NZ600343B - Plasma separation - Google Patents
Plasma separation Download PDFInfo
- Publication number
- NZ600343B NZ600343B NZ600343A NZ60034312A NZ600343B NZ 600343 B NZ600343 B NZ 600343B NZ 600343 A NZ600343 A NZ 600343A NZ 60034312 A NZ60034312 A NZ 60034312A NZ 600343 B NZ600343 B NZ 600343B
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- plasma
- filter
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Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01L2300/00—Additional constructional details
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
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-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
- B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
- B01L2400/049—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics vacuum
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502753—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
-
- 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
Abstract
600343 A plasma separation device 500 comprising a filter comprising a microporous membrane 650 and having an upstream surface and a downstream surface, a housing 400 with an inlet 250a, a downstream chamber 202, and an outlet, and at least one air channel. The housing 400 defines a fluid flow path between the inlet 250a, the downstream chamber 202, and the outlet, with the filter disposed in the housing 400 across the fluid flow path. The outlet and the air channel are spaced apart and are arranged such that, when a negative pressure is created in the downstream chamber 202 through the outlet, air passes into the downstream chamber 202 via the air channel and sweeps plasma from the downstream surface of the filter and through the outlet. between the inlet 250a, the downstream chamber 202, and the outlet, with the filter disposed in the housing 400 across the fluid flow path. The outlet and the air channel are spaced apart and are arranged such that, when a negative pressure is created in the downstream chamber 202 through the outlet, air passes into the downstream chamber 202 via the air channel and sweeps plasma from the downstream surface of the filter and through the outlet.
Description
Received at IPONZ on 11 May 2013
NEW ZEALAND
PATENTS ACT, 1953
COMPLETE SPECIFICATION
PLASMA SEPARATION
Received at IPONZ on 11 May 2013
PLASMA SEPARATION
BACKGROUND OF THE INVENTION
A variety of tests for diagnosing disease, monitoring the course of disease and/or
determining the effectiveness of treatment of a disease, involve obtaining plasma from a
patient and performing tests on the plasma. Typically, blood is obtained from patient and
processed to remove the cellular components to provide the plasma, wherein the processing
includes (a) centrifuging the blood at high G forces for about 5-15 minutes so that the more
dense cellular components can be concentrated at the bottom of the centrifuge tube, and the
supernatant plasma can be removed, or (b) applying a few drops of blood to a lateral flow
device wherein gravity and capillary forces provide for separating the plasma from the other
components, and the separated plasma is wicked into an absorbent pad wherein test reagents
react with the plasma.
However, processing blood by centrifugation generally involves transporting the
blood sample to centralized laboratories containing centrifuges, which are operated by skilled
laboratory personnel. This is costly, as it is time and labor intensive. Alternatively, lateral
flow devices, which can be utilized outside of the laboratory, and without requiring skilled
personnel, cannot easily produce the liquid plasma sample that is desired by most state of the
art and accurate diagnostic tests.
It is an object of the present invention to go some way towards providing for
ameliorating at least some of the disadvantages of the prior art; and or to provide the public
with a useful choice. These and other advantages of the present invention will be apparent
from the description as set forth below.
BRIEF SUMMARY OF THE INVENTION
The present invention provides for the isolation of a suitable volume of
substantially cell-free liquid from a biological fluid without using a centrifuge.
An embodiment of the invention provides a plasma separation device comprising:
(a) a filter having an upstream surface and a downstream surface, the filter comprising a
microporous membrane; and, (b) a housing, having an inlet, a downstream chamber, and an
Received at IPONZ on 11 May 2013
outlet, and at least one air channel; defining a fluid flow path between the inlet, the
downstream chamber, and the outlet, with the filter disposed in the housing across the fluid
flow path, wherein the outlet and the air channel are spaced apart and are arranged such that,
when a negative pressure is created in the downstream chamber through the outlet, air passes
into the downstream chamber via the air channel and sweeps plasma from the downstream
surface of the filter and through the outlet. In some embodiments, the device includes two or
more air channels and/or two or more plasma collection channels.
In another embodiment, a method for processing biological fluid is provided,
comprising applying biological fluid to the upstream surface of the filter of an embodiment of
the plasma separation device; passing plasma from the upstream surface of the filter to the
downstream surface of the filter; creating a negative pressure in the downstream chamber
through the outlet; passing air through the air channel into the downstream chamber and
sweeping plasma from the downstream surface of the filter; and, passing swept plasma
through the outlet.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)
Figure 1 is a view of an embodiment of a plasma separation device according to
the present invention, where Figure 1A and 1B show top and bottom views, respectively,
Figure 1C shows a top view of the base, and Figure 1D shows a cross-sectional view, wherein
the illustrated device has a single air channel, and the filter includes a membrane and an
optional upstream fibrous medium.
Figure 2 is a view of another embodiment of a plasma separation device according
to the present invention, where Figure 2A shows a top view, Figure 2B shows a top view of
the base, and Figure 2C shows a cross-sectional view, wherein the illustrated device has a
plurality of air channels and a central outlet.
Figure 3 is a view of another embodiment of a plasma separation device according
to the present invention, where Figure 3A and 3B show top and bottom views, respectively,
Figure 3C shows a top view of the base, and Figures 3D and 3E shows cross-sectional views,
wherein the illustrated device has a plurality of air channels and a non-central outlet.
Received at IPONZ on 11 May 2013
DETAILED DESCRIPTION OF THE INVENTION
Advantageously, the present invention provides for the isolation of a suitable
volume of substantially cell-free liquid, e.g., cell-free plasma, preferably, from whole blood,
e.g., unmodified and directly from a patient, without using a centrifuge, with minimal or no
hemolysis of red blood cells, in a short period of time. The invention is particularly suitable
for point of care (POC) applications. The invention can be carried out manually,
automatically, or semi-automatically, e.g., wherein at least one aspect of the method (for
example, applying the biological fluid to the surface of the filter) is carried out manually, and
at least one other aspect (for example, creating a negative pressure) is automated.
In accordance with an embodiment of the present invention, a plasma separation
device is provided comprising (a) a filter having an upstream surface and a downstream
surface, the filter comprising a microporous membrane; and, (b) a housing, having an inlet, a
downstream chamber, an outlet, and at least one air channel; defining a fluid flow path
between the inlet, the downstream chamber, and the outlet, with the filter disposed in the
housing across the fluid flow path, wherein the outlet and the air channel are spaced apart and
are arranged such that, when a negative pressure is created in the downstream chamber
through the outlet, air passes into the downstream chamber via the air channel and sweeps
plasma from the downstream surface of the filter and through the outlet.
Preferably, the device includes one or more air channel inlet ports downstream of
the downstream surface of the filter, wherein the air channel inlet port or ports communicate
with one or more air channels.
In some embodiments of the device, the outlet is disposed near one end of the
housing, and at least one air channel and at least one air channel inlet port are both disposed
near the opposite end of the housing from the outlet (e.g., as shown in Figure 1).
Embodiments of the device can include more than one filter, and the filter can
include a plurality of porous layers and/or porous media. For example, the filter can
comprise two or more membranes. Alternatively, or additionally, the filter can comprise at
least one fibrous medium. Typically, in those embodiments including at least one fibrous
medium, the fibrous medium is upstream of the membrane(s), e.g., the fibrous medium can
act as a prefilter.
Received at IPONZ on 11 May 2013
In a preferred embodiment, at least one membrane is an asymmetric microporous
membrane having an upstream surface and a downstream surface and larger openings at the
upstream surface than at the downstream surface.
A method for processing biological fluid according to an embodiment of the
invention comprises applying biological fluid to the upstream surface of the filter of an
embodiment of the plasma separation device; passing plasma from the upstream surface of
the filter to the downstream surface of the filter via gravity; creating a negative pressure in
the downstream chamber through the outlet; passing air through the air channel into the
downstream chamber and sweeping plasma from the downstream surface of the filter; and,
passing swept plasma through the outlet.
Embodiments of the invention are suitable for use with a variety of volumes of
biological fluid. For example, the volume of biological fluid can be in the range of from
about 100 μL to about 1 mL. However, the volume can be less than about 100 μL or greater
than about 1 mL.
Each of the components of the invention will now be described in more detail
below, wherein like components have like reference numbers.
In the illustrated embodiments (e.g., Figures 1D, 2C, and 3D), the plasma
separation device 500 comprises a housing 400 comprising a first housing section or cover
100 comprising an inlet 101 (for applying biological fluid to the device), and a second
housing section or base 200 comprising a downstream chamber 202 comprising plasma
channels 220, and an outlet 201 including an outlet port 201a, and defining a fluid flow path
between the inlet, the downstream chamber, and the outlet, the device also comprising a filter
600 comprising a porous membrane 650 (and optional fibrous medium 650a), the filter
having an upstream surface 651 and a downstream surface 652, wherein the filter is disposed
in the housing across the fluid flow path, and the downstream chamber 202 is downstream of
the downstream surface 652 of the filter. Embodiments of the invention can include two or
more filters and/or a filter can include two or more porous elements.
The device includes one or more air channels communicating with the
downstream chamber, as well as (via one or more air channel inlet ports) the external
environment of the device. The device can have two or more, three or more, or any other
number of air channels and air channel ports. Preferably, the device housing includes one or
Received at IPONZ on 11 May 2013
more air channel inlet ports downstream of the downstream surface of the filter, wherein the
outlet is spaced away from the air channel inlet port(s). In the embodiments of the invention
illustrated in Figures 1-3 (e.g., Figures 1C, 2B, 2C, 3B, and 3C), the device housing includes
one or more air channels 250 including air channel inlet ports 250a downstream of the
downstream surface of the filter (wherein the base 200 comprises the illustrated air channels
and air channel ports). Optionally, the device further comprises hydrophobic microporous
membranes (not shown), e.g., covering the air channels, allowing air to enter the channels
while preventing the entry of undesirable material such as particles and/or bacteria.
The illustrated embodiments of the device also include one or more plasma
channels. For example, in the illustrated embodiments (e.g., Figures 1C and 2B), the
downstream chamber 202 in the base comprises a plurality of plasma channels 220, the
channels comprising ridges 220a and grooves 220b. The device can have any number of
plasma channels. The plasma channels need not be uniform, e.g., with respect to shape,
width, height and/or length between one channel and another and/or along any individual
channel. For example, in the embodiment illustrated in Figure 3C, the base 200 includes
plasma channels of more than three different lengths (e.g., allowing “funneling” of plasma
from the larger cross-sectional area near one end of the device to the smaller cross-sectional
area near the other end of the device). In the embodiment illustrated in Figure 1 (e.g., Figure
1C), the plasma channels have a more uniform width and height (e.g., allowing more
equalized air flow to sweep the downstream surface of the filter), and in the embodiment
illustrated in Figure 2 (e.g., Figure 2B) the plasma channels have more uniform heights but
different widths).
Preferably, the device includes a plurality of ridges supporting the downstream
surface of the filter when a negative pressure is created, while allowing air to sweep plasma
into the plasma channels. For example, in the illustrated embodiments shown in Figures 1C,
1D, and 2B, the base 200 includes ridges 210, providing auxiliary plasma channels 211,
wherein the ridges support the downstream surface 652 of the filter (in the illustrated
embodiment shown in Figure 1D, porous membrane 650 has an upstream surface and a
downstream surface, wherein the downstream surface of the membrane provides the
downstream surface 652 of the filter, and optional fibrous medium 650a has an upstream
surface and a downstream surface, wherein the upstream surface of the fibrous medium
Received at IPONZ on 11 May 2013
provides the upstream surface 651 of the filter). Optionally, as shown in Figure 1C, the base
also includes auxiliary plasma channels 212, e.g., to further improve efficiency of sweeping
plasma into the plasma channels. In accordance with these illustrated embodiments, the
auxiliary plasma channels 211 and 212 feed plasma into the main plasma channels 220.
The following definitions are used in accordance with the invention.
A filter comprising at least one porous filter element, e.g., at least one membrane
and/or at least one fibrous element, can have any suitable pore structure, e.g., a pore size (for
example, as evidenced by bubble point, or by K as described in, for example, U.S. Patent
4,340,479, or evidenced by capillary condensation flow porometry), a pore rating, a pore
diameter (e.g., when characterized using the modified OSU F2 test as described in, for
example, U.S. Patent 4,925,572), or removal rating that reduces or allows the passage
therethrough of one or more materials of interest as the plasma-containing fluid is passed
through the element. The pore structure used depends on the composition of the fluid to be
treated, and the desired effluent level of the treated fluid.
Suitable porous membranes, preferably microporous membranes, can be isotropic
membranes, asymmetric membranes, membranes including both asymmetric and isometric
regions and/or composite membranes. In those embodiments wherein the filter comprises an
isotropic membrane, the filter typically further comprises a fibrous medium upstream of the
isotropic membrane.
An isometric membrane has a porous structure with a distribution characterized by
a pore structure (e.g., a mean pore size) that is substantially the same through the bulk of the
membrane. For example, with respect to mean pore size, an isometric membrane has a pore
size distribution characterized by a mean pore size that is substantially the same through the
membrane.
An asymmetric membrane has a pore structure (e.g., a mean pore size) varying
throughout the bulk of the membrane. For example, the mean pore size decreases in size
from one portion or surface to another portion or surface (e.g., the mean pore size decreases
from the upstream portion or surface to the downstream portion or surface). However, other
types of asymmetry are encompassed by embodiments of the invention, e.g., the pore size
goes through a minimum pore size at a position within the thickness of the asymmetric
membrane. The asymmetric membrane can have any suitable pore size gradient or ratio.
Received at IPONZ on 11 May 2013
This asymmetry can be measured by, for example, comparing the mean pore size on one
major surface of a membrane with the mean pore size of the other major surface of the
membrane.
The pore structure of the filter elements is selected as is known in the art.
Typically, the microporous membrane (or, for example, the downstream surface of an
asymmetric microporous membrane) has a mean pore size in the range of about 5
micrometers to about 0.1 micrometers.
A variety of membranes and fibrous elements are suitable for use in the invention,
including polymeric membranes and polymeric fibrous elements. Suitable polymers include,
but are not limited to, polyolefins, polyesters, polyamides, polysulfones, acrylics,
polyacrylonitriles, polyaramides, polyarylene oxides and sulfides, and polymers and
copolymers made from halogenated olefins and unsaturated nitriles. Examples include, but
are not limited to, polyvinylidene difluoride (PVDF), polyethylene, polypropylene,
polybutylene terephthalate (PBT), polyethylene terephthalate (PET), and any nylon, e.g.,
Nylon 6, 11, 46, 66, and 610. Preferred polymers are polysulfones, polyolefins, polyesters,
and polyamides.
Other suitable materials include cellulosic derivatives, such as cellulose acetate,
cellulose propionate, cellulose acetate-propionate, cellulose acetate-butyrate, and cellulose
butyrate. Non-resinous materials, such as glass fibers, including, for example, borosilicate
glass fibers, may also be used.
Particularly preferred are commercially available media, such as those membranes
™ ® ®
available from Pall Corporation under the trademarks VIVID , SUPOR , VERSAPOR , and
POSIDYNE , as well as those available from Pall Corporation under the trademarks
® ® ® ® ®
ULTIPOR N , ULTIPOR , FLUORODYNE , LOPRODYNE , CARBOXYDYNE ,
® ® ® ®
IMMUNODYNE , BIODYNE A , BIODYNE B , and BIODYNE C .
Exemplary membranes are disclosed in, for example, U.S. Patents 6,110,369;
6,045,899; 5,906,742; 5,979,670; and 5,846,422. Other membranes, including those
disclosed in U.S. Patents 4,702,840; 4,900,449; 4,906,374; 4,886,836; 4,964,989; 5,019,260;
4,340,479; 4,855,163; 4,744,132; 4,707,266; 4,203,848; 4,618,533, 6,039,872; 6,780,327;
6,783,937; and 7,189,322, may also be suitable.
Received at IPONZ on 11 May 2013
Exemplary fibrous elements, including elements prepared from melt-blown fibers,
are disclosed in, for example, U.S. Patents 4,880,548, 4,925,572, 5,152,905, 5,443,743,
,472,621, and 6,074,869. Suitable commercially available media include that available
from Pall Corporation, for example, LEUKOSORB™ , METRIGARD™ , TISSUGLAS™ ,
as well as glass and quartz fiber and microfiber media (binder-free or including binder) such
as binder-free borosilicate glass grades A/B, A/C, A/D, A/E, and A/F.
The filter element, e.g., a membrane and/or a fibrous element, can have any
desired critical wetting surface tension (CWST, as defined in, for example, U.S. Patent .
4,925,572). The CWST can be selected as is known in the art, e.g., as additionally disclosed
in, for example, U.S. Patents 5,152,905, 5,443,743, 5,472,621, and 6,074,869. Typically, the
element has a CWST of greater than about 53 dynes/cm (about 53 x 10 N/cm), more
typically greater than about 58 dynes/cm (about 58 x 10 N/cm), and can have a CWST of
about 66 dynes/cm (about 66 x 10 N/cm) or more. Preferably, the element is hydrophilic,
having a CWST of 72 dynes/cm (72 x 10 N/cm) or more, in some embodiments, having a
CWST of about 75 dynes/cm (about 75 x 10 N/cm) or more.
The surface characteristics of the filter and/or filter element(s) can be modified
(e.g., to affect the CWST, to include a surface charge, e.g., a positive or negative charge,
and/or to alter the polarity or hydrophilicity of the surface) by wet or dry oxidation, by coa-
ting or depositing a polymer on the surface, or by a grafting reaction. Modifications include,
e.g., irradiation, a polar or charged monomer, coating and/or curing the surface with a
charged polymer, and carrying out chemical modification to attach functional groups on the
surface. Grafting reactions may be activated by exposure to an energy source such as gas
plasma, vapor plasma, corona discharge, heat, a Van der Graff generator, ultraviolet light,
electron beam, or to various other forms of radiation, or by surface etching or deposition
using a plasma treatment.
The filter, in some embodiments, comprising plurality of porous filter elements, is
disposed in the housing comprising a biological fluid loading or application inlet and an
outlet and a downstream chamber and defining at least one fluid flow path between the inlet
and the downstream chamber and outlet, wherein the filter is across the fluid flow path, and
the housing includes at least one air channel and at least one air channel inlet port, to provide
a plasma separation device. Preferably, the separation device is sterilizable.
Received at IPONZ on 11 May 2013
Any housing of suitable shape and providing an inlet, a downstream chamber, an
outlet and at least one air channel and air channel inlet port, may be employed. Suitable
shapes include, for example, generally teardrop (e.g., as shown in Figure 3), rectangular (e.g.,
as shown in Figure 1), square, circular (e.g., as shown in Figure 2), oval, or triangular.
If desired, the housing can include one or more connectors. For example, the
outlet can comprise a male or female connector (including a male or female luer fitting), a
barbed connector, or a flange. A variety of connectors are suitable and are known in the art.
The housing can be fabricated from any suitable rigid impervious material,
including any impervious thermoplastic material, which is compatible with the biological
fluid being processed. Typically, the housing is fabricated from a polymer. In a preferred
embodiment, the housing is a polymer, in some embodiments, a transparent or translucent
polymer, such as an acrylic, polypropylene, polystyrene, or a polycarbonated resin. Such a
housing is easily and economically fabricated, and allows observation of the passage of the
biological fluid through the housing.
The housing can be sealed as is known in the art, utilizing, for example, one or
more o-rings, an adhesive, a solvent, laser welding, radio frequency sealing, ultrasonic
sealing and/or heat sealing. Additionally, or alternatively, the housing can be sealed via
injection molding. The filter can be sealed within the housing as is known in the art, e.g., via
o-rings, compression, interference fit, or bonded and/or welded to the housing.
Biological Fluid. A biological fluid includes any treated or untreated fluid
associated with living organisms, particularly blood, including whole blood, warm or cold
blood, and stored or fresh blood; treated blood, such as blood diluted with at least one
physiological solution, including but not limited to saline, nutrient, and/or anticoagulant
solutions; blood components, such as platelet concentrate (PC), platelet-rich plasma (PRP),
platelet-poor plasma (PPP), platelet-free plasma, plasma, fresh frozen plasma (FFP),
components obtained from plasma, packed red cells (PRC), transition zone material or buffy
coat (BC); blood products derived from blood or a blood component or derived from bone
marrow; stem cells; red cells separated from plasma and resuspended in a physiological
solution or a cryoprotective fluid; and platelets separated from plasma and resuspended in a
physiological solution or a cryoprotective fluid. The biological fluid may have been treated
to remove some of the leukocytes before being processed according to the invention. As used
Received at IPONZ on 11 May 2013
herein, blood product or biological fluid refers to the components described above, and to
similar blood products or biological fluids obtained by other means and with similar
properties.
A variety of devices and/or systems are suitable for creating a negative pressure
in the downstream chamber through the outlet and are known to one of ordinary skill in the
art. For example, a syringe, e.g., comprising a barrel and plunger, can be used.
Alternatively, for example, one or more of a manifold plate, adapter, and/or a vacuum system
(including, for example, a vacuum tube blood collection system) can be used.
In accordance with a typical embodiment of a method according to the invention,
a biological fluid is applied to the upstream surface of the filter of an embodiment of the
device, and liquid (e.g., plasma) passes from the upstream surface of the filter to the
downstream surface of the filter. Typically, the liquid passes from the upstream surface of
the filter to the downstream surface of the filter primarily via gravity, but the effect of gravity
can also be assisted by the creation of a negative pressure created in the downstream
chamber. Shortly after applying the biological fluid to the filter (e.g., after at least about 30
seconds), a negative pressure is created in the downstream chamber through the outlet (e.g.,
by withdrawing a plunger within a syringe barrel communicating with an outlet of the device
housing); and air passes through the air channel into the downstream chamber, sweeping
substantially cell-free liquid (e.g., substantially cell-free plasma) from the downstream
surface of the filter; and, swept liquid passes through the outlet. In one illustrative
embodiment, the swept plasma is passed into the syringe barrel communicating with the
outlet, and in another illustrative embodiment, the swept plasma is passed into the vacuum
blood collection tube communicating with the outlet.
The swept collected liquid can be further processed as desired and as known to
one of skill in the art. For example, one or more assays can be carried out using the plasma,
e.g., wherein the plasma is mixed with one or more reagents and/or placed in or on an
analytical device.
The following examples further illustrate the invention but, of course, should not
be construed as in any way limiting its scope.
Received at IPONZ on 11 May 2013
Examples 1-14 are carried out using the embodiment of the device as generally
illustrated in Figure 1 (with or without an upstream fibrous medium as noted below). The
media used to provide the filter are 35 mm x 65 mm. In those examples including an
asymmetric membrane, the membrane is a Vivid (Pall Corporation, East Hills, NY)
asymmetric polysulfone plasma separation membrane (PSM) having a mean pore size of
about 100 μm on one side, and about 2 μm on the other side (asymmetry ratio of about
100:2), used with the larger pore size facing upstream side of the device.
The biological fluid used is blood drawn from a healthy donor into 7 mL
Vacutainer (Becton-Dickinson) blood collection tubes containing EDTA anticoagulant. The
blood, which has a hematocrit of about 35%, is used within about 2 hours of collection.
The blood is loaded onto the surface of the filter using a pipette, and after about
60 to about 90 seconds, a syringe is operated to provide a negative pressure. Plasma is
separated and collected within about 2 minutes of loading. The volume of recovered plasma
is measured.
In Examples 1-10, the collected plasma is analyzed to determine the plasma
cholesterol (% recovery as compared to the control), total protein (% recovery as compared to
the control), and free hemoglobin (% recovery as compared to the control), and the values are
compared to plasma separated and collected using centrifugation (the control). SD=standard
deviation.
In Examples 1-14, the collected plasma is analyzed for residual cellular
components using a Cell-DYN® 3700 analyzer (Abbott Diagnostics, Abbott Park, IL), and
the concentrations of the red blood cells, white blood cells, and platelets are lower than the
detection limit of the instrument.
These examples demonstrate that cell-free plasma can be quickly separated from
blood in accordance with embodiments of the invention.
EXAMPLE 1
This example demonstrates that cell-free plasma can be quickly separated from
blood without significantly adversely affecting the plasma cholesterol, total protein, and free
hemoglobin using an embodiment of a device including a single membrane.
Received at IPONZ on 11 May 2013
The membrane is a Vivid PSM grade GF asymmetric polysulfone membrane.
The results are as follows.
vol blood vol plasma cholesterol SD total SD total free
μL μL cholesterol protein protein hemoglobin
850 55 101 1 102 2 102
EXAMPLE 2
This example demonstrates that cell-free plasma can be quickly separated from
blood without significantly adversely affecting the plasma cholesterol, total protein, and free
hemoglobin using an embodiment of a device including a membrane and a fibrous element
upstream of the membrane.
The membrane is a Vivid PSM grade GF asymmetric polysulfone membrane.
The fibrous element is a layer of binder-free borosilicate glass fibers grade A/D (Pall
Corporation, East Hills, NY) having a mean pore size of 3.1 μm and a thickness of between
about 584 to about 737 μm (about 23 to about 29 mils). The results are as follows.
vol blood vol plasma cholesterol SD total SD total free
μL μL cholesterol protein protein hemoglobin
2800 700 101 3 101 1 103
EXAMPLE 3
This example demonstrates that cell-free plasma can be quickly separated from
blood without significantly adversely affecting the plasma cholesterol, total protein, and free
hemoglobin using an embodiment of a device including a membrane and a fibrous element
upstream of the membrane.
Received at IPONZ on 11 May 2013
The membrane is a Vivid PSM grade GF asymmetric polysulfone membrane.
The fibrous element is a layer of Leukosorb™ media (Pall Corporation, East Hills, NY)
having a mean pore size of about 8 μm and a thickness of between about 356 to about 559
μm. The results are as follows.
vol blood vol plasma cholesterol SD total SD total free
μL μL cholesterol protein protein hemoglobin
1600 280 103 2 100 1 106
EXAMPLE 4
This example demonstrates that cell-free plasma can be quickly separated from
blood without significantly adversely affecting the plasma cholesterol, total protein, and free
hemoglobin using an embodiment of a device including a single membrane.
The membrane is a Vivid PSM grade GX asymmetric polysulfone membrane.
The results are as follows.
vol blood vol plasma cholesterol SD total SD total free
μL μL cholesterol protein protein hemoglobin
850 724 101 3 101 1 108
EXAMPLE 5
This example demonstrates that cell-free plasma can be quickly separated from
blood without significantly adversely affecting the plasma cholesterol, total protein, and free
hemoglobin using an embodiment of a device including a membrane and a fibrous element
upstream of the membrane.
The membrane is a Vivid PSM grade GX asymmetric polysulfone membrane.
The fibrous element is a layer of binder-free borosilicate glass fibers grade A/D (Pall
Received at IPONZ on 11 May 2013
Corporation, East Hills, NY) having a mean pore size of 3.1 μm and a thickness of between
about 584 to about 737 μm (about 23 to about 29 mils). The results are as follows.
vol blood vol plasma cholesterol SD total SD total free
μL μL cholesterol protein protein hemoglobin
2800 704 98 1 101 5 101
EXAMPLE 6
This example demonstrates that cell-free plasma can be quickly separated from
blood without significantly adversely affecting the plasma cholesterol, total protein, and free
hemoglobin using an embodiment of a device including a membrane and a fibrous element
upstream of the membrane.
The membrane is a Vivid PSM grade GX asymmetric polysulfone membrane.
The fibrous element is a layer of Leukosorb™ media (Pall Corporation, East Hills, NY)
having a mean pore size of about 8 μm and a thickness of between about 356 to about 559
μm. The results are as follows.
vol blood vol plasma cholesterol SD total SD total free
μL μL cholesterol protein protein hemoglobin
1600 325 95 1 92 4 98
EXAMPLE 7
This example demonstrates that cell-free plasma can be quickly separated from
blood without significantly adversely affecting the plasma cholesterol, total protein, and free
hemoglobin using an embodiment of a device including a single membrane.
The membrane is a Vivid PSM grade GR asymmetric polysulfone membrane.
The results are as follows.
Received at IPONZ on 11 May 2013
vol blood vol plasma cholesterol SD total SD total free
μL μL cholesterol protein protein hemoglobin
850 292 95 1 90 2 100
EXAMPLE 8
This example demonstrates that cell-free plasma can be quickly separated from
blood without significantly adversely affecting the plasma cholesterol, total protein, and free
hemoglobin using an embodiment of a device including a membrane and a fibrous element
upstream of the membrane.
The membrane is a Vivid PSM grade GR asymmetric polysulfone membrane.
The fibrous element is a layer of binder-free borosilicate glass fibers grade A/D (Pall
Corporation, East Hills, NY) having a mean pore size of 3.1 μm and a thickness of between
about 584 to 737 μm (about 23 to about 29 mils). The results are as follows.
vol blood vol plasma cholesterol SD total SD total free
μL μL cholesterol protein protein hemoglobin
2800 730 78 3 90 2 98
EXAMPLE 9
This example demonstrates that cell-free plasma can be quickly separated from
blood without significantly adversely affecting the plasma cholesterol, total protein, and free
hemoglobin using an embodiment of a device including a membrane and a fibrous element
upstream of the membrane.
The membrane is a Vivid PSM grade GR asymmetric polysulfone membrane.
The fibrous element is a layer of Leukosorb™ media (Pall Corporation, East Hills, NY)
having a mean pore size of about 8 μm and a thickness of between about 356 to about 559
μm. The results are as follows.
Received at IPONZ on 11 May 2013
vol blood vol plasma cholesterol SD total SD total free
μL μL cholesterol protein protein hemoglobin
1600 322 90 1 95 2 102
EXAMPLE 10
This example demonstrates that cell-free plasma can be quickly separated from
blood without significantly adversely affecting the plasma cholesterol, total protein, and free
hemoglobin using an embodiment of a device including a membrane and a fibrous element
upstream of the membrane.
The membrane is an isotropic Supor 450 polyethersulfone membrane (Pall
Corporation, East Hills, NY) having a mean pore size of about 0.45 μm and a thickness of
between about 114 to about 165 μm. The fibrous element is a layer of binder-free
borosilicate glass fibers grade A/D (Pall Corporation, East Hills, NY) having a mean pore
size of 3.1 μm and a thickness of between about 584 to 737 μm (about 23 to about 29 mils).
The results are as follows.
vol blood vol plasma cholesterol SD total SD total free
μL μL cholesterol protein protein hemoglobin
2800 260 101 3 101 1 110
EXAMPLE 11
This example demonstrates that cell-free plasma can be quickly separated from
blood using embodiments of devices including a membrane and a fibrous element upstream
of the membrane.
Both devices include a fibrous element upstream of the membrane which is a layer
of binder-free borosilicate glass fibers grade A/D (Pall Corporation, East Hills, NY) having a
mean pore size of 3.1 μm and a thickness of between about 584 to 737 μm (about 23 to about
29 mils).
Received at IPONZ on 11 May 2013
For one device, the membrane is an isotropic Supor 200 polyethersulfone
membrane (Pall Corporation, East Hills, NY) having a mean pore size of about 0.20 μm and a
thickness of between about 114 to about 165 μm. For the other device, the membrane is an
isotropic Supor 1200 membrane (Pall Corporation, East Hills, NY) having a mean pore size
of about 1.2 μm and a thickness of between about 114 to about 165 μm.
The results are as follows.
Device including Supor 200 polyethersulfone membrane
vol blood vol plasma
μL μL
2700 250
Device including Supor 1200 polyethersulfone membrane
vol blood vol plasma
μL μL
2700 355
EXAMPLE 12
This example demonstrates that cell-free plasma can be quickly separated from
blood embodiment of devices including a membrane and a fibrous element upstream of the
membrane.
Both devices include a fibrous element upstream of the membrane which is a layer
of binder-free borosilicate glass fibers grade A/D (Pall Corporation, East Hills, NY) having a
mean pore size of 3.1 μm and a thickness of between about 584 to 737 μm (about 23 to about
29 mils).
For one device, the membrane is an isotropic Supor 450 polyethersulfone
membrane (Pall Corporation, East Hills, NY) having a mean pore size of about 0.45 μm and a
thickness of between about 114 to about 165 μm. For the other device, the membrane is an
Received at IPONZ on 11 May 2013
isotropic Fluorodyne II PVDF membrane (Pall Corporation, East Hills, NY) having a mean
pore size of about 0.45 μm.
The results are as follows.
Device including Supor 450 polyethersulfone membrane
vol blood vol plasma
μL μL
2700 280
Device including Fluorodyne II PVDF membrane
vol blood vol plasma
μL μL
2700 336
EXAMPLE 13
This example demonstrates that cell-free plasma can be quickly separated from
blood embodiment of devices including a membrane and different fibrous media upstream of
the membrane. The membrane in each device is a Vivid PSM grade GR asymmetric
polysulfone membrane.
One device included a layer of binder-free borosilicate glass fibers grade A/D
(Pall Corporation, East Hills, NY) having a mean pore size of 3.1 μm and a thickness of
between about 584 to 737 μm (about 23 to about 29 mils).
The other device included a layer of binder-free borosilicate glass fibers grade
A/B (Pall Corporation, East Hills, NY) having a mean pore size of 1 μm and a thickness of
between about 610 to 711 μm (about 24 to about 28 mils).
The results are as follows.
Device including borosilicate glass fibers grade A/D
vol blood vol plasma
Received at IPONZ on 11 May 2013
μL μL
2700 720
Device including borosilicate glass fibers grade A/B
vol blood vol plasma
μL μL
2700 780
EXAMPLE 14
This example demonstrates that cell-free plasma can be quickly separated from
blood embodiment of devices including a membrane and fibrous elements including different
thicknesses upstream of the membrane.
The membrane is a Vivid PSM grade GR asymmetric polysulfone membrane.
The fibrous elements are one or four layers of Leukosorb™ media (Pall Corporation, East
Hills, NY) having a mean pore size of about 8 μm and a thickness of between about 356 to
about 559 μm for each layer. The results are as follows.
Device including one layer of Leukosorb™ media
vol blood vol plasma
μL μL
1600 505
Device including four layers of Leukosorb™ media
vol blood vol plasma
μL μL
2700 306
Received at IPONZ on 11 May 2013
All references, including publications, patent applications, and patents, cited
herein are hereby incorporated by reference to the same extent as if each reference were
individually and specifically indicated to be incorporated by reference and were set forth in
its entirety herein.
The use of the terms “a” and “an” and “the” and similar referents in the context of
describing the invention (especially in the context of the following claims) are to be
construed to cover both the singular and the plural, unless otherwise indicated herein or
clearly contradicted by context. The terms “comprising,” “having,” “including,” and
“containing” are to be construed as open-ended terms (i.e., meaning “including, but not
limited to,”) unless otherwise noted. Recitation of ranges of values herein are merely
intended to serve as a shorthand method of referring individually to each separate value
falling within the range, unless otherwise indicated herein, and each separate value is
incorporated into the specification as if it were individually recited herein. All methods
described herein can be performed in any suitable order unless otherwise indicated herein or
otherwise clearly contradicted by context. The use of any and all examples, or exemplary
language (e.g., “such as”) provided herein, is intended merely to better illuminate the
invention and does not pose a limitation on the scope of the invention unless otherwise
claimed. No language in the specification should be construed as indicating any non-claimed
element as essential to the practice of the invention.
Preferred embodiments of this invention are described herein, including the best
mode known to the inventors for carrying out the invention. Variations of those preferred
embodiments may become apparent to those of ordinary skill in the art upon reading the
foregoing description. The inventors expect skilled artisans to employ such variations as
appropriate, and the inventors intend for the invention to be practiced otherwise than as
specifically described herein. Accordingly, this invention includes all modifications and
equivalents of the subject matter recited in the claims appended hereto as permitted by
applicable law. Moreover, any combination of the above-described elements in all possible
variations thereof is encompassed by the invention unless otherwise indicated herein or
otherwise clearly contradicted by context.
Received at IPONZ on 11 May 2013
In this specification where reference has been made to patent specifications, other
external documents, or other sources of information, this is generally for the purpose of
providing a context for discussing the features of the invention. Unless specifically stated
otherwise, reference to such external documents is not to be construed as an admission that
such documents, or such sources of information, in any jurisdiction, are prior art, or form part
of the common general knowledge in the art.
In the description in this specification reference may be made to subject matter
that is not within the scope of the claims of the current application. That subject matter
should be readily identifiable by a person skilled in the art and may assist in putting into
practice the invention as defined in the claims of this application.
Received at IPONZ on 11 May 2013
Claims (14)
1. A plasma separation device comprising: (a) a filter having an upstream surface and a downstream surface, the filter comprising a microporous membrane; and, (b) a housing, having an inlet, a downstream chamber, and an outlet, and at least one air channel; defining a fluid flow path between the inlet, the downstream chamber, and the outlet, with the filter disposed in the housing across the fluid flow path, wherein the outlet and the air channel are spaced apart and are arranged such that, when a negative pressure is created in the downstream chamber through the outlet, air passes into the downstream chamber via the air channel and sweeps plasma from the downstream surface of the filter and through the outlet.
2. The device of claim 1, wherein the housing comprises a base comprising the downstream chamber, the at least one air channel, and the outlet, wherein the base further comprises at least one plasma channel in fluid communication with the outlet.
3. The device of claim 2, wherein the outlet and at least one air channel are respectively disposed near opposite ends of the base.
4. The device of claim 1, wherein the housing includes two or more air channels.
5. The device of any one of claims 1-4, wherein the membrane is an asymmetrical membrane having larger openings at the upstream surface than at the downstream surface.
6. The device of any one of claims 1-5, wherein filter includes a plurality of porous media.
7. The device of claim 6, wherein the filter includes the membrane and a fibrous medium. Received at IPONZ on 11 May 2013
8. The device of claim 7, wherein the fibrous medium includes glass fibers.
9. The device of claim 7 or 8, wherein the fibrous medium includes melt-blown fibers.
10. A method of separating plasma from biological fluid, the method comprising: applying biological fluid to the upstream surface of the filter of the device of any one of claims 1-9; passing plasma from the upstream surface of the filter to the downstream surface of the filter; creating a negative pressure in the downstream chamber through the outlet; passing air through the air channel into the downstream chamber and sweeping plasma from the downstream surface of the filter; and,
11. Separated plasma prepared by the method of claim 10.
12. A device as claimed in claim 1, substantially as herein described with reference to any example thereof and with or without reference to the accompanying drawings.
13. A method as claimed in claim 10, substantially as herein described with reference to any example thereof and with or without reference to the accompanying drawings.
14. Separated plasma as claimed in claim 11, substantially as herein described with reference to any example thereof and with or without reference to the accompanying drawings.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13/153,586 US8440085B2 (en) | 2011-06-06 | 2011-06-06 | Plasma separation |
US13/153,586 | 2011-06-06 |
Publications (2)
Publication Number | Publication Date |
---|---|
NZ600343A NZ600343A (en) | 2013-05-31 |
NZ600343B true NZ600343B (en) | 2013-09-03 |
Family
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