Note: Descriptions are shown in the official language in which they were submitted.
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METHOD AND APPARATUS FOR PREPARING
BUBSTANCEB FOR OPTICAL ANAhY8I8
TECHNICAL FIELD OF THE INVENTION
The present invention is directed to an apparatus
and method for collecting and analyzing matter in a
f luid .
BACKGROUND OF THE INVENTION
In a wide variety of technologies, the ability
and/or facility in separating matter, typically
particulate matter, from a fluid is a critical __
component in the ability to test for the presence of
substances in the fluid. For example, laboratories
are now able to use infra-red spectroscopy to
..determine the presence of cancer cells, but the
utility of this technique is hampered by the
difficulty in sample preparation. Too often,
interference associated with sample preparation
obscures'~the target cells to such a degree that the
process is not 'sufficiently reliable, or too costly.
A similar scenario applies to many other fields
which involve detection and/or diagnosis, including
environmental testing, radiation research, cancer
screening, cytological examination, microbiological
testing, and hazardous waste contamination, to name
just a few.
In all of these endeavors, a limiting factor in
the sample preparation protocol is adequately
separating solid matter from its fluid cart' r (e. g.,
a variety of fluids, such as physiological, biological
and environmental), and in easily and efficiently
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collecting and concentration the solid matter in a
form readily accessible to electromagnetic radiation.
For example, it has been reported that infra red .
technology can be used to differentiate between
malignant cells and normal cells. The cells exhibit .
a characteristic absorbance wavelength which may be
used to identify the presence and type_of cell and its
quantity. The sample preparation processes involves
painstakingly isolating the target cells from tissue
l0 or body fluids, then passing an infra-red beam through
a support which holds the cell sample. In;a typical
process, the cells must be collected and smeared on a
support, such as a microscope slide. The collection
and transfer requires some degree of skill, and even
then, a cell smear may not be suitable for analysis
using infra red technology.
., Diagnostic microbiology and%or cytology,
_ particularly in the area of clinical pathology, bases
diagnoses on a microscopic examination of cells and
other microscopic analyses. The accuracy of the
diagnosis and the preparation of optimally
interpretable specimens typically depends upon
adequate sample preparation.
The present invention is based in part on the
relatively new development of using electromagnetic
radiation, such as infrared radiation, to characterize
matter. For example, an infra red beam may be passed
through some type of support which holds solid matter,
such as cells, in a predetermined position. By
- 30 passing the beam through the solid matter, the solid
matter absorbs a characteristic wavelength within the
. t..sa.~
beam; this absorbance can be measured. - This
measurement, and the characteristic absorbance pattern
may be used to identify the type and quantity of the
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solid matter present in the sample and its molecular
make-up or composition.
As noted above, however, any electromagnetic
protocol is limited by the manner in which the sample
is prepared. The present invention provides an easy,
quick, cost efficient, reproducible, and superior
process and apparatus for collecting the solid matter
suitable for analysis using electromagnetic radiation.
The present invention provides a stark contrast
to the various sample preparation techniques typically
used. In the cast film method, the sample is
dissolved in a solvent, the solution is added dropwise
to an infra red window material (KBr or Csl), and the
solution is allowed to evaporate, forming a thin film ._
on the window material. In some cases, the thin film
must be removed from the window material and placed on
an inert solid support prior to exposure to infra red
radiation.
In the hot press film technique, polymeric
v 20 samples are carefully melted between two infra red
salt plates (KBr or Csl), carefully pressing one of
the plats against the other until a thin film is
formed. In a similar technique, a liquid smear is
formed by pressing a viscous fluid sample until a
capillary film is produced.
In the potassium bromide pellet technique, the
sample is ground to a particle size of about one
micron, the sample is mixed with infra red grade KBr
(carefully, to insure homogeneity), and the powder
mixture is pelletized usinghigh pressure.
Low concentration~samples may also be~.~prepared
using pyrolysis, e.g., forming a dry distillation of
a liquid distillate.
It should be readily apparent that for each of
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these infra red analysis sample preparation protocols,
significant manipulation of the sample is required.
Furthermore, the sample must be transferred to a solid
lass aluminum
support or window material (KBr, Csl, g ,
foil, or a mercury surface) , materials which sometimes
interfere with the sample absorbance pattern.
SUMMARY OF THE INVENTION
The present invention relates to an apparatus and
method for collecting matter for detection, analysis,
l0 quantification, and/or visualization ~ using
electromagnetic radiation. The devices and methods of
the present invention are particularly suitable for
separating matter from biological, physiological, and -
environmental fluids and analyzing the particulate
matter with infra red radiation. For example, a
device according to the invention prepares matter in
the sample for analysis, in combination with
facilitating the actual application of electromagnetic
radiation to the collected matter. Thus, matter is
readily~analyzed and quantified.
Furthermore, sample collection, isolation,
preparation, and analysis may be conducted in a single
device. The devices of the-present invention obviate
the need for a trained technician to properly prepare
a sample substrate. Thus, time, expense, and
expertise are eliminated or reduced as critical
factors in sample preparation protocols.
The devices and methods of the present invention
also provide advantages in sample preparation because
they are suitable for use with fresh, untreated cells,
unmodified--cells, and are particularly designed to '
provide a thin, uniform layer of solid matter (up to
approximately 40 microns or more).
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Furthermore, the devices and methods of the
present invention do not require any manipulation of
the collection site or solid support in order to
properly expose the captured matter to electromagnetic
radiation. This is in contrast to the existing
methods of infra red spectroscopy, where the solid
support, such as a~membrane, must be removed from its
housing, the matter must be fixed on another support,
such as a microscope slide, and then the support must
l0 be properly positioned in a holder. .
The devices of the present invention may also be
disassembled to allow access to the matter capture
- medium, thus facilitating additional tests, if they
are necessary. For example, after subjecting cells to
infra red spectroscopy, the device may be opened, the
membrane containing the cells may be removed, and the
cells may be f fixed on a microscope slide, or may be
further processed, such as culturing or hemolyzing the
cells, both of which process the cells for further
testing.
According to another aspect of the present
inventi~n, the matter collection apparatus may also
include additional modules, removable or integrated,
for treating the fluid. Fob example, the fluid may be
treated with a matter collection module, in
combination with a 3ebris removal module, a
chromatography module, and assay module, or
combinations of these and other devices. These and
other modules or treatment protocols provide features
which may be desirable to incorporate into a sample
preparation apparatus~according to the inve~rtion.
New methodologies, such as immunocytochemistry
' and image analysis which may. involve tagging target
cells with chromophores, or light absorbance or
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emitting probes, require preparations that are
reproducible, fast, biohazard-free and inexpensive.
The solid matter preparation techniques of the present
invention address the issues of non-uniform matter
densities, uneven matter distribution, and sample loss
due to the number of steps involved in the sample
preparation. The preparations of the present
invention result in an even distribution'of solids
that have superior morphology, improved visualization,
to and are readily positioned and available for light
absorbance analysis without the need to further
manipulate or prepare the sample.
For example, these methods have many advantages
for conventional microbiology and hematology. The
collected cells are in a predetermined area easily
accessible to a radiant light source and to a
wavelength absorbance meter. Because cells are
concentrated in a single layer, they are almost always
in one focal plane, thus .eliminating or reducing
interference by other particles and virtually
eliminating technician time and expertise in
. establi'shing a proper reading. The apparatuses of the
present invention even permit the use of automated
devices to detect and ana7~yze any solid matter in a
given population. It also permits a detailed analysis
of the chemical composition of the matter.
The minimal matter overlap, achieved in this
process ensures that all matter can be easily examined
with little chance for critical solids to be obscured
by clumps of overlapping solids or debris.
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In a broad aspect, therefore, the present invention
relates to a solid matter collection apparatus, comprising:
a housing having an inlet and an outlet, said inlet and
outlet defining at least one fluid flow path through said
housing; a solid matter collection element positioned in
the housing across said path, said collection element
having a collection site adapted for collecting solid
matter from the fluid flow, and an optical channel through
which radiant energy from a source of electromagnetic
radiation is adapted for irradiating the collection site.
In another broad aspect, the present invention relates
to a system for collecting and analyzing solid matter,
comprising: a source of electromagnetic radiation; a solid
matter collection module comprising a housing and a
collection element, the collection element having a
collection site disposed in the housing; and an absorbance
meter; wherein said system includes an optical pathway
which passes from the source of the electromagnetic
radiation through the collection site to the absorbance
meter.
In yet another broad aspect, the present invention
relates to a solid matter collection element, comprising:
a porous support having an optical channel through the
porous support; and a collection site disposed on the
porous support and extending across the optical channel,
said collection site being adapted for collecting solid
matter at a predetermined density and position on the
collection site, wherein collected matter will be in the
path of electromagnetic radiation passing through the
optical channel.
In a further broad aspect, the present invention
relates to a method of analyzing solid matter in a fluid,
comprising: separating the solid matter from the fluid and
collecting the solid matter on a collection site at a
predetermined thickness; exposing the solid matter on the
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collection site to electromagnetic radiation; and analyzing
the solid matter exposed to the electromagnetic radiation.
In still another broad aspect, the present invention
relates to a method for preparing solid matter for infra
red spectroscopy, comprising: (a) passing a fluid
containing the solid matter through a collection apparatus
that includes a collection element having a collection site
in a predetermined thickness adapted for collecting the
solid matter and an optical channel through the collection
element adapted for exposing the solid matter on the
collection site to infra red radiation; and (b) depositing
a uniform layer of the solid matter on the collection site.
The accompanying drawings show illustrative
embodiments of the invention from which these and other of
the objectives, novel features and advantages will be
readily apparent.
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DESCRIPTION OF THE DRAWINGS
Figure 1 is a perspective view of a matter
collection apparatus according to the present
invention.
Figure 2 is an exploded perspective view of a
matter collection apparatus according to the present
invention.
Figure 3~is a cross section of a 'collection
element according to the present invention, including
the collection site and an optical channel.
Figure 4 is an exploded cross section ,view of a
matter collection apparatus according to the present
invention.
Figure 5 is a cross section of the outlet portion
of a matter collection apparatus showing the flow path
of matter and fluid through the collection element.
Figure 6 is a cross section view of a syringe and
. matter collection apparatus mounted on a collection
cup. .
2o Figure 7 is a representation of a matter
collection and detection system according to the
present~invention.
DETAILED DESCRIPTIQN OF THE INVENTION
The present invention comprises an apparatus
having a housing, a matter collection element disposed
in the housing, and an optical channel for providing
communication between a radiant energy source and the
matter collection element.
The present invention also comprises an apparatus
for preparing a sample for exposure to,~ a, radiant
energy source having a collection site through which -
the absorbance pattern of the collected matter may be
determined.
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The present invention also includes collecting
fluids, such as biological, physiological, or
environmental fluids, removing the desired matter from
the fluid, without centrifugation, and diagnosing and
testing the matter by applying radiant energy to the
. matter. in the device.
The present invention also includes a method for
analyzing matter comprising collecting matter on a
collection element, and exposing the collected matter
to a radiant energy source. Preferably, the
collection step and the exposure step occur ~iithin the
same housing. A method according to the invention may
also include detecting and/or quantifying the
absorbance of the radiant energy by the matter, may -
further include detecting and/or identifying the
matter by its characteristic absorbance pattern, and
may include detenaining the composition of the
collected sample.
The present invention also includes an automated
method for determining the presence and/or amount of
a prede~ rained matter in a fluid.
The present invention also includes a kit having
an assay module which -includes a matter collection
element according to the iZivention, a fluid specimen
cup, and a pump for inducing fluid flow through the
assay module.
The present invention also includes a solid
matter collection element having a supported
collection site and a channel through the support for
exposing the collection site to electromagnetic .
radiation. ~t~''~
In a preferred embodiment of the invention, a
collection module collects and concentrates solids in
a fluid in a predetermined position and at a
_ g _
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predetermined thickness. In this way, the solids may
be easily and reproducibly subjected to
- electromagnetic radiation in order to identify and
quantify the captured solid matter.
As used herein, fluid refers to any fluid for
which it may be desirable to collect a component of
the fluid for the purpose of establishing its identity
or presence in the fluid. Typically, the component in
the fluid will be a solid matter, such as particulate
l0 matter. For example, the fluid may be air or gas, or
a biological fluid, such as urine, and it may be
desirable to determine the presence of cancer cells or
certain proteins in the biological fluid. In another
example, it may be desirable to evaluate the nature of _
contaminants, such as molecular contaminants, in
ultra-pure water used in the electronics industry.
Other exemplary fluids include but are not limited to
other body fluids, such as blood, spinal fluid, or
amniotic fluid; bronchial lavage; sputum; fine needle
aspirates; ground water; industrial processing fluids;
electronic or medical dialysis fluids; to identify
just a ~ew. It is intended that the invention should
not be limited by the type of fluid being p=ocessed.
As used herein, solid matter refers to any
substance in a fluid which is capable of collection
and evaluation using radiant- energy sources.
Exemplary matter includes, but is not limited to cells
or cell fragments, proteins, molecules, polymers,
rubbers, stabilizers, antioxidants, accelerators,
silicones, alkyds, thiokols, paraffins,
thermoplastics, bacteria, pesticides, and herbicides.
Specific exemplary polymeric matter include, but is-
not limited to polyethylene, polypropylene,
polyisobutylene, polyacrylonitrile, - -polyethylene
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glycol, polyvinylchloride, polystyrene, polysulfide,
polymethylmethacrylates, polyethyleneterephthalates,
bisphenol A (a common environmental contaminant), ,
ethyl cellulose, nitrocellulose, polyurethane, and
nylon. Specific exemplary biological matter includes .
cancer cells,. including distinguishing . between
metastatic and normal cancer cells; proteins, nucleic
acids, antibodies, or the like. It is intended that
the invention should not be limited by the type of
matter being processed.
As used herein, electromagnetic radiation refers
to radiant energy which can be absorbed by solid
matter, including but not limited to infra-red
radiation, near infra-red radiation, the visible __
spectrum, and near ultraviolet radiation. For
example, electromagnetic radiation may be used to
determine structure, stereo-chemistry, types of
additives, degree of degradation, presence of a co-
polymer, chain length, orientation, crystallinity,
carbon-hydrogen stretching region, distinguishing
between unsaturated and saturated carbon-hydrogen
absorpti ns, and the presence of individual molecules.
Electromagnetic radiation may also be used to
determine the composition.- of a sample, e.g., the
composition of a specific cell, protein, molecule, or
polymer. It is intended that the-invention includes
the use of any type of energy which can be used to
identify and/or quantify solid matter.
As used herein, adapted for communication,
communicating, or the like refer to any means or
methods for establishing fluid flow ,though the
system, as are well known by practitioners in the art. '
A well known structure for establishing communication
is a luer lock.
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The systems and devices of the present invention
are particularly suited to fluids and matter in the
fluids which are susceptible to radiant energy
evaluation. For example, cancer cells in urine may be
identified by measuring the absorbance pattern after
exposing the collected cells to infra-red radiation.
An apparatus or assay module according to the
invention includes a housing, an inlet.and~an outlet
defining at least one fluid flow path through the
l0 housing, and a collection element disposed in the
housing across a fluid flow path. In accordance with
the invention, the collection element includes a
collection site. Although it may be variously
configured, as noted in more detail below, the module _
also includes an optical channel that permits
communication between a radiant energy source, such as
..an infra-red spectrometer, the collection site, and an
absorbance meter.
Exemplary methods and apparatuses according to
the invention will now be described in reference to
the Figures.
Ficfure 1 shows a typical module according to the
invention, each~module having a housing 10, an inlet
11, an outlet 12, and a csyllection element 13 (see
Figure 3).
As shown in Figures 2-4, an assay module or
matter collection apparatus comprises a housing 10
having an inlet il and an outlet 12. The housing l0
defines a chamber l8, and the inlet 11 and the outlet
3 0 12 define at least one fluid f low path through the
housing 10. A collection element 13 having a
.,:.1:.~-.
collection site 14 adapted to collect matter may be
pos itioned across , a f luid f low path, the collection
site 14 communicating with the inlet 11. The
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collection element 13 within the matter collection
apparatus is preferably adapted to define a flow path
having first and second branches, the first branch 21
extending through the collection site 14 and the
second branch 22 bypassing the collection site 14.
In a preferred embodiment, the invention includes
a collection element 13 having a first porous medium
23, suitable for preventing the passage of matter
therethrough, and a second porous medium 24, suitable
for allowing fluid to pass therethrough. The second
porous medium may or may not be capable of removing
particulate matter from the fluid, a design choice
according to the needs of a particular device. In a
I preferred embodiment, the first porous medium is w
suitable for capturing or collecting solid matter, and
even more preferably, capturing or collecting solid
matter in a uniform or single layer. A preferred
embodiment also includes a second porous medium which
is suitable as a support for the first porous medium.
The collection element 13 also includes an
optical ~hannel 15b which allows electromagnetic
radiation to contact first porous medium 23 without
contacting second porous medium 24. Optical channel
15a, 15b, and 15c is any optical pathway through the
module or housing which allows the electromagnetic
radiation to contact the solid matter. As illustrated
in Figure 3, the optical channel 15b is a channel,
hole, or the like of any shape through the second
porous medium, e.g., a centrally positioned annular
hole.
The first porous medium and the seco~i.. porous
medium may be positioned in any fashion that functions
as described herein. As one skilled in the art will
recognize, the collection element may be variously '
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configured and positioned as needed to achieve a
particular result. For example, the first and second
porous media may be separate, spaced apart media; the
two media can be laminated together; the first medium
can be integral With or removably engaged with the
second porous medium; ~or the collection element may
comprise a zone of higher density which mimics the
function of the first porous medium asldescribed
above, and zone of lower density which mimics the
function of the second porous medium as described
above. Choice of these various configurations are
well within~the skill of practitioners in the art.
In. a preferred embodiment of the invention, the
first porous medium is a polycarbonate membrane and
the second porous medium is a depth filter.
It should be noted that various types of first
and second porous media can be used. U.S. Patent
5,301,685 discloses several porous media which may be
used in the present invention. While a polycarbonate
membrane is especially suitable for use in the solid
matter collection apparatus of the present invention,
any membrane or septum which does not interfere with
the electromagnetic reading'protocol is suitable. For
example, polycarbonate membranes as well as other
porous membranes, such as ce-llulosic or nylon
membranes, are-also suitable because these membranes
are compatible.with infra red spectroscopy protocols..
Exemplary media which may be used for fluid screening
3 0 include LEUCOSORBr''t, ~, a leucocyte retention medium
manufactured ~by Pall BioSupport Divisioa.~of Pall
Corporation. Other membranes manufactured and sold by
the. Pall Corporation are BIODYNE Ate, an unmodified
nylon with surface chemistry 50% amine and 50%
_ ._ . - 13
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carboxyl group which has an isoelectric point of pH
a surface-modified nylon with surface
BIODYNE B~
5
6
,
;
.
chemistry characterized by a high density of strong
cationic quaternary groups (the zeta potential is
positive to pH>10) ; BIODYNE C'~''~, a surface-modified
nylon with surface chemistry characterized by a high
density of anionic carboxyl groups (the zeta potential
is negative to pH>3; and LOPRODYNE~, a low protein
binding nylon 66 membrane with a tightly controlled
microporous structure having high voids volume for
rapid, efficient throughput of liquids and 'absolute
retention of microparticles designed for cell
- separation and bacterial cell immunoassays. In a
preferred embodiment, the first porous medium is a --
polycarbonate membrane suitable for preventing the
passage of cells therethrough. _ Preferred
~~polycarbonate membranes are commercially available
from Nucleopore, and are well known to those skilled
in the art.
The collection element 13 may further include a
depth f Ater as the second porous medium 24. The
second porous medium permits fluid to pass through by
means of second fluid flow path 22, and may also
function as a support for "the first porous medium.
The depth filter 24 may be made of polypropylene or
high density polyethylene POREX~ porous plastics, as
well as any other material suitable for supporting the '
first porous medium.
As shown in Figures 1 and 6, the first portion 16
or inlet 11 may include a portion configured as a
connector and may be adapted to connect to a.tpontainer
or the like, or may be configured as a needle or
cannula 32 or the like. Second portion 17 or outlet
12 may include a portion configured as a connector and '
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may be adapted to connect to a pump 30, e.g., a
syringe, or the like.
The porous membrane preferably has a pore size
from about 0.22 microns to about 8 microns, more
preferably from about 1 micron to about 6 microns,
most preferably about 2 microns, which allows it to
trap cells which are more than 3 microns.in size. The
membrane, is suitable to allow fluid flow to pass
therethrough while preventing the passage of
particulate matter 20. The second porous medium is
suitable for passing fluid therethrough and inay also
be capable of removing particulate matter from the
fluid. The pore size of the second porous medium may
range from about 5 microns to about 60 microns, --
preferably from about 15 microns to about 45 microns,
most preferably about 35 microns.
Another embodiment of the invention, illustrated
in Figure 6, includes an assay module or matter
collection apparatus l0 mounted on a collection cup
31, and includes a pump 30 for inducing fluid flow
through the collection module. The collection cup 31
may be a specimen cup or the like, and/or the pump 30
may be a syringe or any other device for establishing
fluid flow. As shown i~r Figure 6, either the
collection cup 31 or the collection module may include
a cannula 32 or the like for drawing fluid from the
collection cup into the housing 10. In a preferred
embodiment, the,cannula includes perforations 33 at
various positions along-the cannula in order to draw
fluid from different levels in the collection cup 31.
The assay module housing 10 may be of a~..design
which permits fluid flow through or across the
collection element, e.g., a unitary housing. As shown
in the Figures the assay module housing 10 is
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preferably a two piece housing with a first detachable
portion 16 and a second detachable portion 17,
_ although any housing providing access to the -
collection element 13 is suitable.
Movement of a fluid through the system may be
effected by maintaining a pressure differential
between a source of fluid and a destination of the
fluid. Exemplary means of establishing this pressure
differential may be by applying pressure to any part
of the system on the inlet side of the housing (e. g.,
the collection cup); applying a vacuum to any part of
the system oxl the outlet side of the housing (e. g.,
the syringe); or any form of pump, such as an autovial
spunglass filter (manufactured by Genex Corporation); -
gravity head; or a flexible, collapsible container,
such as a specimen container, which may be squeezed to
.force fluid through the matter collection apparatus
and into the syringe. In a preferred embodiment of
the invention, a syringe draws fluid from a collection
cup through the housing.
As fluid passes through housing 10, the fluid
flows th ough collection site 14 and collection
element 13, as shown in Figure 5. As one skilled in
the art will recognize, adjusting the pore size of the
porous membrane and the porous depth filter in
accordance with the type and/or sire of matter to be
collected permits the collection of the matter on the
collection site 14. In a preferred embodiment of the
invention, the pore size is chosen so that a uniform
layer of matter, preferably a monolayer of matter, is
formed on the collection site.
.,-.,.~-~
One skilled in the art will also recognize that -
the depth of the layer may be adjusted to a
predetermined or desirable depth. For example, from
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about 3 ;tm to about 40 ;tm or more has been shown to be
effective, but it is intended that the invention
should not be limited to a certain range of size or
depth.
Once the uniform or monolayer of matter is
formed, fluid flow along a first flow path 21 is
reduced in the center of the porous membrane and fluid
flow along a second flow path~22 increases towards the
edges of the collection element 13. While not
intending to be restricted to any theory of operation,
it is believed that the increase in the fluid flow
path 22 may be due to the blockage of fluid flow path
21 by the collected matter as it collects on the
collection site 14. Matter in the second fluid flow __
path 22 will then bypass the collection site 14, thus
maintaining a substantially uniform layer or monolayer
collection site 14. The second fluid flow path 22
. .on
sses through an extended side area of the collection
pa
element 13, acts as a vent (with low resistance to
flow) and which prevents the piling up of matter.
The matter collection apparatus or module
1~
describe above may be used in combination with other
suitable filtration or treatment devices. Exemplary
devices include other debris and/or assay devices or
modules which may be attached to housing 10.
Typically, these additional modules will include a
housing having an inlet and an outlet, and will
include a filtration, assay, or detection element
positioned across the fluid flow path in the housing.
For example, the apparatus may comprise a housing
including inlet and outlet ports defining a_~flow path
between the inlet: and the outlet;-a filter positioned
the flow path; and a freely movable
across
chromatography/assay element, such as substrate beads,
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positioned on the outlet side of the filter. The
chromatography/assay element can freely mix with the
matter in the fluid, capture the matter, and can then
be assayed for the presence of the matter. Suitable
devices include those disclosed in U.S. Patents
4,953,567.; 5,224,489; 5,016,644; 5,139,031; 5,301,685;
5,042,502; and 5,137,031,
In accordance with a method of the present
invention, matter is collected on a collection~element
which includes an optical channel for exposing
collected matter to electromagnetic radiation. After
the matter is collected, the matter is analyzed by
passing electromagnetic radiation through the optical
channel and then measuring the amount and/or type of
absorbance.
For example, fluid may be drawn from a collection
cup 31, through housing 10, allowing matter in the
fluid to collect in a uniform layer or a monolayer on
collection site 14. Optionally, additional fluid may
be drawn through the housing, or the same fluid may be
drawn, then returned to, collection cup 31, and then
drawn again, as many times as desirable. Once the
matter is collected, the housing 10 may be placed in
a holder or the like to properly position the optical
channel in the electromagnetic radiation beam, e.g.,
an infra red beam. The beam passes through the outlet
12 along optical channel 15a, 15b, and 15c. In
optical channel i5b, the beam will contact matter
collected on the collection site 14. The collected
matter absorbs a certain wavelength of the radiation,
and this absorbance may be measured by placing an
absorption meter in the path of optical channel 15c.
A iaethod according to the invention may also
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include processing the matter as noted above, and then
transferring the matter to another medium for further
analysis. For example, the present invention may also
include transferring cells to a microscope slide. In
contrast ~to currently available methods, the use of
membrane filtration provides a method of depositing
cells or other matter evenly over a slide with minimal
overlap. This allows for clear observation and
optimal diagnostic accuracy.
Included within the scope of the present
invention is the production of multiple specianens from
a single patient or source sample.
Also, captured microorganisms can be cult~xred in
culture medium such as a standard petri dish. After
the layer of cells has been collected in the
collection apparatus 10, fluid may be passed through
the collection site 14 toward inlet il thereby
. transferring the microorganisms to the petri dish.
In bacteria testing, the collection site 14 can
be used for culturing with a Qualture device (not
shown) to determine the presence of specific bacteria
colonie~~ The Qualture device is a plastic capsule
containing a filter membrane and four nutrient pads of
dehydrated, selective medial
The devices and methods of the present invention
have a wide variety of uses-and applications,
primarily because so many industries and so many
processes involve the separation of solid matter from
a fluid followed by some type of examination of the
solid matter. Exemplary industries include food and
beverage, pharmaceutical, medical and env,'~ronmental
(e. g., water, soil or- air sampling), biology,
microbiology, hematology, cytology, and pathology.
The devices and methods of the present invention
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are particularly useful in any procedure which
involves spectroscopy, the identification of solid
matter such as compounds, molecules, cells, or ,
proteins singly or in mixtures according to the
matter's ability to absorb radiant energy at a _
specific wavelength. The devices and methods of the
present invention are even more useful in any
procedure which involves the study of absorption
patterns when substances are exposed to
l0 electromagnetic radiation in the infra-red region of
the spectrum, especially in the wavelength from about
2 . 5 ~Cm to abof>~t 15 ~.m .
For example, in a hematological analysis, a drop
of blood may be analyzed for the presence and quantity _
of certain cell populations, since every cell has a
certain signature profile under radiation such as
infra red radiation. For example, it may be desirable
.
to determine the ratio of lymphocytes to leukocytes,
j the presence and type of cancer cells, protein level,
~20 or fat level.
In a variety of industries, it may be desirable
to deter~ne the presence of a contaminant in a fluid
such as air or water, e.g., contaminants in drinking
water, or bacteria in food,. and beverage processing
plants. In environmental analysis, it may be
desirable to determine the presence, type, and amount
of a certain contaminant, such as estrogenic
compounds, pesticides (DDT, heptachlor, and atrazine),
aromatic hydrocarbons, and polychlorinated biphenyls.
- 30 In both the medical and.environmental fields it may be
breakdown
desirable to determine the presence of
,
products such as bisphenol-A, an ingredient in '
plastics.
The devices and methods of the present invention
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are also particularly useful when the matter may be
tagged with a chromophore, a light absorbing or
emitting probe, or any other visualization reagent.
For example, cells and DNA may be analyzed by using a
probe which specifically binds (indirectly or
directly) with the matter of interest, and combining' .
that probe with the first porous medium or by mixing
the probe with the fluid sample.
It should be clear that the device and method of
the present invention may be used in a wide variety of
industries, and for determining the presence,~amount,
and composition of virtually any solid matter.
Although the present invention has been described
in terms of a particular preferred embodiments, it is
not limited to those embodiments. Alternative
embodiments, examples, and modifications which would
.still be encompassed by the invention may be made by
those skilled in the art, particularly in light of the
foregoing teachings. Therefore, the following claims
' 20 are intended to cover any alternative embodiments,
examples, modifications, or equivalents which may be
included within the spirit and scope of the invention
as defined by the claims.
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