Apparatus for performing chemical and biological analysis

Abstract

A system for the automated analysis of large numbers of liquid samples, in which a multiplicity of sample tubes are loaded in racks into a cassette and the loaded cassette is transferred from station to station, with operations of sample insertion, dilution, reagent addition and withdrawal for filtering being performed at successive stations. At each station there is a separate processing module adapted to receive the cassette, each module including the apparatus necessary for performing one of the abovementioned operations on each individual sample tube when it is located at a particular operational location in the cassette. Each module also has members for shifting the racks in the cassette in such manner that all tubes pass through the operational location in turn while strictly maintaining the same order of sequence throughout the operations.

We claim: 
     
       1. Apparatus for analysing a plurality of liquid samples, each sample being in a tube, and comprising a cassette having a shell in which a plurality of such tubes are to be contained in sequence, said cassette having apertures in its walls through which means, operated by apparatus external to the cassette, actuate and advance the tubes sequentially and stepwise past a fixed point, said cassette being freely removable from the operating apparatus, without disturbing the contained tubes, to other locations, the initial sequence of tubes being maintained throughout. 
     
     
       2. Apparatus according to claim 1, wherein the cassette is provided with a lid which occludes the open ends of all the tubes contained in the cassette. 
     
     
       3. Apparatus according to claim 1, wherein the cassette carries racks of moulded plastics in which the tubes are an integral part of the rack. 
     
     
       4. Apparatus according to claim 1 wherein said tubes are arrayed in linear series in substantially rigid racks to be received within the cassette shell, and said actuating means advances the racks with the tubes therein sequentially past said fixed point. 
     
     
       5. In combination with the apparatus of claim 1, liquid analysis apparatus comprising at least one module with means to carry out a physical operation on the liquid samples and with a location to receive a selected one of said cassettes at a time and means to actuate operative elements which advance the tubes inside said cassette sequentially past a fixed point. 
     
     
       6. Liquid analysis apparatus according to claim 5 wherein operations of dispensing, transferring and diluting liquid samples are performed by means of pumps actuated by signals received from a control unit which incorporates an electronic data register, according to a sequence of instructions supplied to the control unit by a human operator in at least one prior operation and which instructions may be varied according to the requirements of analytical protocol. 
     
     
       7. Apparatus according to claim 5, wherein liquid transfer and dispensing operations are performed by pumps with fixed stroke volume, multiples of this fixed volume being transferred by repetitive action of such pumps depending on signals from a control unit with a data register operating on prior instructions. 
     
     
       8. Liquid analysis apparatus according to claim 5, comprising means to transfer radioactive components from a multiplicity of reactions occurring in said tubes simultaneously to a corresponding multiplicity of filters on a continuous tape, photomultiplier devices to convert the radioactivity at a multiplicity of filter sites into signals which are accumulated and counted directly in electronic data registers, the accumulated totals associated with prior instructions being stored at other locations in the register, and means to perform calculations and to transfer the accumulated totals and results of the calculations to appropriate output terminals. 
     
     
       9. In combination with apparatus according to claim 8, a tape of strong flexible plastics material, bearing at appropriate intervals a series of locations where the tape is perforated and where the perforations are surmounted by filter discs adherent to the tape at the margins of the filter discs, said tape additionally having holes or indentations to aid in the .[.correction.]. .Iadd.correct .Iaddend.registration of the tape at operational locations. .Iadd. 10. Analysis apparatus for performing at least two operations on a liquid sample in a sample container comprising first and second support means at respective first and second stations, each support means being adapted to removably receive a cassette having therein a plurality of sample containers, means at substantially fixed points on said respective support means for performing respective first and second operations on the liquid samples in the respective containers, drive means carried by the respective support means and arranged to project into a cassette when on said support means and engage the containers therein for moving the same in a closed path sequentially from an initial relationship to one another past an operation performing means at the fixed points on the respective support means and back to the initial relationship, and means for operating the respective operation performing means upon arrival of a container at each of the respective fixed points. .Iaddend. .Iadd. 11. Apparatus as claimed in claim 10, wherein the first operation performing means is adapted to dispense samples to be analysed into the containers and the second operation performing means is arranged to dispense a reaction medium into each container. .Iaddend. .Iadd. 12. Apparatus as claimed in claim 10, wherein the operation performing means each include at least one pump, and control means are provided for controlling operation of the said at least one pump independently for each station. .Iaddend..Iadd. 13. Apparatus as claimed in claim 12, wherein the pumps have fixed stroke volumes and multiples of the fixed stroke volume of each pump are dispensed by repetitive action of the pump in dependence on control signals from the control means. .Iaddend. .Iadd. 14. Apparatus as claimed in claim 10 including a third station at which a third operation is performed on said liquid samples in said sample containers, the apparatus at said third station including support means and drive means substantially identical to said support means and said drive means at said first and second stations. .Iaddend. .Iadd. 15. Apparatus as claimed in claim 14, wherein the first operation performing means is adapted to dispense samples to be analysed into the containers, the second operation performing means is adapted to dispense a reaction medium into the containers and the third operation performing means is adapted to remove liquid from each container. .Iaddend..Iadd. 16. Apparatus as claimed in claim 15, wherein the third station includes means for filtering the liquid removed from each container. .Iaddend..Iadd. 17. The apparatus of claim 16 wherein the filtering means comprises a flexible tape bearing at intervals a series of locations where at each interval (1) the tape is perforated and where at each interval (2) a filter defined by porous membrane filter material surmounts the perforations and is adherent to the tape at the margins of the filter. .Iaddend..Iadd. 18. A filtration tape for use in radioimmunoassay studies or the like comprising: (a) an elongate carrier tape;   (b) the tape having a plurality of longitudinally spaced filtration locations;   (c) each such location including: (i) a set of perforations each of which perforations extends through the tape, and   (ii) a filter disc overlying each set of perforations and secured to the tape at the margin of the filter disc. .Iaddend..Iadd. 19. A tape as claimed in claim 18, including registration means on the carrier tape. .Iaddend..Iadd. 20. A tape as claimed in claim 18, wherein the carrier tape has holes or indentations to aid in correct registration of the tape. .Iadd. 21. A tape as claimed in claim 18, wherein each filter disc is made of glass fibre. .Iaddend..Iadd. 22. A tape as claimed in claim 18, wherein each filter disc is made of cellulose acetate. .Iadd. 23. A tape as claimed in claim 18, wherein the carrier tape is made of polyvinyl chloride. .Iaddend..Iadd. 24. Portable apparatus for receiving a plurality of linear arrays of sample containers and for permitting circulatory movement of the arrays within the apparatus, the apparatus comprising a rectangular cassette having a base wall and two pairs of opposed side walls defining a space for receiving the arrays, the space within the cassette being divided into two compartments by dividing wall means extending parallel to one pair of opposed side walls and terminating short of each wall of the other pair of side walls to leave a gap, each compartment being adapted to receive a plurality of arrays supported on the base wall and arranged side-by-side, each array extending perpendicular to the dividing wall means and being movable in a direction parallel to the dividing wall means through the respective compartment and from one compartment through the respective gap between the dividing wall means and the respective wall of the other pair of side walls, retaining and guide means for preventing withdrawal of arrays when in the compartments from the compartments and for guiding arrays in their movement through each compartment, and aperture means provided in at least some of the walls for providing access to arrays when in the cassette for means for moving the arrays through the compartments and from one compartment to the other compartment. .Iaddend..Iadd. 25. Apparatus as claimed in claim 24, including a lid for closing the open end of containers when in the cassette. .Iaddend..Iadd. 26. Apparatus as claimed in claim 24, wherein the retaining and guide means are provided along the one pair of opposed side walls and correspondingly on the dividing wall means. .Iaddend..Iadd. 27. Apparatus as claimed in claim 24, wherein the retaining and guide means include a lip extending inwardly of the respective compartment on each of the walls of the one pair of side walls and on the dividing wall means. .Iaddend..Iadd. 28. Apparatus as claimed in claim 24, wherein the aperture means are provided in the one pair of opposed side walls. .Iaddend..Iadd. 29. In combination with the apparatus as claimed in claim 24, other apparatus for performing at least one operation of dispensing, transferring and diluting a liquid sample, the other apparatus comprising means for performing the operation, means defining a location for receiving the cassette, and means for moving the arrays when in the cassette along a predetermined path past the operation performing means. .Iaddend..Iadd. 30. Apparatus as claimed in claim 24, including a plurality of arrays received in the compartments of the cassette, each array being provided with a recess at each end for engagement with the retaining and guide means. .Iaddend..Iadd. 31. Apparatus as claimed in claim 30, wherein the arrays are formed of plastics material. .Iaddend. .Iadd. 32. Apparatus as claimed in claim 30, wherein the arrays define a linear array of receptacles each for receiving a sample container. .Iaddend..Iadd. 33. Apparatus as claimed in claim 30, wherein the arrays provide a linear array of sample containers formed integrally therewith. .Iaddend..Iadd. 34. A cassette for use in apparatus for analysing a plurality of liquid samples, each sample being in a container, said cassette comprising wall means defining a space for receiving a plurality of such containers, said wall means having aperture means therethrough having through which means, operated by apparatus external to the cassette, will in use actuate and advance the containers sequentially and stepwise past a fixed point, said cassette being adapted to be freely removable from the operating apparatus, without disturbing the containers when contained therein, to other locations, the initial sequence of such containers being maintained throughout. .Iaddend. .Iadd. 35. A cassette according to claim 34, including a lid for occluding the open ends of containers when contained in the cassette. .Iaddend..Iadd. 36. Apparatus comprising a cassette according to claim 34 and arrays of moulded plastic racks to be received within the cassette, the containers being an integral part of the racks. .Iaddend..Iadd. 37. Apparatus comprising a cassette according to claim 34 and containers for containing liquid samples, said containers being arranged in linear series in substantially rigid racks to be received in the cassette. .Iaddend..Iadd. 38. In combination a cassette according to claim 34 and liquid analysis apparatus comprising at least one module including: means for carrying out a physical operation on a liquid sample, a location to receive said cassette, and means for advancing containers when in said cassette sequentially past a fixed point. .Iaddend. .Iadd. 39. A method of dispensing a plurality of samples to be analysed and of mixing each sample with a reaction medium, the method comprising, at a first station dispensing a plurality of samples to be analysed into a plurality of containers as they are moved sequentially past a sample dispensing head in a closed path, moving the liquid samples in the containers as a group to a second station, at the second station moving the samples in the containers in the order in which they were dispensed past a reaction medium dispensing head in a closed path, dispensing the reaction medium into the containers, and removing the liquid samples and reaction medium in the containers as a group from the second station. .Iaddend..Iadd. 40. A method as claimed in claim 39, including removing the samples and reaction medium from the containers, wherein the samples and reaction medium in the containers are moved as a group from the second station to a third station and, at the third station the containers containing the samples and reaction medium are moved past a removing head in the order in which they were dispensed and in a closed path. .Iaddend..Iadd. 41. A method as claimed in claim 40, wherein the containers are moved between the stations manually. .Iaddend..Iadd. 42. A method as claimed in claim 40, wherein, between the second and the third stations, the containers are placed as a group in an incubator. .Iaddend..Iadd. 43. A method of mixing a plurality of samples to be analysed with a reaction medium and withdrawing the mixture, the method comprising placing containers containing the samples in a first station, at the first station moving the samples in the containers sequentially past a reaction medium dispensing head, dispensing reaction medium into the containers, moving the containers as a group from the first station and placing them in a second station, at the second station moving the sample containers sequentially past a sample withdrawing head in the same order as that in which the sample containers moved through the first station, and withdrawing the samples and reaction medium from the containers. .Iaddend..Iadd. 44. A method as claimed in claim 43, wherein the sample mixtures withdrawn from the containers in the second station are filtered and the components retained by the filter means are analysed. .Iaddend. .Iadd. 45. A method as claimed in claim 44, wherein the reaction medium is radioactive and the radioactivity of the filter means is determined. .Iaddend. .Iadd. 46. Analysis apparatus for performing at least one operation on a liquid sample in a sample container said apparatus comprising support means for removably receiving a cassette having therein a plurality of sample containers, means for performing the operation disposed at a substantially fixed point on said support means, drive means carried by said support means and arranged to project into a cassette on said support means and engage the containers therein for moving the same in a closed path sequentially from an initial relationship to one another past the operation performing means at said fixed point and back to the initial relationship, and means for operating said operation performing means upon arrival of a container at said fixed point. .Iaddend..Iadd. 47. Apparatus as claimed in claim 46 wherein the support means comprises a base module, said base module being one of a plurality of substantially similar base modules, each being adapted to removably receive a cassette transferred thereto from another of said base modules. .Iaddend. .Iadd. 48. A method of performing at least two operations on a liquid sample in each of a plurality of liquid sample containers, the method comprising arranging the sample containers in a predetermined sequence in a portable cassette, removably positioning the cassette at a first station adjacent means for performing a first operation, moving the liquid sample containers in a closed path in the cassette sequentially past the first operation performing means, performing the first operation on the containers, moving the cassette with the liquid sample containers as a group therein from the first station and positioning them in a second station adjacent means for performing a second operation, moving the liquid sample containers in a closed path in the cassette sequentially past the second operation performing means, performing the second operation on the containers, and moving the cassette with the liquid sample containers as a group therein from the second station. .Iaddend. .Iadd. 49. Filtration means for use in radioimmunoassay studies or the like comprising:     (a) a strong flexible tape bearing at intervals a series of locations where at each interval: (i) the tape is perforated; and where at each interval   (ii) a filter disc defined by porous membrane filter material surmounts the perforations and is adherent to the tape at the margins of the filter disc. .Iaddend. .Iadd. 50. Filtration means as claimed in claim 49, including registration means on the carrier tape. .Iaddend..Iadd. 51. Filtration means as claimed in claim 49, wherein the carrier tape has holes or indentations to aid in correct registration of the tape. .Iaddend..Iadd. 52. Filtration means as claimed in claim 49, wherein each filter disc is made of glass fibre. .Iaddend..Iadd. 53. Filtration means as claimed in claim 49, wherein each filter disc is made of cellulose acetate. .Iaddend..Iadd. 54. Filtration means as claimed in claim 49, wherein the carrier tape is made of polyvinyl chloride. .Iaddend.