JPS62502706A - Immunology analyzer and method - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] Immunology analyzer and method field of invention The present invention relates to the field of immunoassay, and more particularly, to an immunoassay and an immunoassay. The present invention relates to a method and a new reaction vessel for use therein.

background In this technique, heterogeneous immunoassays offer higher analytical sensitivity than homogeneous immunoassays. It is well known and accepted that Heterogeneous competitive immunoassays A so-called solid phase or support held within a container is commonly required. medicine A patient sample that may contain an unknown quantity of an analyte, such as a , for example, when added to a container with a known quantity of the analyte labeled as an enzyme. It will be done.

Labeled and unlabeled analytes are bonded to each other on a solid support. Compete for. At equilibrium, the labeled assay is bound to a solid support. The amount of the item is related to the concentration of the unlabeled analyte. competitive reaction Once equilibrium is reached, the patient sample and the unreacted labeled analytes are in opposition. The solid support is removed from the reaction vessel and the remaining unbound labeled It is cleaned to completely remove not only the analytical item but also the patient sample.

The substrate is then added to the reaction vessel and catalyzed by the enzyme to form a fluorescent molecule. produce measurable substances such as After the catalytic reaction is complete, the substrate is removed from the reaction vessel. The removed and measurable substance is quantified using, for example, fluorophotometry. patient The concentration of the unknown analyte in the sample is then determined by determining the measurable amount of the substance in the sample. Uses a predetermined calibration relationship related to the amount of unlabeled analytes in the It can be determined as follows.

Despite the superior sensitivity of heterogeneous immunoassays, the typical assay just described is In particular, the labeling process is characterized by a rather tricky operation of the reaction vessels, including several fluid conveyances. Analytes and patient samples that have been removed must be removed and solids retained. The body must be washed and the substrate must be added and then removed. do not have. The tasks involved are time-consuming, difficult to automate, and When it is desired to use heterogeneous immunoassays for high volume applications such as in clinical laboratories , which is a clear disadvantage.

One approach to simplify the work involved in heterogeneous immunoassays is to The carrier was configured as a filter at the bottom of the reaction vessel. such a fill The labeled assay and patient data flow through the reaction vessel and filter. This results in flow from the wash solution and substrate. base The catalyzed material in the filter precipitates directly onto the filter media, e.g. Leaves colored stains on the body. However, such colored stains cannot be accurately quantified. It is difficult and very often the filter media is Determine the presence or absence of a colored stain indicating the presence or absence of the analytical item be inspected as simply as possible.

Thus, such filter approaches have been used in heterogeneous immunoassays. However, it is possible in an otherwise heterogeneous immunoassay to analyze The advantage of quantitative determination of item concentration is not recognized.

The use of filters as part of the reaction vessel is also useful for other forms of immunoassay, especially filters. It is known in radioimmunoassays that the filter can be a hydrophobic substance. like that When a reaction occurs in a radioimmunoassay reaction vessel, pressure is applied to the fluid inside the vessel. , wetting the filter and drawing fluid from the reaction vessel through the filter. centre Once the filter is wetted, it is then possible to terminate the flow of fluid through the filter. It's not Noh. Such properties of the filter material make it difficult for such analysis to occur from the reaction vessel. Radiation-free in requiring fluid to be drawn only through a filter. It is not disadvantageous to epidemic analysis. However, such filters are not suitable for enzyme immunoassays. If used, stop fluid flow through the filter when it becomes wet. It may also be necessary to provide an external valve to stop. outside like that Partial valves are used in heterogeneous immunoanalyzers, especially when the instrument is automated and has individual reaction chambers. If the device is to be discarded after a single use, there is considerable cost and complexity involved. Add.

summary The present invention is directed to an apparatus and method that overcomes the limitations and disadvantages of the prior art. this The system and method greatly simplify the work required on the reaction vessels and, in particular, Convenient for automated equipment.

Both the system and method of the present invention have not been previously recognized or used. This includes the use of reaction capsules that employ filters of hydrophobic substances with nothing. Fluid flow through the filter is initiated by the reaction of the pressure difference across the filter. can be started. Conveniently, the fluid flow directs the gas through the filter By doing so, the filter can be returned to a hydrophobic state. Fill according to the invention A novel application of the TA can be formed integrally with the reaction capsule and further Perform heterogeneous immunoassays without cumbersome fluid handling equipment or techniques known in the art. The goal is to create an inexpensive and reliable valve that can be implemented. reaction cup The inexpensive nature of the cells allows users of this system and method to remove the capsules after use. Furthermore, it simplifies heterogeneous immunoassays and eliminates the need for conventional techniques. between consecutive analyzes performed in a single reaction vessel, as was common in substantially reduces the possibility of contamination.

The system also includes a wheel or carousel that supports multiple reaction capsules. May include ya. This wheel has an offset wheel in its center that can be rotated by an electric motor. Supported by Tokam. The operation of the electric motor depends on the reaction force carried by the wheels. Creates a vortex action within the reactor to sufficiently stir the fluid contained within the reaction vessel. . A novel single-chamber, dual-portion pump pumps fluid and fluid to the filter in the reaction capsule. It can be employed in the system to pass gas afterward. Thus, a single assembly Combines the pumping action of liquid and gas within.

Brief description of the drawing FIG. 1 is a schematic diagram of an immunoassay device according to the present invention.

FIG. 2 shows a reaction capsule according to the invention useful in the system of FIG. FIG. 2 is a cross-sectional view taken along the central axis of

FIG. 3 is a cross-sectional view of the reaction capsule of the present invention taken along line 3-3 in FIG. Ru.

4 is a side view of the cleaning station taken along line 4--4 of FIG. 1; FIG.

FIG. 5 is a side view of the reading station taken along line 5-5 of FIG. .

FIG. 6 is a partial cross-sectional schematic diagram of a single-chamber pump useful in the system of FIG. FIG.

Detailed description of the invention Referring to FIGS. 1-3, a system 10 according to the present invention is shown generally at 14. It includes a horizontal rotating pulley 12 that supports a plurality of reaction capsules. 1 capsule each 4 includes a lower part 18 , an upper part 20 and a filter 22 . The upper part 20 is open at both ends. a cylindrical tube portion 24 having an open end and an annular flange 26 projecting outwardly at the upper end; including.

The lower portion 18 is formed to snugly receive the outer surface at the lower end of the cylindrical portion 24. It includes a cylindrical base 28 having a curved inner surface 30.

The inner surface 30 slopes outwardly to join the base 28 to the cylindrical wall 34. It is connected to the tapered surface 32. The upper end of the cylindrical wall portion 34 is a ring that projects outward. It is formed as a shaped flange 36.

The base portion 28 slopes downward to form a funnel portion 38, and has an inner portion that opens at the lower end. A partial passageway 40 is formed.

The base 28 also includes a plurality of supports 44 extending from an interior wall of the base 28 to the passageway 40. Supports 44 and 46 extending from the walls of the base 28 to the passageway 40 are respectively connected to the filter 2. 2 having a coplanar support surface 48 formed to support the two. The inner surface 30 is a plurality of surfaces extending from the surface 32 to approximately half the distance between this surface 32 and the support surface 48; A semicircular groove 50 is provided.

The filter 22 has an annular surface 52 in the base 28 and an annular edge at the bottom of the cylindrical tube 24. Sandwiched between them is the first. Annular surface 52 serves to grip filter 22 2 It may be provided with two raised rings 54,56. The upper part 20 has a flap inside the capsule 14. The filter 22 is rigidly secured within the lower portion 18 to secure it.

According to the invention, filter 22 is defined by upper portion 20 and filter 22. The material is selected from hydrophobic substances that allow liquid to remain in the reaction chamber 58. Disclosed here In the embodiment shown, the volume of reaction chamber 58 is approximately 1 milliliter. The reaction chamber 58 Also, solid supports useful for immunoassays may be retained. The filter 22 is in a hydrophobic state By doing so, liquid such as water at atmospheric pressure inside the capsule 5 will moisten the filter 22. Thus, filter 22 retains such liquid within the capsule. It's convenient In particular, when pressure is applied to the reaction chamber 58, the liquid wets the filter 22 and the liquid is allowed to flow through the filter and out of passageway 40 and funnel extension 38. fluid To stop the flow of gas, the gas is passed through reaction chamber 58, filter 22 and passageway 40. The flow removes the wetting liquid from the slits of the filter, thus allowing it to flow through the filter. Return to a hydrophobic or hydrophobic state. Once the filter is returned to its hydrophobic state, 22 will retain the liquid at atmospheric pressure within the capsule 14 again.

Thus, filter 22 effectively forms a simple, inexpensive fluid valve with no moving parts. This is an important advance, especially with respect to heterogeneous immunoassays, as mentioned above. Like water In the embodiments disclosed herein for such reagents and cleaning solutions, the filter 22 is Approximately 0.127 m+n (0,005 inch) thick, with maximum functional slit diameter Sintered tetrafluoroethylene matrix approximately 10 to 20 microns Made from x-coated material. Such substances are From Chemplast Inc. As stated in Chem Blast Publication Number C1 (10-10) 4611ON ``Zytex'' product with catalog number A-145 and type E249-122. Available under the title.

Referring again to FIG. 1, reaction capsule 14 is at loading station 61. It is received on the rotary table 12 within suitable restraining means 60. The restraining means 60 is It includes a plurality of openings 62 formed vertically through the rotary table 12. Each opening 6 2 is below the flange 36 when the capsule 14 is placed on the rotary table 12. Lower part 18 of capsule 14 is placed so that its surface leans against the upper surface of rotary table 12. Formed to accept.

The rotary table 12 of the system 10 is located at its center within a capsule 14, as described below. by an offset or eccentric cam 66 to create a vortex mixing effect. I feel supported. A flexible belt 68 is placed around the periphery of the rotary table 12. is guided by the idler round lure 0.72, and is driven by the stepper motor 76. It extends to a drive pulley 74 which is rotationally driven.

System 10 includes a sample transport track 80 supporting a movable probe 82. Subsystem 78 is included. Subsystem 78 performs the appropriate movement to perform the next movement. A driving means is provided. That is, moving probe 82 along track 80 , lowering the probe 82 into the selected one of the plurality of sample cups 84; , aspirating a certain amount of sample into the probe 82 , and moving the probe 82 on a rotating table. moving to the sample supply station 86 above the bull 12, station 8 6 and lowering the probe 82 into the capsule 14 and the sample supply station. At step 86, the aspirated sample is delivered into the capsule 14. sub-system 78 also indicates that a fixed volume of sample is supplied at sample supply station 86. Thereafter, a cleaning station 88 may be included to clean the probe 82.

System 10 includes a reagent delivery system 90 similar to sample delivery system 78. similarly included. The reagent transport subsystem includes a truck 92, a movable probe 94, wash stations 96, all of which contain one or more reagent cups 97. or a plurality of reagents in capsules located at reagent supply station 98. 14.

Sample and reagent transport subsystems 78.90 are commonly used in automated clinical equipment technology. It will be appreciated that a conventional design may be used. sub Systems 78 and 90 include a sample cup 84, a reagent bottle 96 and a single supply. A single processor moved to an X-Y orthogonal system above station 86 or 98. An equivalent solution would be to replace it with a single X-Y subsystem that utilizes a web head. It would also be appropriate.

System 10 includes a capsule cleaning station 100. As seen in Figure 4 The cleaning station 100 has one end extending above the rotary table 12. The horizontal arm 102 includes a horizontal arm 102. The second end of the arm 102 is connected to the rotary table 12 and It is used to raise and lower the arm 102 with respect to the capsule 14 placed on it. It is fixed to the elevator mechanism 104 used. The elevator mechanism 104 is For example, a stepper motor is provided to drive a lead screw, and the lead screw is fixed to the arm 102. including a threaded member that rotates when the stepper motor is rotated; moves the arm 102 up and down.

An annular seal 106 is fixed to the upper arm 102 of the rotary table 12 and The annular seal 106 is shown in cross section in FIG. Conduit 108 connects arm 102 is fixed to the arm 102 and is coaxially aligned with the annular seal 106. They are lined up. The lower open end 110 of the conduit 108 is connected to the lower open end 110 of the annular seal 106. It extends downward from the surface.

Fluid receiving chamber 112 is coaxially aligned with conduit 108 below rotary table 12. It is. The upper end of the chamber 112 is open and its lower end is narrowed to admit waste fluid. It is connected to a conduit 114 leading to a suitable container (not shown).

As seen in FIGS. 1 and 4, conduit 108 is connected to the air outlet by air conduit 116. 118. Conduit 108 also continues to connect peristaltic pump 12 4 to a wash solution conduit 120 that is connected to a wash solution reservoir 122 via . Conduits 1 and 16 and conduit 120 have solenoid controlled valves 126 and 128. Includes each. Valve 126 controls the flow of gas from the air pump to conduit 108. , while valve 128 controls the flow of cleaning solution from pump 124 to conduit 10B. Ru.

To perform the cleaning operation, the pivot table 12 allows the capsule 14 to be placed in the conduit 108 and and can be positioned so as to be coaxially aligned with chamber 112 . Capsule 14 that way The elevator mechanism 104 is aligned such that the annular seal 106 is aligned with the capsule 14. The arm 10 approaches the annular flange 26 of but does not come into contact with the flange 26. 2 is operated to lower it. The cleaning solution is then routed through conduit 108 to the capsule. 14. Remove the wash solution and filter, as detailed below. The elevator mechanism 104 is operated to return the annular seal 10 to a hydrophobic state. Arm 102 is lowered until 6 is pressed against flange 26. the air is that is then fed to the capsule 14 via conduit 108, passed through filter 22 and passed through the capsule 14. The cleaning solution is blown out from the pump cell 14. Once the cleaning cycle is complete, the elevator machine The structure 104 is actuated and the arm 102 is thus positioned at 110 above the flange 26. rise. Rotary table 12 is then rotated to reposition capsule 14. Ru.

System 10 further includes a substrate station 130 (FIG. 1) and a reading station. 132. The liquid substrate from reservoir 134 is routed through tube 136 to the precision port. 138. Precision pump 138 is routed via conduit 140 to the substrate station. 130 is configured to deliver a precise amount of substrate to 130. Substrate station 130 Similar to wash station 100, but suitably aligned with substrate station 130. The capsule 14 is configured to supply only liquid substrate to the capsule 14.

Read station 132 is also similar to wash station 100 and includes a rotary table. includes a horizontal arm 142 (FIG. 5) extending upwardly from the lever 12. through arm 142 , a single conduit 144 fixed to arm 142 is coaxially connected to an annular seal 146. are aligned. Conduit 144 leads to air pump 148. Fluid receiving chamber 14 9 is disposed below the rotary table 12 and includes a conduit 144 and an annular seal 146. are aligned. Fluid receiving chamber 149 is a cell through which substrate from capsule 14 flows. The fluorometer 150 is in fluidic connection with a fluorometer 150 including 152 . The light source 154 is located in the cell 152. Light is guided at a constant wavelength, and fluorescence at a second wavelength passes through filter 156 and is transmitted to photodetector 15. 8. Filter 156 and photodetector 158 filter light [154] It is arranged at an angle of 90° from the cell 152 with respect to the angle of the light.

The output of photodetector 158 is determined according to the art to provide an output related to the fluorescence of the substrate. In addition to the circuitry 159 well known in the field, it is processed by It will be done. Once a fluorescence measurement is made, pinch valve 160 is opened and the substrate is transferred to cell 152. and drain into a suitable waste container (not shown). System 10 also provides a Afterwards, conventional means for cleaning fluid receiving chamber 149 and fluorometer 150 (not shown). Additionally, the fluorometer 150 measures the absorbance or transmittance of the substrate. It can be replaced by a spectrophotometer configured to measure the excess.

System 10 includes a microprocessor, as is well known in the art. based controller 162 (FIG. 1). controller is configured to receive instructions from a keyboard 164 and a display 166. and the data can be output to the printer on the 16th. The controller 162 controls sample transport. subsystem 78, reagent delivery subsystem 90, wash, substrate and read subsystem Stem 100.130.132, peristaltic and precision pump 124.138, air Operation of pumps 118.148, valves 126.128 and stepper motors 76 control. Controller 162 is also responsive to the output of circuitry 159. analyze fluorescence measurements, correlate such measurements with standard curves, and Determine the concentration of the analyte in the sample. All such techniques are automated clinical analysis Well known in the art.

Once all operations with capsule 14 have been completed, capsule 14 is moved to the removal station. It may be released or removed at 170.

System 10 is placed on a rotating table 12, as is well known in the art. In order to maintain not only the heated capsule 14 but also the rotary table 12 at a constant temperature, , including suitable temperature control means.

The immunoassays to be performed on system 10 are for testing desired by the user. The process begins with the user selecting a capsule 14 containing a suitable solid support.

For example, the selected capsule 14 is a competitive fluorophore for analysis term 1; lT3. It may include a solid support adapted for photoenzyme immunoassay. Capsule 14 is initially 26 has a seal on the face which can be removed by the user. Cap The cell 14 is placed in the restraining means 6o on the rotary table 12.

To control the operation of system 10, the user uses keyboard 164 to Select a particular one of the pull cups 84. Remove the sample from the sample cup. and is identified in the test to be performed, for example T3. Rotary table 12 Based on the position, the controller 162 controls the loading station 61. 14 with selected samples, tested, and will now be discussed. As will be described, the system 1o is controlled to perform certain procedures.

The rotary table 12 and thus the capsule 14 are equipped with a stepper electric [76 and a flexible Ruberto 68 allows capsule 14 to undergo an initial cleaning or pre-cleaning operation. A seal 106 located at the cleaning station 100 is attached to the flange of the capsule 14. 26, but is lowered until it is close to it. Approximately from reservoir 122 0.5 milliliters of cleaning solution is pumped into the valve 128 by the pump 124; It is routed to capsule 14 via conduit 120 and conduit 108.

In its initial or hydrophobic state, the hydrophobic nature of the filter 22 repel a cleaning solution such as water, thus retaining the cleaning solution within the reaction chamber 58. . In embodiments disclosed herein, the cleaning solution may be a saline solution. The arm 102 The seal 106 then contacts the flange 26 and compresses the flange slightly. It is lowered to . Air pump 118 is operated to pump air at approximately 15 psi. to the capseno January 4 via the opened valve 156, conduit 116 and conduit lo8. Ru. Air pressure within capsule 14 moistens filter 14 and transfers cleaning solution to filter 22. is passed through and blown out of the capsule 14. The cleaning solution enters chamber 112 and is (through tube 114) to a waste container. Once the cleaning solution is emptied from the capsule 14 , the air flow through the uniquely selected filter 22 is from the slits of the filter 22. The liquid is blown out, thus reestablishing the hydrophobic nature of the filter 22.

Having completed the pre-cleaning, the rotary table 12 places the capsule 14 on the sample supply station. 86. Operated by sample transport subsystem 78 and withdrawing a predetermined amount of the selected sample from one of the sample cups 84; The probe 82 injects the sample into the capsule 14 at a sample supply station 86. Provide sample volume.

Rotary table 12 is rotated again to transfer capsule 14 to reagent supply station 98. to be located. The reagent transport subsystem 90 was operated and contained in the reagent bottle 97. A predetermined amount of one or more selected antibody reagents is provided to capsule 14 . fill The hydrophobic state of the container 22 allows the sample and one or more reagents to be placed inside the capsule 14. to hold. Immunoassay operations are then allowed to occur within capsule 14. and, Throughout the reaction, the contents of capsule 14 are exposed to the vortex created by eccentric cam 66. exposed to mixing effects. Eccentric cam 66 has a head of approximately 0.1 inch, and It is rotated at 1250-1700 rpm to create a vortex effect within the capsule 14.

When the immunoassay reaction is completed, the capsule 14 is cleaned by rotating the rotary table 12. Moved to station 100. At the washing station 100, the sample and and one or more reagents are blown out of the capsule 14 and multiple wash cycles are performed. will be carried out. Each wash cycle includes a short vortex cycle. If the sample and reagent are As it is blown from the pump cell 14 at the end of each wash cycle, it passes through the filter 22. The air re-establishes the hydrophobic condition of filter 22.

Capsule 14 is then moved to substrate station 130 by rotation of rotary table 12. be moved by At substrate station 130, substrate is encapsulated from reservoir 134. Added to 14. The capsule 14 is stirred again using vortex action to maintain the prescribed culture. During this period, an enzymatic reaction is triggered. At the end of the incubation period, the capsule 14 is placed on the reading station. air is added to the capsule 14 from the air pump 148. and blows the substrate from the capsule 14 into the cell 152 where the fluorescence of the substrate is measured. . According to the fluorescence present in the substrate, the concentration of the analyte in the sample can be determined using well-known techniques. It can be determined using techniques.

Although the above operational example c4 was described for a single capsule performing a single test, The system 10 is configured for each capsule 4 placed on a single rotation table 12. In addition, many different tests can be performed simultaneously. In each case, controller 162 , the location of the individual capsules 14 on the rotary table 12 by the user and correlate with the exam. The test details are used by controller 162. the exact reagent or reagents to be used and introduced into each capsule 14. Select. Controller 162 also controls each capsule according to the specified test. 14 provides the necessary timekeeping functionality. All such control functions are well known. This is easily understood by those skilled in automated clinical analysis techniques.

Appropriate processing times for competitive and sandwiched fluorescent enzyme immunoassays Examples of reagents are:

Higaoka Madanjo A Cellulose covalently attached with two anti-rabbit gamma globulins on a solid support 50u of particles.

Prewash: 1 wash with 0.5ml standard saline, no vortex.

EIA reagents: (1) Specific rabbit antibodies: (2) Alkaline phosphatase Composite analysis items.

EIA incubation time and vortex: Approximately 10-30 minutes (depending on the analysis item), continuous stirring Stir.

Washing, number of cycles: 3 wash cycles with 0.5 ml of standard saline, each cycle Vortex for 3-5 seconds.

Substrate: 4-methyl umbelliferone phosphate 0.05mM.

Substrate incubation time and vortex: Approximately 5-30 minutes at 37°±0.2”C, continuous stirring .

Fluorescence analysis method: Light source: 360r+m±2r+m, half-width of 5nm. Fluorescence: 4500 I11±10r+m, half width from 10 to 200m.

Switch FIjA Solid support: 50u granules of cellulose to which monovalent (1°) antibodies are covalently attached. Child.

Prewash solution and time: Same as competitive FETA.

EIA reagent = alkaline phosphatase conjugated to a divalent antibody.

EIA incubation time and vortex: Approximately 10-60 minutes (depending on the analysis item), continuous vortexing Stir.

Washing, number of cycles: 3 to 4 washing cycles with O-5 + nl standard salt water (analysis item by eye), vortex for 3-5 seconds each cycle.

Substrate: Same as competitive FEIA.

Substrate incubation time and vortex: same as competitive FEIA.

Fluorescence analysis method: Same as competitive FEiA.

The above examples show that vortexing is continuous during different incubation times. However, during such incubation period for analysis processed with specific capsules 14 The vortexing of the For example, if the device is interrupted to perform a sample, reagent or substrate transfer or wash cycle, etc. It can be done.

Air pump 118 and peristaltic pump 124 in FIG. A single pump with few moving parts provides both air blowing through the tank 22. can be replaced by Such a pump 178 has an opening as shown in FIG. The chamber 180 includes a cylindrical chamber 180 having an upper end 182 with a cylindrical shape. Lower end 18 of chamber 180 4 is angled and coupled to conduit 186. Conduit 186 is connected to one-way valve 188 and is coupled to conduit 108 (FIG. 4).

The chamber 180 has two populations, a first lower entrance 190 and a second upper entrance 1 92. The lower inlet 190 connects via conduit 194 to a reservoir 196 for cleaning solution. is combined with Conduit 194 directs cleaning solution from reservoir 196 to pump 178. It includes a one-way valve 198 for flushing.

The upper inlet 192 is connected to the atmosphere by a conduit 200, which may simply be a filter 202. coupled to a suitable air source at pressure. Conduit 200 also directs air to pump 178. It includes a one-way valve 204 that allows flow only when

Piston 206 is positioned within chamber 180. This piston 206 is the piston 2 A suitable seal, such as an O-ring 208, is included between the O-ring 208 and the inner wall of the chamber 180.

The piston 206 is connected to the stepper motor 2 which is sequentially controlled by the controller 162. It is possible to move up and down within the chamber 180 by the rod 210 driven by the rod 12. Ru.

In use, the pump cycle connects the piston 206 to the inlet between 190 and 192. Start closest to 190. The stepper motor 212 operates on a piston within the chamber 180. The reservoir 106 is operated to pull the cleaning solution upwardly and the cleaning solution is introduced from the reservoir 106. Vacuum is transferred to chamber 180 via tube 194 and valve 198. The cleaning solution is a piston The tube 206 is drawn into the chamber 180 until it reaches the upper inlet 192. fixie As air 206 moves above population 192, air flows through filter 202 and conduit 200. and is drawn into chamber 180 via valve 204. Can be used with filter 202 Since the air flowing through the air is at atmospheric pressure, the cleaning solution above the level will reach the piston inside the chamber 180. When it continues to move upward, it cannot be drawn from the reservoir 196.

To complete the cycle of pump 178, stepper motor 212 moves piston 2 06 downwardly within the chamber 180. One way valve 198.20 4 prevents backflow into conduit 194.200. As a result, the lower part of the pump chamber 180 The cleaning solution in the section passes through conduit 186 and one-way valve 188 to conduit 10. 8 (FIG. 4) and is first extruded into a capsule 14. Is the cleaning solution in chamber 180? Once released, the room air then passes through conduit 186 and valve 188. The capsule 14 is extruded. As already mentioned, the water passes through the hydrophobic filter 22. The flowing air causes the filter 22 to become hydrophobic.

Thus, pump 178 of FIG. The air pump 11 is to provide both cleaning solution and compressed air to the air pump 14. 8, replacing peristaltic pump 124 and valves 126, 128, thereby The system 10 of FIG. 1 is simplified.

Several modifications to various aspects of system 10 may be utilized. For example, an air pump Pump 118 is disclosed to create a pressure differential across filter 22 and first , wetting the filter 22, thereby starting a flow of liquid therethrough, and then , the wet liquid is blown out through the slits of the filter 22, and the filter 22 is Return to sexual state. However, to achieve the same result, a vacuum may be passed through passageway 40. can be drawn out. Further, the solid support is such that the capsule 14 is placed on the rotary table 12. Although initially contained within capsule 14, when placed in The rotary table 14 may alternatively be placed on the rotary table 12. In such cases, fixed The body holder is fed to the capsule 14 by the reagent delivery subsystem 90. It will be present in the system 10 in the form of a slurry. slurry The liquid part is first blown out of the capsule by applying air pressure at a cleaning station. This will be followed by pre-cleaning of the solid support as described above.

The foregoing detailed description is limited in accordance with the appended claims and all equivalents thereof. They are not to be construed as limiting the scope of the invention.

F/θ　6 international search report ANNEX To THI-rNTERNATIONAI-5EARC! (R3 FORT ON

Claims (1)

[Claims] 1. A reaction capsule for performing immunoassays, comprising a first end and a second end. a cylindrical member having an end; and a porous hydrophobic film that closes the first end. and a film made of a liquid substance, the substance being a liquid held within the cylindrical member. The body responds to the application of a pressure difference across the membrane when said membrane is in a hydrophobic state. is discharged through the membrane, thereby creating a flow of liquid through the membrane. , and by flowing gas through the membrane, the flow of the liquid is terminated and the flow of the liquid is terminated. have pores of a predetermined size such that the coating is returned to a hydrophobic state. , reaction capsule. 2. The capsule includes a support rib fixed to the first end, and the membrane is 2. A capsule according to claim 1, supported by said support ribs. 3. The capsule further includes a solid holding means for immunoassay within the cylindrical member. , a capsule according to claim 2. 4. A cylindrical member having a first end and a second end, and closing the first end. a membrane made of a porous hydrophobic substance; solid retention means for analysis, wherein the substance is contained in the cylindrical part. The liquid retained within the material increases the pressure across the coating when the coating is in a hydrophobic state. is expelled through the membrane in response to the application of a force difference, thereby causing fluid to flow through the membrane. of the liquid by creating a flow of the liquid and flowing the gas through the film. at a predetermined distance such that the flow is terminated and the coating is returned to its hydrophobic state. a reaction capsule having a narrow slit; means for directing liquid into said capsule above said membrane; and means for directing liquid through said membrane. means for creating a pressure difference sufficient to cause means for flowing a gas through the coating to return the coating to a hydrophobic state; Immunological analysis system. 5. A rotary table that supports multiple reagent capsules and a vortex effect inside the capsules. and eccentric means for displacing said rotary table to produce The device according to item 4. 6. The means for guiding the liquid and the means for flowing the gas include a pump, and the pump: a lower end and an upper end, the lower end being closed and the capsule A cylinder formed to be in fluid connection with a lower liquid inlet and an upper gas a piston movable within said cylinder; and a stroke including said upper inlet. 4. The system according to claim 4, further comprising means for displacing the piston at a Mu. 7. Place the solid support, patient sample, and labeled material on the lower edge. adding it to a reaction capsule having a hydrophobic coating on the part; causing an immunoassay reaction; applying pressure to the reaction capsule to initiate liquid flow through the membrane; and, flowing a gas through the coating to return the coating to a hydrophobic state; Immunoanalytical methods, including. 8. When the membrane is in a state where it does not conduct fluid, introducing a cleaning solution into the capsule. 8. The method of claim 7, further comprising the step of: creating a pressure differential across the membrane to initiate a flow of cleaning solution through the membrane; to give out, flowing a gas through the coating to return the coating to a hydrophobic state. The method described in item 7 of the scope of the request. 9. Furthermore, adding a liquid matrix to said capsule, in said capsule, to cause a reaction that creates a specified substance, A pressure differential is applied across the membrane to initiate the flow of liquids and substances through the membrane. to create Collecting the substrate and substances in a cell, prior to determining the characteristics of the patient sample. 9. The method of claim 8, comprising measuring the amount of the substance in the cell. 10 A method of using a hydrophobic film, the hydrophobic film being applied to the open end of a container. directing liquid into said container; creating a pressure differential across the membrane such that liquid flows through the membrane; and, flowing a gas through the coating to return the coating to a hydrophobic state; A method using a hydrophobic film, including 11 Pre-selected matrix with pore sizes ranging from 10 to 20 microns. Selecting the coating from a material comprising trix tetrafluoroethylene. 11. The method of claim 10, comprising: 12 The step of creating a pressure difference makes the pressure inside the container lower than the pressure outside the container. 12. The method of claim 11, comprising increasing.