BACKGROUND OF THE INVENTION1. Field of the Invention:
The invention relates to the field of microfiltration membranes; it
relates particularly to microfiltration membranes composed of synthetic polymers.
2. Background of the Prior Art:
Highly asymmetric polymeric membranes prepared from phase separated
(inversion) casting mixes have been described in patents by Wrasidlo U.S.
Patent Nos. 4,629,563 and 4,774,039, and Zepf, U.S. Patent Nos. 5,188,734
and 5,171,445, the disclosures of which are hereby incorporated by reference.
Wrasidlo discloses highly asymmetric, integrally skinned membranes, having
high flow rates and excellent retention properties, prepared from a metastable
two-phase liquid dispersion of polymer in solvent/nonsolvent systems.
Zepf discloses improved Wrasidlo-type polymer membranes having a
substantially greater number of skin pores of more consistent size, and greatly
increased flow rates, with reduced flow covariance for any given pore diameter.
The improved Zepf membranes are achieved by modifications to the
Wrasidlo process, comprising reduced casting and quenching temperatures,
and reduced environmental exposure between casting and quenching. Zepf further
teaches that reduced casting and quenching temperatures minimize the sensitivity
of the membrane formation process to small changes in formulation and process parameters.
A phase inversion polymeric membrane is conventionally made by casting
a solution or a mix comprising a suitably high molecular weight polymer(s), a solvent(s).
and a nonsolvent(s) into a thin film, tube, or hollow fiber, and precipitating
the polymer by one or more of the following mechanisms: (a) evaporation of the
solvent and nonsolvent; (b) exposure to a nonsolvent vapor, such as water vapor,
which absorbs on the exposed surface; (c) quenching in a nonsolvent liquid, generally
water; or (d) thermally quenching a hot film so that the solubility of the polymer
is suddenly greatly reduced.
The nonsolvent in the casting mix is not necessarily completely inert
toward the polymer, and in fact it usually is not and is often referred to as
swelling agent. In the Wrasidlo-type formulations, as discussed later, selection
of both the type and the concentration of the nonsolvent is crucial in that it
is the primary factor in determining whether or not the mix will exist in a phase
In general, the nonsolvent is the primary pore forming agent, and
its concentration in the mix greatly influences the pore size and pore size distribution
in the final membrane. The polymer concentration also influences pore size, but
not as significantly as does the nonsolvent. It does, however, affect the strength
and porosity (void volume). In addition to the major components in the casting
solution (mix), there can be minor ingredients, for example, surfactants or release
Polysulfone is especially amenable to formation of highly asymmetric
membranes, particularly in the two-phase Wrasidlo formulations. These are
not homogeneous solutions but consist of two separate phases one a solvent-rich
clear solution of lower molecular weight polymer at low concentrations (e.g., 7%)
and the other a polymer-rich turbid (colloidal) solution of higher molecular weight
polymer at high concentrations (e.g., 17%). The two phases contain the same three
ingredients, that is, polymer, solvent, and nonsolvent but in radically different
concentrations and molecular weight distributions. Most importantly, the two phases
are insoluble in one another and, if allowed to stand, will separate. The
mix must be maintained as a dispersion, with constant agitation up until the time
that it is cast as a film.
It is the nonsolvent and its concentration in the casting mix that
produces phase separation, and not every nonsolvent will do this. The ones that
do probably have a role similar to that of a surfactant, perhaps creating a critical
micelle concentration by aligning some of the larger polymer molecules into aggregates,
or colloids, which are then dispersed in the remaining non-colloidal solution.
The two phases will separate from one another if allowed to stand, but each individual
phase by itself is quite stable. If the temperature of the mix is changed, phase
transfer occurs. Heating generates more of the clear phase; cooling does the reverse.
Concentration changes have the same effect, but there is a critical concentration
range, or window, in which the phase separated system can exist, as discussed by
Wrasidlo.Wrasidlo defines this region of instability on a phase
diagram of thus dispersed polymer/solvent/nonsolvent at constant temperature, lying
between spinodal and binodal curves, wherein the polymer is not completely miscible
Because of the great hydrophobicity of the polymer and because of
the thermodynamically unstable condition of the casting mix, wherein there pre-exist
two phases, one solvent-rich and the other polymer-rich (a condition that other
systems must pass through when undergoing phase inversion), the unstable
Wrasidlo mixes precipitate very rapidly when quenched, form a tight skin
at the interface, and consequently develop into highly asymmetric membranes.
Asymmetric here means a progressive change in pore size across the cross-section
between skin (the fine pored side of the membrane that constitutes the air-solution
interface or the quench-solution interface during casting) and substructure. This
stands in contrast to reverse osmosis and mostultrafiltration membranes which have
abrupt discontinuities between skin and substructure and are also referred to in
the art as asymmetric.
Polymeric membranes can also be cast from homogeneous solutions of
polymer. The composition of these formulations lie outside of the spinodal/binodal
region of the phase diagram of Wrasidlo. Membranes cast from homogeneous
solutions may also be asymmetric, although not usually to the same high degree
of asymmetry as those cast from phase separated formulations.
Increasing the surface pore size of membranes has been described.
See UK Patent No. 2,199,786 to Fuji (herein "Fuji"). The prior art
teaches exposing the cast polymer solution to humid air in order to cause a phase
inversion at a point below the surface of the membrane. See Fuji. The membranes
produced in accordance with the Fuji process have a characteristic structure
of relatively wide pores on the surface (i.e., 0.05 - 1.2 µm), followed
by progressively constricting pore sizes to the phase inversion point below the
surface, followed by an opening of the pores until an isotropic structure is achieved
progressing to the cast surface (i.e., 1 - 10 µm). Accordingly the
Fuji membranes can be thought of as having reverse asymmetry from the skin
surface to the point of inversion and asymmetry progressing into an isotropic
structure. The patent expressly teaches that minimal asymmetry should be used in
order to prolong the life of the membranes. See Page 4, Lines 7-29. Further, it
appears as though the Fuji membranes are generally prepared with formulations
having relatively high viscosities. For example, the polymer concentrations are
usually quite high and in many cases, the membranes are prepared using polymers
as non-solvents. See Example 2, page 12; Example 3, page 15.
Synthetic polymer membranes are useful as highly retentive, highly
permeable filters in many testing applications in the food and beverage industry,
and in medical laboratories. Many of these operations would be more cost effective
and more commercially attractive if the filtration range of the membranes could
be extended over the existing Wrasidlo and Zepf-type membranes.
SUMMARY OF THE INVENTION
In accordance with the present invention, there is provided a polymer
membrane comprising a first porous surface, a second porous surface, and a supporting
structure having a thickness therebetween, the supporting structure defining a
reticular network of porous flow channels between the first surface and the second
surface, wherein the flow channels have a substantially constant mean diameter
from the first surface to a point from 15-50% of the thickness of the supporting
structure from the first surface and an increasing mean diameter from the point
to the second surface.
The present invention also provides a method for preparing a polymer
membrane of the type defined above, comprising preparing a metastable casting dispersion
comprising a polymer-rich phase and a polymer-poor phase at a selected casting
temperature, casting the dispersion into a thin layer at the casting temperature,
contacting the cast layer with a pore forming atmosphere for a period of time
sufficient to form surface pores greater than 1.2 microns, quenching the cast layer
with a non-solvent quench liquid in which the solvent is miscible and in which
the polymer is substantially insoluble to precipitate the polymer as an integral
membrane, and recovering the membrane from the quench liquid.
A polymer membrane of the type defined above can be made by a method
comprising preparing a homogeneous casting solution comprising a polymer, a solvent
for the polymer, and a nonsolvent for the polymer at a casting temperature, casting
the dispersion into a thin layer at the casting temperature, contacting the cast
layer with a pore forming atmosphere for a period of time sufficient to form surface
pores greater than 1.2 microns, and quenching the cast layer with a non-solvent
quench liquid in which the solvent is miscible and in which the polymer is substantially
insoluble to precipitate the polymer as an integral membrane, and recovering the
membrane from the quench liquid.
Also provided in accordance with the present invention is an improved
diagnostic device comprising a filtering means that delivers a filtrate that is
substantially particle free containing an analyte to an analyte-detecting region
of the device, the improvement comprising a filtering means comprising a polymer
membrane of the type defined above.
The present invention also relates to an improved diagnostic device
comprising a lateral wicking means that transfers a sample that is substantially
particle free containing an analyte from a sample receiving region of the device
to an analyte detecting region of the device, the improvement comprising a lateral
wicking means of the type defined above having a lateral transfer rate of greater
than about 2 cm per minute.
In still a further aspect of the present invention, there is provided
a filter unit, comprising a polymer membrane of the type defined above.
In preferred embodiments of the invention, the polymer is a polysulfone.
Preferably, the bubble points of the membranes of the invention or the membranes
produced or used in accordance with the invention are not greater than about 25
psid (about 171769 Pa) and are preferably from .5 psid to 25 psid (3435 to 171769
Pa), even more preferably, the bubble point is from .5 psid to 15 psid (34354 to
103061 Pa). Also, preferably, the membranes of the invention or the membranes
produced or used in accordance with the invention have a mean aqueous flow rate
of from 4.5 to 25 cm/min psid (0.66 to 3.67 cm/min/kPa).
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is a series of scanning electron microscope images of an open pored
membrane prepared in accordance with the invention from a polysulfone polymer dispersion
(Wrasidlo-type) that has a bubble point of 8 psid (54966 Pa). Figure 1a
is a skin surface view of the membrane. Figure 1b is a cast surface view of the
membrane. Figure 1c is a cross-sectional view of the membrane.
Figure 2 is a series of scanning electron microscope images of an open pored
membrane prepared in accordance with the invention from a polysulfone polymer dispersion
(Wrasidlo-type) that has a bubble point of 11 psid (75578 Pa). Figure 2a
is a skin surface view of the membrane. Figure 2b is a cast surface view of the
membrane. Figure 2c is a cross-sectional view of the membrane.
Figure 3 is a series of scanning electron microscope images of an open pored
membrane prepared in accordance with the invention from a polysulfone polymer dispersion
(Wrasidlo-type) that has a bubble point of 16 psid (109932 Pa). Figure
3a is a skin surface view of the membrane. Figure 3b is a cast surface view of
the membrane. Figure 3c is a crosssectional view of the membrane.
Figure 4 is a series of scanning electron microscope images of a membrane prepared
in accordance with the invention from a homogeneous polysulfone formulation. Figure
4a is a skin surface view of the membrane. Figure 4b is a cast surface view of
the membrane. Figure 4c is a cross-sectional view of the membrane.
Figure 5 is a series of scanning electron microscope images of a fine pored
polysulfone membrane prepared in accordance with the method of Zepf
a bubble point value of 65. Figure 5a is a skin surface view of the membrane. Figure
5b is a cast surface view of the membrane. Figure 5c is a cross-sectional view
of the membrane.
Figure 6 is a graph showing the rate at which a liquid front travels while
migrating laterally in a series of membranes having various BTS (bubble point)
Figure 7 is a graph showing the volume of red cell-free plasma filtrate that
is delivered from polysulfone membranes of various bubble points in 10 seconds.
DETAILED DESCRIPTION OF THE INVENTION
The invention provides improved asymmetric polysulfone membranes
with large pores having improved flow rates and wicking performance while retaining
good separation capabilities. Pore size, and indirectly flow rate, is conveniently
measured by bubble point, which is the minimum pressure required to push a bubble
of air through a wetted membrane. Zepf-type polymeric membranes typically
have bubble points greater than 25 psid (171769 Pa). The membranes of the invention,
by comparison, have bubble points less than about 25 psid (about 111769 Pa), in
the range 0.5 to 25 psid (3435 to 171796 Pa) and preferably 2 to 20 psid (13741
to 137415 Pa) or more preferably 5 to 15 psid (34354 to 103061 Pa).
Moreover, the membranes of the invention have relatively large skin
pores in comparison to Wrasidlo and Zepf membranes. For example,
the average skin pore sizes of membranes of the invention generally exceed 1.2
µm and more generally are 2-3 µm or even larger. In contrast, the
and Zepf membranes have average skin pore sizes less than
1.2 µm and usually less than 0.35 µm.
Further, in contrast to the classical asymmetric structure of
and Zepf, the membranes of the invention generally include
asymmetry through no more than 80% of the membrane. In preferred embodiments, in
the remaining at least 20% of the membrane, the membrane exhibits a generally
The improved membranes of the invention have been found to provide
important advantages in filtration applications. For example, the membranes of
the invention are useful in conventional filtration applications, such as those
used in beer and wine filtration and water treatment applications. In addition,
the membranes of the invention are useful in diagnostic or biological applications,
such as in the manufacture of biosensors.
The membranes of the invention can be prepared from homogeneous casting
solutions as well as from the phase separated mixes as delineated in the
Wrasidlo '563 and '039 and in the Zepf '734 and '445 patents.
Generally, in the manufacture of the membranes of the invention, the
cast film is exposed to air in order to create large surface pores on the exposed
side, followed by standard nonsolvent quenching (i.e., in water). The diameter
of the surface pores can be varied through the length of the exposure time as well
as through the humidity of the air. In exposure to the air, any water vapor in
the air acts to precipitate the polymer at and in a region below the exposed liquid
film surface. Unexpectedly, what is observed is that a region forms on and below
the surface in which a generally isotropic structure having relatively large pore
sizes is formed. Below this area, classical asymmetry is observed. In general,
the greater the humidity the larger the surface pores, and conversely the lower
the humidity the tighter the surface.
Architecture of the Open Pore Membranes of the Invention
The polymer membranes of the invention retain a substantial degree
of asymmetry while having relatively large skin pores. A convenient method for
assessing the asymmetry and pore size is the scanning electron microscope (SEM).
Figures 1 through 3 show the cross sections, skin surface and lower surface of
membrane prepared according to the invention, and the features of those aspects
can be compared to those of a conventional Wrasidlo-type fine pore membrane
shown in Figure 5.
In addition to the asymmetry of the membranes and the open pore structures,
the membranes of the invention are unique in the presence of an isotropic region
that extends from the skin surface to a point within the substructure of the membrane.
Typically, this isotropic region extends through at least 20% of the membrane thickness.
In the absence of SEM data, asymmetry can be grossly estimated as
described by Kesting, Synthetic Polymer Mernbranes: A Structural Perspective,
p. 275 (John Wiley & Sons, 2d edition (1985)), by applying a small dot of ink
or dye to the tight face of a membrane and allowing the dye to penetrate the membrane
as well as spread on its surface. The ratio of the areas coated with dye gives
a rough indication of asymmetry, or the degree thereof. Pore size can also be estimated
by porometry analysis and by separate measurement of the bubble point, with a higher
bubble point indicating tighter pores. In a classical asymmetric membrane, it is
the surface pores that are the tightest. In the membranes of the present invention,
the tightest pores lie somewhere between the skin and the asymmetric region. Porometry
consists of utilizing gradually increasing pressures on a wet membrane and comparing
gas flow rates with those of the dry membrane which yields data on pore sizes as
well as the bubble point. For these analyses, a Coulter Porometer Model 0204 was
As mentioned, the membranes of the present invention include a region
that is generally isotropic and a region that is substantially asymmetric. Generally
isotropic (or the isotropic region), as used herein, means a region of generally
constant pore size, as viewed by SEM from the skin down through a portion of the
supporting structure. The isotropic region may, alternatively, be viewed as a region
having flow channels of a substantially constant mean diameter. In general, the
average skin pore size or diameter of the skin pores of the membranes of the invention
are greater than 1.2 µm. In the isotropic region, this skin pore size generally
defines the mean pore size throughout the isotropic region. For example, in preferred
membranes, SEM's suggest that a membrane having a mean skin pore size of 2
µm has a average pore size of 2 µm or greater throughout the isotropic
region. Similar structures are seen in membranes having 3 µm, 4
µm, 5 µm. and etc. skin pore sizes. However, it will be appreciated
that the isotropic region comprises a distribution of pore sizes that visually
appear isotropic. It is expected that the actual pore sizes in the isotropic region
vary (as is the case with any membrane).
Typically, the isotropic region extends from the skin of the membranes
into the supporting substructure through greater than about 15% of the thickness
of the membrane. More preferably, the isotropic region extends through greater
than 20%, 25%, or even 30% or more of the thickness of the membrane. In highly
preferred embodiments, the isotropic region extends greater than about 25% the
thickness of the membrane. For example, in a 125 µm membrane the isotropic
region extends greater than about 25 µm from the skin into the supporting
Substantially asymmetric or anisotropic (herein, the asymmetric region),
as used herein, means a degree of asymmetry similar to that disclosed in, and possessed
by, membranes prepared in accordance with Wrasidlo and Zepf. In that
regard, the membranes of the present invention have average skin pore sizes of
greater than about 1.2 µm, while on the reverse side, the side adjacent
to the support paper or belt during casting, SEM's show that the average pore sizes
are at least greater than twice the average skin pore size. Thus, the ratio of
skin pore size to cast surface pore size is greater than about 2:1, and in highly
preferred embodiments is 3:1, 4:1, 5:1, or even 6:1 or greater. Moreover, the asymmetry
is a continuous gradient only within the asymmetric region.
It should be noted that the ratio of asymmetry mentioned above is
only with respect to the asymmetry measured at the surfaces. In fact the asymmetry
of the membranes of the invention is much greater when the mean pore size in the
asymmetric region, above the cast surface, are viewed on cross-section in scanning
electron microscopy. See, for example, Figures 1c, 2c and 3c When this is done
the asymmetry of the membranes of the invention appears to be greater than about
10:1 or 20:1 or perhaps as high as 100:1 or even 200:1.
It will also be noticed by looking through the skin pores that the
pore sizes in the isotropic region are slightly larger than the pores in the skin.
This fact, in combination with the observed asymmetry based on surface-surface
analysis versus cross-sectional analysis indicates that "skinning" occurs on both
surfaces. Without wishing to be bound by any particular theory or mode of operation,
there are three plausible explanations for the skinning seen in the membranes of
the invention. First, when the cast film is exposed to air, the water vapor begins
to gel the film and form the incipient membrane in the top region. However, not
all of the polymer may be gelled in this brief time. Therefore, when the film hits
the quench liquid, the remaining unprecipitated polymer then forms a skin. Second,
or alternatively, a perhaps better explanation is simply that surface contraction
shrinks the pores due to the inherent difference in surface energies (somewhat
analogous to a water droplet or a soap bubble that minimizes its surface-to-volume
ratio). Or, third, there may be a slight migration of polymer to the surface due
to the steep gradient in chemical potential.
Additionally, due to the fact that the bubble point of the membranes
of the invention are generally higher than what would be predicted for the pore
sizes seen in the isotropic region or in the skin, it is apparent that there must
be some constriction in pore size between the isotropic region and the asymmetric
region. Surprisingly, conventional reasoning would suggest that the pores below
the skin should be smaller than the skin pores. In fact, they should grow progressively
smaller with depth, i.e., "reverse asymmetry". Diffusion is a slow process. Thus,
the pores created or formed below the skin should see less water vapor and, therefore,
The Fuji membranes appear to confirm this conventional reasoning
and have "reverse asymmetry" from the skin to an inversion point a short depth
into the membrane. In contrast, the pores below the skin in the membranes of the
invention appear to be of the same size or larger than the pores in the skin and
remain with such isotropic or homogeneous pore distribution throughout the region.
Therefore, it appears that the isotropic region of the membranes of
the invention is created by or is at least initiated by a "dry process" interaction
between the water vapor in the air and the polymer film, which causes homogeneous
or isotropic formation. This is analogous to cellulose mixed esters or cellulose
nitrate membranes. However, it appears as though there is negligible evaporation
of solvent or non-solvent, so that, when quenched, the quench liquid rushes in
and fixes the isotropic region and creates and fixes the asymmetric region.
With respect to the possible constriction of the pore size distribution
between the isotropic region and the asymmetric region, discussed above, which
would assist in explaining the tighter pores observed in porometry analyses (i.e.,
1.0 µm maximum and 0.8 µm mean pore size), there may be a process
of internal "skinning" akin to the skin formation in Wrasidlo and
Zepf membranes. Support for this possibility is given by Michaels in U.S.
Patent No. 3,615,024, Col. 5, lines 43-54, where it is disclosed that a gradient
pore structure occurs when water permeation into a cast film is restricted by a
tightened skin, which is formed by the water in the first instance. Or, alternatively,
as discussed above, it is possible that while the membranes in the isotropic region
appear to be isotropic on visual inspection, they actually have a pore distribution
that accounts for the porometry data and higher bubble point than one might anticipate
in view of the large pore sizes.
Accordingly, the structure of the membranes of the present invention
is distinct from classic asymmetry in that the membranes of the invention are
substantially nonasymmetric (i.e., are isotropic) from the skin to a point below
the surface, defined herein as the isotropic region, discussed above. Accordingly,
the asymmetric region of the membrane occurs in less than about 75% of the thickness
of the membrane. Whereas, in conventional or classic asymmetry, for example, in
Wrasidlo and Zepf membranes, the asymmetric region occurs throughout
the entire, or substantially the entire, membrane thickness. In the Fuji
membranes, in contrast, the region below the skin has inverse or reverse asymmetry,
and below that, has slight conventional asymmetry. It is expected that the probable
higher viscosities of the Fuji casting formulations contributes to this
Therefore, colloquially speaking, the membranes of the invention can
be viewed as having a funnel structure in terms of the flow channel configuration
throughout the thickness of the membranes. For example, the pores meeting liquids
flowing into the membrane from the surface that was unexposed during casting is
very large. This is the asymmetric region, which would correspond to the conical
portion of a funnel. As the liquid flows through the membrane, the pore sizes or
flow channels gradually constrict, until, finally, the liquid enters the generally
isotropic region which contains pore sizes or flow channels of substantially constant
diameter, then flows out through the skin, the isotropic region corresponding to
the spout of the funnel.
The structure of a typical open pored membrane of the invention prepared
from a Wrasidlo-type dispersion is shown in Figures 1 through 3. The membrane
has skin surface pores of, on average, 3 µm (Figure 1a), cast surface pore
sizes of, on average, 20 µm (Figure 1b), and, in cross-section, demonstrate
an isotropic region including pores sizes around 3 µm extending from the
skin through approximately 25% of the thickness of the membrane, followed by an
asymmetric region that opens from pore sizes of approximately 3 µm to about
20 µm from the end of the isotropic region to the cast surface (Figure 1c).
As will be appreciated, the degree of asymmetry based on these observations is
approximately 6:1. The particular membrane of the Figure has a bubble point of
8 psid (54966 Pa). The membranes shown in Figures 2 and 3 have very similar structures
but possess bubble points of 11 psid (75578 Pa) and 16 psid (109932 Pa) respectively.
Membranes of the invention can also be prepared from homogeneous
solutions. Such membranes can be prepared with bubble points in the same general
range as those made from Wrasidlo mixes, but they tend to require longer
periods of exposure to the air and do not possess quite the degree of asymmetry
as those made from Wrasidlo-type formulations. Figure 4 shows the structure
as seen in scanning electron microscopy of a membrane produced from a homogeneous
polysulfone solution, including skin surface (Figure 4a), casting surface (Figure
4b), and a cross-section of the membrane (Figure 4c). This particular membrane
has a bubble point of 12 psid (82449 Pa).
In operation of the method of manufacture with Wrasidlo-type
formulations, the water vapor acts on the exposed surface of the cast film to
create fairly large pores both on the surface and in a region extending below the
surface, while the subsequent water quench transforms the rest of the film into
a highly asymmetric substructure. Because the film may be exposed to the humid
air for periods of a second or more in these syntheses, it is prudent, though not
necessary, to select a Wrasidlo mix that is reasonably stable with respect
to phase separation, for example, formulations that under the conventional casting
procedure produce asymmetric membranes of 0.45 µm or 0.2µm pore size
Exemplary membranes are formed using a polysulfone polymer in selected
solvent/non-solvent systems; however, the polymers from which membranes of the
invention can be cast are innumerable and, therefore, the suggested formulations
are provided as exemplary only.
The casting formulations for these membranes are made up of a polymer,
a solvent, and a non-solvent. The polymers which can be used include any polymer
capable of forming a membrane. Polymers which have been found to be particularly
useful in the methods of the invention include polysulfones, polyamides, polyvinylidene
halides, including polyvinylidene fluoride, polycarbonates, polyacrylonitriles,
including polyalkylacrylonitriles, and polystyrene. Mixtures of polymers can be
used. Preferred polymers include Lexan polycarbonate, AMOCO P-3500 polyarylsulfone,
Nylon 6/T polyhexamethylene terepthalamide, and polyvinylidine fluoride. A particularly
preferred polymer is AMOCO P-3500 polyarylsulfone.
Preferred solvents which can be used in the formulations of the invention
include dipolar aprotic solvents such as dimethylformamide, dimethylacetamide,
dioxane, N-methyl pyrrolidone, dimethylsulfoxide, chloroform, tetramethylurea,
or tetrachloroethane. Other polymer/solvent pairs are disclosed, for example, in
U.S. Patent No. 3,615,024 to Michaels.
Suitable nonsolvents include alcohols, for example, methanol, ethanol,
isopropanol, amyl alcohols, hexanols, heptanols, and octanols; alkanes such as
hexane, propane, nitropropane, heptane, and octane; and ketone, ethers and esters
such as acetone, butyl ether, ethyl acetate, and amyl acetate.
Formulations for Wrasidlo type membranes are prepared according
the methods set forth in Zepf, which is hereby incorporated by reference.
In general, polymer is dissolved in solvent at the casting temperature, and the
amount of nonsolvent is controlled to achieve the desired turbidity of the formulation
to the desired optical density as taught by Zepf.
Homogenous casting formulations can have the composition lying outside
the spinodal/binodal region of the phase diagram. Useful homogeneous formulations
are any mixture that contains at least sufficient concentration of polymer to give
the membrane sufficient integrity and mechanical strength and not in excess of
the concentration at which the mixture becomes too viscous to cast. Usually homogeneous
casting formulations comprise from about 7 to 28% polymer or mixtures of polymers
and from 0 to 30% nonsolvent (w/v), the balance being solvent. The solvent and
nonsolvent can also be mixtures.
In the liquid quench systems, the liquid should be chemically inert
with respect to the polymer and preferably miscible with the solvent in the casting
solution. The preferred quench liquid is water.
The membrane as cast is hydrophobic. However, as will be appreciated,
a surfactant or wetting agent may be added to either the formulation, the quench
liquid, or the rinse liquid to increase the hydrophilicity of the membrane. Preferred
agents are polyhydroxycellulose, sodium dodecylsulfate, ethoxylated alcohols, glyceryl
ethers, and non-ionic fluorocarbon surfactants, for example, those of the Zonyl™
type (DuPont). The concentration of surfactant in solution is not critical, and
may range from a fraction of a percent (w/v) to over 10 percent.
Membrane Casting Process
The membranes of the invention can be cast using any conventional
procedure wherein the casting dispersion or solution is spread in a layer onto
a nonporous support from which the membrane can be later separated after quenching.
The membranes can be cast either manually (i.e., poured, cast, or spread by hand
onto a casting surface and quench liquid applied onto the surface) or automatically
(i.e. poured or otherwise cast onto a moving bed). A preferred support is polyethylene
coated paper. In casting, particularly in automatic casting, mechanical spreaders
can be used. Mechanical spreaders comprise spreading knives, a "doctor blade,"
or spray/pressurized systems. A preferred spreading device is an extrusion die
or slot coater, which comprises a chamber into which the casting formulation can
be introduced and forced out under pressure through a narrow slot. In Examples
1 to 3, membranes were cast by means of a doctor blade with a knife gap of typically
250 to 450 microns, often about 300 microns. After the quenching step, the microporous
membrane product is typically 105 to 145 microns thick.
Following casting, the dispersion is quenched. In a preferred embodiment,
quenching is accomplished by moving the cast membrane on a moving bed into the
quenching liquid, i.e., as a bath. The quenching liquid is most commonly water,
the temperature of which is frequently at or near the casting temperature. In the
bath, the quench operation precipitates the polymer and can produce a "skin" having
the requisite pore sizes and a support region having the characteristic structure.
The resulting membrane is ordinarily washed free of entrained solvent and may be
dried to expel additional increments of solvent, diluent, and quench liquid, and
thus recover the membrane.
Generally, in preparing the membranes of the invention, the cast film
should be exposed to air for a time sufficiently long enough to induce the formation
of large surface pores, as discussed previously. The shorter the exposure, the
higher the humidity must be, and vice versa. The total humidity is the important
factor. At higher ambient air temperatures, the relative humidity can be lower
for the same effect. The temperatures of the casting mix and the quench bath are
also important parameters. In general, the warmer the mix, the tighter the membrane,
while the warmer the quench, the more open will be the membrane.
Large Open Pore Membrane from a Wrasidlo Type Formulation
An initial attempt was made to produce a membrane having more open
pores than the 0.45µm polysulfone membrane (BTS-25) described in the
patent by modifying the phase inversion formulation according to the
membrane formation theory set forth in the Wrasidlo and Zepf patents,
that is, increasing the optical density of the casting formulation by decreasing
the polymer concentration and increasing the nonsolvent concentration, and also
increasing the quench temperatures. The cast film was also exposed to humid air
briefly before quenching.
It was expected that a casting formulation having an optical density
in the range of 1.800 as compared to 0.600 would probably form a membrane more
open than available asymmetric membranes. Indeed, the membrane produced was quite
open. Permeability testing showed that the membrane had a bubble point of 4 psid
(27483 Pa), water flow rate of 17.7 cm/minpsid (2.57 cm/min/kPa) and a mean flow
pore size of 2.0 µm.
A more highly preferred membrane was formed by using a dispersed
phase Wrasidlo type phase inversion formulation of the standard 0.2 micron
polysulfone membrane (BTS 45) type and casting at lower temperature as taught
by Zepf, Example 2. The low casting index of 0.176 indicates a relatively
stable casting dispersion. The cast film was exposed briefly to humid air before
quenching. The cast membrane was comparable in quality to the standard product,
having a highly asymmetric substructure, but also having a bubble point of 8 psid
(54966 Pa) and a water flow rate of 19.9 cm/min-psid (2.92 cm/min/kPa). Porometry
analysis indicated a mean flow pore size of 0.9 µm rather than the 0.2
µm pore diameter type and 45 psid (309184 Pa) bubble point that would have
been obtained from the standard BTS-45 formulation if cast in the usual manner.
Scanning electron microscope photographs (Figure 1) showed a highly asymmetric
structure, free of any large macrovoids.
Large Open Pore Membrane from a Homogenous Formulation
Example 8 demonstrates the preparation of membranes with open surface
pores and a high flow rate by exposing a film cast from a homogeneous solution
to humid air prior to quenching it in water. When cast with minimal exposure to
humid air, the homogeneous solution, comprising 9% polysulfone in 72% solvent and
19% nonsolvent generates highly asymmetric membranes, 0.2µm or tighter,
with bubble points greater than 45 psid (309184 Pa). Under the humid air exposure
described in the example, membranes having an average bubble point of about 12
psid (about 82449 Pa), and a water flow rate of 8.4 cm/min-psid (1.23 cm/min/kPa)
Example 8 describes the preparation of membranes from various homogeneous
formulations and varying times of exposure to humid air. Independent of formulation,
increased time of environmental exposure produced membranes having larger surface
pores, up to 8 microns, on the tight side, and water flow rates up to greater than
19 cm/min-psid (2.79 cm/min/kPa), with corresponding bubble points of 3 to 4 psid
(20612 to 27483 Pa). These membranes were reasonably asymmetric, having pores on
the open side of over 100 microns. See Annex I.
The initial experiments used 2-methoxyethanol as a nonsolvent; however,
polyethylene glycol (PEG 400) and polyvinylpyrrolidone (PVP 10,000) also were successfully
substituted in concentrations up to 25% of the total nonsolvent concentration.
It is interesting to note that PVP-10,000 also acted as a good co-solvent in this
In the experiments, air temperature and humidity were measured about
twelve inches (30.48 cm.) above the casting plate. Air flow velocities, where
recorded, were measured with a Pitot tube about one inch (2.54 cm.) above the casting
plate, prior to casting.
A good example of the effects of humidity can be seen by comparing
experiments 1 and 2 in Annex.I. In the first experiment, stagnant air was present
and in the second experiment, under otherwise comparable conditions, the air was
moving. The bubble point in the membrane was halved, and the water flow rate increased
by a factor of 1.7. As will be appreciated, low humidity exposures result in membranes
with consequent low permeabilities and high bubble points, while higher humidity
(i.e., 60%) and blowing air, the membranes had significantly reduced bubble points
(i.e., 4-psid [27483 Pa] and correspondingly high water flow rates (of up to 20.6
cm/min psid [3.02 cm/min/kPa]).
The movement of humid air across the surface of the cast film increases
the pore size; however, excessive air flow can disturb the liquid film in its formative
stages and create distortions in the product. Therefore, we believe that the air
flow should be high enough to renew continually the humid air but not so rapid
as to distort the surface, preferably at a speed just slightly faster than the
The homogeneous formulations are advantageous from the standpoint
that they have greater stability than the Wrasidlo type phase separation
formulations, but the latter formulations provide membranes that appear to have
Applications of the Open Pore Membranes of the Invention
The open pore polymeric membranes of the invention can improve the
performance of many types of analytical devices, in particular, those devices
designed to detect and measure various analytes directly in a single application
step from a heterogenous fluid sample. The particular suitability of highly asymmetric
open membranes for diagnostics arises from:
(a) the graded pore (asymmetric) structure with enormous size pores on the
(b) increasingly smaller (but still very large) internal pores;
(c) the isotropic region below the skin; and
(d) large open pores on the "skin" side, large at least in comparison with
These features create superb wicking tendencies, both laterally and
vertically, with a liquid front travelling through these membranes at 3 to 4 times
the rate of travel in the comparable tight pore membranes. At the same time they
provide filtration capability. In analyses of blood samples, for example, the plasma
from a blood drop quickly wicks through to the skin while the red cells are restrained
by the membrane's network of filter cells. Plasma can be recovered from the skin
side and analyzed in a separate layer below the membrane. With appropriate chemical
reagents and enzymes imbedded in the membrane, the plasma can be rapidly analyzed
for its various ingredients by colorimetry or coulometry, for example. Also, by
fixing specific antibodies to the membrane, various analytes can be bound and measured.
Non specific binding to the membrane is eliminated by preliminary treatment of
the membrane with a solution of biologically inert material, such as human or bovine
serum albumin, as is known to those skilled in the art. Accurate analysis requires
the absence of nonspecific binding of soluble components of the fluid sample to
the membrane. A hydrophilic membrane coated with surfactants has low nonspecific
binding properties; however, a hydrophobic membrane can be used in test devices
and blocked in the conventional manner to give low non-specific binding. The handling
capabilities, and lateral/vertical wicking properties are the same with hydrophobic
membranes. Efficient performance of the analysis procedure depends on rapid filtration
or transport of the separated fluid samples.
Membranes composed of cellulose nitrate, cellulose acetate, and mixtures
thereof and occasionally their polymer blends are typically used for the porous
membrane layers of such analytical devices. These membrane materials can be unsatisfactory
in mechanical strength, often subject to cracking on handling, storage, and particularly
in automated manufacturing processes. Nylon materials exhibit significant nonspecific
binding due to the numerous active sites on the polyamide surface of the material.
The substitution of the open pore polymeric membranes of the invention
for cellulose nitrate, nylon, or less open polymeric membranes in the devices described
can improve both the efficiency and accuracy of the specific analytical procedure
to which the device is directed. Conventional devices can be easily adapted for
use with the membranes of the invention. Some of the broad applications include:
Vertical Filter Device
One class of analytical devices contains a porous membrane that delivers
a filtrate either to the membrane underside or to a reaction site lying below.
Chromogenic reagents for detecting analytes can be incorporated in the membrane
and the colored product in the filtrate is visualized from below. See, for example,
U.S. Patent No. 4,774,192 to Terminello, where chemical test systems for glucose,
urea, alpha-amylase, bilirubin, triglycerides, total cholesterol, and creatinine
are described, as well as test strip immunoassays comprising enzyme labelled immunoconjugates
Other examples of devices of this type include U.S. Patent No. 4,987,085
to Allen et al. for a blood filtering and metering device and U.S. Patent No. 4,935,346
to Phillips et al. which includes a porous membrane impregnated with analyte-specific
reagents to simultaneously separate a soluble filtrate from a whole blood sample
applied to the upper surface of the membrane and to generate a colored reaction
product which indicates the concentration of the analyte.
The membranes of the invention possess the necessary inherent properties
required for performing the functions of the chemistry system as to physical characteristics,
chemical inertness, and optical properties.
Lateral Wicking Device
Lateral wicking devices operate based on the capillarity or wicking
properties of a substrate, such as a membrane. See, for example, U.S. Patent No.
4,168,146 to Grubb et al. which discloses a diagnostic device for immunological
quantitation having a porous carrier material to which antibodies are covalently
The efficiency of such devices depend on the capillary wicking speed
of solution across the antibody or reactant coated membrane, and the adequate
wicking speed, superior handling, and reduced levels of non-specific binding of
the membranes of the invention can accordingly provide a more accurate reading
than devices currently available in the art.
Membrane Absorbent Device
Absorbent devices are disclosed generally in U.S. Patent No.
4,125,372 to Kawai et al.
The membranes of the invention, have superior porosity or void volume
to many of the conventionally preferred absorptive materials described in the art,
due to their highly asymmetric structure. Therefore, the membranes of the invention
are well suited for substitution into such devices. Using the membrane-modified
device of the invention and suitable reagents known to those skilled in the art,
the presence of a variety of substances can be carried out with greater sensitivity
than is currently possible in the art.
Similarly, occult blood testing devices and a variety of other biosensors
can also be suitably modified to include the membranes of the invention as will
be appreciated by those of skill in the art. It is expected that such modified
devices will perform as well as, if not better than, current state of the art devices,
sensors, and the like.
The polymeric membranes of the invention can also be advantageously
substituted for microporous filters used in continuous laminar flow systems for
separation of plasma from whole blood. A system of this type is disclosed in U.S.
Patent No. 4,212,742 to Solomon et al.
The membranes of the invention, have the ability to retain red blood
cells in their larger pores and, therefore, appear to increase the separation efficiency
of such laminar flow systems.
Similarly, the membranes of the invention can be used in a variety
of other applications. A highly preferred embodiment of the invention, for example,
is a membrane used for filtering the yeasts from beers and wines. Because of the
unique structural aspects of the membranes, yeast cells tend to be collected in
the pores, but the yeast is retained in substantially an intact form without falling
apart. This reduces the bitterness of the flavor of the beers and wines.
In such applications, the membranes of the invention may be packaged
and used in conventional applications. In this regard, the membranes of the invention
have utility in applications currently served by classic asymmetric membranes such
as the VARA-FINE™ filter cartridges, VARA-FINE™ filter capsules, and
FILTERITE™ products that are manufactured and sold by MEMTEC AMERICA CORPORATION.
In such products, the cartridges and/or capsules are prepared from potting the
chosen membrane into a supporting housing. Usually, as will be appreciated, the
membrane is pleated to increase the available surface area of the membrane. The
housing is typically made from an inert material, such as simple polymer materials
(i.e., polypropylene), specialty polymer materials (i.e., PVDF), or metals (i.e.,
stainless steel), depending on the end use of the filter assembly, for example,
number of intended uses, environmental exposures, such as solvents, temperatures,
filtrates, and the like, and pressures. Potting is usually accomplished through
heat sealing or appropriate adhesives.
Typical applications of the above-described filtration systems are
in the chemical, photographic, food, beverage, cosmetics, magnetic tape, and electronics
industries. In such industries, the filtration systems are utilized in a variety
of processes and contexts, for example, solvent filtration, acid filtration, deionized
water preparation and filtration, beer and wine clarification, and a host of other
uses. In general, since the membranes of the invention are so inert they can be
used in almost any application. The membranes stand up well in extremely acid and
extremely basic conditions, tolerate sanitizing and oxidizing agents well, and
are thermally and chemically stable. As evidence of the extreme versatility and
stability of the membranes, it is interesting to note that the membranes have been
used with great success in filtration of hydrofluoric acid and sulfuric acid etching
solutions from electronics industry waste streams. On the other end of the extreme,
the membranes of the invention are capable of highly refined filtration in extreme
organic exposure, such as in magnetic tape waste and supply streams.
The purpose, objects, and advantages of the membranes of the present
invention will become more apparent through reference to the following Examples,
Tables, and Figures. While the following Examples detail certain preferred features
of the invention, they are intended to be exemplary and not limiting of the invention
in any way.
EXAMPLE 1PREPARATION OF LARGE PORE ASYMMETRIC POLYSULFONE MEMBRANE USING STANDARD
WRASIDLO BTS-45 (0.2µ M) FORMULATION
A membrane of the invention having large diameter skin surface pores
was prepared as described below. In general, the membrane was prepared from a
standard Wrasidlo polysulfone formulation that is used to prepare highly
asymmetric membranes having a bubble point of 45 psid (309184 Pa). The casting
technique to prepare the membranes of the invention was similar. However, the air
gap was increased and the relative humidity of the cast was monitored. The formulation
was as follows:
The formulation was cast in an automatic casting machine (conventional diagnostic
grade). The formulation was spread using a spreading knife onto polyethylene coated
paper under the following conditions:
Casting Conditions: Casting dope temperature105°F (41°C) Quench water temperature118°F (47.7°C) Air gap6 in (15.24 cm) Casting speed20 ft/min (609.6 cm/min) Room temperature77°F (25°C) Relative humidity59%
Following drying of the resultant membrane, the membrane was recovered.
The recovered membrane had the following properties:
The casting dope, as indicated by the index, was stable. The resultant
membrane had a uniform, defect-free surface appearance. Thickness, breaking strength,
and elongation were typical of the standard BTS-45 product. However, in contrast
to the typical BTS-45 product, the membrane had a significantly lower bubble point
with highly improved flow rates. This membrane is referred to herein as Sample
EXAMPLE 2PREPARATION OF MEMBRANES OF THE INVENTION HAVING DIVERSE BUBBLE POINTS
Two additional membranes were prepared in accordance with Example
1. The air gap was decreased slightly, down to 5.5 inches (13.97 cm) and 5 inches
(12.70cm) respectively, and two membranes having different bubble points were
obtained. The membrane prepared with a 5.5 inch (13.97 cm) air gap had a bubble
point of 11 psid [75578 Pa] (Sample B), while the membrane prepared with the 5
inch (12.70 cm) air gap had a bubble point of 16 psid [109932 Pa] (Sample C).
Other than the difference in bubble point, the Sample B and Sample
C membranes had similar properties to the Sample A membrane prepared in Example
EXAMPLE 3SCANNING ELECTRON MICROSCOPY OF THE MEMBRANES PREPARED IN EXAMPLES
1 AND 2
Scanning electron micrographs were prepared from the membranes synthesized
in Example 1 and 2. Generally, micrographs of the skin surface, the casting surface,
and the cross section of the membranes were taken. The samples were cut and sputtered
with gold using conventional techniques. The micrographs were prepared on a JEOL
Model No. 5200 Scanning Electron Microscope equipped with a Polaroid Camera. The
results of the micrographs are shown in Figures 1 through 3.
Figure 1a shows a skin surface micrograph taken at 5,000 X of the
membrane of Sample A, which had a bubble point of 8 psid (54966 Pa). Figure 1 b
is a cast surface micrograph taken at 1,500 X, and Figure 1c is a cross-sectional
micrograph taken at 500 X of the same membrane.
Figure 2a shows a skin surface micrograph taken at 5,000 X of the
membrane of Sample B, which had a bubble point of 8 psid (54966 Pa). Figure 2b
is a cast surface micrograph taken at 1,500 X, and Figure 2c is a cross-sectional
micrograph taken at 500 X of the same membrane.
Figure 3a shows a skin surface micrograph taken at 5 000 X of the
membrane of Sample C, which had a bubble point of 8 psid (54966 Pa). Figure 3b
is a cast surface micrograph taken at 1,500 X, and Figure 3c is a cross-sectional
micrograph taken at 500 X of the same membrane.
As will be seen, in each of the cross-sectional views, the membranes
exhibit a generally isotropic region in the area below and including the skin
surface. This isotropic region appears to extend through greater than a quarter
of the membrane thickness and perhaps as much as a third of the membrane thickness.
Below the isotropic region, the membranes have an asymmetric region.
The degree of asymmetry of the membranes is most clearly seen through
looking at the surface micrographs, where the pore sizes at the surfaces can be
observed. In Sample A, Figures 1a and 1b, on average, the pore sizes are approximately
3 µm on the skin surface and 20 µ m on the cast surface. Sample B,
in Figures 2a and 2b, on average, the pore sizes are approximately 2.5
µm on the skin surface and 15 µm on the cast surface. And, in Sample
C, Figures 3a and 3b, on average, the pore sizes are approximately 2
µm on the skin surface and 12 µm on the cast surface. In each case,
the degree of asymmetry is approximately 1:6. Recall, however, that this degree
of asymmetry occurs in the last two-thirds to three-quarters of the thickness of
the membrane, so the pore ratio is not as great as if it had progressively spread
through the total thickness of the membrane.
EXAMPLE 4PREPARATION OF ZEPF-TYPE MEMBRANES HAVING DIVERSE BUBBLE POINTS
In addition to the above formulations, two conventional
Zepf-type membranes were prepared. The membranes were prepared in accordance
with the Zepf patent, Example 2, with an air gap of less than one inch (2.54
cm). The resultant membranes had bubble points of 25 and 65 psid (171769 and 446599
Pa), respectively, and are referred to herein as Sample D and Sample E.
SEM's of the membranes showed classical Zepf membrane structure.
Figures 5a through 5c are SEM's showing the skin surface, the cast surface, and
the cross-section of the Sample E membrane, which has a bubble point of 65 psid
(446599 Pa). In Figure 5a, which is the skin surface micrograph of the Sample E
membrane, the pores are clearly smaller than 1 µm, and, on average, are
0.3µm in mean diameter. In the cross-sectional view, Figure 5c, the complete
asymmetry of the membrane is seen. The pore sizes gradually increase from the
skin surface to the cast surface. The porosity of the cast surface is shown in
Figure 5b. The size of the pores on the cast surface, on average, are 20
µm in mean diameter.
EXAMPLE 5PORE SIZES BASED ON SEM ANALYSES
The pore sizes of the various membranes prepared above, were analyzed
in an effort to provide a quantitative determination of their sizes. The results
of the analysis is presented in the following Table:
Sample Figures Skin Surface Cast Surface A1a and 1b3µm20µm B2a and 2b2.5µm15µm C3a and 3b2µm12µm E5a and 5b0.3µm20µm
EXAMPLE 6COULTER DATA
The structures of several of the membranes in the Examples were characterized
using a Coulter porometer, Model No. 0204. The results are shown in the following
Characteristic Sample A*Sample B*Sample C*Sample D*Sample E*Bubble Point (psid)811162565 Thickness (µm)124.67127.7118138.3134.3 Weight (mg)16.717.216.0316.0719.4 Dead Volume (cc)0.05050.05160.04760.05790.0533 Percent Porosity79.249479.127178.951582.005777.6295 Minimum Pore Size0.84330.76870.80300.37630.1390 Maximum Pore Size1.20271.04231.18850.53030.2460 Mean Pore Size0.99700.84470.94500.44430.2040 Diffusive Number of Pores at MPFS3.55 x 1076.08 x 1073.47 x 1075.14 x 1086.66 x 109Maximum Diffusive Number of Pores4.05 x 1078.11 x 1073.69 x 1075.18 x 1086.74 x 109Total Number of Pores1.58 x 1091.87 x 1091.45 x 1092.72 x 10104.25 x 1011Diffusive Flow at MPFS2.30133.22932.38831.93232.1237 Maximum Diffusive Flow2.35503.59232.39971.96302.1827
* Based on the average calculated from three samples
EXAMPLE 7COMPARISON OF COULTER DATA TO EMPIRICAL DATA
A striking structural feature or phenomenon of the membranes of the
invention is that the Coulter data differs markedly from the actual physical structure
of the membranes as determined empirically from SEM's of the membranes. For example,
in the following Table, the minimum, maximum, and mean pore sizes as determined
by Coulter are contrasted to measurements from the SEM's of the membranes.
BUBBLE POINT Minimum COULTER DATA Maximum Mean EMPIRICAL Skin Pore Size v. Open Pore Size Sample A8 psid (54956 Pa)0.84431.20270.99703/20 Sample B11 psid (75578 Pa)0.76771.04230.84472.5/15 Sample C16 psid (109932 Pa)0.80301.18850.94502/12
As will be observed, in Coulter analysis, the membranes appear to
have similar pore sizes. Yet, empirically the membranes have very different surface
strucures from one another. Further, the maximum and minimum pore sizes seen in
Coulter analysis is not even approximated in the SEM cross sectional views of the
membranes. Also, the bubble point in view of the open pore structure would be expected
to be lower than the observed or actual bubble point
EXAMPLE 8PREPARATION OF POLYSULFONE MEMBRANES FROM HOMOGENEOUS SOLUTIONS
Laboratory casting of a homogeneous solution of 9% polysulfone (Amoco
P-3500), 19% 2-methoxyethanol, and 72% dimethylformamide yielded a membrane with
a bubble point of 72 psid (494694 Pa) when cast with 0.25 second exposure to humid
air (temperature 22°C, relative humidity 44%) before quenching in water (45°C).
The same formulation gave a membrane with a.12-psid (82449 Pa) bubble point when
subjected to 4 seconds exposure to air at 22 Cand 60% relative humidity. The casting
operation was carried out using conventional diagnostic grade casting equipment
with a plastic tent around the unit to increase the humidity.
EXAMPLE 9SCANNING ELECTRON MICROSCOPY OF THE MEMBRANE OF THE INVENTION PREPARED
IN EXAMPLE 7
Scanning electron micrographs were prepared from the membrane of
the invention that was prepared in Example 7. As mentioned, this membrane had a
bubble point of 12 psid (82449 Pa). The SEM's were run in accordance with Example
3. The results of the SEM's are shown in Figure 4. As will be appreciated, the
membrane has an open skin surface pore structure (Figure 4a). Also, the cast surface
pore structure is very open, demonstrating substantial asymmetry (Figure 4b). On
cross-section, the membrane is similar to the dispersed formulation membranes in
the presence of the isotropic region and the asymmetric region (Figure 4c).
EXAMPLE 10PREPARATION OF OTHER MEMBRANES OF THE INVENTION FROM HOMOGENEOUS FORMULATIONS
Several different homogeneous polymer solutions were prepared and
cast into sheet membranes according to the procedure set forth in Example 2. Exposure
to humid air was varied as described in Annex I.
EXAMPLE 11BIOLOGICAL USES OF THE MEMBRANES OF THE INVENTIONI. Lateral wicking on open-pore membrane prepared from a phase inversion
A quantity of 60 µl of sheep whole blood was applied to the
open dull side of 1 x 4 cm strips of asymmetric membrane of BTS range of from BTS-25
to BTS-65 as well as the open pore BTS-4 membrane prepared as described in Example
9, and a reading was taken of the time required for the plasma front to reach a
set distance from the point of application for each membrane. Both across web (A)
and down web (D) samples were investigated. The results are shown in Figure 6.
A. Lateral wicking: A quantity of 60 µ 1 of sheep whole blood
was applied to a 1 x 4 cm strip of a BTS 8 membrane prepared by the method of
Example 1. The plasma front had travelled a distance of 25mm in 40 sec. By comparison,
the rate of lateral wicking on tight pore membranes was 25mm in 180 sec.
B. Vertical Separation: A quantity of 25 µ1 of sheep whole blood
was applied to the dull side of the membrane as described in (a) having a surface
area of 1cm2. The weight of plasma drawn off the tight side and absorbed
into filter paper was approximately 10mg.
C. Protein Binding: Protein determinations were made for the following
enzymes according to the Pierce BCA protein test and the optical density read at
λ = 562nm. Sensitivity of the assay was lug/ml, and protein on the membranes
could be read at <0.3mg/cm2.
1. Acid phosphatase at concentrations of 100-500 µg/ml showed less than
or equal to 10% adsorption to the membrane when filtered through a 47mm disk of
the filter materials prepared as indicated in Examples 1-4 at 0-10 psi (0-68707
Pa) and across a pH range of 4.5-9.5.
2. Malate dehydrogenase at concentrations of 100-500 µg/ml showed less
than or equal to 10% adsorption to the membrane when filtered through a 47mm disk
of the fitter materials prepared as indicated in Examples 1-4 at 0-10 psi (0-68707
Pa) and across a pH range of 4.5-9.5.
3. Lactate Dehydrogenase at concentrations of 100-500 µg/ml showed less
than or equal to 10% adsorption to the membrane when filtered through a 47mm disk
of the filter materials prepared as indicated in Examples 1-4 at 0-10 psi (0-68707
Pa) and across a pH range of 4.5-9.5.
Polymermembran mit einer ersten porösen Oberfläche, einer zweiten porösen Oberfläche
und einer tragenden Struktur mit einer Dicke zwischen Ihnen, wobei die tragende
Struktur als Netzwerk poröser Strömungskanäle zwischen der ersten Oberfläche und
der zweiten Oberfläche definiert ist und die Strömungskanäle von der ersten Oberfläche
zu einem Punkt, der von der ersten Oberfläche um 15-50 % der Dicke der tragenden
Struktur entfernt ist, einen im Wesentlichen konstanten mittleren Durchmesser haben
und von dem Punkt zur zweiten Oberfläche einen allmählich zunehmenden mittleren
Membran nach Anspruch 1, bei der im Wesentlichen alle Poren der ersten Oberfläche
Durchmesser von mehr als etwa 1,2 Mikron haben.
Membran nach Anspruch 1 oder Anspruch 2, bei der das Polymer ein Polysulfon
Membran nach einem der Ansprüche 1 bis 3 mit einem Blasenbildungspunkt, der
nicht größer als etwa 25 psid (etwa 171769 Pa) ist.
Membran nach einem der Ansprüche 1 bis 4 mit einem Blasenbildungspunkt von
0,5 bis 25 psid (3435 bis 171769 Pa).
Membran nach Anspruch 5, bei der der Blasenbildungspunkt 5 bis 15 psid (34354
bis 103061 Pa) beträgt.
Membran nach einem der Ansprüche 1 bis 6 mit einer mittleren wässrigen Strömungsgeschwindigkeit
von 4,5 bis 25 cm/Min./psid (0,66 bis 3,67 cm/Min./kPa).
Diagnostisches Gerät mit einer Filtereinrichtung, die ein im Wesentlichen teilchenfreies
Filtrat liefert, das einen Analyten für einen Analytbestimmungsteil des Geräts
enthält, wobei die Verbesserung darin besteht, dass
eine Filtereinrichtung die Polymermembran nach einem der Ansprüche
1 bis 7 enthält.
Diagnostisches Gerät mit einem Queraufsaugmittel, das eine im Wesentlichen
teilchenfreie, einen Analyten enthaltende Probe von einem Probenempfangsbereich
zu einem Analytbestimmungsbereich des Geräts überträgt, dadurch gekennzeichnet,
es ein Queraufsaugmittel mit einer Polymermembran nach einem
der Ansprüche 1 bis 7 aufweist, die eine Querübertragungsgeschwindigkeit von mehr
als etwa 2 cm je Minute hat.
Filtereinheit mit einer Polymermembran nach einem der Ansprüche 1 bis 7.
A polymer membrane comprising a first porous surface, a second porous surface,
and a supporting structure having a thickness therebetween, the supporting structure
defining a reticular network of porous flow channels between the first surface
and the second surface, wherein the flow channels have a substantially constant
mean diameter from the first surface to a point from 15-50% of the thickness of
the supporting structure from the first surface and a gradually increasing mean
diameter from the point to the second surface.
A membrane according to claim 1, wherein substantially all of the pores of
the first surface have diameters greater than about 1.2 microns.
A membrane according to claim 1 or claim 2, wherein the polymer is a polysulfone.
A membrane according to any one of claims 1 to 3, having a bubble point not
greater than about 171769 Pa (25 psid).
A membrane according to any one of claims 1 to 4, having a bubble point of
from 3435 to 171769 Pa (.5 to 25 psid).
A membrane according to claim 5, wherein the bubble point is from 34354 to
103061 Pa (5 to 15 psid).
A membrane according to any one of claims 1 to 6, having a mean aqueous flow
rate of from 0.66 to 3.67 cm/min/kPa (4,5 to 25 cm/min/psid).
A diagnostic device comprising a filtering means that delivers a filtrate that
is substantially particle free containing an analyte to an analyte-detecting region
of the device, the improvement comprising:
a filtering means comprising the polymer membrane according to
any one of claims 1 to 7.
A diagnostic device comprising a lateral wicking means that transfers a sample
that is substantially particle free containing an analyte from a sample receiving
region of the device to an analyte-detecting region of the device, characterized
in that it comprises:
a lateral wicking means comprising a polymer membrane according
to any one of claims 1 to 7 having a lateral transfer rate of greater than about
2 cm per minute.
A filter unit, comprising a polymer membrane according to any one of claims
1 to 7.
Membrane polymère comprenant une première surface poreuse, une seconde surface
poreuse et une structure de support ayant une épaisseur entre celles-ci, la structure
de support définissant un réseau réticulaire de canaux poreux d'écoulement entre
la première surface et la seconde surface, dans laquelle les canaux d'écoulement
présentent un diamètre moyen pratiquement constant de la première surface jusqu'à
un point de 15-50 % de l'épaisseur de la structure de support à partir de la première
surface et un diamètre moyen progressivement croissant du point jusqu'à la seconde
Membrane selon la revendication 1, dans laquelle pratiquement tous les pores
de la première surface ont des diamètres supérieurs à environ 1,2 microns.
Membrane selon la revendication 1 ou la revendication 2, dans laquelle le polymère
est une polysulfone.
Membrane selon l'une quelconque des revendications 1 à 3 ayant une point de
bulle d'au plus environ 25 psid (environ 171 769 Pa).
Membrane selon l'une quelconque des revendications 1 à 4 ayant un point de
bulle de 0,5 psid à 25 psid (3 435 à 171 769 Pa).
Membrane selon la revendication 5, dans laquelle le point de bulle est compris
entre 5 psid et 15 psid (34 354 à 103 061 Pa).
Membrane selon l'une quelconque des revendications 1 à 6 ayant un débit aqueux
moyen de 4,5 à 25 cm/min-psid (0,66 à 3,67 cm/min/kPa).
Dispositif de diagnostic comprenant un moyen de filtration qui délivre un filtrat
qui est pratiquement exempt de particules contenant un analyte dans une région
de détection d'analyte du dispositif, l'amélioration comprenant :
un moyen de filtration comprenant la membrane polymère selon l'une
quelconque des revendications 1 à 7.
Dispositif de diagnostic comprenant un moyen de mèche latérale qui transfère
un échantillon qui est pratiquement exempt de particules contenant un analyte d'une
région de réception d'échantillon du dispositif vers une région de détection d'analyte
du dispositif, caractérisé en ce qu'il comprend:
un moyen de mèche latérale comprenant une membrane polymère selon
l'une quelconque des revendications 1 à 7 ayant une vitesse de transfert latéral
supérieure à environ 2 cm par minute.
Unité de filtration comprenant une membrane polymère selon l'une quelconque
des revendications 1 à 7.