Method for filtering a whole blood sample using an in-line fluid filter for an automated analyzer

A method for filtering a whole blood sample using a filter element constructed and arranged to block the passage of fibrous and particulate matter which may be present in a liquid sample, such as a whole blood sample, while allowing the blood cells to pass is disclosed. In one embodiment, the filter element is part of an in-line filter assembly which assembly may include two complementary mating components. One component may take the form of a coupling provided with a male threaded portion adapted to be received into and engage the female threaded portion of the complementary mating component. This complementary mating component may be another coupling or an analysis system component, such as a valve. Each complementary mating component is adapted to receive a liquid sample carrying conduit therethrough. The coupling is also adapted to receive a filter mount which holds a filter element constructed and arranged as discussed hereinabove. When the complementary mating components are assembled, their respective conduits and the filter element are brought into alignment and fluid tight seal. In an alternative embodiment, the filter element is permanently retained in a section of conduit which is provided with appropriate connecting means to allow the conduit section to be readily removed from the apparatus when cleaning or replacement is desired.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention relates to in-line fluid-type filters for use in 
automated clinical instrumentation, and more particularly to an in-line 
fluid-type filter which may be advantageously used to filter whole blood. 
2. Prior Art 
Clinical apparatus for the analysis of fluids are well known. See, for 
example, U.S. Pat. Nos. 2,797,149, 2,879,141 and 3,241,432. Typically, 
analysis apparatus of the automated type provide for the feeding of 
samples in a flowing stream by means of a take-off device or probe which 
aspirates liquid sample from a sample container. The aspirated portion of 
liquid sample is then conveyed through suitable conduits for analysis. 
In present day analysis apparatus, only a small quantity of sample may be 
employed for analysis purposes. Typically, sample flow in the take-off 
device is at a relatively slow rate, e.g. 1.5 ml/min. The sample conduit 
and the conduits employed in such apparatus extending from the take-off 
device to the point of analysis must be relatively small. By way of 
example only, the sample conveying conduit may have an internal diameter 
of approximately 0.02 to 0.033 inch. Such a conduit may become clogged 
during the performance of a series of tests and necessitate the shutdown 
of the system to clear the conduit. Such clogging or other interference 
from debris may be the result of foreign matter in the sample or may be 
due to the existence in the sample of a naturally occurring substance, 
such as, for example, fibrin, that the substance in whole blood which acts 
to form the fibrous network in the coagulation of blood. 
The prior art has attempted to solve the clogging problem by proposing 
diverse filtering schemes, but this is not as simple a solution as might 
first appear. In any contemplated device designed to filter the sample to 
remove such potential clog-causing matter, care must be taken to avoid 
restricting significantly the flow of the sample through the filtering 
device. In view of the relatively small sample size, the amount of sample 
retained in the filtering device must be kept to a minimum. It is also 
important when dealing with filtering of whole blood samples that the 
laminar flow within the conduit be disturbed as little as possible, and 
that there be a smooth transition downstream from the filter so as not to 
disrupt the integrity of, e.g. rupture, the cells within the sample. 
Filters may be provided at various locations in the conduit systems to 
catch the clogging or interference causing debris. For example, there are 
disclosed in U.S. Pat. No. 3,795,149, a method and apparatus for supplying 
samples for automated analysis wherein liquid from a liquid sample 
container is aspirated through a filter-equipped inlet end of a probe 
while the latter is immersed in the liquid. The probe is subsequently 
removed from the container and immersed in the liquid of a wash 
receptacle. Prior to immersion in another liquid sample, a fluid other 
than sample is flushed through the aforementioned filter in a reverse 
direction to cleanse it of particulate matter, the flushing being in timed 
relation to the movements of the probe. More particularly, the probe 
includes a cup-shaped filter extending over the inlet end of a take-off 
tube. The filter may be formed from a disc of stainless steel, for 
example, which is suitably etched to provide filter holes therethrough and 
which is bent up to provide the cup shape. The filter surrounds the inlet 
in a manner to provide a filtering action. It has been found, however, 
that cup-shaped filters such as that just described require a 
significantly high pressure on backflushing to dislodge the material 
caught in the filter. Although filters formed of material such as 
stainless steel may appear to the eye to be smooth, nevertheless, there 
are sharp protuberances and burrs on the surfaces which can trap fibrous 
matter so that it is not easily dislodged from the filter by backflushing 
under normal flow pressure, necessitating increased flow pressure for the 
backflushing cycle. Also, as will be noted hereinbelow, such fibrous 
matter often becomes further entwined in the filter on backflushing, 
leading to permanent clogging of the filter after a relatively few cycles. 
This leads to a high frequency of instrument down time required to clean 
and/or replace the filter. Furthermore, filters of the type disclosed in 
U.S. Pat. No. 3,795,149 are preferably fixedly secured to the inlet of the 
take-off tube, requiring the replacement of the take-off tube assembly 
each time the filter needs to be replaced. 
The use of disc or wafer-shaped filters in an in-line fluid filter 
arrangement is quite common. In U.S. Pat. No. 4,263,140, there is 
disclosed such an arrangement which includes a pair of body sections 
coaxially secured to each other. A filter element is fixedly disposed 
transversely across a filter chamber defined by the body section 
intermediate a fluid filter inlet and outlet. This filter element includes 
an annular mounting flange interposed between mating annular body section 
end faces. A generally cup-shaped filter element support is fixedly 
located on at least the outlet side of the filter element and is 
dimensioned so that the filter element is at least partially received in 
the cup-shaped area thereof. This support includes an annular mounting rim 
which is also interposed between the body section end faces. The support 
allows the filter to experience greatly increased fluid pressure 
differentials across the filter element. The filter element mounting 
flange and the support mounting rim are dimensioned to at least extend to 
the outside diameter of the mating body section annular end faces. The 
body sections are rigidly affixed to each other at the end faces by means 
of a fusion type weld with at least a portion of the filter element 
mounting flange and the support mounting rim comprising a filler material 
for the weld to assist in producing a joint of high integrity. A pair of 
the filter element supports may be advantageously employed wherein the 
supports are in an opposed relationship to each other having the filter 
element positioned therebetween. 
While in-line disc-type filters may prove effective in restricting the 
passage of particulate foreign matter through the conduit in which they 
are placed, it has been found that such filters, particularly when used in 
clinical apparatus for the analysis of whole blood, readily become clogged 
by the fibrin in the sample. As the aspirated sample of whole blood passes 
through the filter, the fibrous matter becomes trapped by the filter as 
intended, but problems often arise in cleaning the trapped matter from the 
filter. The fibrous matter generally has a length much greater than the 
width of the filtering element. Attempts to clean the filter by 
backflushing usually result in the fibrous strand becoming further 
entangled in the filter, and permanently lodged therein, clogging one or 
more passages in the filter. The filter is usually sized so that the 
entanglement of a few fibrous strands will not significantly effect fluid 
flow therethrough; however, it will be readily appreciated that the filter 
will eventually become so clogged by the fibrous matter that it seriously 
restricts fluid flow therethrough, and cannot be cleaned by simple 
backflushing. It must be replaced. Replacing such in-line filters requires 
shutting down the apparatus, thus interfering with sample analysis. 
A representative sampling of other prior art filtering arrangements 
intended for filtering blood and other body fluids includes U.S. Pat. Nos. 
3,493,503, 3,882,026, 4,170,056, 4,157,967, 4,476,023 and 4,370,381, each 
of which describes a disc-type filter. 
While the prior art demonstrates the development of filter arrangements for 
automated clinical analyzers to the best of our knowledge, the prior art 
does not teach or describe a filter arrangement which will effectively 
remove potential clog causing materials from the sample fluid stream while 
at the same time lengthening the interval between filter backflushing and 
replacements. It is a principal object of the present invention to provide 
such a filter. 
SUMMARY OF THE INVENTION 
The present invention contemplates a new and improved in-line filter 
arrangement which overcomes the above and other problems, and which is 
simple, reliable and which increases, significantly, the time between 
filter replacements. 
The unique feature of the subject invention is a filter element constructed 
and arranged to block the passage of fibrous and particulate matter which 
may be present in a liquid sample such as whole blood, while allowing the 
blood cells to pass. A further feature of the filter element is its 
construction which resists permanent clogging by such fibrous and 
particulate matter. Specifically, the filter element includes a generally 
cylindrical body portion having a multiplicity of equal size passageways 
therethrough. Preferably, the diameter of each passageway is smaller than 
the diameter of the smallest passageway or conduit in the automated 
clinical analyzer through which the filtered sample will flow. The 
passageways are oriented parallel to the longitudinal axis of the body 
portion. The body portion and consequently the passageways preferably have 
a length at least as long as the average length of the fibrous matter 
believed to be present in the whole blood sample. In such an arrangement, 
the fibrous matter trapped within the passageways is readily displaced 
therefrom by backflushing of the filter element. 
In one embodiment, the filter element is part of an in-line filter assembly 
which assembly may include two complementary mating components. One 
component may take the form of a coupling provided with a male threaded 
portion adapted to be received into and engage the female threaded portion 
of the complementary mating component. This complementary mating component 
may be another coupling or an analysis system component, such as, a valve. 
Each complementary mating component is adapted to receive a liquid sample 
carrying conduit therethrough. The coupling is also adapted to receive a 
filter mount which holds a filter element constructed and arranged as 
discussed hereinabove. When the complementary mating components are 
assembled, their respective conduits and the filter element are brought 
into alignment and fluid tight seal. 
In an alternative embodiment, the filter element is permanently retained in 
a section of conduit which is provided with appropriate connecting means 
to allow the conduit section to be readily removed from the apparatus when 
cleaning or replacement of the filter element is desired. 
It is among the advantages of a filter arrangement embodying the present 
invention that it can be used with assurance that the filtered sample will 
actually be substantially free of fibrous material, and particulate matter 
found in the unfiltered sample. 
The filter arrangement can be reused many times by backflushing it while in 
place in the apparatus with a suitable liquid, such as isotonic saline, to 
remove the material which has accumulated on the upstream side of the 
filter element and in the longitudinal passages thereof. 
The filter element may be cleared of debris by ultrasonic or conventional 
washing techniques. The material used in the filter construction is 
compatible with commonly used cleaning agents. 
The invention accordingly comprises the construction hereinafter described, 
the scope of invention being indicated in the claims.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
Referring now to the drawings, there is illustrated in FIG. 1 an exploded 
view of one preferred embodiment of the in-line filter arrangement of the 
subject invention which is identified generally by the reference numeral 
10. As will be appreciated, the in-line filter arrangement of the present 
invention is intended for use primarily in a clinical apparatus for 
analyzing blood samples, e.g. whole blood. A number of materials could be 
advantageously employed for the components of the in-line filter as are 
commonly used in such applications, although, with respect to certain 
components described below preferred materials will be specified. 
The filter arrangement 10 includes a filter adapter 12 adapted to be 
positioned on the flared end 14 of a conduit 16 as will be described 
hereinafter, for free rotational motion with respect to the conduit. A 
filter assembly 18 is provided and includes a filter mount 20 having a 
filter element 22 positioned therein. As can be best seen in FIG. 2, the 
filter adapter 12 may take the form of a conventional coupling that is 
threaded as shown at 24 for the screwing thereof into a complementarily 
mating component, as will be described hereinafter. The coupling 12 has 
stepped bore 26 extending centrally thereof. Stepped bore 26 includes 
first and second portions 28 and 30 with the former being of a smaller 
diameter than the latter. The end 32 of the coupling 12 includes a 
relatively small unthreaded portion as indicated at 34 in FIG. 2. The 
stepped bore 26 may include a section of gradually increasing diameter 36 
to allow a certain freedom of angular displacement or movement of the 
coupling 16 with respect to the conduit. 
The conduit 16, which extends through the axially bore 26, terminates at 
its flared end 14 in bore section portion 30. 
In this embodiment of the present invention, the filter arrangement is 
designed to be releasably fastened to a complementary system component, 
such as valve assembly or mating coupling component. With continued 
reference to FIG. 2, the coupling 12 is shown in conjunction with a mating 
coupling member 38. The mating coupling member 38 may comprise a body 
member 40 having a stepped, generally axial bore 42 extending 
therethrough, including axially aligned bore sections 44, 46, 48 and 50. 
Bore section 50 is threaded as indicated at 52 almost to the inner end 
thereof, leaving an unthreaded bore section 54 of relatively small axial 
extent at the inner bore end. 
A conduit 56 extends through the axial bore 42 and terminates at a flared 
end 58 in bore section 46. 
FIGS. 3, 4 and 5 comprise a more detailed showing of the preferred filter 
assembly, including filter mount 20 and filter element 22 as utilized in 
the subject invention. More particularly, with reference to FIG. 3, the 
filter mount includes a generally cylindrical body portion 60 having an 
axially extending bore 62 therethrough. The bore 62 is sized with respect 
to the outer dimension of the cylindrical filter element 22 so that the 
latter may be close-fitted and then ring staked and thus securely held 
therein. 
The filter element 22 includes a generally cylindrical body portion 64 
having opposed, generally parallel faces 66 and 68 which are substantially 
perpendicular to the longitudinal axis of the filter element. The filter 
element is preferably formed of a glass material processed as 
Fotoform.RTM. glass material, manufactured in accordance with procedures 
established by Corning Glass Works, Corning, N.Y. Reference should be had 
to U.S. Pat. No. 2,628,160 and 4,572,611 in which the process for the 
manufacture of such material, and its composition, respectively, are 
disclosed. The subject matter of U.S. Pat. No. 2,628,160 and 4,572,611 are 
incorporated herein by reference. Alternatively, the filter element may be 
formed from ceramic, an extruded material such as polytetrafluoroethylene, 
or from other materials and by other techniques known to those skilled in 
the art. The body portion 64 preferably has a diameter of approximately 
0.060 inches and a length of approximately 0.080 inches. Extending axially 
through the filter element body portion 64 are a multiplicity of flow 
passages 70 as shown. Each flow passage 70 extends parallel to the axis of 
the body portion 64, and is approximately 0.008 inch in diameter. In the 
preferred embodiment of the present invention, there are 19 passageways. 
Obviously, the exact number of passages in the filter element is dependent 
upon the diameter of the filter element and the required fluid flow rate. 
Ideally, the filter should be designed to provide the greatest percentage 
of open area possible without effecting the structural integrity of the 
filter. The passages should be in number and size to minimize the effect 
of the filter on laminar flow of the sample through the conduit and the 
disruptive effects on sample cell integrity. It has been found that 
passages of the aforenoted number, e.g. 19, with a diameter of 
approximately 0.008 inch each have a minimal effect on pressure loss 
through the filter and are effective to trap fibrin and other clog-forming 
matter in the whole blood sample while allowing the cells in the sample to 
pass undisturbed therethrough. Preferably, the edge 70a of each passage 70 
is rounded to eliminate sharp protuberances or burrs which may catch 
fibrous matter and prevent the same from being backflushed from the filter 
as will be described hereinafter. 
Referring now back to FIG. 2, it is clear that the conduit 16 extends 
through the coupling 12 and its flare 14 is in firm surface contact with 
the face 72 of the filter mount 20. The latter may be provided with a 
deformable annulus 74 which is adapted to butt against the flared end 14 
of conduit 16 to form a fluid-tight seal when the filter is assembled as 
will be described. Similarly, the conduit 56 extends through the coupling 
member 40 and its flared end 58 is in firm contact with the face 76 of the 
filter mount 20. 
Assembly of the in-line filter arrangement of this embodiment is readily 
accomplished by the simple insertion of the conduits 16 and 56 into the 
passageways 26 and 42 so that their flared ends 14 and 58 are positioned 
in the bores 30 and 46 respectively. The filter mount 20 is then closely 
fitted into the axial bore 30 of coupling 12. Thereafter, the coupling is 
positioned so that the threads 24 thereon engage the mating threads 52 of 
the complementary member 38 and the coupling is then tightened into the 
complementary member to firmly press the flared ends 14 and 58 of the 
conduits against the opposed surfaces of the filter mount as depicted in 
FIG. 2 to form an extremely fluid-tight juncture, or pressure fitting 
there between, and place the same in unrestricted fluid flow 
communication. 
As noted hereinabove, while the complementary mating component 38 has been 
described as a mating coupling or fitting, it will be appreciated that it 
may be, in the alternative, the body of a valve or other system component, 
in which instance, the conduit 56 and flare 58 may be replaced by a 
suitable seat or washer adapted to ensure a fluid-tight seal between the 
filter mount and component 38 when the in-line filter assembly is 
completed. In either situation, it will be appreciated that the filter 
assembly can be thought of as including first and second body components 
having axial passages therethrough, and when the components are assembled, 
the axial passages are brought into fluid communication, with the filter 
element positioned within the path of fluid flow. 
There is illustrated in FIGS. 6 and 7 another preferred embodiment of the 
present invention wherein the filter element is fixedly held within a 
section of flexible or heat shrinkable tubing. In this embodiment, 
generally identified by reference numeral 100, a length of tubing 102 is 
provided with conventional coupling members 104 and 106 at each end, for 
connecting the tubing section between various system components. While 
coupling members 104 and 106 are shown as having male threaded portion 108 
and female threaded portion 110 respectively, other coupling means may be 
utilized, such as, for example, quick-disconnect fittings. A filter 
element 112 is similar to filter element 22 described hereinabove, but 
optionally may be provided as shown with convex faces 114 and 116 in lieu 
of the parallel faces 66 and 68 respectively as in element 22. As will be 
appreciated by those skilled in the art, this configuration has the effect 
of spreading any debris in the flowing stream across the upstream face of 
the filter rather than concentrating it at the longitudinal axis of the 
filter, since the pressure drop through the filter element is less for 
those passages closer to the tubing interior wall 118 than for those 
proximate the axial centerline of the tubing, and the fluid sample will be 
urged to the former passageways. The filter element 112 may then be 
fixedly situated in the length of conduit 102 as shown by first 
positioning the filter element within the tubing and then heat shrinking 
the tubing around the filter element to hold it firmly in position 
therein. Alternatively, the filter element 112 may be simply forced into 
flexible tubing such as silicone rubber. The axial extent 120 of the 
filter element body aids in maintaining the filter element in proper 
alignment within the conduit. As with the element 22, the axial extent of 
the filter element 112 need only be greater than the average length of the 
fibrous matter believed to be present in the sample. 
Tests were performed to evaluate the effectiveness of the filter of the 
present invention, and particularly the effect such a filter would have on 
the cell integrity of whole blood samples. A filter arrangement such as 
that described in FIGS. 1 to 5 was installed in a Technicon H*1 hematology 
analyzer manufactured by Technicon Instruments Corporation, Tarrytown, 
N.Y. Comparison of the results of samples run on the analyzer so modified 
and identical samples run on an analyzer without the filter showed no 
detectable change on the parameters measured. Thus, it was demonstrated 
that the filter construction does not disturb the integrity of the cells 
in the sample. 
It is believed that the superior performance of the filter of the present 
invention is due to the fact that the average length of the fibrin and 
other fibrous material that may become lodged in the passageways of the 
filter is shorter than the longitudinal dimension of the filter element 
body, so that on backflushing of the filter, this material does not become 
entangled in adjacent passages as its downstream end does not extend 
beyond the face of the filter element and is readily flushed from the 
filter. 
While the subject filter is adapted for prolonged use and backflushing 
before serious clogging, it will be necessary, at some point in its 
operation, to remove the filter element from the system to flush debris 
clogging the filter passageways. 
The clogged filter may be cleaned ultrasonically by displacing or 
dissolving the clogging material from the passageway. If the arrangement 
of the preferred embodiment illustrated in FIGS. 1 to 5 is used, the 
filter mount is removed from the coupling by disassembling the coupling 12 
from the complementary component 38. It may then be placed in a small 
glass or polyethylene container with a suitable wash solution, which may 
have sodium hydroxide and/or sodium hyperchloride or other strong cleaning 
agents such as acids, as its active ingredient. The ultrasonic cleaner is 
then activated for approximately five minutes. The filter mount is then 
removed from the container and placed into distilled water with the 
ultrasonic cycle repeated for an additional five minutes. Such treatment 
should readily remove debris from the filter passages. 
If the filter arrangement of the alternative embodiment of FIGS. 6 and 7 is 
used, the conduit section may be removed from the apparatus and placed in 
an ultrasonic cleaning device. 
The filter assembly may be cleaned without the use of ultrasonics. The 
filter mount is placed in the wash solution such as that described 
hereinabove, and left to sit for at least one hour. It is then removed 
from the wash and placed in distilled water for approximately another 
hour. 
It will be appreciated by those skilled in the art that the filter element 
should be formed from a material capable of withstanding strong cleaning 
agents. 
While the in-line filter arrangement in accordance with the present 
invention has been described in conjunction with its use in an automated 
clinical analyzer for filtering fibrous matter from whole blood, it will 
be appreciated by those skilled in the art that our invention may have 
application in the filtering of fibrous material from other fluids. 
Some advantages of the present invention evident from the foregoing 
description include an in-line filter arrangement adapted for use in an 
automated clinical analyzer, which is highly effective and readily 
replaceable in the system when clogged. 
In view of the above, it will be seen that several objects of the invention 
are achieved and other advantageous results obtained. 
As various changes can be made in the above constructions without departing 
from the scope of the invention, it is intended that all matter contained 
in the above description or shown in the accompanying drawings shall be 
interpreted as illustrative, not in a limiting sense.