to as a check valve that permits flow in only one direction, and the check valve automatically opens when there is sufficient flow in a single direction; flow in the opposite direction closes the valve. A 2-way valve is a valve with one open and one closed position, and flow usually occurs from the side of the valve having fluid pressure, to the side of the valve having lower fluid pressure, and this flow can occur in one of two different directions. A 3-way and a 4-way valve are valves with 3 and 4 operating positions respectively. 
         [0091]    The valves and any valve features discussed above are examples only, and shall not limit the scope of the invention in any way, except where a valve is described in specific terms. Illustrations of some embodiments of the filtration apparatus include 1-way, 2-way, 3-way and 4-way valves. 
         [0092]    A person of ordinary skill in the art will appreciate that a 3-port valve disposed along a straight channel could function as a “straight” 2-port valve. 
         [0093]    The type of valve included in the various embodiments of the present invention is discerned by the shape of the valve handle illustrated in top views of the embodiments. For example:  FIG. 14B  provides illustration of two “straight” 2-port valves  41  and  49 , and two 3-port “T” valves  51  and  45 ;  FIG. 16C  provides illustration of one “straight” 2-port valve  53 , and two “L” 2-port valves  51  and  45 .  FIG. 16B  also shows a check valve  55 , which is not manually operable, and therefore no valve handle is shown in  FIG. 16C . It should be understood that these are just examples of valves included in the various embodiments, and they should not be considered limiting in any way, to other similar embodiments. 
         [0094]    Still referring to  FIG. 3C , the blood flows approximately orthogonal to the hollow membranes of the bundle  76   a , and around the hollow membrane  82 . Details of the bundle  76   a  are shown collectively in  FIGS. 5A-5D . The blood stays on the blood side  74  of the membrane  82  (see  FIG. 3D ). The blood flow in this embodiment is also controlled by a manually operable valve  33 , which is disposed in the blood flow channel  58 . Valve  33  is a “straight” 2-port valve, but as explained previously, a 3-port valve can provide the same function when it is disposed in a straight channel. 
         [0095]    An advantage to having valve  33  in the blood flow channel  58 , over the prior art, is that by slowly opening the valve, the patient&#39;s vein is less likely to collapse, and if it appears that the vein is collapsing, the valve can be closed rendering any negative pressure in the compression chamber  62  ineffective with respect to the patient&#39;s vein. 
         [0096]    A filtration chamber illustrated in  FIG. 3D  as detail D of  FIG. 3C , is a chamber in a filtration assembly comprising a membrane  82  of a membrane assembly  76   a . In this particular embodiment, the membrane assembly  76   a  is in the form of a hollow fiber bundle, illustrated collectively as  FIGS. 5A-5D . The membrane assembly  76   a  comprises a plasma side  72  and a blood side  74 . A plasma reservoir  78  is in fluid connection with the plasma side  72  of the membrane  82 . In this embodiment, because the membrane  82  is configured as tubes, the plasma side of the membrane includes the lumen of the membrane tubes. This is not always the case as will be seen in assembly  70  illustrated collectively in  FIGS. 10A-10C , where the lumen of the membrane tube is the blood side of the membrane. In some embodiments, the membrane  82  is flat, and a person of ordinary skill in the art will appreciate that the membrane could take on any shape, provided that the membrane allows plasma to travel from the blood side to the plasma side, and a barrier is maintained between the plasma side and the blood side. In this case the primary sample is blood, but the present invention is not limited to processing blood. At the beginning of the filtration process, the primary sample is in contact with the blood side of the membrane. During filtration, the filtrate (in this case, plasma) penetrates the membrane and the filtrate maintains contact with the opposite side of the membrane. After filtration begins, the primary sample becomes converted to retentate (in this case, concentrated blood) and the blood side of the membrane maintains contact with the retentate. For a more general description of a membrane that is not limited to processing blood, the side of the membrane in contact with retentate is referred to as the retentate side, and the side of the membrane in contact with the filtrate is referred to as the filtrate side. In other words, the blood side is more generally referred to as the retentate side and the plasma side is more generally referred to as the filtrate side. Therefore, in more general terms, a blood compression chamber is referred to as a retentate compression chamber. Also, in more general terms, a plasma compression chamber is referred to as a filtrate compression chamber. For consistency, a blood flow path is also referred to as a retentate flow path, and a plasma flow path is also referred to as a filtrate path, in order to include different embodiments of the invention and different primary samples. 
         [0097]    Still referring to  FIG. 3C , a first plasma flow path begins at the plasma side  72  of the membrane  82 , and terminates at a manually operable plasma compression chamber  64 . The first plasma flow path comprises a plasma reservoir  78 , a plasma flow channel  68  fluidly connecting the plasma side  72  and the plasma compression chamber  64 , and a manually operable valve  35  disposed in the plasma flow channel  68 . A person of ordinary skill in the art will appreciate that the plasma flow channel  68  is considered to be an extension of the plasma reservoir  78 , and plasma reservoir is considered to be an extension of the plasma side  72 ; these sections are identified in order to explain the plasma flow path. As will be seen in other embodiments, for example  FIG. 12C , the plasma flow channel  68  is torturous and has a greater volume than the reservoir  78   c.    
         [0098]    Referring to the plasma flow path illustrated in  FIG. 12C , the plasma flow path is defined as the path along which the plasma is free to travel, beginning at the plasma side  72  of the filtration chamber (see  FIG. 3D ) and terminating at the plasma compression chamber  64 , via a plasma reservoir  78   c  and a plasma flow channel  68 . A person of ordinary skill in the art will appreciate that due to the length of the plasma channel  68  in filtration assembly  90 , it is unlikely that plasma will reach the compression chamber  64 . An advantage to having a plasma reservoir and a plasma flow channel is the avoidance of plasma flow into the compression chamber, where the plasma could become trapped, depending on the geometry of the plasma compression chamber. Nevertheless, the plasma flow path is defined according to where the plasma is free to travel to and from. 
         [0099]    Still referring to  FIG. 3C , a second plasma flow path is defined for ejecting plasma from the filtration assembly  30 . This second plasma flow path begins at the plasma compression chamber  64 , and terminates at a plasma flow path outlet  54 , via a manually operable valve  31  in an open position. A cap like cap  122  in filtration assembly  60 , illustrated in  FIGS. 8B and 8C , and which is disclosed in the prior art, can be used as a valve, but a manually operable valve  31  offers the following advantages over a cap  122 : a) the valve is an integral part of the assembly and cannot be misplaced, whereas a cap can easily be misplaced; b) a valve is less cumbersome to manually open and close compared with attaching and removing a cap; c) a valve provides more secured closure of a passage, whereas a cap is easily dislodged creating an open passage; and d) a valve can be opened to various degree, providing the flow required, whereas a cap provides either a fully open passage or a fully closed passage. Therefore, since the cap  122  is not an integral part of the filtration assembly  60 , the cap is not implied when reference is made to a valve. Moreover, even if a cap like the cap  122  is attached to a filtration assembly, the cap is still not implied when reference is made to a valve. 
         [0100]    Regarding the first and second plasma flow paths of assembly  30  illustrated in  FIG. 3C , the distal part of the first plasma flow path overlaps with the proximal part of the second flow path. Proximal part of a member refers to the part nearest the point of origin, and the distal part of the member is refers to the part opposite to the proximal part, i.e. towards the other end. In the case of a flow path, the proximal part refers to the part of the flow path where flow begins, and the distal part refers to the part of the flow path where flow ends. The plasma compression chamber  64  of assembly  30  is an essential component of the first plasma flow path and the second plasma flow path. In the first plasma flow path, the flexible member  44  of the compression chamber  64  is in a depressed state and functions by creating negative pressure when the depressed flexible member  44  rebounds; in the second plasma flow path, the flexible member  44  of the compression chamber  64  is in a normally expanded state and functions by creating positive pressure when the flexible member  44  is depressed. 
         [0101]    Still referring to  FIG. 3C  is shown an optional vent  56   a  and a manually operable 3-port Type-T valve  35  for opening and closing the vent, as well as maintaining fluid connection between plasma compression chamber  64  and the plasma reservoir  78 . In the prior art, it is recognized that the apparatus performs more efficiently when there is a delay in rebound of the plasma compression chamber flexible member, allowing the blood to first fill the filtration chamber. Valve  35  regulates the pressure in the first plasma flow path. When the filtration chamber is filled with blood, the blood side of the membrane becomes sealed, making the plasma compression chamber more effective. 
         [0102]    Also shown in  FIGS. 3B and 3C  is a structure  52  for housing the outlet  54 , and a tube-like structure  46  that allows one to use a double-ended needle assembly, for example assembly  20  show in  FIGS. 1A-1D , as explained previously regarding tube  26  shown in  FIG. 2A . 
         [0103]    Referring collectively to  FIGS. 4A-4D , shown are schematic drawings showing details of the assembly  30  shown collectively in  FIGS. 3A-3D  in the holder  10  of the double-ended needle assembly  20  shown collectively in  FIGS. 1A-1D .  FIG. 4A  is a top view of the assemblies  30  and  20 .  FIG. 4B  is a first cross-sectional view through the assembly  30  shown in  FIG. 4A  along line B-B.  FIG. 4C  is a second cross-sectional view through the assemblies  30  and  20  shown in  FIG. 4A  along line C-C.  FIG. 4D  is a perspective view of the assemblies  30  and  20  shown in  FIG. 4A . 
         [0104]    Referring collectively to  FIGS. 5A-5D , shown are schematic drawings illustrating details of the hollow fiber bundle (also referred to as a hollow fiber filter bundle, and also hollow fiber membrane bundle)  76   a  shown inside the body  32  of the apparatus  30  illustrated collectively in  FIGS. 3A-3D .  FIG. 5A  is schematic drawing showing details of a hollow fiber membrane bundle  76   a  shown in  FIGS. 3C and 3D .  FIG. 5B  is a cross-sectional view through the hollow fiber membrane bundle  76   a  shown in  FIG. 5A  along line B-B.  FIG. 5C  is a perspective view of the hollow fiber membrane bundle  76   a  shown in  FIG. 5A .  FIG. 5D  is a detailed view of detail D shown in  FIG. 5B  showing a schematic representation of the membrane  82 . 
         [0105]    Assembly  30  comprises a hollow fiber membrane or filter bundle  76   a . The hollow fiber filters in the hollow fiber filter bundle  76   a  run approximately orthogonal to the blood flow in the blood flow path of assembly  30 . In an alternative apparatus  70  illustrated collectively in  FIGS. 10A-10C , the hollow fiber filters in the hollow fiber filter bundle  76   a  run approximately parallel to the blood flow in the blood flow path. The hollow fiber filter bundle  76   a  in this embodiment comprises seven hollow fiber filters (or referred to as membrane tubes), held together by two flanges  84  and  86 . As an example, seven hollow fiber filters are shown tightly inserted inside perforations in the flange  84 . As shown in  FIG. 5B , flange  86  is similarly perforated. In some embodiments, only one flange needs to be perforated, for example the bundle  76   b  shown in  FIG. 11C . Since plasma does not flow through the hollow fibers in bundle  76   b , perforations are only required in the flange through which plasma flows, however the bundle will still function if both flanges were perforated, for example, bundle  76   a  shown in  FIG. 12C  (assembly  90 ). The membrane tubes are sealed at the juncture of the hollow fibers and the flange. The wall  82  of the membrane is porous, and in some embodiments, the pores have an approximate distribution of pore diameters ranging from about 0.1 micrometer to about 30 micrometers, and in some embodiments the thickness of the wall  82  ranges from about 0.1 mm to about 0.5 mm. In some embodiments, the internal diameter of the hollow fiber filters ranges approximately from about 0.1 mm to about 1 mm. These pore sizes are more suitable for preventing cells of comparable sizes from penetrating the membrane, but one of reasonable skill in the art will appreciate that various combination of pore sizes, wall thicknesses, and internal diameters of the hollow fiber filters could be used, and are within the scope of the invention. For example, when the sample is plasma, the size of the pores will depend on the molecular weight of the substances one wants to keep in the retentate, i.e., substances that do not penetrate the membrane. A person of ordinary skill in the art will appreciate that a flange can be substituted with potting material that serves to provide a barrier between the retentate and the filtrate. The potting material could be liquid resin that is allowed to solidify after application, for example at the site occupied by the flanges shown in  FIG. 6B . 
         [0106]    A person of ordinary skill in the art will appreciate the membrane  82  is a partition between the blood flow path (more generally referred to as the retentate flow path, when the primary sample is any liquid), and the plasma flow path (more generally referred to as the filtrate path, when the primary sample is any liquid). Moreover, the filtrate flow path includes the lumen  72  of the hollow fiber filters, and the retentate flow path includes the exterior of the hollow fiber filters. A reversed design is illustrated collectively in  FIGS. 10A-10C , where the retentate flow path includes the lumen of the hollow fiber filters  76   a , and both flanges must be perforated; the filtrate flow path includes the exterior surface of the hollow fiber filters. 
         [0107]    The periphery of the flanges  84  and  86  are sealed in the body  32  of the assembly  30 , to separate the blood flow path (a portion shown as  74  in  FIG. 3D ) from the plasma flow path (a portion shown as  72  in  FIG. 3D ). In this embodiment of the apparatus, the flanges are a schematic representation of the seal between the blood flow path, and the plasma flow path. From a manufacturing perspective, it is preferred that the hollow fiber filters are assembled in bundles (e.g.  76   a ), and sandwiched in position between the top and bottom halves of the assembly. As mentioned before, the hollow fibers can be installed in the housing  32  using potting material at the time of installation, instead of prefabricating the bundles with flanges. In some embodiments, the housing  32  comprises a top and a bottom portion, and double-sided sticky gasket is used to assemble the top and bottom portions of the assembly. 
         [0108]    In some embodiments of the assembly, at least the first section of the blood flow path is coated with an appropriate anticoagulant, to minimize clotting and promote fluidity of the blood. Anticoagulant could also be impregnated in a piece of filter material, dried and inserted at the beginning of the blood flow path. Fluidity of the blood provides more efficient plasma extraction. However, when the blood sample is already anticoagulated (i.e., blood mixed with an anticoagulant, for example, heparin) in a tube, an anticoagulant within the flow paths of the apparatus is not essential. 
         [0109]    Referring collectively to  FIGS. 6A-6C , shown are schematic drawings illustrating details of a filtration assembly  40  suitable for extraction of plasma from a whole blood sample according to a second embodiment of the invention.  FIG. 6A  is a front view of the filtration assembly  40 .  FIG. 6B  is a first cross-sectional view through the assembly  40  shown in  FIG. 6A  along line B-B.  FIG. 6C  is a second cross-sectional view through the assembly  40  shown in  FIG. 6B  along line C-C. 
         [0110]    The filtration assembly  40  is similar to filtration assembly  30  illustrated collectively in  FIGS. 3A-3D , and accordingly, some elements common to them share common reference numerals. Some reference numerals are altered with a letter at the end, indicating that the elements are similar but some differences may exist. The first difference is that valve  33  is replaced with manually operable valve  37  disposed in the blood flow path as shown. The second difference is that assembly  40  does not have vent  56   a  and valve  35 . The third difference is that assembly  40  has a structure  46   b  for engaging the hub of a hollow needle, and does not have a pierceable septum  48 . Valve  37  is advantageous to assembly  40  since the inlet opening  22   b  is not covered with a pierceable septum. 
         [0111]    Referring collectively to  FIGS. 7A-7C , shown are schematic drawings illustrating details of a filtration assembly  50  suitable for extraction of plasma from a whole blood sample according to a third embodiment of the invention, with a hollow needle assembly  144  attached.  FIG. 7A  is a front view of the filtration assembly  50 , engaged with a hollow needle assembly  144 .  FIG. 7B  is a cross-sectional view through the assemblies shown in  FIG. 7A  along line B-B.  FIG. 7C  is a perspective view of the assemblies shown in  FIG. 7A . 
         [0112]    The filtration assembly  50  is similar to filtration assembly  40  illustrated collectively in  FIGS. 6A-6C , and accordingly, some elements common to them share common reference numerals. Some reference numerals are altered with a letter at the end, indicating that the elements are similar but some differences may exist. The first difference is that assembly  50  has separate manually operable valves in the blood flow path (valve  33 ) and plasma flow path (valve  39 ), and does not have a valve between the inlet opening and the filtration chamber, i.e., valve  37  shown in  FIG. 6B . The attached needle assembly  144  comprises a hub  148  with threads, a shaft with a sharp open end  156 , and a barrel  146  with threads that mate with the hub threads. The threads allow the sharp open end  156  to be sheathed and unsheathed with the barrel  146 . 
         [0113]    Referring collectively to  FIGS. 8A-8C , shown are schematic drawings illustrating details of a filtration assembly  60  suitable for extraction of plasma from a whole blood sample according to a forth embodiment of the invention.  FIG. 8A  is a front view of a filtration assembly  60 .  FIG. 8B  is a perspective view of the assembly  60  shown in  FIG. 8A .  FIG. 8C  is a cross-sectional view through the filtration assembly  60  shown in  FIG. 8A  along line C-C. 
         [0114]    The filtration assembly  60  is similar to filtration assembly  30  illustrated collectively in  FIGS. 3A-3D , and accordingly, some elements common to them share common reference numerals. Some reference numerals are altered with a letter at the end, indicating that the elements are similar but some differences may exist. The first difference is that assembly  60  has a cap  122  instead of the valve  31  at the second plasma flow path outlet of assembly  30  illustrated in see  FIG. 3C . The second difference is that valve  39  in assembly  60  is not vented (see vent  56   a  of assembly  30  shown in  FIG. 3C ). 
         [0115]    Referring collectively to  FIGS. 10A-10C , shown are schematic drawings illustrating details of a filtration assembly  70  suitable for extraction of plasma from a whole blood sample according to a fifth embodiment of the invention.  FIG. 10A  is a front view of a filtration assembly  70 .  FIG. 10B  is a first cross-sectional view through the filtration assembly  70  shown in  FIG. 10A  along line B-B.  FIG. 10C  is a second cross-sectional view through the filtration assembly  70  shown in  FIG. 10B  along line C-C. 
         [0116]    The filtration assembly  70  is similar to filtration assembly  30  illustrated collectively in  FIGS. 3A-3D , and accordingly, some elements common to them share common reference numerals. Some reference numerals are altered with a letter at the end, indicating that the elements are similar but some differences may exist. The first difference is that assembly  70  allows the blood to flow through the lumen of the membrane tubes. Therefore, the plasma side and the blood side of the membrane are reversed in assembly  70 , relative to assembly  30 . The second difference is that there is no valve in assembly  70  corresponding to valve  33  in assembly  30 , shown in  FIG. 3C . The third difference is that there is no valve and vent in assembly  70  corresponding to valve  35  and vent  56   a  in assembly  30 , shown in  FIG. 3C . 
         [0117]    Referring collectively to  FIGS. 11A-11D , shown are schematic drawings illustrating details of a filtration assembly  80  suitable for extraction of plasma from a whole blood sample according to a sixth embodiment of the invention.  FIG. 11A  is a front view of the filtration assembly  80 .  FIG. 11B  is a top view of the filtration assembly  80  shown in  FIG. 11A .  FIG. 11C  is cross-sectional view through the filtration assembly  80  shown in  FIG. 11A  along line C-C.  FIG. 11D  is a perspective view of the filtration assembly  80  shown in  FIG. 11A . 
         [0118]    The filtration assembly  80  has some similarities to filtration assembly  30  illustrated collectively in  FIGS. 3A-3D , and accordingly, some elements common to them share common reference numerals. Some reference numerals are altered with a letter at the end, indicating that the elements are similar but some differences may exist. Some elements of assembly  80  are described next. 
         [0119]    Referring to  FIG. 11C , assembly  80  comprises an auxiliary blood flow channel  58   b  for creating an auxiliary flow path. The auxiliary blood flow path begins at a manually operable 3-port valve  43  and terminates at a second blood compression chamber  62   b  having a flexible member  42   b  for operating the compression chamber  62   b . This auxiliary blood flow path is not a complete flow path, and is used to define a second blood flow path. The advantage of the auxiliary blood flow path is to increase the plasma yield by rerouting the blood through the filtration chamber more than once. During the first pass of the blood through the filtration chamber, the 3-port valve  43  is positioned so that the auxiliary blood flow path is not fluidly connected to the first blood flow path, which begins at inlet opening  22   a  and terminates at the first blood compression chamber  62 . As shown in  FIG. 11C , the first blood flow path is analogous to the blood flow path in assembly  30  (see  FIG. 3C ), except that the first blood flow path shown in  FIG. 11C  is torturous, to prevent the blood from entering the compression chamber  62 , and valve  43  in assembly  80  replaces valve  33  in assembly  30 . In operation, after blood enters the filtration chamber and channel  58 , valve  43  is turned so that inlet opening  22   a  is no longer fluidly connected to the filtration chamber and instead, the auxiliary blood flow path becomes fluidly connected to the filtration chamber. At this position of valve  43 , a second blood flow path is created, which begins at the first blood compression chamber  62 , and terminates at the second blood compression chamber  62   b . After opening valve  41 , and bleeding air out of the second blood compression chamber  62   b  through vent  56   b  by depressing flexible member  42   b , the blood can be pulled through the filtration chamber by releasing flexible member  42   b  after closing valve  41 ; blood flow through the filtration chamber can be increased by depressing flexible member  42  of the first blood compression chamber  62 . 
         [0120]    Still referring to  FIG. 11C , shown is a second plasma flow path that includes channel  68  and flows away from the filtration chamber instead of through the filtration chamber. The second plasma flow path begins at the manually operable plasma compression chamber  64  and terminates at outlet  54 . The second plasma flow path has an outlet tubing  52  directed away from the filtration chamber, with the aid of a 3-port valve  45  located at the intersection of the first plasma flow path and the flow direction in tubing  52 . As defined for assembly  30 , a first plasma flow path begins at the plasma side  72  of the membrane  82 , and terminates at a manually operable plasma compression chamber  64 . An advantage of the second plasma flow path of assembly  80  over the prior art is that extracted plasma can be stored in the torturous channel plasma flow channel  68  for later use, and when the stored plasma is required, it is ejected through the outlet  54  of the second plasma flow path, bypassing the filtration chamber. In this embodiment, plasma flow channel  68  functions as the main plasma reservoir. The formed elements of the blood can rupture more easily during storage, and substances released from the formed elements can diffuse across the membrane into the plasma, if the plasma was stored in the reservoir  78  of embodiment  30  shown in  FIG. 3C . Bypassing the filtration chamber in embodiment  80  eliminates the risk of contaminating the plasma with the contents of the formed elements. 
         [0121]    Plasma reservoir  78   b  in embodiment  80  (see  FIG. 11C ) is drawn to appear smaller than the plasma reservoir  78  in embodiment  30  shown in  FIG. 3C . It is advantageous to make the volume of  78   b  as small as possible since the plasma flows away from the filtration chamber instead of through it, making  78   b  dead volume. The next embodiment provides a way to recover some of the plasma in the dead volume, by installing a bleed valve  47 , shown in  FIG. 12C  at the back side of the filtration chamber. 
         [0122]    Referring collectively to  FIGS. 12A-12D , shown are schematic drawings illustrating details of a filtration assembly  90  suitable for extraction of plasma from a whole blood sample according to a seventh embodiment of the invention.  FIG. 12A  is a front view of the filtration assembly  90 .  FIG. 12B  is a first perspective view of the filtration assembly  90  shown in  FIG. 12A .  FIG. 12C  is a cross-sectional view through the filtration assembly  90  shown in  FIG. 12A  along line C-C.  FIG. 12D  is a second perspective view of the filtration assembly  90  shown in  FIG. 12A . 
         [0123]    The filtration assembly  90  has some similarities to filtration assembly  40  illustrated in  FIGS. 6A-6C , and filtration assembly  80  illustrated collectively in  FIGS. 11A-11D , and accordingly, some elements common to them share common reference numerals. Some reference numerals are altered with a letter at the end, indicating that the elements are similar but some differences may exist. As alluded to when discussing embodiment  80 , illustrated collectively in  FIGS. 11A-11D , the filtration chamber is vented (see vent  56   d  in  FIG. 12C ) to assist in recovering some plasma from the dead space. Plasma compression chamber  64  is optionally vented at vent  56   c  using valve  49  shown in  FIG. 12C , so that the flexible member  44  of compression chamber  64  can be depressed with plasma channel  68  closed at valve  45 . Compression chamber  64  maintains negative pressure by closing valve  49  and keeping valve  45  positioned so there is no fluid communication between channel  68  and both outlet  54  and the filtration chamber. By positioning valve  45  so that channel  68  is in fluid communication with the filtration chamber and not in fluid communication with the outlet  54 , and opening vent  56   d  (using manually operable valve  47 ), plasma can be drawn out of the dead space ( 78   c  and the lumens of the membrane tubes). 
         [0124]    Referring collectively to  FIGS. 13A-13C , shown are schematic drawings illustrating details of a filtration assembly  100  suitable for extraction of plasma from a whole blood sample according to an eight embodiment of the invention.  FIG. 13A  is a perspective view of the filtration assembly  100 , with a syringe  184  attached.  FIG. 13B  is a front view of the filtration assembly  100  shown in  FIG. 13A , with the syringe  184  attached.  FIG. 13C  is cross-sectional view through the filtration assembly  100  shown in  FIG. 13B  along line C-C, showing opening  54   b  absent the syringe  184 . 
         [0125]    The filtration assembly  100  is similar to filtration assembly  30  illustrated collectively in  FIGS. 3A-3D , and accordingly, some elements common to them share common reference numerals. Some reference numerals are altered with a letter at the end, indicating that the elements are similar but some differences may exist. The first difference is that assembly  100  has a single plasma flow path, beginning at the plasma side of the membrane of hollow fiber bundle  76   b  and terminating at the outlet  54   b ; the plasma can be drawn directly into a syringe  184 , which replaces the plasma compression chamber  64  of filtration assembly  30  (shown in  FIG. 3C ). The advantage of assembly  100  over the prior art is that, like assembly  30  assembly  100  can be used with a double-ended needle assembly, because of the pierceable septum  48 . 
         [0126]    Referring collectively to  FIGS. 14A-14D , shown are schematic drawings illustrating details of a filtration assembly  110  suitable for extraction of plasma from a whole blood sample according to a ninth embodiment of the invention.  FIG. 14A  is a front view of the filtration assembly  110 .  FIG. 14B  is a top view of the filtration assembly  110  shown in  FIG. 14A . FIG.  14 C is a cross-sectional view through the filtration assembly  110  shown in  FIG. 14A  along line C-C.  FIG. 14D  is a perspective view of the filtration assembly  110  shown in  FIG. 14A . 
         [0127]    The filtration assembly  110  is similar to filtration assembly  80  illustrated collectively in  FIGS. 11A-11D , and accordingly, some elements common to them share common reference numerals. Some reference numerals are altered with a letter at the end, indicating that the elements are similar but some differences may exist. The first difference is that the first blood flow path and the auxiliary blood flow path  58   c  terminate at the same blood compression chamber  62   c , but via a 3-port valve  51 ; the 3-port valve  43  in assembly  80  (shown in  FIG. 11C ) is absent in assembly  110 . The second difference is that the blood compression chamber  62   c  has a closeable vent  56   b  via valve  41 . The third difference is that the plasma compression chamber  64  also has a closeable vent  56   c  via valve  49 . By positioning the 3-port valve  51  so that the blood compression chamber  62   c  is in fluid communication with channel  58   c , and not in fluid communication with the channel  58  (i.e., simultaneously open to channel  58   c  and closed to channel  58 ), the blood can make a second pass through the filtration chamber. Because blood compression chamber  62   c  and plasma compression chamber  64  are optionally vented, their flexible members can be depressed and released any number of times, to modulate the pressure in compression chambers. A person of ordinary skill in the art will appreciate that movement of blood in the filtration chamber in both directions can be improved by installing closeable vents close to valve  51 , in channel  58  or in both channels  58  and  58   c . In operation, the vent in channel  58  only needs to be open when valve  51  positioned for fluid communication between compression chamber  62   c  and channel  58   c  only; if there is a vent in channel  58   c , it only needs to be open when valve  51  is positioned for fluid communication between compression chamber  62   c  and channel  58  only. 
         [0128]    Referring to  FIG. 14C , a person of ordinary skill in the art will appreciate that channel  58   c  is equivalent to a dead-end channel when valve  51  is positioned to cease fluid communication between channel  58   c  and both channel  58  and compression chamber  62   c . A function of a dead-end channel is to trap air, and by compression and decompression of the trapped air, facilitate filtration by allowing the retentate to flow through the filtration chamber more than once. Use of a dead-end channel is explained more in the description of assembly  120 . The prior art (U.S. Pat. Nos. 7,816,124 and 7,807,450) does not disclose dead-end channels for trapping air, and compressing and decompressing the trapped air. 
         [0129]    Referring collectively to  FIGS. 15A-15E , shown are schematic drawings illustrating details of a filtration assembly  120  suitable for extraction of plasma from a whole blood sample according to a tenth embodiment of the invention.  FIG. 15A  is a front view of a filtration assembly  120 , with a syringe  184   b  attached.  FIG. 15B  is a cross-sectional view through the filtration assembly  120  shown in  FIG. 15A  along line B-B.  FIG. 15C  is a perspective view of the filtration assembly  120  shown in  FIG. 15A , showing inlet opening  22   c  absent the syringe  184   b .  FIG. 15D  is a cross-sectional view through the filtration assembly  120  and the syringe  184   b  shown in  FIG. 15B  along line D-D.  FIG. 15E  is an enlarged perspective view of a pivotal or pivotal frictionally engaged plunger  44   b  of the compression chamber  64  shown in  FIG. 15D . A longitudinal axis of the plunger  44   b  makes reference to an axis that runs through the center of the plunger  44   b , orthogonal to the sectional view shown in  FIG. 15B  (or parallel to the front view shown in  FIG. 15A ). A person of ordinary skill in the art will appreciate that pivotal motion of the plunger  44   b  about the longitudinal axis is translated into up and down motion of the plunger  44   b  in the plasma compression chamber  64 . Plunger  44   b  is described as a pivotal frictionally engaged plunger. 
         [0130]    As already explained, a person of ordinary skill in the art would recognize that assembly  120  and the previous assemblies illustrated are also suitable for other functions, for example, which should not be considered limiting in any way, the extraction of a plasma or serum ultra-filtrate, and the collection of a plasma or serum concentrate from plasma and serum respectively. 
         [0131]    The filtration assembly  120  is similar to filtration assemblies already illustrated, and accordingly, some elements common to them share common reference numerals. Some reference numerals are altered with a letter at the end, indicating that the elements are similar but some differences may exist. Some significant differences in assembly  120  are: 1) the manually operable plasma compression chamber  64  comprises a pivotal frictionally engaged plunger  44   b  for modulating pressure in the chamber  64 , instead of the flexible member  44  illustrated in  FIGS. 14A , B and D, for example; 2) the inlet opening  22   c  for introducing the sample comprises a Luer fitting for accepting a syringe  184   b  containing the blood; 3) the blood flow path terminates at a dead-end of a tube-like structure  58 , instead of a blood compression chamber illustrated as  62  in  FIG. 12C . The advantage of a dead-end channel  58  over the prior art is to trap and compress air when blood is injected into assembly  120 , using syringe  184   b ; after the syringe plunger is released, the compressed air in the dead-end channel  58  becomes decompressed, reversing the blood flow and pushing the syringe plunger out. This process can be repeated any number of times, depending on the liquid sample. A person of ordinary skill in the art will appreciate that if the sample is blood, the red blood cells will burst if the blood is allowed to pass through the filtration chamber too many times. However, if the sample is, for example, plasma (the filtrate being an ultra-filtrate of plasma), the plasma can pass through the filtration chamber more times than a blood sample since plasma does not contain cells that can rupture. 
         [0132]    Referring to  FIGS. 15A and 15C , the wall  64   x  of the plasma compression chamber  64  is illustrated. Threads along the inside of the wall  64   x  are illustrated in  FIG. 15D . Also illustrated in FIGS.  15 A and  15 C- 15 E is a finger holder  108  in plunger  44   b  that provides a means for manually rotating the plunger  44   b  about its longitudinal axis. In this particular embodiment, as an example, maximum movement of the plunger  44   b  inside the compression chamber  64  can be achieved by rotating the plunger  44   b  between 1 and 2 full turns, based on the pitch of the thread displayed. However, the pitch of the thread displayed is not meant to limit the size of the thread pitch in any way. The prior art (U.S. Pat. Nos. 7,816,124 and 7,807,450) does not disclose the use of compression chambers with frictionally engaged plungers. 
         [0133]    Referring to  FIG. 15E , shown is an enlarged perspective view of a pivotal frictionally engaged plunger  44   b  of the compression chamber  64  shown in  FIG. 15D . Shown also is an O-ring  34   a  used to create a seal between the compression chamber wall  64   x  and the plunger  44   b , whereby the plunger  44   b  is frictionally engaged with the compression chamber  64 . A person of ordinary skill in the art will appreciate that beside an O-ring, other circular structures for creating a seal between the compression chamber wall  64   x  and the plunger  44   b , can be used. Some features of assembly  120  offers the following advantages over a flexible member described in some embodiments as well as the prior art (U.S. Pat. Nos. 7,816,124 and 7,807,450): 1) modulation of pressure inside the compression chamber does not depend on the rebound property of the flexible member; 2) positive and negative pressures are generated in the compression chamber  64  by rotating the plunger  44   b  clockwise and counter-clockwise about its longitudinal axis; 3) easier to control plunger movement, for providing fine pressure modulation, and the pitch of the thread in the plunger  44   b  determines how much turning is required to generate a certain amount of positive or negative pressure in the compression chamber  64 ; 4) hands-off system where fingers do not have to remain in contact with the top of the pivotal plunger  44   b , in order to prevent activation of negative pressure, as is the case with a depressed flexible member; 5) the threads precisely determines the maximum travel of the plunger  44   b  in the compression chamber  64 , in both the in and out direction; 6) the vent  56   c  (via valve  49 ) allows the plunger  44   b  to eject and inject air from and into the plasma compression chamber  64  respectively, in order to modulate the pressure inside the compression chamber  64 , after blood is drawn into the assembly  120 . 
         [0134]    A person of ordinary skill in the art will appreciate that assembly  120  provides multiple passes of the blood through the filtration chamber, with the combined use of the syringe and the dead-end channel  58  by simply pushing and releasing the syringe plunger. The volume of the torturous structure  58  is sufficient to trap air which, when compressed by pushing down on the syringe plunger, can become decompressed after the syringe plunger is released, so as to push back the syringe plunger. Compression and decompression of the air trapped in the dead-end channel can be performed repeatedly to facilitate filtration of a liquid sample across a porous membrane. 
         [0135]    Referring collectively to  FIGS. 16A-16E , shown are schematic drawings illustrating details of a filtration assembly  130  suitable for extraction of plasma from a whole blood sample according to an eleventh embodiment of the invention.  FIG. 16A  is a front view of the filtration assembly  130 .  FIG. 16B  is a first cross-sectional view through the filtration assembly  130  shown in  FIG. 16A  along line B-B.  FIG. 16C  is a top view of the filtration assembly  130  shown in  FIG. 16A .  FIG. 16D  is a second cross-sectional view through the filtration assembly  130  shown in  FIG. 16C  along line D-D.  FIG. 16E  is a third cross-sectional view through the filtration assembly  130  shown in  FIG. 16C  along line E-E. 
         [0136]    The filtration assembly  130  is similar to filtration assembly  80  illustrated collectively in  FIGS. 11A-11D , and accordingly, some elements common to them share common reference numerals. Some reference numerals are altered with a letter at the end, indicating that the elements are similar but some differences may exist. Some significant differences in assembly  130  are: 1) the manually operable blood compression chamber  62  comprises a spring-assisted frictionally engaged plunger  42   c  for modulating the pressure in the blood compression chamber  62  (instead of a flexible member  42  illustrated in  FIGS. 11A ,  11 B and  11 D), fitted with O-rings  34   b  and  34   c  to provide a seal between the wall  62   x  of the blood compression chamber  62  and the plunger  42   c;  2) blood compression chamber  62  comprises annular stops  104   a  and  106   a  for limiting movement of the plunger  42   c;  3) a spring  92   a  for pushing the plunger  42   c  against annular stop  104   a;  4) the manually operable plasma compression chamber  64  comprises a spring-assisted frictionally engaged plunger  44   c  for modulating the pressure in the chamber  64  (instead of a flexible member  44  illustrated in  FIGS. 11A ,  11 B and  11 D), fitted with O-rings  34   d  and  34   e  to provide a seal between the wall  64   x  of the plasma compression chamber and the plunger  44   c;  5) chamber  64  comprises annular stops  104   b  and  106   b  for limiting movement of the plunger  44   c;  5) a check valve  55  is disposed between the inlet opening  22   a  and the filtration chamber, to prevent back flow of blood into a patient&#39;s blood vessel; 6) a spring  92   b  for pushing the plunger  44   c  against annular stops  104   b;  7) an auxiliary dead-end channel  58   d ; and 8) a valve  53  at the intersection of channel  58   d  and the first blood flow path, wherein the auxiliary dead end channel  58   d  replaces the blood compression chamber  62   b  (as well as the valve  41  and vent  56   b ) illustrated in  FIG. 11C . 
         [0137]    The function of the dead-end channel  58   d  is to trap sufficient air, which can be compressed and decompressed by opening valve  53 , after blood is drawn into the housing  32  of assembly  130 , and pressing and releasing plunger  42   c . When plunger  42   c  is pushed down, the blood is pushed across the filtration chamber and compresses the air in the dead-end channel  58   d . Subsequently, when plunger  42   c  is released, the compressed air in the dead-end channel  58   d  becomes decompressed, and pushes the blood across the filtration chamber in the opposite direction. A person of ordinary skill in the art will appreciate that the spring  92   a  is essential to create negative pressure in the blood compression chamber  62  for drawing blood through the inlet opening  22   a  (with valve  53  closed), but the spring is not essential for compression and decompression of the trapped air in the dead-end channel  58   d  (with valve  53  open). The plungers  42   c  and  44   c  are examples of a second type of frictionally engaged plungers that are used to operate compression chambers of the present invention, and are not intended to limit the scope of frictionally engaged plungers used with compression chambers of the present invention. The other frictionally engaged plunger disclosed is the pivotal plunger  44   b  shown in  FIGS. 15E and 15D . 
         [0138]    Assembly  130  also has some similarities with assembly  120 , illustrated collectively in  FIGS. 15A-15D , with respect to the plasma compression chamber  64 . Referring to  FIG. 16D , shown are two O-rings  34   b  and  34   c  used to create a seal between the compression chamber wall  62   x  and the plunger  42   c . Also shown is a spring  92   a  used to facilitate rebound of the plunger  42   c , after it is pushed downward and then released. A person of ordinary skill in the art will appreciate that for certain embodiments, the plunger  42   c  can function without the spring  92   a , depending on the manner in which the assembly  130  is used. Similarly (referring to  FIG. 16E ), shown are two O-rings  34   d  and  34   e  used to create a seal between the compression chamber wall  64   x  and the plunger  44   c . Also shown is a spring  92   b  used to facilitate rebound of the plunger  44   c , after it is pushed downward and then released. A person of ordinary skill in the art will appreciate that for certain embodiments, the plunger  44   c  can function without the spring  92   b , depending on the manner in which the assembly  130  is used. 
         [0139]    Referring to  FIGS. 16B and 16D  is shown a cavity  96 , for facilitating fluid communication between the blood compression chamber  62  and channel  58 . Similarly, referring to  FIG. 16B  and  FIG. 16E  is shown a cavity  98 , for facilitating fluid communication between the plasma compression chamber  64  and channel  68 . 
         [0140]    Some features of assembly  130  offers the following advantages over a flexible member described in some embodiments as well as the prior art (U.S. Pat. Nos. 7,816,124 and 7,807,450), for modulating the pressure inside a compression chamber: 1) the rebound of the plunger depends on the spring tension; 2) the annular stops  104   a  and  106   a  precisely determine the maximum travel of plunger  42   c  in the blood compression chamber  62 , in both in and out directions (similar features are shown for the plasma compression chamber  64 ); 3) the vent  56   b  allows the plunger  42   c  to eject and inject air from and into the blood compression chamber  62  respectively, in order to modulate the pressure inside the compression chamber  62 , after blood is drawn into the assembly  130 . 
         [0141]    A person of ordinary skill in the art will appreciate that if blood is injected into assembly  130  through the septum  48 , a spring  92   a  shown in  FIG. 16D  is not essential. In operation, plunger  42   c  shown in  FIG. 16D  must be in a depressed position before the blood is injected into assembly  130 , and the injection force will push the plunger  42   c  out. 
         [0142]    Referring collectively to  FIGS. 17A-17E , shown are schematic drawings illustrating details of a filtration assembly  140  suitable for extraction of plasma from a whole blood sample according to a twelfth embodiment of the invention.  FIG. 17A  is a front view of a filtration assembly  140 .  FIG. 17B  is a first cross-sectional view through the filtration assembly  140  shown in  FIG. 17A  along line B-B.  FIG. 17C  is a second cross-sectional view through the filtration assembly  140  shown in  FIG. 17B  along line C-C.  FIG. 17D  is a perspective view of the filtration assembly  140  shown in  FIG. 17A .  FIG. 17E  is the perspective view of the filtration assembly  140  shown in  FIG. 17D , with all the parts hidden except the plunger  42   c  (with O-rings  34   b  and  34   c ), plunger  44   c  (with O-rings  34   d  and  34   e ), and the springs  92   a  and  92   b.    
         [0143]    As already explained, a person of ordinary skill in the art would appreciate that assembly  140  and the previous assemblies illustrated are also suitable for other functions, for example, which should not be considered limiting in any way, the extraction of plasma (or serum) ultra-filtrate and the collection of a plasma (or serum) concentrate from plasma (or serum). 
         [0144]    The filtration assembly  140  is similar to filtration assembly  130  illustrated in  FIGS. 16A-16E , and accordingly, some elements common to them share common reference numerals. Some reference numerals are altered with a letter at the end, indicating that the elements are similar but some differences may exist. Some significant differences in assembly  140  are: 1) an inlet opening  22   d , designed to accommodate a first open end of a piece of flexible or rigid tubing having the first open end and a second open end, the tubing commonly referred to as a sipper, whereby sample can be drawn into the assembly  140  after the second open end of the sipper is inserted into a sample; 2) an auxiliary blood flow channel  58   e  for creating a second blood flow path; 3) a manually operable multi-directional valve  61 , disposed at the intersection of the first flow path and the auxiliary flow path (no check valve included); 4) a manually operable multi-directional valve  59 , disposed at the intersection of the direction of plasma flow through the outlet  54  (from the filtration chamber) and the blood flow path in the auxiliary blood flow channel  58   e ; and 5) a manually operable multi-directional valve  57 , disposed at the intersection of the plasma reservoir  68  and a channel for vent  56   c . A person of ordinary skill in the art will appreciate that auxiliary channel  58   e  is a dead-end channel when valve  59  is positioned so that there is no fluid communication between auxiliary channel  58   e  and both outlet  54  and the filtration chamber of assembly  140 . 
         [0145]    It should be noted that valve  61  of assembly  140  (see  FIG. 17D ) is shown as a Type-T valve but, analogous valve  53  of assembly  130  (see  FIG. 16C ) is shown as a “straight” valve. Valve  61  is a Type-T valve because there is no check valve disposed between the inlet opening  22   d  and the filtration chamber of assembly  140  (see  FIG. 17B ), whereas there is a check valve  55  disposed between the inlet opening  22   a  and the filtration chamber of assembly  130  shown in  FIG. 16B . 
         [0146]    Operation of assembly  140  comprises the following: 
         [0147]    a) Manually turning valve  59  to simultaneously cut off fluid communication between plasma reservoir  78   f  and outlet  54 , and between plasma reservoir  78   f  and auxiliary channel  58   e , whereby auxiliary channel  58   e  becomes an dead-end channel like dead-end channel  58   d  in assembly  130  shown in  FIG. 16B ; 
         [0148]    b) Manually turning valve  61  to cut off fluid communication between auxiliary channel  58   e  and the first blood flow path (also referred to as retentate flow path, which begins at inlet opening  22   d  and ends at blood/retentate compression chamber  62 ); 
         [0149]    c) Inserting first open end of sipper into inlet opening  22   d;    
         [0150]    d) Inserting second open end of sipper into blood supply after step c); 
         [0151]    e) Displacing air out of blood compression chamber  62  (also referred to as a retentate compression chamber) at any time, by depressing plunger  42   c  with vent  56   b  open (for an embodiment with no vent  56   b , this step has to precede step c) because inlet  22   d  can function as vent  56   b  as long as the first flow path is unoccupied with sample); 
         [0152]    f) Manually turning valve  51  to cut off fluid communication between blood compression chamber  62  and channel  58 , and between blood compression chamber  62  and vent  56   b , following step e); 
         [0153]    g) Displacing air out of plasma compression chamber  64  (also referred to as a filtrate compression chamber) at any time, by depressing plunger  44   c  with vent  56   c  open (for an embodiment with no vent  56   c , this step has to precede step a) because outlet  54  can function as vent  56   c ); 
         [0154]    h) Manually turning valve  57  to cut off fluid communication between plasma compression chamber  64  and plasma flow channel  68 , and between plasma compression chamber  64  and vent  56   c , following step g); 
         [0155]    i) Manually turning valve  61  to simultaneously make fluid communication between sipper open end and filtration chamber (there is no fluid communication between auxiliary channel  58   e  and first blood flow path due to the position of valve  61 ); 
         [0156]    j) Manually turning valve  51  to make fluid communication between blood compression chamber  62  and filtration chamber, following step i); 
         [0157]    k) Manually turning valve  57  to make fluid communication between plasma compression chamber  64  and filtration chamber, following step j), 
         [0158]    l) Manually turning valve  61  to simultaneously cut off fluid communication between sipper open end and filtration chamber and fluidly connect auxiliary channel  58   e  and the first blood flow path, after sufficient blood enters housing  32 ; 
         [0159]    m) Repeatedly depressing and releasing plunger  42   c  of the blood compression chamber  62  until sufficient plasma enters the plasma flow channel  68 . 
         [0160]    After step m), either the plasma can be ejected through outlet  54  by turning valve  59  to make fluid communication between the outlet  54  and the plasma reservoir  78   f  only, or concentrated blood can be ejected through outlet  54  by turning valve  59  to make fluid communication between the outlet  54  and the auxiliary channel  58   e  only. A person of ordinary skill in the art will appreciate that although assembly  140  uses the same outlet  54  for plasma and concentrated blood, facilitated by the multi-directional valve  59 , other embodiments of the invention comprise independent outlets for plasma and concentrated blood, wherein the use of a multi-directional valve  59  becomes optional. 
         [0161]    The steps described before for preparing retentate of filtrate from a primary sample are numerous, and one of ordinary skill in the art will appreciate that the procedures can be simplified by strategically designing embodiments of the invention with certain non-essential elements absent. 
         [0162]    The inventor has described various types of compression chambers for manually modulating pressure in a retentate or a filtrate compression chamber, wherein the compression chambers are distinguished by one of the following combination of activities and elements: 1) Depression and releasing of a flexible member attached to a compression chamber; 2) Rotating a frictionally engaged plunger having threads on its circumferential sides about a longitudinal axis, in a compression chamber having mating threads, whereby the rotational motion is translated into plunger movement along the longitudinal axis; 3) Depression and release of a frictionally engaged spring-loaded plunger in a compression chamber; and 4) Depression of a frictionally engaged plunger in a compression chamber, absent any spring (i.e., the plunger is not spring-loaded). A person of ordinary skill in the art will appreciate that an embodiment of the present invention can comprise any combination of elements described above for modulating pressure in a compression chamber. 
         [0163]    Although not shown in any of the embodiments, it will be understood that some embodiments of the filtration assembly comprise signal providing means for measuring at least one analyte in any of the fluid chambers, as described by the inventor in U.S. Pat. Nos. 7,816,124 and 7,807,450. Some non-limiting examples of measurement techniques include at least an optical chamber having at least one optical window for performing spectroscopic measurement, or a biosensor chamber comprising at least one biosensor in contact with the fluid containing the analyte being measured. 
         [0164]    An essential feature of the apparatus is a flow-through filtration chamber comprising a porous membrane, sometimes simply referred to as a membrane or a filter. The membrane has optional shapes and sizes, and includes a wall with a wall thickness, and pores through the wall of the membrane. Filtration is enhanced by the following: a) increased sample flow along the sample side of the membrane; b) increased size and number of pores in the membrane; c) decreased membrane wall thickness; d) increased surface area of the membrane; and e) applying negative pressure to the filtrate side of the membrane, i.e., the trans-membrane pressure. A person of ordinary skill in the art will appreciate that the general function of the present invention is to prepare a filtrate or concentrate of any liquid, which may or may not comprise cellular or particulate matter. Therefore, although the embodiments of the invention described uses blood as the primary sample, the invention is not limited in any way to processing blood. As explained before, blood was used because the prior art (U.S. Pat. Nos. 7,816,124 and 7,807,450) was specifically described for processing blood, and blood facilitates description of the invention because the filtrate is plasma, and the parts of the embodiments can be described with reference to one or more blood flow path, and one or more plasma flow path. Increased blood flow decreases the apparent viscosity of the blood, but if the flow is too forceful, hemolysis could occur. Also, if the pores are too large, the formed elements of blood (e.g., red blood cells) could filter through with the plasma. Furthermore, the formed elements of blood could plug up the pores, hindering filtration, and hemolysis could occur as the red blood cells squeeze through the pores. As mentioned before, where plasma or serum is used as the primary sample, the term filtrate, although described more appropriately as a plasma ultra-filtrate and a serum ultra-filtrate respectively, is still used since the primary samples used to describe the present invention, are not intended to limit the scope of the invention in any way. 
         [0165]    As explained before, a filtration chamber does not point to any isolated structure in the embodiments of the invention, but points to a general structure that comprises a porous membrane assembled in any configuration, a sample inlet to the filtration chamber, an outlet for outflow of the fraction of sample that does not penetrate the membrane (referred to as the retentate or concentrate), and an outlet for the fraction of sample that penetrates the membrane (referred to as the filtrate). A person of ordinary skill in the art will appreciate that the inlet to the filtration chamber of a filtration assembly is not necessarily the inlet opening designated by the numbers  22   a ,  22   b ,  22   c  and  22   d . Similarly, a person of ordinary skill in the art will appreciate that the outlet of the filtration chamber of a filtration assembly is not necessarily the outlet designated by the numbers  54  and  54   b . A schematic representation of a filtration chamber is provided in  FIGS. 3C and 3D , and it should be noted that the inlet opening  22   a  and outlet  54  of this embodiment are not included in the schematic representation of the filtration chamber. The filtration membrane in this embodiment is in the form of hollow fibers, but membrane in other embodiments are flat, and the configuration of the membrane is not intended to limit the scope of the invention in any way. As explained before, the side of the membrane in contact with retentate is referred to as the retentate side, and the side of the membrane in contact with the filtrate is referred to as the filtrate side. 
         [0166]    In some embodiments, the interior walls of the apparatus are treated with a hydrophilic coating to promote even spreading of the blood within an optical chamber, and to promote movement of blood along the flow path. A flow path may also contain one or more reagents, anywhere along the flow path, for example without limitation, an anticoagulant, a hemolyzing reagent, or a reagent that reacts with an analyte to enhance detection. In some use of the apparatus, anticoagulated blood is collected in a microtube, for example blood collected from the heel of a neonate after a pin or lancet prick, for diagnosing and treating neonatal jaundice. 
         [0167]    While the above description provides example embodiments, it will be appreciated that the present invention is susceptible to modification and change without departing from the fair meaning and scope of the accompanying claims. Accordingly, what has been described is merely illustrative of the application of aspects of embodiments of the invention. Numerous modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described herein. Furthermore, the discussed combination of features might not be absolutely necessary for the inventive solution.