Apparatus for monitoring chemical reactions and employing moving photometer means

Abstract

Apparatus for measuring progressively the absorbance changes of a large number of aliquots from a plurality of different samples. The sample introduction, testing instructions, aliquot preparation, reagent dispensing, absorbance measuring and data recording all can be accomplished in a continuous mode of processing. Stat and batch operation also can be accomplished. The aliquots are in an array of cuvettes which is advanced slowly along a circular path. Photometer means, preferably having several photometric detectors, are mounted in fixed orientation on a common support that advances rapidly along a similar circular path, such that radiation passing through each of the cuvettes is monitored many times by a specific photometric detector by the time that cuvette completes one circuit of its path. The photometric detectors can operate at several different wavelengths. Many different chemical reactions can be monitored at the same time. The radiant energy passing through each cuvette is received by the continuously moving photometer means, is converted electrically into a digitized value proportional to absorbance and is transmitted digitally from the moving assemblage of photometric detectors, cuvettes and electrical components to a stationary receiver. In one embodiment, the digital transmission is in the form of a pulsed train of light signals. In another embodiment, one or more slip rings transmit electric signals from the moving assemblage to the stationary portion. Suitable drive elements, sample and reagent storage and transfer mechanisms as well as cuvette laundry means may be provided as part of the complete apparatus.

What it is desired to secure by Letters Patent of the United States is: 
     
       1. Apparatus for monitoring chemical reactions occurring in a plurality of liquid or the like sample substantances carried .[.in.]. .Iadd.by .Iaddend.a plurality of respective .[.cuvettes whose wallS are at least to some extent capable of transmitting .]. .Iadd.sample support members, said sample substances and support members being capable of producing an optical effect when exposed to radiant .Iaddend.energy which comprises: A. support means,   B. a rotor mounted on said support means for rotation thereon on an axis,   C. a turntable mounted coaxially with the rotor for rotation relative to said support means, a plurality of .[.radiant energy transmissive cuvettes.]. .Iadd.sample support members .Iaddend.mounted to the turntable and disposed in a circular arrangement coaxially with said axis and adapted to have sample substances producing chemical reactions carried .[.in.]. .Iadd.by .Iaddend.at least some of said .[.cuvettes.]. .Iadd.sample support members.Iaddend.,   D. first drive means for rotating the turntable on its axis in a first program of rotation whereby the .[.cuvettes.]. .Iadd.sample support members .Iaddend.describe an annular path as the turntable rotates,   E. second drive means for rotating the rotor on said axis in a second program of rotation in which the number of total revolutions of the rotor for a given period of time is greater than the number of revolutions of the turntable for the same period of time,   F. photometer means mounted on the rotor and defining at least one beam path for radiant energy which extends at least .[.through.]. .Iadd.toward .Iaddend.said annular path such that the beam path includes and traverses at least a portion of the sample substance which may be contained in any of said .[.cuvettes.]. .Iadd.sample support members .Iaddend.which intersects such beam path during rotation of the turntable .Iadd.will be exposed to said beam when so intersected and produce an optically changed beam leaving said sample support member.Iaddend.,   G. the photometer means including means responsive to any radiant energy projected along said beam path to produce electrical signals as the .[.cuvettes.]. .Iadd.sample support members .Iaddend.intersect the beam path, which signals are related to chemical conditions of the sample substances, if any, which may be contained in said .[.cuvettes.]. .Iadd.sample support members.Iaddend., there being two radiant energy detectors and means for dividing the beam path into two parts and directing the parts through different strata of the .[.cuvettes.]. .Iadd.sample support members.Iaddend.,   H. means for generating usable data from any such signals, and   I. means for coupling at most all of the electrical signals from said photometer means to said data generating means.   
     
     
       2. In apparatus for monitoring chemical reactions, a plurality of .[.cuvettes.]. .Iadd.sample support members .Iaddend.adapted to have respective liquid or the like samples contained therein, the chemical reaction of which it is desired to monitor, photometer means including a beam path for radiant energy adapted to intersect and .[.pass through .Iadd.and scan .Iaddend.all of the .[.cuvettes.]. .Iadd.sample support members .Iaddend.to provide respective electrical signals related to the chemical reactions occurring in the respective .[.cuvettes.]. .Iadd.sample support members.Iaddend., and means for generating data based upon and responding to said signals, the invention comprising a photometric detector means constructed and arranged as part of the photometer means for generating the electrical signals and also means to cause movement of both said .[.cuvettes.]. .Iadd.sample support members .Iaddend.and photometer means relative to each other and also relative to a reference location, said movement means comprising: first movable carrier means having the photometer means mounted thereon and arranged to cause the beam path to trace a certain first repetitive pattern during movement thereof,   second movable carrier means having the .[.cuvettes.]. .Iadd.sample support members .Iaddend.mounted thereon and arranged to cause the .[.cuvettes.]. .Iadd.sample support members .Iaddend.to trace a certain second repetitive pattern during movement thereof, said first and second movable carrier means both having drive means for their independent moving,   the first and second repetitive patterns being geometrically related to one another such that there is a significant portion of each which coincide, such that when the photometer means moves through said significant portion it will scan the .[.cuvettes.]. .Iadd.sample support members .Iaddend.which are simultaneously located thereat and the photometric detector means will generate the related electrical signals, the speed of movement of the first carrier means being substantially greater than that of the second carrier means to an extent that each .[.cuvette.]. .Iadd.sample support member .Iaddend.moving through said coincident portion will be scanned at least once by said beam path during its presence in said coincident portion, said photometer means including means providing an output proportional to the .[.transmittance.]. .Iadd.optical effect produced upon said beam by the .Iaddend.scanning of the contents of each .Iadd.sample support member .Iaddend.scanned,   photoemissive transmitter and photoresponsive receiver means coupled to receive said output, said transmitter means being mechanically connected for movement along with said photometer means and said receiver means being stationary,   said first movable carrier means being movable about an axis and said transmitter means being mounted proximate to said axis,   a plurality of photometric detectors being mounted to the said first movable carrier means, each photometric detector providing its own digital output, and   output routing and control means by which said digital output is associated with respect to the originating .[.cuvette.]. .Iadd.sample support member.Iaddend., and a chemical reaction test result is obtainable for each .[.cuvette.]. .Iadd.sample support member.Iaddend..   
     
     
       3. Apparatus according to claim 2 in which said output routing and control means have one portion mounted for movement with said photometer means carrier means and is coupled between said photometric detectors and said transmitter means, and there is another portion of said output routing and control means which is coupled to said receiver means, is stationary and includes a master control unit. 
     
     
       4. Apparatus according to claim 3 in which additional transmitter means are coupled to said another portion and transmit to additional receiver means that are coupled to said one portion and are movable therewith for establishing two-way communications between said portions. 
     
     
       5. Chemical reaction monitoring apparatus comprising: A. .[.cuvette.]. .Iadd.sample support member .Iaddend.carrier means,   B. photometer carrier means,   C. a plurality of photometers mounted on the photometer carrier means and including a detector for search photometer and source means of radiant energy also mounted on the photometer carrier means projecting an energy beam to each said detector,   D. the .[.cuvette.]. .Iadd.sample support member .Iaddend.carrier means adapted to have at least one .[.radiant energy transmissive cuvette.]. .Iadd.sample support member responsive to radiant energy .Iaddend.carried thereby and said .[.cuvette.]. .Iadd.sample support member .Iaddend.adapted to .[.have a liquid.]. .Iadd.carry a .Iaddend.sample .[.container therein.]. to enable a condition of chemical reaction therein to be monitored,   E. means for moving the .[.cuvette.]. .Iadd.sample support member .Iaddend.carrier means and the photometer carrier means in a repetitious cycling movement relative to one another so that each beam intersects and .[.passes through and cuvette.]. .Iadd.scans said sample support member .Iaddend.repeatedly once each cycle,   F. means for generating signals relating to said condition and responsive to the outputs of said detectors,   G. means for acquiring usable data from said signals and,   H. said signal generating means including A/D conversion circuitry carried on said .[.rotor and rotating therewith.]. .Iadd.photometer carrier means.Iaddend..   
     
     
       6. The apparatus as claimed in claim 5 in which said A/D conversion circuitry is connected with each photometer carried on said .[.rotor and rotating therewith.]. .Iadd.photometer carrier means.Iaddend.. .[.7. Apparatus for measuring the absorbance of chemical reactions occurring and/or occurred in a plurality of liquid or the like sample substances carried respectively in a plurality of cuvettes which comprises: A. a support structure,   B. a horizontally disposed cuvette carrier having a plurality of cuvettes disposed thereon in a circular array about a central vertical axis, the cuvette carrier being mounted on the support structure, the cuvettes having walls capable of transmitting radiant energy,   C. a rotor horizontally disposed parallel with the cuvette carrier and mounted for rotation on said axis,   D. a photometer secured to said rotor and including a source of radiant energy of a type which said cuvettes are capable of transmitting, a photoresponsive element aligned with the source of radiant energy and adapted to receive a beam of radiant energy emerging from said source, the source and photoresponsive element being arranged such that the beam lies on a radius of the rotor with one of the element and source located inside the circular array and the other of said element and source located outside of said circular array, the rotation of the rotor causing the beam to describe a locus which is an annular disc,   E. the vertical relationship between the array of cuvettes and the locus being such as to cause the disc to intersect the cuvettes at a level where sample substances carried thereby will be traversed by the beam,   F. means for driving the rotor in a rotary movement to cause the beam to intersect all of the cuvettes in sequence, at least once for each revolution of the rotor if the rotor is rotated more than one revolution relative to said array and a proportionally lesser number of times if the rotor is rotated less than a revolution relative to said array,   G. the photoresponsive element being responsive to said beam to produce an analog signal, the signal resulting when the beam passes through a cuvette being related to the transmittance of said cuvette plus the sample substance, if any, carried by said cuvette,   H. means for producing data on the absorbance of the substances through which the beam has passed during rotation of the rotor, said data producing means being associated with the support structure, being nonrotatable and being responsive to digital information,   I. an A/D converter carried on said rotor and connected with the photoresponsive element for converting the analog signals generated by said photoresponsive element into digital information and   J. coupling means including a fixed portion carried by said support structure and a rotary portion secured to said rotor, the rotary portion being connected to the A/D converter to receive the output thereof and the   
     
     
        fixed portion being connected to said data producing means..]. .[.8.  The apparatus as claimed in claim 7 in which the coupling means comprise a slip ring device located at said axis..]. .[.9. The apparatus as claimed in claim 7 in which the cuvette carrier is also mounted for rotation on said axis and drive means are provided to rotate said carrier slower than 
     
     
        the rotor..]. 10. Apparatus for monitoring chemical reactions occurring in a plurality of liquid or the like sample substances carried in a plurality of respective cuvettes whose walls are at least to some extent capable of transmitting radiant energy which comprises: A. support means,   B. a rotor mounted on said support means for rotation thereon on an axis,   C. a turntable mounted coaxially with the rotor for rotation relative to said support means, a plurality of radiant-energy-transmissive cuvettes mounted to the turntable and disposed in a circular arrangement coaxially with said axis and adapted to have sample substances producing chemical reactions carried in at least some of said cuvettes,   D. first drive means for rotating the turntable on its axis in a first program of rotation whereby the cuvettes describe an annular path as the turntable rotates,   E. second drive means for rotating the rotor on said axis in a second program of rotation in which the number of total revolutions of the rotor for a given period of time is greater than the number of revolutions of the turntable for the same period of time,   F. said photometer means are mounted on said rotor and comprise a plurality of photometers spaced about said rotor circumferentially, each photometer having structure defining a beam path for radiant energy disposed radially relative to the axis of said rotor such that all beam paths will extend through said annular path and the cuvettes will intersect all of the beam paths as said rotor rotates and each beam path will traverse at least a portion of the sample substance which may be contained in said cuvettes during rotation of said rotor,   G. each photometer including independent means responsive to its radiant energy beam projected along its respective path to produce electrical signals as the cuvettes pass through the beam, which signals are related to chemical conditions of the sample substances, if any, with regard to all of the beam paths, said means to produce electrical signals of each photometer include an analog to digital converter,   H. means for generating usable data concerning the absorbance of the sample substances from any such signals, said data generating means comprising the following elements in series connection: a digital multiplexer having its inputs coupled to the output of each said converter, means for presenting the digital data concerned with absorbance into serial bit order, and data bit transmitter means, such elements being mounted to said rotor, and said data generating means further comprising the following elements structurally mounted to said support means and connected in series: a data bit receiver, series bit to parallel bit order logic communication means, and a master control unit, and   I. means for coupling all of the electrical signals from said photometer   
     
     
        means to said data generating means. 11. The apparatus as claimed in claim 10 in which the data generating means comprise at least a computing device and the coupling means include receiving structure carried on the support means and providing a fixed communication link between the computing device and the photometers and transmitting structure carried on the rotor and providing a rotating communication link between the computing device 
     
     
        and the photometers. 12. Apparatus for monitoring chemical reactions occurring in a plurality of liquid samples carried in a plurality of respective cuvettes which comprises: A. support means,   B. a generally planar carrier mounted on said support means and having a plurality of radiant-energy-transmissive cuvettes disposed thereon in a generally circular array and adapted to have liquid samples producing chemical reactions respectively held in said cuvettes, each cuvette having a portion freely protruding from said carrier and all cuvettes thereby defining an annular ring projecting from said carrier,   C. a rotor mounted on said support means for rotation on an axis which coincides generally with the center of said circular array and there being drive means for rotating the rotor in a movement parallel to the plane of the carrier,   D. a plurality of photometers mounted on the rotor and each being radially arranged relative to the axis and including source means of radiant energy and a radiant-energy-responsive element spaced apart whereby to define a beam path therebetween, including at least an A/D converter connected to each photometer to process said electrical signals of the radiant-energy-responsive element of said photometer mounted on the rotor,   E. the rotor and carrier being arranged in proximity so that the annular ring is located in the beam paths whereby during rotation of the rotor each beam path will be intercepted by substantially all cuvettes for each rotation of the rotor,   F. the radiant-energy-responsive elements adapted to generate electrical signals respectively related to the absorbtivity of the liquids, if any, contained in the cuvettes which intercept the said beam paths during rotation of said rotor,   G. means for generating usable data from said signals relating to the chemical reactions, if any, in the respective cuvettes, and   H. means for coupling the electrical signals from the rotating photometers to said data generating means. .Iadd. 13. The chemical reaction monitoring apparatus as claimed in claim 6 in which the photometers are arranged so that the beams thereof lie on radii of a circle having an axis and in which the cycling relative movement is rotary about said axis. .Iaddend..Iadd. 14. The chemical reaction monitoring apparatus as claimed in claim 13 in which there is a plurality of sample support members comprising cuvettes arranged in a circle on said cuvette carrier means coaxially relative to said photometer carrier means and the relative movement causes each of the cuvettes to be scanned by all of the beams sequentially. .Iaddend..Iadd. 15. The chemical reaction monitoring apparatus as claimed in claim 13 in which the photometer carrier means is a rotor and during the relative movement at least the rotor rotates on said axis. .Iaddend..Iadd. 16. The apparatus as claimed in claim 5 or 6, in which the said carrier has a plurality of openings arranged in a circle and said sample support members are removably engaged in said openings. .Iaddend. .Iadd. 17. The apparatus as claimed in claim 5 or 6 in which at least one of said sample support members comprises at least one well capable of transmission of said radiant energy for impingement of said sample substance and measurement of the resulting interaction by said detector. .Iaddend. .Iadd. 18. Apparatus for measuring chemical reactions occurring and/or occurred in a plurality of liquid or the like sample substances carried respectively by a plurality of sample support members which comprises:   A. a support structure,   B. a horizontally disposed sample support member carrier having a plurality of sample support members disposed thereon in a circular array about a central vertical axis, the sample support member carrier being mounted on the support structure,   C. a rotor horizontally disposed parallel with the sample support member carrier and mounted for rotation on said axis,   D. a photometer secured to said rotor and including source means of radiant energy of a type which said sample support members are capable of modifying, a photoresponsive element having a fixed geometric relation with the source means of radiant energy and adapted to receive a beam of radiant energy emerging from said source means but after modification through impingement upon a sample support member, the source means and photometer being arranged such that at least the portion of the beam between the source means and the circular array is rectilinear and lies on a radius of the rotor, the rotation of the rotor causing the beam to describe a locus which is an annular disc,   E. the vertical relationship between the array of sample support members and the locus being such as to cause the disc to intersect the sample support members at a level where sample substances carried thereby will be scanned by the beam and will cause said modification of said beam including at least an optical change therein,   F. means for driving the rotor in a rotary movement to cause the beam to intersect all of the sample support members in sequence at least once for each rotation of the rotor if the rotor is rotated more than one revolution relative to said array and a proportionally lesser number of times if the rotor is rotated less than a revolution relative to said array,   G. the photoresponsive element being responsive to said beam after modification to produce an analog signal, the signal resulting when the beam impinges against a sample support member and being related to optical modification caused by said sample support member and the chemical reaction of the sample substance, if any carried by said sample support member,   H. means for producing data on the chemical reaction of the sample subsbtances which the beam has scanned during rotation of the rotor, said data producing means being associated with the support structure, being nonrotatable and beng responsive to digital information,   I. an A/D converter carried on said rotor and connected with the photoresponsive element for converting the analog signals generated by said photoresponsive element into digital information and   J. coupling means including a fixed portion carried by said support structure and a rotary portion secured to said rotor, the rotary portion being connected to the A/D converter to receive the output thereof and the fixed portion being connected to the said data producing means.   
     
     
        .Iaddend..Iadd. 19.  The apparatus as claimed in claim 18 in which a plurality of photometers is secured to said rotor, the source means and said photometers being related in such a manner as to produce a separate beam of radiant energy for each photometer, there being a separate photoresponsive element individual to each photometer adapted to receive one of said beams emerging from said source means but after modification through infringement upon a sample support member, all of the beams lying on radii of the rotor and being rectilinear between the source means and said array, the rotation of the rotor causing all of the beams to describe a locus which is an annular disc, the disc intersecting all of the sample support members at a level where sample substances carried thereby will cause modificatfion of all of said beams including at least optical changes therein, each photoresponsive element being responsive to its respective beam to produce analog signals, each photoresposive element having an A/D converter carried on the rotor for converting its analog signals to digital information and the coupling means being arranged to transmit all of said digital information to said data producing means. .Iaddend..Iadd. 20. The apparatus as claimed in claim 19 in which the sample support member carrier is also mounted for rotation on said axis and drive means are provided to rotate said sample support member carrier slower than said rotor..Iaddend. .Iadd. 21. The apparatus as claimed in claim 20 in which the rotation of the sample support member is a stepping action and the dwell periods of said stepping action occur when there is a sample support member aligned with each beam. .Iaddend..Iadd. 22. The apparatus as claimed in claim 18 in which the coupling means comprise a slip ring device located at said axis. .Iaddend..Iadd. 23. The apparatus as claimed in claim 19 in which the coupling means comprise a slip ring device located at said axis. .Iaddend..Iadd. 24. The apparatus as claimed in claim 18 in which the sample support member carrier is also mounted for rotation on said axis and drive means are provided to rotate said sample support member carrier slower than said rotor. .Iaddend.