CA1320142C - Separator for cell-containing liquids - Google Patents
Separator for cell-containing liquidsInfo
- Publication number
- CA1320142C CA1320142C CA000582244A CA582244A CA1320142C CA 1320142 C CA1320142 C CA 1320142C CA 000582244 A CA000582244 A CA 000582244A CA 582244 A CA582244 A CA 582244A CA 1320142 C CA1320142 C CA 1320142C
- Authority
- CA
- Canada
- Prior art keywords
- cell
- area
- housing
- fraction
- receiving
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 239000007788 liquid Substances 0.000 title claims abstract description 25
- 239000012528 membrane Substances 0.000 claims abstract description 23
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 239000012780 transparent material Substances 0.000 claims description 2
- 239000012510 hollow fiber Substances 0.000 claims 2
- 239000008280 blood Substances 0.000 abstract description 8
- 210000004369 blood Anatomy 0.000 abstract description 8
- 238000000926 separation method Methods 0.000 abstract description 4
- 239000000835 fiber Substances 0.000 description 15
- 238000010276 construction Methods 0.000 description 10
- 238000001914 filtration Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000004033 plastic Substances 0.000 description 5
- 229920003023 plastic Polymers 0.000 description 5
- -1 polypropylene Polymers 0.000 description 4
- 230000002349 favourable effect Effects 0.000 description 3
- 206010018910 Haemolysis Diseases 0.000 description 2
- 239000004952 Polyamide Substances 0.000 description 2
- 239000004697 Polyetherimide Substances 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 229920001971 elastomer Polymers 0.000 description 2
- 230000008588 hemolysis Effects 0.000 description 2
- 229920002647 polyamide Polymers 0.000 description 2
- 229920001601 polyetherimide Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 239000005060 rubber Substances 0.000 description 2
- ZAMLGGRVTAXBHI-UHFFFAOYSA-N 3-(4-bromophenyl)-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(CC(O)=O)C1=CC=C(Br)C=C1 ZAMLGGRVTAXBHI-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004642 Polyimide Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 229920001328 Polyvinylidene chloride Polymers 0.000 description 1
- 229940081735 acetylcellulose Drugs 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000013536 elastomeric material Substances 0.000 description 1
- 238000011841 epidemiological investigation Methods 0.000 description 1
- 239000000727 fraction Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000002616 plasmapheresis Methods 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 229920001721 polyimide Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 239000005033 polyvinylidene chloride Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 229920001169 thermoplastic Polymers 0.000 description 1
- 239000004416 thermosoftening plastic Substances 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
- B01D61/14—Ultrafiltration; Microfiltration
- B01D61/18—Apparatus therefor
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D63/00—Apparatus in general for separation processes using semi-permeable membranes
- B01D63/02—Hollow fibre modules
- B01D63/024—Hollow fibre modules with a single potted end
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D63/00—Apparatus in general for separation processes using semi-permeable membranes
- B01D63/02—Hollow fibre modules
- B01D63/025—Bobbin units
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/49—Blood
- G01N33/491—Blood by separating the blood components
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D2313/00—Details relating to membrane modules or apparatus
- B01D2313/90—Additional auxiliary systems integrated with the module or apparatus
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Water Supply & Treatment (AREA)
- Hematology (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Urology & Nephrology (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Ecology (AREA)
- External Artificial Organs (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Abstract A device for separating a cell-containing liquid into a cell-containingand a cell-free fraction, which device comprises an essentially elongated housing at one end of which there is provided a closable inlet, which housing contains an area for the cell-containing fraction, an area for the cell-free fraction and a membrane separator, which separator comprises a narrow feed channel through which the cell-containing liquid is passed over the wall of a separation membrane, which is formed by one or more hollow fibres which are connected at their open ends to the area for the cell-free fraction.
Thus, for example, whole blood is separated very rapidly after its introduction into the device. The device may be manufactured simply and inexpensively and is pre-eminently suitable to be used for diagnostic purposes.
Thus, for example, whole blood is separated very rapidly after its introduction into the device. The device may be manufactured simply and inexpensively and is pre-eminently suitable to be used for diagnostic purposes.
Description
13~01~2 P lgo R
Separator for cell-containing liquids The invention relates to a device for separating d cell-containing liquid into a cell-containing and a cell-free fraction, which device comprises an essentially elongated housing at one end of which there is provided a closable inlet, which housing contains an area for the cell-containing fraction, an area for the cell-free fraction, and a membrane separator, which separator comprises a nar.ow feed channel through which the cell-containing liquid is passed over the wall of a separation membrane.
An apparatus of the type indicated above has been proposed before in European Patent Application 184 852.
In the device described therein the membrane separator comprises a space containing a flat membrane which is attached to a grid and which membrane is positioned between two walls spaced slightly therefrom.
From the upper end of the separator the cell-containing liquid is passed down over the membrane and at the lower end it is discharged as cell-con-taining frac-tion to an area for collecting this fraction. Through channels on the other side of the membrane the cell-free fraction is passed to an area for collecting that fraction. In the closable inlet there are various provisions for a uniform distribution of the cell-containing liquid across the entire width of the membrane.
Although the separating devices described therein permit obtaining a cell-free fraction (plasma) in an amount sufficiently high for diagnostic pur-poses, in view of the single use of these devices in medical practice there is a great need for separating devices of a simpler and less expen-sive construction.
The present invention provides a device which largely meets said need.
The invention consists in that with an apparatus of the known type men-tioned in the opening paragraph the membrane is formed by one or more hollow fibres which are connected at their open ends to the area for the cell-free fraction.
'' ' ~
. ' " . ' ' , 2 132~42 It should be added that separators for cell-containing liquids comprising membranes composed o-f one or more hollow fibres are known in themselves.
GB-A-2 173 711, for example, describes a separator for blood, for in-stance, in which the driving force needed to bring about filtration is ob-tained either by a difference in pressure created between the outside and the inside of the hollow fibre or by the use of a centrifugal force.
In Patent Abstracts of Japan7 Vol. 9, No 184 (C-294)(1907) July 30, 1985 also mention is made of a hollow fibre membrane. In that case, however, the liquid to be filtered is passed through a thin tube inside the lumen of a hollow fibre. Unlike the device according to the invention, this known filter is a dead-end filter as is the one according to GB-A 2 173 711.
In Patent Abstracts of Japan, Vol. 10, No. 119 (P-453)(2176), May 6, 1986 mention is made of a separator comprising a bundle of hollow fibres. In this device, too, the blood to be ~iltered is passed through the hollow fibres. In the separators according to the present invention, however, the cell-containing liquid is passed over the outside of the hollow fibre(s).
The use of one or more hollow fibres in a narrow feed channel results in a far simpler construction permitting a proper contact between the cell-containing liquid and the separation membrane.
For a proper functioning of the separating device according to the inven-tion it is of importance that the cell-containing liquid should pass along the wall of the hollow fibres at a sufficiently high shear rate. The at-tendant shear stress acting as driving force will then bring about the desired filtra-tion.
In this connection the distance between the wall of the feed channel and that of the hollow fibres will generally be in the range of 20 to 200 um.
A distance smaller than 20 ~m will readily give rise to hemolysis and possibly to long filtration times, and at a distance greater than 200 ~m the shear rate will generally be too low, resulting in a low plasma yield.
According to the invention it is preferred that in the separating device the distance between the wall of the feed channel and that of the hollow fibres should be in the range of 50 to 100 ~m.
As hollow fibres suitable for use according to the invention may be em-ployed such fibres as are also used in dialysis, ultrafiltration and plas-mapheresis. They generally have an inner diame-ter of 250-750 ~um, prefer-~ ably 300-400 ~m, and their wall thickness is usually in the range of 100 :
:~
Separator for cell-containing liquids The invention relates to a device for separating d cell-containing liquid into a cell-containing and a cell-free fraction, which device comprises an essentially elongated housing at one end of which there is provided a closable inlet, which housing contains an area for the cell-containing fraction, an area for the cell-free fraction, and a membrane separator, which separator comprises a nar.ow feed channel through which the cell-containing liquid is passed over the wall of a separation membrane.
An apparatus of the type indicated above has been proposed before in European Patent Application 184 852.
In the device described therein the membrane separator comprises a space containing a flat membrane which is attached to a grid and which membrane is positioned between two walls spaced slightly therefrom.
From the upper end of the separator the cell-containing liquid is passed down over the membrane and at the lower end it is discharged as cell-con-taining frac-tion to an area for collecting this fraction. Through channels on the other side of the membrane the cell-free fraction is passed to an area for collecting that fraction. In the closable inlet there are various provisions for a uniform distribution of the cell-containing liquid across the entire width of the membrane.
Although the separating devices described therein permit obtaining a cell-free fraction (plasma) in an amount sufficiently high for diagnostic pur-poses, in view of the single use of these devices in medical practice there is a great need for separating devices of a simpler and less expen-sive construction.
The present invention provides a device which largely meets said need.
The invention consists in that with an apparatus of the known type men-tioned in the opening paragraph the membrane is formed by one or more hollow fibres which are connected at their open ends to the area for the cell-free fraction.
'' ' ~
. ' " . ' ' , 2 132~42 It should be added that separators for cell-containing liquids comprising membranes composed o-f one or more hollow fibres are known in themselves.
GB-A-2 173 711, for example, describes a separator for blood, for in-stance, in which the driving force needed to bring about filtration is ob-tained either by a difference in pressure created between the outside and the inside of the hollow fibre or by the use of a centrifugal force.
In Patent Abstracts of Japan7 Vol. 9, No 184 (C-294)(1907) July 30, 1985 also mention is made of a hollow fibre membrane. In that case, however, the liquid to be filtered is passed through a thin tube inside the lumen of a hollow fibre. Unlike the device according to the invention, this known filter is a dead-end filter as is the one according to GB-A 2 173 711.
In Patent Abstracts of Japan, Vol. 10, No. 119 (P-453)(2176), May 6, 1986 mention is made of a separator comprising a bundle of hollow fibres. In this device, too, the blood to be ~iltered is passed through the hollow fibres. In the separators according to the present invention, however, the cell-containing liquid is passed over the outside of the hollow fibre(s).
The use of one or more hollow fibres in a narrow feed channel results in a far simpler construction permitting a proper contact between the cell-containing liquid and the separation membrane.
For a proper functioning of the separating device according to the inven-tion it is of importance that the cell-containing liquid should pass along the wall of the hollow fibres at a sufficiently high shear rate. The at-tendant shear stress acting as driving force will then bring about the desired filtra-tion.
In this connection the distance between the wall of the feed channel and that of the hollow fibres will generally be in the range of 20 to 200 um.
A distance smaller than 20 ~m will readily give rise to hemolysis and possibly to long filtration times, and at a distance greater than 200 ~m the shear rate will generally be too low, resulting in a low plasma yield.
According to the invention it is preferred that in the separating device the distance between the wall of the feed channel and that of the hollow fibres should be in the range of 50 to 100 ~m.
As hollow fibres suitable for use according to the invention may be em-ployed such fibres as are also used in dialysis, ultrafiltration and plas-mapheresis. They generally have an inner diame-ter of 250-750 ~um, prefer-~ ably 300-400 ~m, and their wall thickness is usually in the range of 100 :
:~
3 :~3201~
to 300 ,um. Their outer diameter generally ranges from 0,2 to 1,5 mm. The individual pores in the membrane generally measure from 0,1 to 1,2 ,um and are preferably about 0,45 um.
The material from which the hollow fibres are made shoùld be hydrophilic.
As examples of suitable fibre materials may be mentioned polyamide, cel-lulose acetate and hydrophilized polypropylene. Very favourable results have been obtained with an asymmetric hollow fibre of polyimide having an outer diameter of 0,85 mm.
As in the case o~ the known device, the device according to the invention comprises an essentially elongated housing at one end of which there is provided a closable inlet. The closing element to be used to that end is preferably made of an elastomeric material and, as is the case with the known blood collection tubes, is so constructed that it can be penetrated by the needle of an hypodermic syringe.
Partly in view of the simple construction, it is preferred that use should be made of a separator which extends in longitudinal direction of the housing.
Preferably, the separator is connected at one end to said inlet.
The hollow fibres may extend in the feed channels in many different ways.
A favourable embodiment consists in that one or more hollow fibres extend longitudinally within the feed channel and are closed at the end near the inlet of the housing. In that case the hollow fibres may extend practical-ly parallel to the direction of the housing. Alternatively, one or more hollow fibres may extend helically within the feed channel about a longitudinally positioned pin. Instead of being closed at one end, the fibres may be doubled upon themselves and have their two ends connected to the area for the cell-free fraction.
For the construction of the housing and the separator various~ preferably thermoplastic, materials may be employed. As examples of suitable materials may be mentioned glass, polyethylene, polypropylene, polysty-rene, polyvinylidene chloride, polyamide and polyethylene terephthalate.
These rnaterials also may be used if in the device according to the inven-tion, as in the case of the known blood collecting tubes, a vacuum need be created and maintained for a considerable period.
The separator is essentially formed by a narrow feed channel through which -the cell-containing liquid is passed over the wall of the hollow fibres.
For the feed channel various shapes are conceivable both as far as the cross-section perpendicular to the liquid stream is concerned and as -: ~ .
l32al~
regards the variation in shape from the beginning to the end of the chan-nel. The cross-section may for instance be rectangular, elliptical, square or round. Particularly when two or more hollow fibres are employed, use may be made of a channel having a multi-lobal cross-section, each lobe containing one or more fibres. For simplicity of construction it will generally be preferred to use a round cross-section. In this connection a distinction may still be made between a construction in which the cell-containing liquid passes through a hollQw tube serving as a narrow feed channel and a construction in which the cell-containing liquid is passed externally of a concentric tube closed at both ends and positioned within the housing, in which tube at a short distance from the downstream end then are provided openings for admitting the cell-containing fraction. A
suitable embodiment consists in that the hollow fibres are so arranged about the tube that in the annular feed channel they run practically parallel to the axis of the tube of which the outer diameter is only a little smaller than the inner diameter of the housing. If the hollow fibres are kept in their position by means of grooves provided in a feed channel, use may with advantage be made of a construction in which the fibres are helically wound about the inner tube. The variation in shape from the beginning to the end of the channel is generally defined by the dimensions and the shape of the housing.
A favourable embodiment of an apparatus according to the invention con-sists in that the housing comprises a part with a closable inlet, an area for the cell-containing fraction and a membrane separator and a part sealed off therefrom except for the passage o-f the hollow fibres, in which latter part there is the area for the cell-free fraction. This bipartite housing may be composed of an integrated whole or of separate pieces. In the case where the housing is made up of two separate pieces, these may advantageously be joined by a screw and/or with a glue. Upon admitting the cell-containing liquid an excess pressure will be created which will sub-sequently be made use of to bring about the separation process. To this end the device is provided with a deaeration filter both in the area for the cell-containing fraction and in the area for the cell-free fraction.
In the case where the cell-containing liquid is passed through the feed channel under the action of a vacuum prevailing throughout the device, the deaeration filters are left out. Preference is then given to a construc-tion comprising a tube which is closable at one end or at two ends.
~32014~
The device according to the invention is not only suitable for collecting samples of plasma, which plasma can subsequently be examined in situ. It also excellently lends itself for use in an epidemiological investigation, in which a large group of persons are to be examined for the presence or absence of contagious diseases. In that case use is made of a housing of a transparent material and the area for the cell-free fraction contains a diagnostic reagent. An advantageous embodiment consists in that the diag-nostic reagent is on the wall of the area for the cell-free fraction.
The invention will be further described with reference to the accompanying figures. The embodiments described below are, of course, not to be con-strued as limiting the scope of the present invention.
Figure 1 is a strongly enlarged sectional view of a device according to the invention in longitudinal direction.
Figure 2 is a cross-sec-tional view of the same device along the line II-II .
Figure 3 is a strongly enlarged section in longitudinal direction of a alternative embodiment of a device according to the invention.
Figure 4 is a strongly enlarged section in longitudinal direction of a variant embodiment comprising means for conducting a diagnostic test.
In Figure 1 one part of the housing of the device is referred to by the numeral 3 and the other part with the area for collecting the cell-free fraction by the numeral 4. Inside part 3 of the housing is the separator in the form of a hollow tube 2 which contains a hollow fibre 1 which has a closed end 14. The inlet of the housing 3 ;s closed with a rubber cap 5 which also serves -to seal the hollow tube 2. ~t its other end the tube 2 ends in the area 4 and is sealed off therefrom, except for the discharge opening 15 of the hollow fibre, by means of, for instance, polyurethane 10. Just above the point where the tube 2 ends in the area 4 are a number of blood outflow openings 9 through which the cell-containing fraction has access to an area ~. In both parts~of the housing 3, 4 are deaeration filters 6, 11.
As appears from the cross-sectional view along the line II II in Figure 2, the housing 3 has a round cross-sectional area within which both -the hol-low tube 2 and the hollow fibre 1 are accommodated.
,.. ~, .. ... . .. .
6 :~32~2 When the above-described device is employed in actual practice a needle 12 is used to penetrate the rubber cap through an opening in a protective plate 16, after which a cell-containing liquid 7, such as blood, is injec-ted into the hollow tube 2 with a syringe.
The small distance between the wall of the hollow fibre 1 and the inner wall of the hollow tube 2 causes the liquid to flow in contact with the wall of the hollow fibre 1 at a high shear rate. The resulting increase in pressure relative to the pressure prevailing in a lumen 13 will cause cell-free liquid (plasma) to flow into the lumen 13 of the hollow fibre 1 and subsequently pass into the area 4.
Figures 3 and 4 show variant embodiments according to the invention, with a vacuum being created throughout the device.
Figure 3 shows a provision in the form of a breaking groove 19, which makes it possible for the area 4 with the cell-free liquid (plasma) to be detached from the device. Figure 4 shows a conceivable combination with a means for conducting a!diagnostic test. The reagents for a test may be on a filter material 17 or form a layer 18 on the wall of the area 4.
The invention will be further elucidatçd in the following examples.
Example I
In this example use was made of device illustrated in Fig. 3. The outside was formed by a plastic tube having a length of 8 cm and an internal dia-meter of 12 mm. The membrane separator fixed inside it co,nsisted of a plastic tube having an internal diameter of 0,93 mm in which there extended a hollow, polyether imide fibre closed at one end and having an external diameter of 0,82 mm and a length of 6 cm. In the device a vacuum prevailed. Through the closable inlet 4 ml of bovine blood were introduced into the device and in a relatively short time 0,48 ml of plasma were ob-ta;ned. During this filtration no hemolysis was observed. When the test was repeated with the same fibre in a plastic tube having an internal dia-meter of 1,16 mm, 0,03 ml of plasma were obtained.
.
7 ~3~142 Example II
The construction of the device used in this example was analogous to that of the device in Example I, except that the plastic tube having a length of 8 cm and a diameter of 12 mm contained three membrane separators positioned parallel to each other. Each membrane separator consisted of a plastic tube having an internal diameter of 0,93 mm in which there extended a hollow, polyether imide fibre closed at one end and having an external diameter of 0,82 mm and a length of 6 cm. By filtration of 4 ml of pig's hlood 0~65 ml of plasma were obtained in a short time.
to 300 ,um. Their outer diameter generally ranges from 0,2 to 1,5 mm. The individual pores in the membrane generally measure from 0,1 to 1,2 ,um and are preferably about 0,45 um.
The material from which the hollow fibres are made shoùld be hydrophilic.
As examples of suitable fibre materials may be mentioned polyamide, cel-lulose acetate and hydrophilized polypropylene. Very favourable results have been obtained with an asymmetric hollow fibre of polyimide having an outer diameter of 0,85 mm.
As in the case o~ the known device, the device according to the invention comprises an essentially elongated housing at one end of which there is provided a closable inlet. The closing element to be used to that end is preferably made of an elastomeric material and, as is the case with the known blood collection tubes, is so constructed that it can be penetrated by the needle of an hypodermic syringe.
Partly in view of the simple construction, it is preferred that use should be made of a separator which extends in longitudinal direction of the housing.
Preferably, the separator is connected at one end to said inlet.
The hollow fibres may extend in the feed channels in many different ways.
A favourable embodiment consists in that one or more hollow fibres extend longitudinally within the feed channel and are closed at the end near the inlet of the housing. In that case the hollow fibres may extend practical-ly parallel to the direction of the housing. Alternatively, one or more hollow fibres may extend helically within the feed channel about a longitudinally positioned pin. Instead of being closed at one end, the fibres may be doubled upon themselves and have their two ends connected to the area for the cell-free fraction.
For the construction of the housing and the separator various~ preferably thermoplastic, materials may be employed. As examples of suitable materials may be mentioned glass, polyethylene, polypropylene, polysty-rene, polyvinylidene chloride, polyamide and polyethylene terephthalate.
These rnaterials also may be used if in the device according to the inven-tion, as in the case of the known blood collecting tubes, a vacuum need be created and maintained for a considerable period.
The separator is essentially formed by a narrow feed channel through which -the cell-containing liquid is passed over the wall of the hollow fibres.
For the feed channel various shapes are conceivable both as far as the cross-section perpendicular to the liquid stream is concerned and as -: ~ .
l32al~
regards the variation in shape from the beginning to the end of the chan-nel. The cross-section may for instance be rectangular, elliptical, square or round. Particularly when two or more hollow fibres are employed, use may be made of a channel having a multi-lobal cross-section, each lobe containing one or more fibres. For simplicity of construction it will generally be preferred to use a round cross-section. In this connection a distinction may still be made between a construction in which the cell-containing liquid passes through a hollQw tube serving as a narrow feed channel and a construction in which the cell-containing liquid is passed externally of a concentric tube closed at both ends and positioned within the housing, in which tube at a short distance from the downstream end then are provided openings for admitting the cell-containing fraction. A
suitable embodiment consists in that the hollow fibres are so arranged about the tube that in the annular feed channel they run practically parallel to the axis of the tube of which the outer diameter is only a little smaller than the inner diameter of the housing. If the hollow fibres are kept in their position by means of grooves provided in a feed channel, use may with advantage be made of a construction in which the fibres are helically wound about the inner tube. The variation in shape from the beginning to the end of the channel is generally defined by the dimensions and the shape of the housing.
A favourable embodiment of an apparatus according to the invention con-sists in that the housing comprises a part with a closable inlet, an area for the cell-containing fraction and a membrane separator and a part sealed off therefrom except for the passage o-f the hollow fibres, in which latter part there is the area for the cell-free fraction. This bipartite housing may be composed of an integrated whole or of separate pieces. In the case where the housing is made up of two separate pieces, these may advantageously be joined by a screw and/or with a glue. Upon admitting the cell-containing liquid an excess pressure will be created which will sub-sequently be made use of to bring about the separation process. To this end the device is provided with a deaeration filter both in the area for the cell-containing fraction and in the area for the cell-free fraction.
In the case where the cell-containing liquid is passed through the feed channel under the action of a vacuum prevailing throughout the device, the deaeration filters are left out. Preference is then given to a construc-tion comprising a tube which is closable at one end or at two ends.
~32014~
The device according to the invention is not only suitable for collecting samples of plasma, which plasma can subsequently be examined in situ. It also excellently lends itself for use in an epidemiological investigation, in which a large group of persons are to be examined for the presence or absence of contagious diseases. In that case use is made of a housing of a transparent material and the area for the cell-free fraction contains a diagnostic reagent. An advantageous embodiment consists in that the diag-nostic reagent is on the wall of the area for the cell-free fraction.
The invention will be further described with reference to the accompanying figures. The embodiments described below are, of course, not to be con-strued as limiting the scope of the present invention.
Figure 1 is a strongly enlarged sectional view of a device according to the invention in longitudinal direction.
Figure 2 is a cross-sec-tional view of the same device along the line II-II .
Figure 3 is a strongly enlarged section in longitudinal direction of a alternative embodiment of a device according to the invention.
Figure 4 is a strongly enlarged section in longitudinal direction of a variant embodiment comprising means for conducting a diagnostic test.
In Figure 1 one part of the housing of the device is referred to by the numeral 3 and the other part with the area for collecting the cell-free fraction by the numeral 4. Inside part 3 of the housing is the separator in the form of a hollow tube 2 which contains a hollow fibre 1 which has a closed end 14. The inlet of the housing 3 ;s closed with a rubber cap 5 which also serves -to seal the hollow tube 2. ~t its other end the tube 2 ends in the area 4 and is sealed off therefrom, except for the discharge opening 15 of the hollow fibre, by means of, for instance, polyurethane 10. Just above the point where the tube 2 ends in the area 4 are a number of blood outflow openings 9 through which the cell-containing fraction has access to an area ~. In both parts~of the housing 3, 4 are deaeration filters 6, 11.
As appears from the cross-sectional view along the line II II in Figure 2, the housing 3 has a round cross-sectional area within which both -the hol-low tube 2 and the hollow fibre 1 are accommodated.
,.. ~, .. ... . .. .
6 :~32~2 When the above-described device is employed in actual practice a needle 12 is used to penetrate the rubber cap through an opening in a protective plate 16, after which a cell-containing liquid 7, such as blood, is injec-ted into the hollow tube 2 with a syringe.
The small distance between the wall of the hollow fibre 1 and the inner wall of the hollow tube 2 causes the liquid to flow in contact with the wall of the hollow fibre 1 at a high shear rate. The resulting increase in pressure relative to the pressure prevailing in a lumen 13 will cause cell-free liquid (plasma) to flow into the lumen 13 of the hollow fibre 1 and subsequently pass into the area 4.
Figures 3 and 4 show variant embodiments according to the invention, with a vacuum being created throughout the device.
Figure 3 shows a provision in the form of a breaking groove 19, which makes it possible for the area 4 with the cell-free liquid (plasma) to be detached from the device. Figure 4 shows a conceivable combination with a means for conducting a!diagnostic test. The reagents for a test may be on a filter material 17 or form a layer 18 on the wall of the area 4.
The invention will be further elucidatçd in the following examples.
Example I
In this example use was made of device illustrated in Fig. 3. The outside was formed by a plastic tube having a length of 8 cm and an internal dia-meter of 12 mm. The membrane separator fixed inside it co,nsisted of a plastic tube having an internal diameter of 0,93 mm in which there extended a hollow, polyether imide fibre closed at one end and having an external diameter of 0,82 mm and a length of 6 cm. In the device a vacuum prevailed. Through the closable inlet 4 ml of bovine blood were introduced into the device and in a relatively short time 0,48 ml of plasma were ob-ta;ned. During this filtration no hemolysis was observed. When the test was repeated with the same fibre in a plastic tube having an internal dia-meter of 1,16 mm, 0,03 ml of plasma were obtained.
.
7 ~3~142 Example II
The construction of the device used in this example was analogous to that of the device in Example I, except that the plastic tube having a length of 8 cm and a diameter of 12 mm contained three membrane separators positioned parallel to each other. Each membrane separator consisted of a plastic tube having an internal diameter of 0,93 mm in which there extended a hollow, polyether imide fibre closed at one end and having an external diameter of 0,82 mm and a length of 6 cm. By filtration of 4 ml of pig's hlood 0~65 ml of plasma were obtained in a short time.
Claims (5)
1. A device for separating a cell-containing liquid into a cell-containing fraction and a cell-free fraction, which device comprises an essentially elongated housing at one end of which there is provided a closable inlet, which housing contains a first area for receiving the cell-containing fraction, a second area located adjacent an opposite sealed end of said housing for receiving the cell-free fraction, and a membrane separator, which membrane separator comprises an enclosed narrow feed channel which is at one end in flow communication with the closable inlet for introduction of the cell-containing liquid and at the other end with the first area for receiving the cell-containing fraction which lies between said enclosed narrow feed channel and said housing, said membrane separator contains one or more hollow fibers which pass through said sealed end of the housing and at their open ends are in flow communication with the second area for receiving the cell-free fraction.
2. A device according to claim 1, wherein said one or more hollow fibers extend helically within the membrane separator about a longitudinally positioned pin.
3. A device according to claim 1, wherein both in the first area for the cell containing fraction and in the second area for receiving the cell-free fraction there is provided a deaeration filter.
4. A device according to claim 1, wherein the housing is of a transparent material and the second area for receiving the cell-free fraction contains a diagnostic reagent.
5. A device according to claim 4, wherein the diagnostic reagent is on the wall of the second area for receiving the cell-free fraction.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/177,410 US4845338A (en) | 1988-04-04 | 1988-04-04 | Inflatable boot liner with electrical generator and heater |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NL8702652 | 1987-11-06 | ||
NL8702652 | 1987-11-06 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1320142C true CA1320142C (en) | 1993-07-13 |
Family
ID=19850877
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA000582244A Expired - Fee Related CA1320142C (en) | 1987-11-06 | 1988-11-04 | Separator for cell-containing liquids |
Country Status (6)
Country | Link |
---|---|
US (1) | US4995967A (en) |
EP (1) | EP0315252B1 (en) |
JP (1) | JPH01151909A (en) |
CA (1) | CA1320142C (en) |
DE (1) | DE3852375T2 (en) |
ES (1) | ES2065332T3 (en) |
Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5132086A (en) * | 1990-02-06 | 1992-07-21 | Chemtrak Corporation | Non-instrumented cholesterol assay |
SE465355B (en) * | 1989-12-07 | 1991-09-02 | Provivo Ab | DISPOSABLE AND PROCEDURE FOR FILTERING OF A PARTICULATED WATER VOLUME |
US5112484A (en) * | 1990-10-11 | 1992-05-12 | Zuk, Inc. | Filtration apparatus |
US5217627A (en) * | 1990-11-06 | 1993-06-08 | Pall Corporation | System and method for processing biological fluid |
WO1993005880A1 (en) * | 1991-09-19 | 1993-04-01 | Innovative Biochemical Product, Inc. | An apparatus for use in chemical, enzymatic and immunoassay reactions |
CA2074671A1 (en) * | 1991-11-04 | 1993-05-05 | Thomas Bormann | Device and method for separating plasma from a biological fluid |
US5316731A (en) * | 1992-11-09 | 1994-05-31 | Carter-Wallace, Inc. | Device for collection and processing of biological samples |
FR2713091B1 (en) * | 1993-12-06 | 1996-02-09 | Hemodia Sa | Method and device for measuring the concentration of at least one substance contained in a complex medium. |
US5888826A (en) * | 1994-06-30 | 1999-03-30 | Dade Behring Inc. | Combination reagent holding and test device |
JPH10504834A (en) * | 1994-08-29 | 1998-05-12 | アクゾ・ノベル・エヌ・ベー | Equipment used for isolation of biological materials such as nucleic acids |
EP0718618A3 (en) * | 1994-09-30 | 1997-12-03 | Becton, Dickinson and Company | Apparatus and method for sorting and separating particles |
GB9422504D0 (en) | 1994-11-08 | 1995-01-04 | Robertson Patricia M B | Blood testing |
GB9424703D0 (en) * | 1994-12-07 | 1995-02-01 | Fsm Technologies Ltd | Plug |
GB9426251D0 (en) * | 1994-12-24 | 1995-02-22 | Fsm Technologies Ltd | Device |
CA2211190A1 (en) * | 1995-01-25 | 1996-08-01 | Therakos, Inc. | Disposable hemolysis detector |
US5674394A (en) * | 1995-03-24 | 1997-10-07 | Johnson & Johnson Medical, Inc. | Single use system for preparation of autologous plasma |
US5603899A (en) * | 1995-04-12 | 1997-02-18 | Pharmacia Biotech, Inc. | Multiple column chromatography assembly |
WO1997015380A1 (en) * | 1995-10-23 | 1997-05-01 | Hemasure, Inc. | Extra-lumenal crossflow plasmapheresis devices |
GB9523854D0 (en) * | 1995-11-22 | 1996-01-24 | Bratton Graham J | Water removal device |
US5945070A (en) * | 1996-10-31 | 1999-08-31 | Merck & Co., Inc. | Reaction vessel filter for combinatorial chemistry or biological use |
US7001774B1 (en) | 1999-03-05 | 2006-02-21 | Microliter Analytical Supplies, Inc. | Sample collection and processing device |
US7798021B2 (en) * | 2006-01-12 | 2010-09-21 | Gamble Kimberly R | Method and apparatus for sample processing and injection |
US20080017577A1 (en) * | 2006-07-21 | 2008-01-24 | Becton, Dickinson And Company | Membrane-based Double-layer Tube for Sample Collections |
AT505433B1 (en) * | 2007-07-06 | 2009-10-15 | Technoclone Ges M B H | PLASMA FILTRATION |
GB2504138A (en) * | 2012-07-20 | 2014-01-22 | Emco Packaging Systems Ltd | A self-contained, rapid field diagnostic system for blood samples |
DE102013112863A1 (en) * | 2013-11-21 | 2015-05-21 | Sartorius Stedim Biotech Gmbh | filter module |
CN114130203A (en) * | 2021-11-18 | 2022-03-04 | 上海拜高乐生物技术有限公司 | Novel cell filtering device |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3608730A (en) * | 1969-10-02 | 1971-09-28 | Selas Corp Of America | Desalination apparatus |
US3774771A (en) * | 1971-12-09 | 1973-11-27 | Interior | Reverse osmosis module |
FR2212166A1 (en) * | 1973-01-02 | 1974-07-26 | Rhone Poulenc Sa | Sepn processes using hollow fibres - spirally wound on core to form cartridge of small cylindrical membranes |
JPS52126682A (en) * | 1976-04-16 | 1977-10-24 | Toyobo Co Ltd | Membrane separation apparatus |
JPS5949018B2 (en) * | 1976-10-15 | 1984-11-30 | 旭化成株式会社 | drug syringe |
US4412916A (en) * | 1981-06-24 | 1983-11-01 | Cordis Dow Corp. | Airless artificial kidney assembly |
NL8105341A (en) * | 1981-11-26 | 1983-06-16 | Akzo Nv | DIAGNOSTIC TEST METHOD. |
JPS6084110A (en) * | 1983-10-17 | 1985-05-13 | Asahi Medical Kk | Composite type filtering concentrator |
US4639316A (en) * | 1984-12-14 | 1987-01-27 | Becton, Dickinson And Company | Automatic liquid component separator |
JPS61209010A (en) * | 1985-03-12 | 1986-09-17 | Toyo Soda Mfg Co Ltd | Minute amount liquid filter |
US4668401A (en) * | 1985-06-19 | 1987-05-26 | Mitsubishi Rayon Co., Ltd. | Hollow-fiber filter module and filtration method using the same |
-
1988
- 1988-10-24 US US07/261,326 patent/US4995967A/en not_active Expired - Fee Related
- 1988-10-26 DE DE3852375T patent/DE3852375T2/en not_active Expired - Fee Related
- 1988-10-26 EP EP88202379A patent/EP0315252B1/en not_active Expired - Lifetime
- 1988-10-26 ES ES88202379T patent/ES2065332T3/en not_active Expired - Lifetime
- 1988-11-02 JP JP63276377A patent/JPH01151909A/en active Pending
- 1988-11-04 CA CA000582244A patent/CA1320142C/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
ES2065332T3 (en) | 1995-02-16 |
DE3852375T2 (en) | 1995-05-24 |
EP0315252B1 (en) | 1994-12-07 |
DE3852375D1 (en) | 1995-01-19 |
JPH01151909A (en) | 1989-06-14 |
EP0315252A1 (en) | 1989-05-10 |
US4995967A (en) | 1991-02-26 |
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