CA1332911C - Sliding test device for assays - Google Patents
Sliding test device for assaysInfo
- Publication number
- CA1332911C CA1332911C CA000593735A CA593735A CA1332911C CA 1332911 C CA1332911 C CA 1332911C CA 000593735 A CA000593735 A CA 000593735A CA 593735 A CA593735 A CA 593735A CA 1332911 C CA1332911 C CA 1332911C
- Authority
- CA
- Canada
- Prior art keywords
- filter
- pad
- absorbent material
- absorbent
- liquid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
- B01D61/14—Ultrafiltration; Microfiltration
- B01D61/18—Apparatus therefor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/5302—Apparatus specially adapted for immunological test procedures
Abstract
There is disclosed an improved test device useful in conducting reactions. The device comprises a) a well configured to confine temporarily a liquid patient sample admixed with at least one reagent, such as an immunoreagent, to conduct such a reaction, b) a filter at the bottom of the well with pores effective to pass free, unreacted reagent but not reacted or complexed reagent, and c) an absorbent material underneath the filter effective to draw off liquid in the well after the reaction. The device further includes d) a non-absorbent pad underneath the filter, adjacent to the absorbent material, and e) means for moving the filter and the absorbent material relative to each other, and the filter and the pad relative to each other, between two positions, one in which the filter contacts the non-absorbent pad and the other in which the filter contacts the absorbent material.
Description
SLIDING TEST DEVICE FOR ASSAYS
FIELD OF THE INVENTION
This invention relates to a construction of Q test device that allows it to alternate between no-liquid flow, and liquid flow, through a filter, the filter belng used to separate a reaction product from the reagents that provide the reaction product.
BACKGROUND OF THE INVENTION
Diagnostic devices have been provided in the past for conducting immunoreactions in one or more test wells to determine the qualitative existence of pregnancy or an infectious disease. Such devices commonly include a filter membrane at the bottom of the well to separate out free, unreacted immunoreagents, from complexed immunoreagents. (The former pass through the membrane.) Underneath such membranes is preferably located an absorbent material to absorb the liquid of the reaction mixture. It has been conventional in such devices to provide for control of liquid flow, so as to first retain the liquid in the well above the membrane for an incubation period, and then to allow flow through the membrane. Previously provided mechanisms for controlling the flow include an aperture in the housing for the absorbent material underneath, and seals for opening and closing the aperture. When the aperture is open, normal liquid wetting causes the liquid to flow though the membrane into the absorbent material. Such seals, although effective, require careful tolerances and assembly techniques, so as to insure the apertures are normally closed, while at the same time are openable using manual forces easily avsilable to the user.
Thus, prior to this invention there has been a need to provide liquid flow control for such devices that do not have such high tolerance 9 1 ~
requirements, while at the same time allowing easy use by the operator.
A recent development towards this end is that described in U.S. Patent 4,734,262 by Bagshawe.
In this device, a non-absorbent seal is provided at the bottom of the well, between the opening in the well and the filter membrane that is combined with an absorbent material. The device is constructed to provide relative movement in the form of reciprocation, between the seal and the opening, but not between the seal and the filter membrane. That is, both the seal and membrane are caused to deflect away from the opening, such as by applying pressure to the top chamber, allowing liquid to pour out onto the filter membrane. Such a construction has several disadvantages. One is that the seal covers the surface of the filter membrane at the top, thus decreasing the area available for filtration, and most importantly, it prevents the filter from being observed through the opening for a detectable change indicative of a positive reaction. A second disadvantage is a requirement that there be a positive driving pressure to open the seal. This requires an auxillary instrument, such as a vacuum source, besides what can be done using ~ust the operator's own manipulation.
SUMMARY OF THE INVENTION
I have constructed a diagnostic device with flow control means that avoid the above-noted problems concerning tolersnces and difficulties of pressurizing and reading.
More specifically, there is provided a test device useful for conducting a reaction, the device comprising a) a well configured to confine temporarily a liquid patient sample admixed with at least one reagent, to provide the reaction, b) a 1332~1~
filter at the bottom of the well with pores effective to p~s9 free, unreacted reagent but not complexed or rescted reagent, and c) an absorbent material underneath the filter effective to dr~w off liquid in the well after the reaction. The device is lmproved in that it further includes d) a non-absorbent pad underneath the filter, ad~acent to the absorbent material, and e) means for moving the filter and the absorbent m~terial relative to each other, and the filter and the pad relative to each other, between two positions, one in which the filter contacts the non-absorbent pad and the other in which the filter contacts the absorbent material.
Accordingly, it is an advantageous feature of the invention that a liquid testing device is provided w~th a liquid-confining well, a filter, and an absorbent material underneath, that allows flow or no flow of liquid through the filter without the use of vent seals of carefully controlled tolerances.
It is another advantageous feature of the invention that such a liquid testing device is provided that allows filtering of the liquid to occur without having to apply a pressure differential across the filter to open the filter to flow.
It is a related advantageous feature of the invention that such a device is provided wherein the results are easily read from a color change on the filter, after flow is readily initiated by the user.
Other advantageous features will become apparent upon reference to the following Description of the Preferred Embodiments, when read in light of the attached drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
Figures lA and lB ~re fragment~ry section~l views of ~ prior art device, requiring ~ pressure 133~9~
differential to be applied across the filter to cause liquid flow to occur through the filter;
Flgure 2 is a plan view of a device constructed in accord with the invention;
Figures 3A and 3B are sectional views of the device of Figure 2, taken along the line III - III of Figure 4, with that of 3B being of a slightly different embodiment;
Figure 4 is a sectional plan view, taken along the line IV - IV of Figure 3;
Figure 5 is an exploded plan view, partially broken away, of a comparative example;
Figures 6 and 7 are fragmentary sectional views similar to that of Figure 3, but illustrating alternate embodiments;
Figure 8 is a section view taken generally along the line VIII - VIII of Figure 7; and Figure 9 is a section view taken generally along the line IX - IX of Figure 8.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The invention is described herein in the context of the preferred embodiments, in which the device has three pairs of upper/lower compartments, to immunoassay a) the patient sample, b) a positive control and c) a negative control, all more or less simultaneously. The filters are shown as sliding between two positions. In addition, aspects of the invention are useful with only a single pair of compartments, and with any kind of reaction and any form of relative movement between the filter and its absorbent material.
The actusl chemistries of the assay are not described in detail, primarily because the mechanics of the device are applicable to any, or even no, chemistry, provided it is appropriate that flow not -5- 13~2~1 take place instantaneously into the liquid-receiving compartment.
In the most preferred embodiment, the chemistries provide for an immunoassay, in which there is separately received st three filters in three compartments, a patient antigen complexed with an antigen, a positive control for the complex so formed, and a negative control for the complex so formed, respectively, as is conventional.
Figures lA and lB illustrate a related device 10 provided by the prior art, specifically one taught by U.S. Patent No. 4,734,262 noted above. An upper compartment or well 12 has at the bottom of it, an aperture 14 that has mounted below it, a non-absorbent seal 16, that sits on the filter-absorbent material 18 held in place by member 20. Liquid placed in well 12 will not pour into or through material 18 because seal 16 blocks it, Figure lA. However, when a differential pressure is applied across material 18, Figure lB, such as by a positive pressure applied to well 12 (arrow 22) or a vacuum applied to material 18, both the seal and materisl 18 pull away from aperture 14 and liquid flow into the filter-absorbent material occurs, arrows 24. As noted above, the disadvantages of such a device are that the presence of seal 16 prevents reading any color change through the top, and it requires the application of a pressure differential to unseat seal 16.
In accordance with the invention, an improved device 50 comprises, Figure 2, three upper compartments or wells 52a, 52b, and 52c. The bottom 53 of esch well, Figure 3A, is covered with a porous filter 58 which will pass liquid through it unless such flow is blocked either by a liquid lock or some other means. Both the well and its filter are -6- 1332~1 carried on an upper housing 59 having a sloped forward edge 61 and a rear groove 63.
Below housing 59 is a lower housing member 60, Figures 2-4, having in an ad~acent, ~nd preferably contiguous relationship, both an absorbent material 66 and a non-absorbent seal or pad 68, Figure 4. The footprint 58 of the filter of each well 52a, 52b and 52c, is shown ~s contacting pad 68, Figure 4, before each well moves to where the filter contacts the ad~acent absorbent material 66. The height "h", Figure 3A, of both material 66 and the pad 68 is such as to compress material 66 or pad 68 slightly, when filter 58 contacts either one.
The material 66 and pads 68 are held within lower housing 60, as shown in Figure 4. Such lower housing has a forward edge 70 that optionally bears one or more vent apertures 72, and a track groove 74, Figure 3A, that accommodates edge 61 of upper housing 59 in a sliding relationship. Rearward portion 76 of housing 60 has a lip 78 that slidably extends into groove 63. Vertical ribs (not shown) can be located in housing 60 between, e.g., each material 66, to keep them in place.
Thus, as is apparent, upper housing 59 moves relative to lower housing 60 preferably by sliding with respect thereto. This in turn provides a sliding relationship between filter 58 of each well, and both its non-absorbent pad 68 and its absorbent material 66. As shown in Figure 4, the footprint 58 of the filter (shown in phantom) slides as per arrow 80, from contact with non-absorbent pad 68, to absorbent material 66. That is, each well goes from a non-liquid-flow condition to a liquid-flowing condition, respectively, since apertures 72 insure there is no liquid lock. The word "closed" can be printed at 85 on the top of housing 60, Figure 2, to `~ 7 1332~
inform the user that, when configured as shown in Figure 2, the wells are closed off from flow. A
printing of the word "open" (not shown) is useful at the other end 87 of the top of housing 60.
Other sliding motions are useful as well, for example, one in which the upper housing rotates with respect to the lower housing (not shown).
Yet another useful sliding motion is one in which the lower housing slides relative to the upper housing, which is kept stationary. Such an alternative embodiment appears in Fig. 3B, in which parts similar to those previously described bear the same reference numerals, to which the distinguishing suffix (') (prime) is attached. Thus, device 50' comprises an upper housing 59' and a lower housing 60'. Housing 59' includes wells such as well 52b', and filter 58', and housing 60' houses absorbent material 66' and non-absorbent pad 68', all constructed as described above.
However, in this embodiment upper housing 59' remains stationary by reason of its four supports 89 that are attached, for example, at the four corners of such housing. Housing 59' also includes a lip 61' that fits in a groove 74' provided in housing 60', and a rear groove 63' that accommodates lip 78' of housing 60'.
Housing 60' is slung to slide within groove 63' and on lip 61' as a track support, in and out of the plane of Fig. 3B.
Useful materials for either embodiment include the following: Filters 58 can be polyamides, such as nylon, and for example nylon-66 microporous membranes manufactured under the trademarks BIODYNE A
or ULTRIPOR N-66 by Pall Corporation. Most preferably, the membranes are precoated (prior to use) with one or more water-soluble proteins, such as casein derivatives obtained form acylation, 1 3 ~
alkylation or sulfonylation of the casein. Various optional Hdditional treatments can be given to the filter upper surface during or before assembly.
Absorbent material 66 can be any bibulous material, having a sufficient pore volume to soak up about 2 cc of liquid. Useful materials include cellulose acetate, cotton, and rayon.
As noted, pads 68 are selected from non-absorbent materials, such as resilient neoprene laminated with a hydrophobic plastic, for example, polypropylene. The resiliency is selected to allow filter 58 to compress pad 68 with sufficient pressure as to withstand about 3 cm of water as a liquid head of pressure, without leaking. Such compression does not significantly interfere with the upper housing 59 being easily slid by a user, relative to lower housing 60, by simply using finger pressure.
As a result, the devices of the invention are particularly useful to provide an immunoreaction within one or all of the wells, between an immunoreagent (such as labeled antibodies) that is pre-applied or added to the well, and the patient's sample. When housing 59 is slid to the open position (by sliding leftward, Figure 2), the liquid is then free to flow into the absorbent material underneath, carrying with it unreacted (uncomplexed) immunoreagent. However, complexed immunoreagent remains behind on the filter, either because of its size or because a sandwich has formed using beaded antibodies which will not pass through the filter.
The labeled antibodies so trapped on the filter are then caused to react to produce a detectable signal.
Figure 5 illustrates a comparative example, wherein no movement occurs between the filter 124 and its absorbent material 128. Instead, those parts occupy a fixed relationship and a slide valve 150 13~2~
g acts to open or close apertures 144, using a compressed elastomeric material inside valve 150 (not shown). Although such a device works well, care is needed in the selection of materials and in the manufacture of related dimensions to insure that valve 150 can be moved by finger pressure. In contrast, less care need be given to the tolerances used to assemble filter 58 of the present invention, in sliding contact with pad 68 or absorbent material 66.
Figure 6 illustrates Hnother embodiment, in which a rigid non-absorbent pad is used. Parts similar to those previously described bear the same reference numeral to which " is added Thus, as in the previous embodiment, filter 58" is mounted over the bottom of each well, such as well 52b", that is part of upper housing 59". Housing 59" slides with respect to lower housing 60", having in an adjacent configurstion, an absorbent material 66" and a non-absorbent pad 68" for each well. Unlike the previous embodiment, however, pad 68" is relatively rigid. To insure that it seats against filter 58"
with sufficient pressure as to prevent leakage, a spring 100 is used to bias pad 68" upwardly with a force equivalent to about 3 cm of water as a liquid head of pressure. (2.5 cm is the maximum height of liquid used in the wells.) The corners of pad 68"
c~n be optionally rounded (not shown) to allow filter 58" to cam pad 68" down when filter 58" is moved back over it, if such resealing is desired.
An ex~mple of such a relatively rigid non-absorbent pad 68" includes a hydrophobic plastic such as polyproplyene.
A rigid non-absorbing pad can be used without the need for a spring 100 that is Qeparate from the rest of the assembly. Such an embodiment is -lo- 13~
shown in Figures 7--9,wherein parts similar to those previously described bear the same reference numeral, to which the distinguishing mark ( "') is appended.
Thus, in Figure 7, as in the embodiment of Figure 6, upper housing 59 "' has a well 52b"' with a filter 58 "', constructed as before. Lower housing 60 "' has both an absorbent material 66"' and a rigid non--absorbent pad 68 "' with respect to which filter 58"' slides, also as in the embodiment of Figure 6.
However, in this embodiment the characteristic resilience of material 66"' is used to bias the rigid pad 68"' against filter 58"' with the necessary force. In addition, Figure 9, material 66 has a tendency to protrude at 190 into apertures 200 of pad 68"', thus providing the desired contiguous location of the absorbent material immediately ad~acent to portions 202 of the pad on which the footprint of filter 58"' presses, Figure 8. As a result, when well 52a"' moves as per arrow 204, Figure 9, it goes from its closed contact with portion 202 of pad 68 "', to the "open" contact with portions 190 of material 66"'.
Alternatively, material 66"' can be cut to have the shape shown in Fig. 9 even before pad 68 is placed on top of material 66"' .
To allow reclosing of the wells by movement back onto pad 68"', edges 210 of the portions 202 are preferably beveled.
The embodiment of Figs. 7--9can also be arranged as shown in Fig. 3B, to provide the relative sliding motion between the two housings.
The invention has been described in detail with particular reference to preferred embodiments thereof, but it will be understood that variations and modifications can be effected within the spirit and scope of the invention.
FIELD OF THE INVENTION
This invention relates to a construction of Q test device that allows it to alternate between no-liquid flow, and liquid flow, through a filter, the filter belng used to separate a reaction product from the reagents that provide the reaction product.
BACKGROUND OF THE INVENTION
Diagnostic devices have been provided in the past for conducting immunoreactions in one or more test wells to determine the qualitative existence of pregnancy or an infectious disease. Such devices commonly include a filter membrane at the bottom of the well to separate out free, unreacted immunoreagents, from complexed immunoreagents. (The former pass through the membrane.) Underneath such membranes is preferably located an absorbent material to absorb the liquid of the reaction mixture. It has been conventional in such devices to provide for control of liquid flow, so as to first retain the liquid in the well above the membrane for an incubation period, and then to allow flow through the membrane. Previously provided mechanisms for controlling the flow include an aperture in the housing for the absorbent material underneath, and seals for opening and closing the aperture. When the aperture is open, normal liquid wetting causes the liquid to flow though the membrane into the absorbent material. Such seals, although effective, require careful tolerances and assembly techniques, so as to insure the apertures are normally closed, while at the same time are openable using manual forces easily avsilable to the user.
Thus, prior to this invention there has been a need to provide liquid flow control for such devices that do not have such high tolerance 9 1 ~
requirements, while at the same time allowing easy use by the operator.
A recent development towards this end is that described in U.S. Patent 4,734,262 by Bagshawe.
In this device, a non-absorbent seal is provided at the bottom of the well, between the opening in the well and the filter membrane that is combined with an absorbent material. The device is constructed to provide relative movement in the form of reciprocation, between the seal and the opening, but not between the seal and the filter membrane. That is, both the seal and membrane are caused to deflect away from the opening, such as by applying pressure to the top chamber, allowing liquid to pour out onto the filter membrane. Such a construction has several disadvantages. One is that the seal covers the surface of the filter membrane at the top, thus decreasing the area available for filtration, and most importantly, it prevents the filter from being observed through the opening for a detectable change indicative of a positive reaction. A second disadvantage is a requirement that there be a positive driving pressure to open the seal. This requires an auxillary instrument, such as a vacuum source, besides what can be done using ~ust the operator's own manipulation.
SUMMARY OF THE INVENTION
I have constructed a diagnostic device with flow control means that avoid the above-noted problems concerning tolersnces and difficulties of pressurizing and reading.
More specifically, there is provided a test device useful for conducting a reaction, the device comprising a) a well configured to confine temporarily a liquid patient sample admixed with at least one reagent, to provide the reaction, b) a 1332~1~
filter at the bottom of the well with pores effective to p~s9 free, unreacted reagent but not complexed or rescted reagent, and c) an absorbent material underneath the filter effective to dr~w off liquid in the well after the reaction. The device is lmproved in that it further includes d) a non-absorbent pad underneath the filter, ad~acent to the absorbent material, and e) means for moving the filter and the absorbent m~terial relative to each other, and the filter and the pad relative to each other, between two positions, one in which the filter contacts the non-absorbent pad and the other in which the filter contacts the absorbent material.
Accordingly, it is an advantageous feature of the invention that a liquid testing device is provided w~th a liquid-confining well, a filter, and an absorbent material underneath, that allows flow or no flow of liquid through the filter without the use of vent seals of carefully controlled tolerances.
It is another advantageous feature of the invention that such a liquid testing device is provided that allows filtering of the liquid to occur without having to apply a pressure differential across the filter to open the filter to flow.
It is a related advantageous feature of the invention that such a device is provided wherein the results are easily read from a color change on the filter, after flow is readily initiated by the user.
Other advantageous features will become apparent upon reference to the following Description of the Preferred Embodiments, when read in light of the attached drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
Figures lA and lB ~re fragment~ry section~l views of ~ prior art device, requiring ~ pressure 133~9~
differential to be applied across the filter to cause liquid flow to occur through the filter;
Flgure 2 is a plan view of a device constructed in accord with the invention;
Figures 3A and 3B are sectional views of the device of Figure 2, taken along the line III - III of Figure 4, with that of 3B being of a slightly different embodiment;
Figure 4 is a sectional plan view, taken along the line IV - IV of Figure 3;
Figure 5 is an exploded plan view, partially broken away, of a comparative example;
Figures 6 and 7 are fragmentary sectional views similar to that of Figure 3, but illustrating alternate embodiments;
Figure 8 is a section view taken generally along the line VIII - VIII of Figure 7; and Figure 9 is a section view taken generally along the line IX - IX of Figure 8.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The invention is described herein in the context of the preferred embodiments, in which the device has three pairs of upper/lower compartments, to immunoassay a) the patient sample, b) a positive control and c) a negative control, all more or less simultaneously. The filters are shown as sliding between two positions. In addition, aspects of the invention are useful with only a single pair of compartments, and with any kind of reaction and any form of relative movement between the filter and its absorbent material.
The actusl chemistries of the assay are not described in detail, primarily because the mechanics of the device are applicable to any, or even no, chemistry, provided it is appropriate that flow not -5- 13~2~1 take place instantaneously into the liquid-receiving compartment.
In the most preferred embodiment, the chemistries provide for an immunoassay, in which there is separately received st three filters in three compartments, a patient antigen complexed with an antigen, a positive control for the complex so formed, and a negative control for the complex so formed, respectively, as is conventional.
Figures lA and lB illustrate a related device 10 provided by the prior art, specifically one taught by U.S. Patent No. 4,734,262 noted above. An upper compartment or well 12 has at the bottom of it, an aperture 14 that has mounted below it, a non-absorbent seal 16, that sits on the filter-absorbent material 18 held in place by member 20. Liquid placed in well 12 will not pour into or through material 18 because seal 16 blocks it, Figure lA. However, when a differential pressure is applied across material 18, Figure lB, such as by a positive pressure applied to well 12 (arrow 22) or a vacuum applied to material 18, both the seal and materisl 18 pull away from aperture 14 and liquid flow into the filter-absorbent material occurs, arrows 24. As noted above, the disadvantages of such a device are that the presence of seal 16 prevents reading any color change through the top, and it requires the application of a pressure differential to unseat seal 16.
In accordance with the invention, an improved device 50 comprises, Figure 2, three upper compartments or wells 52a, 52b, and 52c. The bottom 53 of esch well, Figure 3A, is covered with a porous filter 58 which will pass liquid through it unless such flow is blocked either by a liquid lock or some other means. Both the well and its filter are -6- 1332~1 carried on an upper housing 59 having a sloped forward edge 61 and a rear groove 63.
Below housing 59 is a lower housing member 60, Figures 2-4, having in an ad~acent, ~nd preferably contiguous relationship, both an absorbent material 66 and a non-absorbent seal or pad 68, Figure 4. The footprint 58 of the filter of each well 52a, 52b and 52c, is shown ~s contacting pad 68, Figure 4, before each well moves to where the filter contacts the ad~acent absorbent material 66. The height "h", Figure 3A, of both material 66 and the pad 68 is such as to compress material 66 or pad 68 slightly, when filter 58 contacts either one.
The material 66 and pads 68 are held within lower housing 60, as shown in Figure 4. Such lower housing has a forward edge 70 that optionally bears one or more vent apertures 72, and a track groove 74, Figure 3A, that accommodates edge 61 of upper housing 59 in a sliding relationship. Rearward portion 76 of housing 60 has a lip 78 that slidably extends into groove 63. Vertical ribs (not shown) can be located in housing 60 between, e.g., each material 66, to keep them in place.
Thus, as is apparent, upper housing 59 moves relative to lower housing 60 preferably by sliding with respect thereto. This in turn provides a sliding relationship between filter 58 of each well, and both its non-absorbent pad 68 and its absorbent material 66. As shown in Figure 4, the footprint 58 of the filter (shown in phantom) slides as per arrow 80, from contact with non-absorbent pad 68, to absorbent material 66. That is, each well goes from a non-liquid-flow condition to a liquid-flowing condition, respectively, since apertures 72 insure there is no liquid lock. The word "closed" can be printed at 85 on the top of housing 60, Figure 2, to `~ 7 1332~
inform the user that, when configured as shown in Figure 2, the wells are closed off from flow. A
printing of the word "open" (not shown) is useful at the other end 87 of the top of housing 60.
Other sliding motions are useful as well, for example, one in which the upper housing rotates with respect to the lower housing (not shown).
Yet another useful sliding motion is one in which the lower housing slides relative to the upper housing, which is kept stationary. Such an alternative embodiment appears in Fig. 3B, in which parts similar to those previously described bear the same reference numerals, to which the distinguishing suffix (') (prime) is attached. Thus, device 50' comprises an upper housing 59' and a lower housing 60'. Housing 59' includes wells such as well 52b', and filter 58', and housing 60' houses absorbent material 66' and non-absorbent pad 68', all constructed as described above.
However, in this embodiment upper housing 59' remains stationary by reason of its four supports 89 that are attached, for example, at the four corners of such housing. Housing 59' also includes a lip 61' that fits in a groove 74' provided in housing 60', and a rear groove 63' that accommodates lip 78' of housing 60'.
Housing 60' is slung to slide within groove 63' and on lip 61' as a track support, in and out of the plane of Fig. 3B.
Useful materials for either embodiment include the following: Filters 58 can be polyamides, such as nylon, and for example nylon-66 microporous membranes manufactured under the trademarks BIODYNE A
or ULTRIPOR N-66 by Pall Corporation. Most preferably, the membranes are precoated (prior to use) with one or more water-soluble proteins, such as casein derivatives obtained form acylation, 1 3 ~
alkylation or sulfonylation of the casein. Various optional Hdditional treatments can be given to the filter upper surface during or before assembly.
Absorbent material 66 can be any bibulous material, having a sufficient pore volume to soak up about 2 cc of liquid. Useful materials include cellulose acetate, cotton, and rayon.
As noted, pads 68 are selected from non-absorbent materials, such as resilient neoprene laminated with a hydrophobic plastic, for example, polypropylene. The resiliency is selected to allow filter 58 to compress pad 68 with sufficient pressure as to withstand about 3 cm of water as a liquid head of pressure, without leaking. Such compression does not significantly interfere with the upper housing 59 being easily slid by a user, relative to lower housing 60, by simply using finger pressure.
As a result, the devices of the invention are particularly useful to provide an immunoreaction within one or all of the wells, between an immunoreagent (such as labeled antibodies) that is pre-applied or added to the well, and the patient's sample. When housing 59 is slid to the open position (by sliding leftward, Figure 2), the liquid is then free to flow into the absorbent material underneath, carrying with it unreacted (uncomplexed) immunoreagent. However, complexed immunoreagent remains behind on the filter, either because of its size or because a sandwich has formed using beaded antibodies which will not pass through the filter.
The labeled antibodies so trapped on the filter are then caused to react to produce a detectable signal.
Figure 5 illustrates a comparative example, wherein no movement occurs between the filter 124 and its absorbent material 128. Instead, those parts occupy a fixed relationship and a slide valve 150 13~2~
g acts to open or close apertures 144, using a compressed elastomeric material inside valve 150 (not shown). Although such a device works well, care is needed in the selection of materials and in the manufacture of related dimensions to insure that valve 150 can be moved by finger pressure. In contrast, less care need be given to the tolerances used to assemble filter 58 of the present invention, in sliding contact with pad 68 or absorbent material 66.
Figure 6 illustrates Hnother embodiment, in which a rigid non-absorbent pad is used. Parts similar to those previously described bear the same reference numeral to which " is added Thus, as in the previous embodiment, filter 58" is mounted over the bottom of each well, such as well 52b", that is part of upper housing 59". Housing 59" slides with respect to lower housing 60", having in an adjacent configurstion, an absorbent material 66" and a non-absorbent pad 68" for each well. Unlike the previous embodiment, however, pad 68" is relatively rigid. To insure that it seats against filter 58"
with sufficient pressure as to prevent leakage, a spring 100 is used to bias pad 68" upwardly with a force equivalent to about 3 cm of water as a liquid head of pressure. (2.5 cm is the maximum height of liquid used in the wells.) The corners of pad 68"
c~n be optionally rounded (not shown) to allow filter 58" to cam pad 68" down when filter 58" is moved back over it, if such resealing is desired.
An ex~mple of such a relatively rigid non-absorbent pad 68" includes a hydrophobic plastic such as polyproplyene.
A rigid non-absorbing pad can be used without the need for a spring 100 that is Qeparate from the rest of the assembly. Such an embodiment is -lo- 13~
shown in Figures 7--9,wherein parts similar to those previously described bear the same reference numeral, to which the distinguishing mark ( "') is appended.
Thus, in Figure 7, as in the embodiment of Figure 6, upper housing 59 "' has a well 52b"' with a filter 58 "', constructed as before. Lower housing 60 "' has both an absorbent material 66"' and a rigid non--absorbent pad 68 "' with respect to which filter 58"' slides, also as in the embodiment of Figure 6.
However, in this embodiment the characteristic resilience of material 66"' is used to bias the rigid pad 68"' against filter 58"' with the necessary force. In addition, Figure 9, material 66 has a tendency to protrude at 190 into apertures 200 of pad 68"', thus providing the desired contiguous location of the absorbent material immediately ad~acent to portions 202 of the pad on which the footprint of filter 58"' presses, Figure 8. As a result, when well 52a"' moves as per arrow 204, Figure 9, it goes from its closed contact with portion 202 of pad 68 "', to the "open" contact with portions 190 of material 66"'.
Alternatively, material 66"' can be cut to have the shape shown in Fig. 9 even before pad 68 is placed on top of material 66"' .
To allow reclosing of the wells by movement back onto pad 68"', edges 210 of the portions 202 are preferably beveled.
The embodiment of Figs. 7--9can also be arranged as shown in Fig. 3B, to provide the relative sliding motion between the two housings.
The invention has been described in detail with particular reference to preferred embodiments thereof, but it will be understood that variations and modifications can be effected within the spirit and scope of the invention.
Claims (13)
1. In a test device useful for conducting a reaction, said device comprising a) a well configured to confine temporarily a liquid patient sample admixed with at least one reagent, to provide said reaction, b) a filter at the bottom of said well with pores effective to pass free, unreacted reagent but not complexed or reacted reagent, and c) an absorbent material underneath said filter effective to draw off liquid in said well after said reaction, the improvement wherein said device further includes d) a non-absorbent pad underneath said filter, adjacent to said absorbent material, and e) means for moving said filter and said absorbent material relative to each other, and said filter and said pad relative to each other, between two positions, one in which said filter contacts said non-absorbent pad and the other in which said filter contacts said absorbent material.
2. A device as defined in claim 1, wherein said pad and said absorbent material are stationary within said device, and said filter is mounted for movement between said two positions.
3. A device as defined in claim 2, wherein said moving means comprise means for sliding said filter between said two positions.
4. A device as defined in claim 3, wherein said pad comprises a rigid material selected from the group consisting of hydrophobic plastics, said device further including means for biasing said filter against said rigid material to temporarily seal said filter from liquid flow occurring through the filter.
5. A device as defined in claim 4, wherein said pad rests on a portion of said absorbent material, whereby said portion of said absorbent material functions as said biasing means.
6. A device as defined in claim 4, wherein said moving means include a beveled surface on said non-absorbent pad that facilitates relative movement of said filter and said pad into contacting relationship.
7. A device as defined in claim 3, wherein said pad comprises a resilient material selected from the group consisting of hydrophobic plastics, and wherein said filter is assembled against said material to slidably seal said filter thereagainst with a pressure effective to temporarily prevent liquid flow through the filter.
8. A device as defined in claim 1, wherein said absorbent material and said pad are contiguous.
9. A device as defined in claim 1, wherein said filter is stationary within said device, and said pad and said absorbent material are mounted for movement between said two positions.
10. In a test device for an immunoreaction, said device comprising a) a well configured to confine temporarily a liquid patient sample admixed with at least one immunoreagent, to provide said immunoreaction, b) a filter at the bottom of said well with pores effective to pass free, unreacted immunoreagent but not complexed immunoreagent, c) an absorbent material underneath said filter effective to draw off liquid in said well after said immunoreaction, and d) means for controlling liquid flow from said filter to said absorbent;
the improvement wherein said device further includes a non-absorbent pad underneath said filter, and wherein said liquid-controlling means comprise means for providing relative sliding movement between said filter and said pad and said absorbent material, to provide contact of said filter with either said non-absorbing pad or said absorbent material, so that proper alternating conditions of no flow or flow occur.
the improvement wherein said device further includes a non-absorbent pad underneath said filter, and wherein said liquid-controlling means comprise means for providing relative sliding movement between said filter and said pad and said absorbent material, to provide contact of said filter with either said non-absorbing pad or said absorbent material, so that proper alternating conditions of no flow or flow occur.
11. A device as defined in claim 10, wherein said pad comprises a rigid material selected from the group consisting of hydrophobic plastics, said device further including means for biasing said filter against said rigid material to temporarily seal said filter from liquid flow occurring through the filter.
12. A device as defined in claim 11, wherein said biasing means includes a portion of said absorbent material.
13. A device as defined in claim 10, wherein said filter is stationary within said device, and said pad and said absorbent material are mounted for movement between said two positions.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/224,831 US4877586A (en) | 1988-07-27 | 1988-07-27 | Sliding test device for assays |
| US224,831 | 1988-07-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1332911C true CA1332911C (en) | 1994-11-08 |
Family
ID=22842413
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000593735A Expired - Fee Related CA1332911C (en) | 1988-07-27 | 1989-03-15 | Sliding test device for assays |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US4877586A (en) |
| EP (1) | EP0353025B1 (en) |
| JP (1) | JPH0274863A (en) |
| CA (1) | CA1332911C (en) |
| DE (1) | DE68906479D1 (en) |
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| IT1006557B (en) * | 1971-09-08 | 1976-10-20 | Bagshawe Kenneth Dawson | REACTION CELL PARTICULARLY USEFUL IN RADIOIMMUNITY TESTS |
| US4246339A (en) * | 1978-11-01 | 1981-01-20 | Millipore Corporation | Test device |
| US4558013A (en) * | 1983-04-08 | 1985-12-10 | Mast Immunosystems, Ltd. | Calibrated reaction measurement system |
| GB8311730D0 (en) * | 1983-04-29 | 1983-06-02 | Bagshawe K D | Handling of reaction mixtures |
-
1988
- 1988-07-27 US US07/224,831 patent/US4877586A/en not_active Expired - Lifetime
-
1989
- 1989-03-15 CA CA000593735A patent/CA1332911C/en not_active Expired - Fee Related
- 1989-07-25 DE DE8989307548T patent/DE68906479D1/en not_active Expired - Lifetime
- 1989-07-25 EP EP89307548A patent/EP0353025B1/en not_active Expired - Lifetime
- 1989-07-25 JP JP1192455A patent/JPH0274863A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0274863A (en) | 1990-03-14 |
| EP0353025A3 (en) | 1991-03-20 |
| DE68906479D1 (en) | 1993-06-17 |
| EP0353025B1 (en) | 1993-05-12 |
| US4877586A (en) | 1989-10-31 |
| EP0353025A2 (en) | 1990-01-31 |
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