U.S. patent application number 14/644294 was filed with the patent office on 2015-07-02 for cards for sample storage and delivery comprising sintered porous plastic.
This patent application is currently assigned to POREX CORPORATION. The applicant listed for this patent is POREX CORPORATION. Invention is credited to Guoqiang Mao, James P. Wingo.
Application Number | 20150185211 14/644294 |
Document ID | / |
Family ID | 46028168 |
Filed Date | 2015-07-02 |
United States Patent
Application |
20150185211 |
Kind Code |
A1 |
Mao; Guoqiang ; et
al. |
July 2, 2015 |
Cards for Sample Storage and Delivery Comprising Sintered Porous
Plastic
Abstract
This application discloses cards comprising sintered porous
plastic which may be employed in liquid sample collection, storage,
transport and/or delivery to an analytical device. Sintered porous
plastic materials provide a unique porous structure, an inert
substrate, precise liquid holding capability, are quick drying, and
easy to cut and handle.
Inventors: |
Mao; Guoqiang; (Peachtree
City, GA) ; Wingo; James P.; (Peachtree City,
GA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
POREX CORPORATION |
Fairburn |
GA |
US |
|
|
Assignee: |
POREX CORPORATION
Fairburn
GA
|
Family ID: |
46028168 |
Appl. No.: |
14/644294 |
Filed: |
March 11, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14254550 |
Apr 16, 2014 |
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14644294 |
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14007486 |
Sep 25, 2013 |
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PCT/US2012/034046 |
Apr 18, 2012 |
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14254550 |
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61476834 |
Apr 19, 2011 |
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Current U.S.
Class: |
436/174 ;
422/400 |
Current CPC
Class: |
B01L 3/5023 20130101;
A61B 5/15101 20130101; A61B 10/0045 20130101; B01L 2300/0861
20130101; B01L 3/50 20130101; B01L 2200/12 20130101; B01L 3/508
20130101; B01L 2300/042 20130101; H01J 49/0436 20130101; A61B
5/150358 20130101; G01N 1/10 20130101; B01L 3/5029 20130101; Y10T
29/49826 20150115; G01N 2001/028 20130101; A61B 10/0096 20130101;
G01N 33/521 20130101; B01L 2300/069 20130101; Y10T 436/25 20150115;
H01J 49/0031 20130101; G01N 1/02 20130101; A61B 5/151 20130101;
B01L 2300/0832 20130101; B01L 2400/0406 20130101; A61B 5/150343
20130101; B01L 3/5088 20130101; B01L 3/5085 20130101 |
International
Class: |
G01N 33/52 20060101
G01N033/52 |
Claims
1. A card for receiving a liquid sample comprising: a card
comprising a sintered porous plastic matrix comprising at least one
liquid sample receiving spot; and a region surrounding the at least
one liquid sample receiving spot.
2. The card of claim 1, wherein the plastic is selected from the
group consisting of polyethylene, polypropylene, polyvinylidene
fluoride, polyamide, polyacrylate, polyacrylic nitrile,
ethylene-vinyl acetate, polyester, polycarbonate, polystyrene,
polytetrafluoroethylene or a blend thereof.
3. The card of claim 2, wherein the polyethylene is selected from
the group consisting of high density polyethylene, low density
polyethylene and ultra high molecular weight polyethylene, or a
blend thereof.
4. The card of claim 1, wherein the at least one liquid sample
receiving spot and the region surrounding the at least one liquid
sample receiving spot are independently hydrophilic or
hydrophobic.
5. The card of claim 1, wherein the at least one liquid sample
receiving spot comprises a perimeter which is weaker than the area
of the at least one liquid sample receiving spot within the
perimeter.
6. The card of claim 1, wherein the at least one s liquid ample
receiving spot is suitable for introduction into a mass
spectrometer.
7. The card of claim 1, further comprising a functional
additive.
8. The card of claim 1, wherein the functional additive comprises a
color change indicator, a surfactant, a chelating agent, an
anti-clotting agent, a polyelectrolyte, an enzyme inhibitor, a cell
lysing reagent, an antioxidant, a DNA stabilizing agent, or a
chaotropic agent or a combination thereof.
9. The card of claim 1, wherein the region surrounding the at least
one liquid sample receiving spot comprises porous plastic,
non-porous plastic, glass, paper or cardboard.
10. The card of claim 1, wherein the sintered porous matrix of
claim comprises a porosity of from about 20% to about 80%, from
about 25% to about 70%, from about 30% to about 60%, or from about
30% to about 50%.
11. The card of claim 1, wherein the sintered porous matrix
comprises a pore size of from about 1 .mu.m to about 200 .mu.m,
from about 10 .mu.m to about 100 .mu.m, or from about 20 .mu.m to
about 60 .mu.m.
12. The card of claim 1, wherein the sample receiving spot
comprises a thickness of from about 100 .mu.m to about 5 mm, from
about 200 .mu.m to about 3 mm, or from about 0.5 mm to about 2
mm.
13. The card of claim 1, further comprising a channel connecting
the least one liquid sample receiving spot to at least one sample
storage spot.
14. The card of claim 1, wherein the region surrounding the liquid
sample receiving spot has a region to accept labeling, writing, a
barcode, a QR code, a magnetic strip, or a combination thereof.
15. Use of the card of claim 1 for liquid sample collection,
storage, transport and/or delivery to an analytical device.
16. The use of claim 15, wherein the liquid sample is a biological
fluid or a non-biological fluid.
17. The use of claim 16, wherein the biological fluid comprises
blood, plasma, urine, peritoneal fluid, pulmonary fluid,
pericardial fluid, tears, saliva, cerebrospinal fluid, lymphatic
fluid, gastrointestinal fluid, feces, a fluid of the reproductive
system, amniotic fluid, culture medium, cells, microorganisms or
plasmids.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. Ser. No.
14/254,550 titled "Cards for Sample Storage and Delivery Comprising
Sintered Porous Plastic" filed Apr. 16, 2014, which is a
continuation of U.S. Ser. No. 14/007,486 titled "Cards for Sample
Storage and Delivery Comprising Sintered Porous Plastic" filed Sep.
25, 2013, which application is a U.S. national phase patent
application under 35 U.S.C. 371 of International Patent Application
No. PCT/US2012/034061 entitled "Cards for Sample Storage and
Delivery Comprising Sintered Porous Plastic" filed Apr. 18, 2012,
which claims benefit of priority of U.S. Patent Application No.
61/476,837 filed on Apr. 19, 2011. These applications are
incorporated herein by reference in their entireties.
FIELD OF THE INVENTION
[0002] The present invention provides cards comprising sintered
porous plastic which may be employed in liquid sample collection,
storage, transport and/or delivery to an analytical device.
BACKGROUND
[0003] Sample cards found in the prior art are made of cellulose
and are used to collect blood samples. Such cards include the
Whatman FTA cards known to one of ordinary skill in the art as
DMPK-A, DMPK-B and DMPK-C cards. Some of these cards may provide
problems with increased background noise or interference in an
analytical method such as mass spectroscopy due to interfering
substances in the card. These cards also display long drying times
after application of a liquid sample. Cellulose based products in
certain cases may not be compatible with analytes of interest for
measurement. Accordingly, there is a need for new media that can
overcome the shortfalls of current sample card media and provide
reliable, fast and broad range of compatibilities for sample
collection, storage and subsequent analysis.
SUMMARY
[0004] This application solves the problems inherent in prior art
cards and discloses cards comprising sintered porous plastic which
may be employed in liquid sample collection, storage, transport
and/or delivery to an analytical device. This application also
discloses methods of making and using these cards.
[0005] These cards comprise sintered porous plastic which is used
to receive, transport or store the liquid sample. These regions of
sintered porous plastic to which a sample is applied are called
sample receiving spots. Optionally, the sample receiving spots may
be linked through channels to sample storage spots. These channels
and sample storage spots are also comprised of sintered porous
plastic.
[0006] Sample receiving spots are located or configured in a card.
When present, the channels and sample storage spots are also
located or configured in the card.
[0007] The regions of the card other than the sample receiving
spot, the channel and the sample storage spot comprise materials
which may be the same as or different from the sintered porous
plastic. These regions may be sintered porous plastic, paper,
cardboard, glass, and transparent or non-transparent solid
non-porous plastic.
[0008] Sintered porous plastic sample receiving spots comprise a
sintered porous matrix made by fusing individual plastic particles
together in a sintering process to form the sintered porous matrix.
These sintered porous plastic sample receiving spots configured in
a card provide a unique porous structure, an inert substrate,
precise liquid holding capability, dry quickly and are easy to cut
and handle.
[0009] The card contains one or more liquid sample receiving spots
for receipt of a liquid sample. In one embodiment, a portion of the
spot may be later removed for subsequent processing and analysis of
the sample contained in the spot. In another embodiment, the entire
sample receiving spot may be later removed from the card for
subsequent processing and analysis of the sample contained in the
spot. The perimeter of the sample receiving spot may be configured
for easy removal from the card.
[0010] The sintered porous matrix in the liquid sample receiving
spot, in the channel and in the sample storage spot each optionally
comprises functional additives. Functional additives include, but
not limited to the following: polyelectrolytes, C-18, C-8 or C-4
modified silica, silica gel, ion exchange material, controlled
porous glass (CPG), solid phase extraction (SPE) media, cell lysis
reagents, protein denaturing additives, chemicals that denature or
de-activate proteins and/or lyse cells, anti-oxidants, chemicals
that preserve the analyte to be measured in the sample, enzyme
inhibitors, antimicrobials, color change indicators, chelating
agents, surfactants, DNA stabilizing agents, a weak acid, such as
Tris(hydroxymethyl)aminomethane (TRIS), a chaotropic agent, an
anti-coagulant, or a combination thereof.
BRIEF DESCRIPTION OF THE FIGURES
[0011] FIG. 1. Schematic representation of a sample card showing
three sample spot receiving regions A, B, and C comprised of
sintered porous plastic, surrounded by a region of the card that
does not receive a sample.
[0012] FIG. 2. Schematic representation of a sample card showing
three sample spot receiving regions A, B, and C comprised of
sintered porous plastic, surrounded by a region of the card that
does not receive a sample. The perimeter of each sample spot
comprises weak edges for easy detachment of the sample receiving
spot from the card.
[0013] FIG. 3. Schematic representation of a sample card showing
three sample spot receiving regions A, B, and C comprised of
sintered porous plastic, surrounded by a region of the card that
does not receive a sample. Each sample spot receiving region
comprises a shallow region as the thickness of the card in the
sample spot receiving region is less than the surrounding region of
the card that does not receive a sample.
[0014] FIG. 4. Schematic representation of a sample card showing
three sample spot receiving regions A, B, and C comprised of
sintered porous plastic, surrounded by a region of the card that
does not receive a sample. Each sample spot receiving region is
hydrophilic while the surrounding region of the card that does not
receive a sample is hydrophobic.
[0015] FIG. 5. Schematic representation of a
hydrophilic-hydrophobic sample card. The center of the card
contains a hydrophilic sample receiving spot connected by
hydrophilic channels to hydrophilic sample storage spots all
comprised of sintered porous plastic. The area of the card
surrounding the hydrophilic sample receiving spot, the hydrophilic
channels, and the hydrophilic sample storage spots is
hydrophobic.
[0016] FIG. 6. Schematic representation of a sharp point of
sintered porous plastic containing a sample. Following application
of voltage, charged particles containing the sample are released
from the sharp point and introduced into a mass spectrometer for
analysis of selected analytes.
[0017] FIG. 7. Schematic representation of a sample card showing
three sample spot receiving regions A, B, and C comprised of
sintered porous plastic, surrounded by a region of the card
comprised of paper, cardboard, glass or solid non-porous plastic
that does not receive a sample. Each sample spot receiving region
comprises a shallow region as the thickness of the card in the
sample spot receiving region is less than the surrounding region of
the card that does not receive a sample.
[0018] FIG. 8. Standard curve of UV Absorption for serial dilution
of caffeine in water.
DETAILED DESCRIPTION
[0019] This application discloses cards comprising sintered porous
plastic which may be employed in liquid sample collection, storage,
transport and/or delivery to an analytical device. This application
also discloses methods of making and using these cards.
[0020] These cards comprise sintered porous plastic which is used
to receive, transport or store the sample. These regions of
sintered porous plastic to which a sample is applied are called
sample receiving spots. Optionally, the sample receiving spots may
be linked through channels to sample storage spots. These channels
and sample storage spots are also comprised of sintered porous
plastic.
[0021] Sample receiving spots are located or configured in a card.
When present, the channels and sample storage spots are also
located or configured in the card.
[0022] The regions of the card other than the sample receiving
spot, the channel and the sample storage spot comprise materials
which may be the same as or different from the sintered porous
plastic. These regions may be sintered porous plastic, paper,
cardboard, glass, and transparent or non-transparent solid
non-porous plastic.
[0023] Sintered porous plastic sample receiving spots comprise a
sintered porous matrix made by fusing individual plastic particles
together in a sintering process to form the sintered porous matrix.
These sintered porous plastic sample receiving spots configured in
a card provide a unique porous structure, an inert substrate,
precise liquid holding capability, dry quickly and are easy to cut
and handle.
[0024] The card contains one or more sample receiving spots for
receipt of a liquid sample. In one embodiment, a portion of the
spot may be later removed for subsequent processing and analysis of
the sample contained in the spot. In another embodiment, the entire
sample receiving spot may be later removed from the card for
subsequent processing and analysis of the sample contained in the
spot. The perimeter of the sample receiving spot may be configured
for easy removal from the card.
[0025] Each of the sintered porous matrix in the sample receiving
spot, in the channel and in the sample storage spot optionally
comprises functional additives. Functional additives include, but
not limited to the following: polyelectrolytes, C-18, C-8 or C-4
modified silica, silica gel, ion exchange material, controlled
porous glass (CPG), solid phase extraction (SPE) media, cell lysis
reagents, protein denaturing additives, chemicals that denature or
de-activate proteins and/or lyse cells, anti-oxidants, chemicals
that preserve the analyte to be measured in the sample, enzyme
inhibitors, antimicrobials, color change indicators, chelating
agents, surfactants, DNA stabilizing agents, a weak acid, such as
Tris(hydroxymethyl)aminomethane (TRIS), a chaotropic agent, an
anti-coagulant, or a combination thereof.
Cards
Composition and Properties of Cards
[0026] Cards are comprised of one or more sample receiving spots
comprising a sintered porous plastic matrix and regions that do not
receive a sample. The cards may be any shape including circular,
oblong, polygonal, triangular, trapezoidal, rectangular or
square.
Sample Receiving Spots
[0027] The sintered porous matrix in the sample receiving spot, the
channel or in the sample storage spot may be made from a variety of
plastics such as polyethylene. Polyethylenes (PE) which may be
employed include but are not limited to high density polyethylene
(HDPE), low density polyethylene (LDPE), or ultra high molecular
weight polyethylene (UHMWPE), or a blend thereof. The sintered
porous matrix may also be made from polypropylene (PP),
polyvinylidene fluoride (PVDF), polystyrene, polyamides,
polyacrylates, polyacrylic nitrile (PAN), ethylene-vinyl acetate
(EVA), polyesters, polycarbonates, or polytetrafluoroethylene
(PTFE), or a blend thereof. In one embodiment the plastic is HDPE.
In other embodiment the plastic is UHMWPE, PP, polyamides, or
polyacrylic nitrile or a blend thereof. The sintered porous matrix
may also be made from a blend of any of the plastics disclosed in
this paragraph. In other embodiments when PP and PE are combined,
PP may be present in a range of from about 100% to about 0% and PE
may be present in a range of from about 0 to about 100% (100% to
0%:0% to 100% wt:wt %). When PE is combined with other polymers,
the PE is present in at least about 50% (wt %).
[0028] In addition to plastic, the sintered porous matrix may also
comprise hydrophilic polymers, such as celluloses, polyvinyl
alcohol (PVA), polyethylene glycol (PEG) or polyvinylpyrrolidone
(PVP).
[0029] The sintered porous matrix has a porosity of from about 20%
to about 80%, from about 25% to about 70%, from about 30% to about
60%, or from about 30% to about 50%. The sintered porous matrix has
a pore size of from about 1 .mu.m to about 200 .mu.m, from about 10
.mu.m to about 100 .mu.m, or from about 20 .mu.m to about 60 .mu.m.
The sample receiving spots can have a thickness of from about 100
microns (.mu.m) to about 5 mm, or from about 200 .mu.m to about 3
mm, or from about 0.5 mm to about 2 mm.
[0030] Cards can contain one or more sample receiving spots. The
number of sample receiving spots per card and their diameters and
thicknesses are selected based on a variety of factors such as the
volume capacity of an individual spot, the suspected analyte
concentration within the sample applied to the sample receiving
spot and the assay sensitivity, and the sample volume to be applied
to an individual spot. The sample receiving spot may be any shape
including circular, oblong, polygonal, triangular, trapezoidal,
rectangular or square.
[0031] A sample receiving spot may be hydrophobic or hydrophilic,
and this property is chosen depending on the sample to be applied
to the sample receiving spot. In one embodiment, the sample
receiving spots are hydrophilic so that hydrophilic samples may be
absorbed into the card. Hydrophilic sample receiving spots are
preferred for use with blood samples. Hydrophobic sample receiving
spots may be desirable if the sample contains surfactant or has a
surface tension of the liquid sample less than about 40
dynes/cm.
[0032] The amount of absorbed sample is controlled by the cross
sectional area, thickness and pore volume of the sample receiving
spot in the card. In one embodiment, the sample is absorbed into
the sample receiving spot by capillary force.
[0033] The sample capacity of a sample receiving spot on a card may
be from about 0.1 .mu.l to about 500 .mu.l, from about 1 .mu.l to
about 250 .mu.l, from about 2 .mu.l to about 225 .mu.l, from about
3 .mu.l to about 200 .mu.l, from about 5 .mu.l to about 150 .mu.l,
from about 10 .mu.l to about 100 .mu.l, from about 5 .mu.l to about
50 .mu.l, from about 10 .mu.l to about 40 .mu.l, or from about 10
.mu.l to about 30 .mu.l. The pore volume of a sample receiving spot
on a card may be greater than about 1 .mu.l or less than about 1000
.mu.l, or any value between about 1 .mu.l and about 1000 .mu.l, or
from about 0.1 .mu.l to about 500 .mu.l, from about 1 .mu.l to
about 250 .mu.l, from about 2 .mu.l to about 225 .mu.l, from about
3 .mu.l to about 200 .mu.l, from about 5 .mu.l to about 150 .mu.l,
from about 10 .mu.l to about 100 .mu.l, from about 5 .mu.l to about
50 .mu.l, from about 10 .mu.l to about 40 .mu.l, or from about 10
.mu.l to about 30 .mu.l.
Regions of the Card that do not Receive Sample
[0034] The regions of the card that do not receive sample may be
made from plastic, paper, cardboard, glass or other materials
[0035] When the regions of the card that do not receive sample are
made from plastic, they may be porous or non-porous in different
embodiments. A variety of plastics may be used, such as
polyethylene. Polyethylenes (PE) which may be employed include but
are not limited to high density polyethylene (HDPE), low density
polyethylene (LDPE), or ultra high molecular weight polyethylene
(UHMWPE), or a blend thereof. Other plastics which may be used
include polypropylene (PP), polyvinylidene fluoride (PVDF),
polystyrene, polyamides, polyacrylates, polyacrylic nitrile (PAN),
ethylene-vinyl acetate (EVA), polyesters, polycarbonates, or
polytetrafluoroethylene (PTFE), or a blend thereof. In one
embodiment the plastic is HDPE. In other embodiment the plastic is
UHMWPE, PP, polyamides, or polyacrylic nitrile or a blend thereof.
A blend of any of the plastics disclosed in this paragraph may also
be employed. In other embodiments when PP and PE are combined, PP
may be present in a range of from about 100% to about 0% and PE may
be present in a range of from about 0 to about 100% (100% to 0%:0%
to 100% wt:wt %). When PE is combined with other polymers, the PE
is present in at least about 50% (wt %).
[0036] When these regions of the card that do not receive sample
are comprised of sintered porous plastic, the porosity is from
about 20% to about 80%, from about 25% to about 70%, from about 30%
to about 60%, or from about 30% to about 50%. The pore size is of
from about 1 .mu.m to about 200 .mu.m, from about 10 .mu.m to about
100 .mu.m, or from about 20 .mu.m to about 60 .mu.m. These regions
of the card that do not receive sample can have a thickness of from
about 100 .mu.m to about 5 mm, or from about 200 .mu.m to about 3
mm, or from about 0.5 mm to about 2 mm.
[0037] These regions of the card that do not receive sample may be
hydrophobic or hydrophilic.
Functional Additives
[0038] Sample receiving spots comprising a sintered porous plastic
matrix as well as the regions of the card that do not receive a
sample may contain functional additives. Functional additives
include but are not limited to the following: polyelectrolytes,
C-18, C-8 or C-4 modified silica, silica gel, ion exchange
material, controlled porous glass (CPG), solid phase extraction
(SPE) media, cell lysis reagents, protein denaturing additives,
chemicals that denature or de-activate proteins and/or lyse cells,
anti-oxidants, chemicals that preserve the analyte to be measured
in the sample, enzyme inhibitors, antimicrobials, and color change
indicators, etc. Functional additives are generally located in the
sample receiving spot. Functional additives are added to the sample
receiving spots during the sintering process or after the sintering
process using solution treatment, depending on the sensitivity and
stability of the functional additive to sintering conditions, as
known to one of ordinary skill in the art.
[0039] Functional additives also include but are not limited to
chelating agents, such as ethylene diaminetetraacetic acid (EDTA),
surfactants, such as anionic surfactant, cationic surfactant or
non-ionic surfactant, DNA stabilizing agents, such as uric acid or
urate salt, or a weak acid, such as Tris(hydroxymethyl)aminomethane
(TRIS). Functional additives also include but are not limited to a
chaotropic agent, such as urea, thiourea, guanidinium chloride, or
lithium perchlorate. Cards may also contain an anti-coagulant, such
as heparin, citrate and/or chelating agents. A surfactant can be an
anionic surfactant, for example sodium dodecylsulfate (SDS), sodium
dodecyl sulfate (SDS), sodium dodecyl benzenesulfonate, sodium
lauryl sarcosinate, sodium di-bis-ethyl-hexyl sulfosuccinate,
sodium lauryl sulfoacetate or sodium N-methyl-N-oleoyltaurate, a
cationic surfactant, such as cetyltrimethylammonium bromide (CTAB)
or lauryl dimethyl benzyl-ammonium chloride, a non-ionic
surfactant, such as nonyl phenoxypolyethoxylethanol (NP-40),
Tween-20, Triton-100 or a zwitterionic surfactant, such as
3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate.
Fluorosurfactants may also be used, such as Zonyl.RTM.
fluorosurfactant from DuPont. Other surfactants may be employed as
known to one of ordinary skill in the art.
[0040] Sample cards, including sample receiving spots as well as
other regions of the card, may also be coated with layers of
polyelectrolytes, such as polyethyleneimine which may be applied in
solution form. Polyelectrolyte coatings may optionally be combined
with surfactants and/or an anticoagulant such as heparin.
[0041] The sintered porous plastic matrix in the sample receiving
spot, the channel or the sample storage spot may contain color
change indicators that dissolve upon contact with liquid and
indicate the extent of sample application. In one embodiment, the
sample receiving spot changes color upon contact with a liquid
sample. Such color change indicators are disclosed in US
2008/0199363. In one embodiment, the sample receiving spot changes
from white to another color provided by the dye the dissolves upon
contact with liquid, indicating the extent of sample application.
In another embodiment, the sample receiving spot may be colored and
a dye dissolves upon contact with liquid to modify or reduce the
coloration, indicating the extent of sample application. These
color change indicators are particles that are located in the
sintered porous plastic matrix. These particles of color change
indicators are added to the particles of plastic and mixed before
sintering to form the sintered porous plastic matrix in the area of
the sample receiving spot. In another embodiment, these particles
of color change indicators are added to the particles of plastic
and mixed before sintering to form the sintered porous plastic
matrix in the area of the sample receiving spot and also in the
sintered porous plastic matrix in the region of the card outside of
the sample receiving spot in order to indicate that the sample
volume has exceeded the sample receiving spot. These particles of
color change indicators retain particulate characteristics in the
sintered porous plastic matrix as they have a higher melting
temperature than the plastic particles. When particles of color
change indicators are employed, the sintering temperature is chosen
to sinter plastic particles but not to melt the dye particles.
Manufacture of Cards
[0042] Cards may be made with different methods depending on the
composition of the card. In one embodiment, when cards are made
entirely of sintered porous plastic, cards are made by placing
plastic particles in a mold of desired shape and then sintering
using heat to form the card. Sintering temperatures for specific
plastics are known to one of ordinary skill in the art. The sample
receiving spots and non-sample receiving regions on the card may
have the same chemical composition or a different chemical
composition. In this embodiment, sample receiving spots are used to
collect, store, transport and/or deliver the samples and non-sample
receiving regions are used to make the card in the desired shapes
and to provide a surface for labeling the card. Based on the
design, cards may have variety of shapes and arrangements.
[0043] In one embodiment, plastic cards are molded. The molding and
sintering conditions to make sintered porous cards depends on the
polymer. One of ordinary skill in the art is familiar with the
temperatures and pressures that are appropriate for specific
polymers.
[0044] A representative method of making a single component card
follows. Plastic particles, in some embodiments, are sintered at a
temperature ranging from about 200.degree. F. to about 700.degree.
F. In other embodiments, plastic particles are sintered at a
temperature ranging from about 300.degree. F. to about 500.degree.
F. The sintering temperature, according to embodiments of the
present invention, is dependent upon and selected according to the
identity of the plastic particles as known to one of ordinary skill
in the art.
[0045] Plastic particles, in some embodiments, are sintered for a
time period ranging from about 30 seconds to about 30 minutes. In
other embodiments, plastic particles are sintered for a time period
ranging from about 1 minute to about 15 minutes or from about 5
minutes to about 10 minutes. In some embodiments, the sintering
process comprises heating, soaking, and/or cooking cycles.
Moreover, in some embodiments, sintering of plastic particles is
performed under ambient pressure (1 atm). In other embodiments
sintering of plastic particles is performed under pressures greater
than ambient pressure.
[0046] A representative method of making a dual component card with
different sample receiving spots and non-sample receiving regions
follows. The first plastic particle mix is deposited in a sample
receiving spot portion of a mold. The second plastic mix is
deposited in the non-sample receiving portion of the mold adjacent
to the first portion of the mold. Next the first plastic particle
mix and second plastic particle mix are sintered to form the cards
containing a sampling region and non sampling region with different
properties.
[0047] First plastic particles and second plastic particles, in
some embodiments, have average sizes ranging from about 1 .mu.m to
about 1 mm. In another embodiment, first plastic particles and
second plastic particles have average sizes ranging from about 10
.mu.m to about 900 .mu.m, from about 50 .mu.m to about 500 .mu.m,
or from about 100 .mu.m to about 400 .mu.m. In a further
embodiment, first plastic particles and second plastic particles
have average sizes ranging from about 200 .mu.m to about 300 .mu.m.
In some embodiments, first plastic particles and second plastic
particles have average sizes less than about 1 .mu.m or greater
than about 1 mm. Sizes of first plastic particles and second
plastic particles, in some embodiments, are selected
independently.
[0048] First plastic particles and second plastic particles, in
some embodiments, are sintered at a temperature ranging from about
200.degree. F. to about 700.degree. F. In some embodiments, first
plastic particles and second plastic particles are sintered at a
temperature ranging from about 300.degree. F. to about 500.degree.
F. The sintering temperature, according to embodiments of the
present invention, is dependent upon and selected according to the
identity of the first plastic particles and second plastic
particles as known to one of ordinary skill in the art.
[0049] First plastic particles and second plastic particles, in
some embodiments, are sintered for a time period ranging from about
30 seconds to about 30 minutes. In other embodiments, first plastic
particles and second plastic particles are sintered for a time
period ranging from about 1 minute to about 15 minutes or from
about 5 minutes to about 10 minutes. In some embodiments, the
sintering process comprises heating, soaking, and/or cooking
cycles. Moreover, in some embodiments, sintering of first plastic
particles and second plastic particles is conducted under ambient
pressure (1 atm). In other embodiments sintering of first plastic
particles and second plastic particles is conducted under pressures
greater than ambient pressure.
[0050] A polymeric material, such as a card, produced by sintering
first plastic particles and second plastic particles, in some
embodiments of the present invention, can comprise a sample
receiving spot and a non-sample receiving region, the sample
receiving spot comprising the sintered first plastic particles
optionally with other additives, and the non-sample receiving
region comprising the sintered second plastic particles. The shape
of the mold can be any desired shape allowing for the facile and
single-step production.
[0051] In another embodiment, the sintered porous plastic sample
card can be sintered into a sheet form on a flat heating moving
belt. The heating temperature and belt moving speed depend on the
polymers as known to one of ordinary skill in the art. The sintered
porous plastic sheet then can be die cut to the desired size and
shape. The sheet can be also thermally formed into desired
shapes.
[0052] In one embodiment, cards are manufactured such that the
perimeter of the sample receiving spot is somewhat thinner or
weaker than the sample receiving spot or the plastic material
outside the perimeter. This perimeter may be perforated with
thinner, break away regions of plastic. This arrangement
facilitates separation of the sample receiving spot from the
surrounding porous plastic through application of force to the
sample receiving spot.
[0053] In another embodiment, cards are manufactured such that the
perimeter of the sample receiving spot is somewhat thicker than the
center of the sample receiving spot or the plastic material outside
the perimeter. This arrangement facilitates containment of the
applied sample to the desired location. The size and shape of a
region of the card are pre determined by the design of the
mold.
[0054] In yet another embodiment, cards are manufactured such that
the perimeter of the sample receiving spot is somewhat thinner or
weaker than the center of the sample receiving spot or the plastic
material outside the perimeter of the sample receiving spot. This
arrangement facilitates separation of the sample receiving spot
from the surrounding porous plastic through application of force to
the sample receiving spot. In one embodiment, the perimeter of the
sample receiving spot may appear perforated, with discontinuities
in the sintered porous plastic where a perforation occurs. These
cards also contain a somewhat thicker region of plastic within the
perimeter of the thinner or weaker zone. Such arrangement
facilitates containment of the applied sample to the desired
location and also facilitates separation of the sample receiving
spot from the surrounding porous plastic through application of
force to the sample receiving spot.
[0055] In another embodiment, cards are manufactured such that the
sample receiving spot has a different hydrophobicity from
non-sample receiving regions. In a specific embodiment, the sample
receiving spot is hydrophilic and the non-sample receiving region
is hydrophobic. The blood sample only wets and wicks into the
hydrophilic sample receiving spot. The method of making regions of
discrete hydrophobic and hydrophilic porous plastic is described in
US Patent Application publication number US2003134100. Cards can be
manufactured in the mold or by thermoforming. Thermoforming is a
process of forming a profiled product from a flat sheet by applying
heat and pressure to selected locations of flat sheet. In the
present invention, in one embodiment, the flat sheet of sintered
porous plastic is passed through a heated die with a profile that
generates a desired pattern.
[0056] In another embodiment the card comprises sample receiving
spots comprising a sintered porous plastic matrix and regions of
non-porous plastic surrounding the sample receiving spots. In one
embodiment, this card is made using an injection molding process
with a hole that accommodates sintered porous plastic components,
such as the sample receiving spot, channel or sample storage spot.
These sintered porous plastic components are inset into the hole in
the card. In another embodiment in which sample receiving spots are
contained in a paper, cardboard, glass or non-porous plastic card,
the sample receiving spots, and optionally channels and sample
storage spots are made by sintering plastic to make a sintered
porous plastic matrix. The sample receiving spots, and optionally
channels and sample storage spots are then inserted into a
preformed paper, cardboard, glass or non porous plastic card
containing openings configured to accept the sample receiving
spots, and optionally channels and sample storage spots. Such
insertion may be accomplished through a frictional fit. In another
embodiment, a preformed paper, cardboard, glass or non porous
plastic card contains openings with flanges configured to accept
the sample receiving spots, and optionally channels and sample
storage spots.
Operation of the Card.
[0057] A liquid sample is applied to the card. In one embodiment,
the sample requires that it is maintained in a wet state and the
card is stored in a moist environment for subsequent use or
transport, such as mailing. In another embodiment, the sample is
permitted to dry. In one embodiment the card may then be stored for
subsequent use or transport, such as mailing. Alternatively, after
the sample dries, a portion of the card containing the sample may
be obtained by cutting the card with a knife, scissors, a sharp
punch of desired shape at the cutting surface, or another tool
known to one of ordinary skill in the art. In another embodiment,
the sample receiving spot may be punched away from the card by
application of force to the sample receiving spot, especially in
embodiments wherein the perimeter of the sample receiving spot is
somewhat thinner or weaker that the plastic material on either
side. When color change indicators are included in the sample
receiving spot, the sharp punch of desired shape may be applied to
the region of the sample receiving spot that changed color upon
application of the liquid sample. At this point, several options
exist. The cut portion of the sample receiving spot may be covered
and stored until the appropriate time to perform a test on the
sample contained therein. Alternatively, the cut portion of the
sample receiving spot may be processed to perform a desired test to
detect a selected analyte. In one embodiment, the cut portion of
the sample receiving spot with a sharp edge may be treated with an
ionic solution and then placed in a mass spectrometer for
aerosolization of analytes on the sample receiving spot. The ionic
solution can be any solution used for electrospray ionization, such
as, a solution containing 5 mM ammonium bicarbonate and 100 mM
ammonium acetate, pH=7.8. Other ionic solutions may be used as
known to one of ordinary skill in the art. This aerosolization may
be achieved through a variety of means such as applying a voltage
to the sharp edge of the sample receiving spot fragment. When the
sample receiving spot is polygonal in shape, for example triangular
in shape, cutting the sample receiving spot may not be required as
a sharp edge is provided upon punching the triangular sample
receiving spot from the card. Then the corner of the triangular
sample receiving spot may be treated with an ionic solution and
then placed in a mass spectrometer for aerosolization of analytes
on the sample receiving spot.
[0058] Alternatively, the sample receiving spot or a fragment
thereof may be added to a receptacle such as a test tube,
centrifuge tube or assay tube, and the sample may be processed, for
example, by eluting the sample for assay of an analyte in the
sample. The sample receiving spot or a fragment thereof may be cut
or punched into a receptacle based on the card design and
requirement. Such receptacles may also contain reagents useful in
performing an assay of one or more analytes in the sample.
Appropriate reagents are known to one of ordinary skill in the art
and are chosen based on the analyte to be measured. For example,
analyte-specific antibodies, optionally in addition to a
colorimetric indicator may be used to bind to a protein and develop
a color. In one embodiment, the sample may contain a protein or a
peptide and the elution of the protein or a peptide from the spot
or fragment thereof makes the protein or peptide available for
measurement with an enzyme linked immunoabsorbent assay (ELISA) or
radioimmunoassay (RIA). In another embodiment, the sample may
contain another type of biological molecule, such as a lipid, a
nucleic acid (for example DNA or RNA), or a neurotransmitter (such
as catecholamines, indoleamines, acetylcholine) or metabolites
thereof.
[0059] The sample card of the present invention can be used in a
similar way described by GE Healthcare on their website
(http://www.whatman.com) and in their literature concerning the
cellulose-based GE DMPK FTA card. The sample card of the present
invention has similar applications and can be used in similar ways
as described in following US patents or patent applications: U.S.
Pat. No. 6,627,226, US 2001/0000149, US 2007/0259445, U.S. Pat. No.
5,496,542, U.S. Pat. No. 5,756,126, U.S. Pat. No. 5,807,527, U.S.
Pat. No. 5,985,327, U.S. Pat. No. 6,168,922, U.S. Pat. No.
6,447,804, U.S. Pat. No. 6,746,841, and U.S. Pat. No.
6,958,392.
Housing
[0060] The card may be used without a housing. The card has good
mechanical strength, rigidity and can be used alone. Print can be
applied to the card to indicate the company logo, to label the
sample receiving spots, to label the type of card or other desired
labels. A barcode and quick response (QR) code can be also directly
printed onto the card. The card may also comprise a magnetic strip
for information storage.
[0061] The card can be laminated to the other materials, such as
cardboard or a plastic sheet using techniques familiar to one of
ordinary skill in the art. The card can also be inserted into a
frame sheet using techniques familiar to one of ordinary skill in
the art.
[0062] The card may be placed in the appropriate storage conditions
until the operator decides to perform the sample analysis. Cards
may optionally contain a storage stabilizing agent, such as a
desiccant or an oxygen scavenger. Cards may optionally be stored
with a storage stabilizing agent, such as a desiccant or an oxygen
scavenger.
Types of Samples
[0063] Liquid samples include but are not limited to biological and
non-biological fluids. Biological fluids include, but are not
limited to, bodily fluids such as blood, plasma, urine, peritoneal
fluid, pulmonary fluid, pericardial fluid, tears, saliva,
cerebrospinal fluid, lymphatic fluids, gastrointestinal fluids,
feces, fluids of the reproductive system, and amniotic fluid. Other
biological fluids include but are not limited to culture medium
such as cell or tissue culture medium. Non-biological fluids
include water samples including fresh water, sea water, and
wastewater samples, organic solution samples, inorganic solution
samples, samples from the petrochemical industry such as samples
from oil fields, environmental samples and food samples. Biological
and non-biological fluids may contain cells.
[0064] In one embodiment, when the biological sample is blood, the
sample receiving spot may contain preservatives, chelating agents
or chemicals useful in lysing cells and/or denaturing proteins,
including enzymes. Samples also include but are not limited to
tissues, animal or plant cells, microorganisms (for example,
bacteria, viruses, mold, and fungi), and plasmids. Cells include,
but are not limited to, cultured cells, epithelial cells,
mesothelial cells, endothelial cells and stem cells or other
progenitor cells. Cells may be obtained from tissues, organs and
biological fluids using techniques known to one of ordinary skill
in the art.
[0065] Target analytes include any desired analyte, such as nucleic
acid (DNA, RNA), carbohydrates, lipids, proteins, peptides,
hormones, antibodies, metabolites, neurotransmitters,
immunomodulators, drugs, drug metabolites, alcohol, ions, or
electrolytes.
[0066] The following examples will serve to further illustrate the
present invention without, at the same time, however, constituting
any limitation thereof. On the contrary, it is to be clearly
understood that resort may be had to various embodiments,
modifications and equivalents thereof which, after reading the
description herein, may suggest themselves to those skilled in the
art without departing from the spirit of the invention.
Example 1
Porous Plastic Card for Use in Delivery of Small Volume Blood
Samples to an Assay
[0067] A 100 gm young rat is injected with a drug and blood is
sampled over time to examine the concentration of the drug and its
metabolites in order to establish a pharmacokinetic and metabolic
profile.
[0068] The rat is anesthetized and its tail vein is used to obtain
a 10 .mu.l sample of blood with a capillary tube. The 10 .mu.l
sample is applied to a sample receiving spot on a porous plastic
card and dries. This sampling process continues every 30 min for 4
hours and each 10 .mu.l sample is applied to a different sample
receiving spot. The card containing the 10 .mu.l blood samples is
stored until a time selected for analysis.
[0069] Next, a sample of each blood spot is obtained using a punch
with a circular shape. The punched circular region of the card
containing the sample is then introduced into a centrifuge vial. A
methanol solution is introduced into the vial to extract the drug
metabolites. The clear solution is injected into a LC-MS in order
to separate, detect and analyze the drug and its metabolites and
establish a pharmacokinetic and metabolic profile.
Example 2
Porous Plastic Card for Use in Delivery of Small Volume Blood
Samples to a Mass Spectrometer
[0070] A 100 gm young rat is injected with a drug and blood is
sampled over time to examine the concentration of the drug and its
metabolites in order to establish a pharmacokinetic and metabolic
profile.
[0071] The rat is anesthetized and its tail vein is used to obtain
a 10 .mu.l sample of blood with a capillary tube. The 10 .mu.l
sample is applied to a sample receiving spot on a porous plastic
card and dries. This sampling process continues every 30 min for 4
hours and each 10 .mu.l sample is applied to a different sample
receiving spot. The card containing the 10 .mu.l blood samples is
stored until a time selected for analysis.
[0072] Next, a sample of each blood spot is obtained using a punch
with a triangular shape. The punched triangular region of the card
containing the sample is then introduced into the mass spectrometer
in order to detect and analyze the drug and its metabolites and
establish a pharmacokinetic and metabolic profile.
Example 3
Porous Plastic Card for Use in Forensic Pathology
[0073] A crime scene investigator arrives at a crime scene
involving multiple blood spatters. The investigator uses a pipette
to apply 5 .mu.l samples of blood to individual sample receiving
spots on a porous plastic card. Ultraviolet analysis of the crime
scene reveals several samples of reproductive fluids which are
collected and applied to sample receiving spots on another porous
plastic card. The cards are stored until the laboratory is
available for DNA analysis. A sample is eluted from each spot and
the polymerase chain reaction is used for genomic analysis of DNA
contained in white blood cells and in the reproductive fluids. The
results are used to identify the crime victim and the
perpetrator.
Example 4
Multi-Channel Hydrophilic/Hydrophobic Porous Plastic Card for Use
in Delivery of Small Volume Blood Samples to an Assay
[0074] A 100 gm young rat is injected with a drug and blood is
sampled over time to examine the concentration of the drug and its
metabolites in order to establish a pharmacokinetic and metabolic
profile.
[0075] The rat is anesthetized and its tail vein is used to obtain
a 100 .mu.l sample of blood with a capillary tube. The 100 .mu.l
sample is applied to the sample receiving spot on a multi-channel
hydrophilic-hydrophobic porous plastic card (FIG. 5). The blood
wicks through the hydrophilic channels and reaches the sample
storage spots. The card is dried. The card containing the 100 .mu.l
blood sample is stored until a time selected for analysis.
[0076] Next, a sample of blood from each sample storage spot is
obtained using a punch with a circular shape. The punched circular
region of the card containing the sample is then introduced into a
centrifuge vial. Different storage spots may be punched into
different vials for different assays or using different protocols.
Some storage spots may be retained for future assays.
Example 5
Sintered Porous Dry Blood Card
[0077] Powdered polyethylene having an average particle size of
about 150 .mu.m was disposed in a metal sheet
(8''.times.11''.times. 1/16'') mold, heated to 350.degree. F. for
about three minutes and subsequently cooled to room temperature in
about five minutes. The sintered porous polyethylene sheet had an
average pore size of about 30 .mu.m and pore volume of about
40%.
Example 6
Sintered Porous Dry Blood Card
[0078] Powdered UHMWPE polyethylene having an average particle size
of about 30 .mu.m was disposed in a metal sheet
(8''.times.11''.times. 1/16'') mold, heated to 350.degree. F. for
about three minutes and subsequently cooled to room temperature in
about five minutes. The sintered porous UHMWPE sheet had an average
pore size of about 10 .mu.m and pore volume of about 40%.
Example 7
Sintered Porous Dry Blood Card
[0079] Powdered high density polyethylene (HDPE) having an average
particle size of about 300 .mu.m was disposed in a metal sheet
(8''.times.11''.times. 1/16'') mold, heated to 350.degree. F. for
about three minutes and subsequently cooled to room temperature in
about five minutes. The sintered porous HDPE sheet had an average
pore size of about 80 .mu.m and pore volume of about 40%.
Example 8
Sintered Porous Dry Blood Card
[0080] Powdered polystyrene having an average particle size of
about 180 .mu.m was disposed in a metal sheet
(8''.times.11''.times. 1/16'') mold, heated to 370.degree. F. for
about three minutes and subsequently cooled to room temperature in
about five minutes. The sintered porous polyethylene sheet had an
average pore size of about 45 .mu.m and pore volume of about
40%.
Example 9
Hydrophilic Sintered Porous Dry Blood Card
[0081] Sintered porous dry blood cards from examples 5-8 were
treated with low pressure plasma. The sample cards were treated
with oxygen plasma at 100 mtorr and 100 watts (W) for 10 minutes in
a plasma machine (Europlasma, Oudenaards, Belgium). The cards
became hydrophilic and adsorbed 20 .mu.l deionized water in less
than 3 seconds when 20 .mu.l deionized water was placed on top of
the cards with a pipette.
Example 10
Hydrophilic Sintered Porous Dry Blood Card
[0082] Sintered porous dry blood cards from examples 5-8 were
treated with surfactants. The sample cards were immersed in a
solution comprises of 79% deionized water, 20% isopropyl alcohol
and 1% Tween.RTM. 20 at room temperature for 12 hours and dried at
70.degree. F. for 8 hours in an oven. The cards became hydrophilic
and adsorbed 20 .mu.l deionized water in less than 3 seconds when
20 .mu.l deionized water was placed on top of the cards with a
pipette.
Example 11
Sintered Hydrophilic Porous Dry Blood Card Comprising Dry Anionic
Surfactant
[0083] A powdered mixture comprising 99.5% of polyethylene powders
having an average particle size of about 150 .mu.m and 0.5% of
sodium dodecyl sulfate (SDS) was disposed in a metal sheet
(8''.times.11''.times. 1/16'') mold, heated to 350.degree. F. for
about three minutes and subsequently cooled to room temperature in
about five minutes. The resulting sintered porous polyethylene
sheet had an average pore size of about 30 .mu.m and pore volume of
about 40%. The cards were hydrophilic and adsorbed 20 .mu.l
deionized water in less than 3 seconds when 20 .mu.l deionized
water was placed on top of the cards with a pipette.
Example 12
Sintered Hydrophilic Porous Dry Blood Card Comprising Dry Anionic
Surfactant
[0084] A powdered mixture comprising 99.5% of UHMWPE polyethylene
having an average particle size of about 30 .mu.m and 0.5% of
sodium dodecyl sulfate (SDS) powder is disposed in a metal sheet
(8''.times.11''.times. 1/16'') mold and is heated to 350.degree. F.
for about three minutes and subsequently is cooled to room
temperature in about five minutes. The resulting sintered porous
UHMWPE sheet has an average pore size of about 10 .mu.m and pore
volume of about 40%. The cards are hydrophilic and adsorb 20 .mu.l
deionized water in less than 3 seconds when 20 .mu.l deionized
water is placed on top of the cards with a pipette.
Example 13
Sintered Hydrophilic Porous Dry Blood Card Comprising Dry Cationic
Surfactant
[0085] A powdered mixture comprising 99% of polyethylene powders
having an average particle size of about 150 .mu.m and 1% of
cetyltrimethylammonium bromide (CTAB) is disposed in a metal sheet
(8''.times.11''.times. 1/16'') mold, heated to 350.degree. F. for
about three minutes and subsequently cooled to room temperature in
about five minutes. The resulting sintered porous polyethylene
sheet has an average pore size of about 30 .mu.m and pore volume of
about 40%. The cards are hydrophilic and adsorb 20 .mu.l deionized
water in less than 3 seconds when 20 .mu.l deionized water is
placed on top of the cards with a pipette.
Example 14
Sintered Hydrophilic Porous Dry Blood Card Comprising Dry Cationic
Surfactant
[0086] A powdered mixture comprising 99% of UHMWPE polyethylene
having an average particle size of about 30 .mu.m and 1% of
cetyltrimethylammonium bromide (CTAB) is disposed in a metal sheet
(8''.times.11''.times. 1/16'') mold, heated to 350.degree. F. for
about three minutes and subsequently cooled to room temperature in
about five minutes. The resulting sintered porous polyethylene
sheet has an average pore size of about 10 .mu.m and pore volume of
about 40%. The cards are hydrophilic and adsorb 20 .mu.l deionized
water in less than 3 seconds when 20 .mu.l deionized water is
placed on top of the cards with a pipette.
Example 15
Hydrophilic Sintered Porous Dry Blood Card with Multilayer
Polyelectrolyte Coating
[0087] Sintered porous dry blood cards from example 9 were further
treated with an polyelectrolyte solution to improve hydrophilic
stability. The freshly plasma treated sample cards were immersed in
0.25% polyethylenimine (750 KDa) water-alcohol solution (80%
deionized water and 20% isopropyl alcohol) at room temperature for
10 minutes, dried at 50.degree. F. for 10 minutes in an oven,
immersed in 0.25% polyacrylic acid (250 KDa) water-alcohol solution
(80% deionized water and 20% isopropyl alcohol) at room temperature
for 10 minutes and dried at 50.degree. F. for 10 minutes. The cards
were hydrophilic and adsorbed 20 .mu.l deionized water in less than
3 seconds when 20 .mu.l deionized water was placed on top of the
cards with a pipette.
Example 16
Hydrophilic Sintered Porous Dry Blood Card with Polyelectrolyte and
Surfactant Coating
[0088] Sintered porous dry blood cards from example 9 were further
treated with polyelectrolyte solution to improve hydrophilic
stability. The freshly plasma treated sample cards were immersed in
0.25% polyethylenimine (750 KDa) water-alcohol solution (80%
deionized water and 20% isopropyl alcohol) at room temperature for
10 minutes, dried at 50 degree for 10 minutes in an oven, immersed
in 0.1% Zonyl.RTM. FSK water-alcohol solution (80% deionized water
and 20% isopropyl alcohol) at room temperature for 10 minutes and
dried at 50.degree. F. for 10 minutes. The cards were hydrophilic
and adsorbed 20 .mu.l deionized water in less than 3 seconds when
20 .mu.l deionized water was placed on top of the cards with a
pipette.
Example 17
Hydrophilic Sintered Porous Dry Blood Card with Heparin
[0089] Sintered porous dry blood cards from examples 5-8 are
treated with surfactant and heparin. The sample cards are immersed
in a water-isopropyl alcohol solution (80:20) comprising 1%
Tween.RTM. 20 and 0.5% heparin sodium salt at room temperature for
12 hours and dried at 70.degree. F. for 8 hours in an oven. The
cards become hydrophilic and adsorb 20 .mu.l deionized water in
less than 3 seconds when 20 .mu.l deionized water is placed on top
of the cards with a pipette.
Example 18
Hydrophilic Sintered Porous Dry Blood Card with Polyelectrolyte and
Heparin Coating
[0090] Sintered porous dry blood cards from example 9 are further
treated with polyelectrolyte solution and heparin solution to
improve blood compatibility. The freshly plasma treated sample
cards are immersed in 0.25% polyethylenimine (750 KDa)
water-alcohol solution (80% deionized water:20% isopropyl alcohol)
at room temperature for 10 minutes, dried at 50.degree. F. for 10
minutes in an oven and then immersed in 0.1% heparin sodium salt
water solution (80% deionized water:20% isopropyl alcohol) at room
temperature for 10 minutes and dried at 50.degree. F. for 10
minutes The cards are hydrophilic and adsorb 20 .mu.l deionized
water in less than 3 seconds when 20 .mu.l deionized water is
placed on top of the cards with a pipette.
Example 19
Sintered Hydrophilic Porous Dry Blood Card Comprising C-18 Silica
Gel
[0091] A powdered mixture comprising 70% of UHMWPE polyethylene
having an average particle size of about 30 .mu.m and 30% of C-18
silica gel with average particle size of 30 .mu.m is disposed in a
metal sheet (8''.times.11''.times. 1/16'') mold, heated to
350.degree. F. for about three minutes and subsequently cooled to
room temperature in about five minutes. The sintered porous
composite sheet has an average pore size of about 10 .mu.m and pore
volume of about 40%. The cards are optionally further treated with
surfactant solution to provide hydrophilicity.
Example 20
Sintered Hydrophilic Porous Dry Blood Card Comprising Ion Exchange
Resins
[0092] A powdered mixture comprising 70% of UHMWPE polyethylene
having an average particle size of about 30 .mu.m and 30% of
Dowex.RTM. 50WX2 fine mesh resin (200 to 400 meshes) with average
particle size of 50 .mu.m is disposed in a metal sheet
(8''.times.11''.times. 1/16'') mold, heated to 350.degree. F. for
about three minutes and subsequently cooled to room temperature in
about five minutes. The sintered porous composite sheet has an
average pore size of about 12 .mu.m and pore volume of about 40%.
The cards are optionally further treated with surfactant solution
to provide hydrophilicity.
Example 21
Sintered Hydrophilic Porous Dry Blood Card Comprising Chelating
Agents
[0093] A powdered mixture comprising 95% of UHMWPE polyethylene
having an average particle size of about 30 .mu.m and 5% of
ethylenediaminetetraacetic acid (EDTA) powder with average particle
size of 50 .mu.m is disposed in a metal sheet
(8''.times.11''.times. 1/16'') mold, heated to 350.degree. F. for
about three minutes and subsequently cooled to room temperature in
about five minutes. The sintered porous composite sheet has an
average pore size of about 10 .mu.m and pore volume of about 40%.
The cards are optionally further treated with surfactant solution
to provide hydrophilicity.
Example 22
Sintered Hydrophilic Porous Dry Blood Card Comprising DNA
Stabilizing Agents
[0094] A powdered mixture comprising 98% of UHMWPE polyethylene
having an average particle size of about 30 .mu.m and 2% of uric
acid powder with average particle size of 50 .mu.m is disposed in a
metal sheet (8''.times.11''.times. 1/16'') mold, heated to
350.degree. F. for about three minutes and subsequently cooled to
room temperature in about five minutes. The sintered porous
composite sheet has an average pore size of about 10 .mu.m and pore
volume of about 40%. The cards are optionally further treated with
surfactant solution to provide hydrophilicity.
Example 23
Sintered Hydrophilic Porous Dry Blood Card Comprising Chaotropic
Agents
[0095] A powdered mixture comprising 98% of UHMWPE polyethylene
having an average particle size of about 30 .mu.m and 2% of
guanidinium chloride powder with average particle size of 50 .mu.m
is disposed in a metal sheet (8''.times.11''.times. 1/16'') mold,
heated to 350.degree. F. for about three minutes and subsequently
cooled to room temperature in about five minutes. The sintered
porous composite sheet has an average pore size of about 10 .mu.m
and pore volume of about 40%. The cards are optionally further
treated with surfactant solution to provide hydrophilicity.
Example 24
Sintered Hydrophilic Porous Dry Blood Card Comprising Multiple
Additives for Blood Preservation
[0096] A powdered mixture comprising 90% of UHMWPE polyethylene
having an average particle size of about 30 .mu.m and 2% of uric
acid powder with average particle size of 50 .mu.m, 2% of
guanidinium chloride powder with average particle size of 50 .mu.m,
5% of ethylenediaminetetraacetic acid (EDTA) powder with average
particle size of 50 .mu.m and 1% of sodium dodecyl sulfate (SDS)
powder is disposed in a metal sheet (8''.times.11''.times. 1/16'')
mold, heated to 350.degree. F. for about three minutes and
subsequently cooled to room temperature in about five minutes. The
sintered porous composite sheet has an average pore size of about
12 .mu.m and pore volume of about 40%. The cards are hydrophilic
and adsorb 20 .mu.l deionized water in less than 3 seconds when 20
.mu.l deionized water is placed on top of the cards with a
pipette.
Example 25
Recovery of Caffeine from Sintered Hydrophilic Porous Cards
[0097] Three hydrophilic sintered polyethylene sheets were selected
for test sampling properties. The sheets had different pore sizes
(100 .mu.m, 50 .mu.m, and 8 .mu.m) with thicknesses of 1.6 mm, 1.6
mm and 0.25 mm, respectively, as shown in Tables 1 and 2. The 100
.mu.m sheet comprised 0.2% of the anionic surfactant sodium
N-methyl-N-oleoyltaurate. The 50 .mu.m sheet comprised 0.2% of the
anionic surfactant sodium N-methyl-N-oleoyltaurate. The percentage
of the surfactant is the blended weight percentage before
sintering. The 8 .mu.m sheet was treated with plasma activation and
sequentially treated with an aqueous solution of 0.25%
polyethylenimine an aqueous solution of 0.25% poly(acrylic
acid).
[0098] Artificial plasma was formulated with phosphate buffer, red
food dye, bovine serum albumin and sodium azide. Caffeine was
obtained from Sigma Aldrich. Caffeine was mixed with artificial
plasma to form a 10 mg/ml solution. A caffeine standard solution
(10 mg caffeine/ml) was made and serially diluted in deionized
water solution. The standard UV absorption curve for these serially
diluted caffeine solutions is show in FIG. 8. The UV absorption was
measured on a Thermo-Fisher NanoDrop 2000 machine. The caffeine was
measured at the wavelength of 273 nm. The wavelength selection was
based on the caffeine UV absorption curve and the UV absorption
curve for artificial plasma.
[0099] 20 .mu.l of artificial plasma was pipetted onto each
hydrophilic sheet. The different sheets had clearly visible
differences in sample spot diameters as indicated in Table 1.
Properties of the sheet samples are list in Table 1. These samples
were used as a background measurement in order to measure caffeine
samples.
TABLE-US-00001 TABLE 1 Artificial plasma spot on the card samples.
Porex Sheets Sample size (.mu.l) Spot diameter (mm) Thickness (mm)
100 .mu.m 20 6 1.6 50 .mu.m 20 8 1.6 8 .mu.m 20 18 0.25
[0100] 20 .mu.l of artificial plasma containing 10 mg/ml caffeine
(total of 200 .mu.g caffeine) was pipetted onto separate sheet
samples with the same properties. The samples were dried at room
temperature for 2 hours. Then sample spots were punched with a 6 mm
diameter paper punch. The resulting 6 mm diameter disks were
separately transferred into 7 ml glass vials. The samples in the
vials were extracted with 1 ml deionized water for 2 hours. The UV
absorption of these aqueous extracts were measured for the samples
with artificial plasma and the samples with caffeine in the
artificial plasma. The difference for the same sample with and
without caffeine was measured for caffeine released from the
sampling cards. The readings were estimated to the closest 5
.mu.g/ml using the caffeine deionized water standard curve. The
results in Table 2 show caffeine recoveries of 65% to 87.5% .
TABLE-US-00002 TABLE 2 Caffeine recovery from Porex sheets. Factor
Measured Caffeine Porex UV Absorption (punch Concentration Sheets
(273 nm) size) (.mu.g) Recovery % 100 .mu.m 0.77 1 175 87.5 50
.mu.m 0.35 1.78 150 75 8 .mu.m 0.065 9 130 65
[0101] All patents, publications and abstracts cited above are
incorporated herein by reference in their entirety. It should be
understood that the foregoing relates only to preferred embodiments
of the present invention and that numerous modifications or
alterations may be made therein without departing from the spirit
and the scope of the present invention as defined in the following
claims.
* * * * *
References