GB2083616A - Monitoring chemical reactions photoelectrically - Google Patents

Abstract

A fixed carrier holds an annular array of cuvettes (32), and a plurality of photometric detectors (52) are mounted on a rotor to move along a concentric circular path so that radiation passing through each of the cuvettes is monitored by each photometric detector during one revolution. There may be a plurality of light sources (50) or a single common source for the detectors (fig 4, not shown). The photometric detectors can operate at several different wavelengths. Many different chemical reactions can be monitored at the same time. Detector signals are converted into digital signals proportional to absorbance and transmitted from the moving assemblage to a stationary receiver, e.g. as a pulsed train of light signals by optical transmitters and receivers (110-116) or by slip rings (not shown). <IMAGE>

Description

1

SPECIFICATION

Apparatus for monitoring chemical reactions This invention relates to apparatus for monitoring 70 chemical reactions.

Many chemical reactions, for example enzyme 7eactions, require from a few seconds to many minutes to be completed and, during such kinetic reaction time, it is often importaritto observe the progress of the reaction by making measurements several times. One form of measurement is ascertaining the absorbance of electromagnetic radiation of a particular wavelength by the anaiyte. Typically enzyme reaction measurements have been accomplished by batch handling methods and apparatuses requiring a considerable amount of preparation and manipulation by the laboratory technician. The nature of the process cannot help but result in rela- tively low throughput.

It is an object of the invention to provide improved apparatus for monitoring chemical reactions.

The present invention provides:

Apparatus for monitoring chemical reactions occurring in a plurality of liquid or the like sample substances carried by a plurality of respective sample support members and which produce an optical effect when exposed to radiant energy which comprises, A. a support structure, B. a sample support member carrier disposed in a first plane and having a plurality of sample support members disposed thereon in a circular array around the periphery of the carrier and the array hav- ing a central axis normal to said first plane, the sample support member carrier being nonrotatably mounted on the support structure, C. a rotor disposed paral let with the sample support member carrier and mounted for rotation on said axis.

D. a plurality of photometers arranged on said rotor and each including a photoresponsive element and there being radiant energy source means serving all ofthe photoresponsive elements and direct- ing a beam of radiant energy to each ofthem whereby there is at least one beam for each element, each beam having a fixed orientation relative to its associated photoresponsive element that is maintained at all times during rotation ofthe rotor, the source means and elements being geometrically arranged in a radial configuration around the rotor, and the beams being so located that each will be intercepted by all the sample support members in sequence during rotation ofthe rotor, E. means for driving the rotor in a rotary movement, F. the photoresponsive elements being responsive to the beams to produce electrical signals when intercepted by sample support members, the signals being related to the chemical conditions of sample substances, if any, carried by the respective sample support members, G. means for generating usable data from any such signals associated with said support structure and nonrotatabie carrier and nonrotatable carrier GB 2 083 616 A 1 and H. means for coupling the signals from the rotorto said last mentioned means.

The sample support member carrier can be wholly removable from the support structure to enable replacement thereof by another such carrier.

The source means can comprise a single lamp in the center of the rotor and each beam can emanate from said lamp.

The source means can comprise a lamp associated with each photometer, the movement of the rotor resulting in the sample support members being brought into intercepting relationship between the beam of the lamp and the photoresponsive element of each photometer.

An. A/D converter can be mounted on said rotor between each respective photoresponsive element and said coupling means whereby the photoresponsive elements pass analog signals while said coupl- ing means pass digital signals.

Each sample support member can comprise a cuvette having at least one wall which is capable of transmitting radiant energy, said cuvette can'be adapted to hold a liquid sample and each beam of radiant energy can be arranged to pass through said wall and at least through a portion of the liquid sample, if any, in said cuvette and thence to the photoresponsive element associated with said each beam.

Said first plane can be horizontal and said axis can be vertical.

A second wall of each cuvette opposite said one wall can also be capable of transmitting radiant energy and the photoresponsive element of each beam can be arranged to receive the radiant energy from each second wall in sequence as the rotor is rotated.

Each beam, its associated photoresponsive element and the source means serving said photoresponsive element can be in rectilinear alignment. The said carrier can have a plurality of openings arranged in a circle about said axis and said sample support members can be removably engaged in said openings to form said circular array.

At least one of said sample support members can comprise at least one wall capable of transmission of said radiant energy for impingement of said sample substance and measurement of the resulting interaction by said photoresponsive element.

It is to be noted that according to the invention the sample support member is nonrotatably mounted on the support structure. To give an example of such an arrangement we now quote from Patent Application No. 2,000,284 which described both rotatablymounted and non- rotatably mounted support member carriers. The present application is, of course, a divisional application of Patent Application No. 2,000,284.

The specific description of Patent Application No. 2,000,284 reads as follows:

By way of example only, certain illustrative embodiments of the invention will now be described with reference to the accompanying drawings in which:

Figure 1 is a perspective, somewhat diagramma- tic, view of a complete apparatus embodying the 2 GB 2 083 616 A 2 invention; Figure 2 is a fragmentary perspective view of a euvette turntable and a photometer rotor illustrating one form of photometer means, portions being shown in section and other portions being broken 70 away; Figure 3 is a median fragmentary sectional view through the data generating components of the apparatus further detailing the embodiment of Fig- ure2; Figure 4 is a view similar to that of Figure 3, but detailing a second form of photometer means and a second form of data transmission arrangement; Figure 4a is a fragmentary view of a portion of Figure 4 but illustrating a modified form of the inven- 80 tion utilizing a split beam arrangement; and Figure 5 is an electrical block diagram primarily of the portions of the apparatus concerned with the generation and transmission of digitized absorbance data.

The drawings show apparatus for monitoring repeatedly the absorption of electromagnetic radiation by a plurality of specimens occurring during a period of time. More particularly, apparatus by which each of a plurality of samples provides a plurality of aliquots which can be subjected to chemical reaction with different reagents. The absorbance of each aliquot repeatedly is measured during a predetermined reaction time. The inputting of the sam- ples, obtaining their aliquots, selecting and adding of reagents, and the absorbance measuring all can be effected in a continuous mode as well as a stat and a batch mode of operation. The term---aliquoC as employed herein is a noun meaning a portion of a sample.

Apparatus described hereinafter is well suited for the measurement of kinetic reactions such as useful in enzyme analysis as well as end point measurement. Many chemical reactions require from a few seconds to many minutes to be completed and, during such kinetic reaction time, it is often important to observe the progress of the reaction by making measurements several times. One form of measurement is ascertaining the absorbance of elec- tromagnetic radiation of a particular wavelength by the analyte.

The present apparatus reduces the limitations found in the prior art, while at the same time providing increased measuring accuracy and testing ver- satility, especially for monitoring kinetic reactions. Apparatus is provided which operates in the continuous mode and in which photometer means pceferably comprising a plurality of photometric detectors, (but which can comprise a single photometer) continuously scan an array of cuvettes that is being indexed at a slower speed around a preferably circular path. As employed herein, 'Index" is a verb which encompasses both stepping and continuous or smooth movement.

In one embodiment, the photometer means include a plurality of radiation sources and radiation detectors of the photo-responsive type that are respectively mated. Each source is aligned with its associated detector in a fixed orientation that is maintained at all times during rotation of the rotor which carries the photometer means, the axis of alignment lying on a radius of the rotor and also lying on a radius of a cuvette-carrying turntable that is mounted for rotation coaxial with the rotor. The axis of alignment is such as to intersect a circular array of circumferentially arranged cuvettes mounted on the turntable, there being a clearspace between each source and its associated detector through which the circular array of cuvettes passes without mechanical interference.

In another embodiment, the photometer meam comprise a single rotating radiation source in the center of the rotor which radiates its beams of radfation to an array of axially arranged detectors spaced around the rotor. The photometer means define radial optical trains including a clear area, these trains sweep circular areas concentric with the array of cuvettes carried by the turntable about the axis where the single light source is positioned. The cuvettes pass through the clear area of each train; the alignment of the light source relative to its associated detector never changes because the light source is fixed relative to all of the optical trains. On this account during one rotation of the rotor and its detectors there will be a plurality of scannings of each cuvette, specifically, each of the photometers will scan every cuvette. For example, if there are eight photometric detectors each cuvette will be scanned eight times and there will be provided eight measurements of absorbance. This, of course is true for both of the embodiments mentioned, that is, where there is a single light source or a plurality thereof. The cuvette turntable will normally be moving at a very slow speed, enabling the aliquots to be loaded and unloaded continuously, say of the order of a fraction of a revolution a minute. The rotor carrying the photometer means on the other hand will be rotating at a relatively higher speed, say of the order of 500 to 1000 revolutions per minute. The amount of information which can be gathered in a very short time is clearly quite voluminous. When it is appreciated that the photometric detectors are preferably operated at different wave lengths, for example by using different filters in their respective optical 11.0 trains, then it becomes clearthat not only is the quantity of information gathered voluminous but that information is made up of many different kinds.

The movement of the rotor is continuous while the movement of the turntable is preferably intermittent, 1 T5 that is, stepped. The apparatus is programmed in such case, by suitable electronic circuitry, to make the measurements of absorbance while the cuvettes are not moving but are in a dwell period. This is more easily accomplished than attempting to have the turntable moving at a continuous slow speed and programming the photometers to do their scanning for short periods of time while the cuvettes are aligned with the respective photometer trains during rotation. A structure of this lattertype is, however, a possible alternative.

Where the materials comprising the samples to be measured by the apparatus comprise sources of radiation in and of themselves, being luminescent, fluorescent or radioactive, the light source is not required. The source in such case can be turned off 3 or blocked.

The amount of radiation transmitted by each specimen or aliquot carried in the cuvettes is detected on each scan and is converted into a digital value proportional to absorbance by means of an electrical circuit which includes an A/D converter. The A/D converter of each photodetector is carried by the rotor itself adjacent to the photodetector thereby economizing in connections and rendering transmission from the moving rotorto the fixed portion of the apparatus relatively simple. The digital value is transmitted from the photometer rotor by suitable means coupling the rotating part with the fixed part of the apparatus. One embodiment includes a light emitting diode and another has slipring means. The signals are transmitted to a receiver which is stationary and thence to suitable storage or processing means. For example, the signals can pass fi rst to a console where they receive routing information from a master control unit that governs the programming and operation of the entire apparatus.

The apparatus is arranged to provide end point information as well as information on kinetic reac- tions.

The apparatus has an important advantage in that the relationship between the light source and photodetector in every case is geometrically fixed so that there can be no variation during rotation of the rotor.

Since the turntable of cuvettes is mounted on the same axis any slight eccentricity which exists by reason of construction or develops during use has no practical effect on measurements made.

The apparatus measures progressively the absor- bance 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 Aquots 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 orienta- tion 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 bythe 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 con- verted electrically into a digitized value proportional to absorbance and is transmitted digitallyfrom the moving assemblage of photometric detectors, cuvettes and electrical components to a stationary receiver. In one embodiment, the digital transmis- sion 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 mechan65 isms as well as cuvette laundry means can be pro- GB 2 083 616 A 3 vided as part of the complete apparatus.

Referring to Figures 1 and 5 which are somewhat diagrammatic, an apparatus embodying the invention comprises a control console 10 and a chemistry processing portion 12. Input information, concerning each sample and the different chemical tests to be performed on aliquots of each specific sample, can be supplied by way of a keyboard 14 andlor data cards fed into a receiver 16 of suitable data input means 18. The input information then is applied to a master control unit 20, which has many functions, only some of which need be mentioned hereinafter, as those skilled in the art will appreciate from this description the more complete control ambit of this unit. A first function of the master control unit 20 is to feed the input information to a readout unit 22, which includes a visual display 24 and a printer of a tape 26, from which the operator can verify that the input information has been entered accurately.

The master control unit 20 can store a list of com mands pertinent to each of the chemistry tests that the apparatus is capable of performing. Thus, when the input information associates a specific sample with a specific set of tests, and assuming the apparatus has needed diluent and reagents, all that remains to be accomplished bythe human operator is to have placed the sample into an appropriate one of the sample holders 28 in a sample disc 30. Thereupon the master control unit 20 can control the transferring of sample aliquots into cuvettes 32 mounted in an annular array in a turntable which is part of a data generating portion 34. An aliquot and diluent transfer mechanism 36, forms of which are known, accomplishes the transferring, with each required chemistry test being associated with an identified cuvette 32 for that specific sample. As the several aliquots are being dispensed, the cuvette array is indexed forward one step for each cuvette and its associated aliquot. As used herein, "step" and "indexed" include but are not limited to discrete movements, since the cuvette array could be continuously moving slowly.

A reagent supply area 38 has separate reagent containers 40 in a reagent disc 42. First and second reagent dispensers 44 and 46 add appropriate reagents to specific cuvettes as those cuvettes advance around the path of movement of the annular array. The dispensing point of the first reagent dispenser relative to the euvette path is spaced several steps prior to that of the second dispenser 46 so that in this space interval, which corresponds to a known time interval, the first reagent can have reacted with an aliquot prior to the introduction of the second reagent. Some chemical tests may require the addition of reagent from only one of the dispensers.

The aliquot and diluent transfer mechanism 36 as well as the reagent dispensers 44 and 46 are of the type which swing arcuately between the source of fluid 28 or 40 and a cuvette 32. Both when receiving and dispensing fluid the probe of the dispensers moves down into the vessels 28,32 and 40, but is elevated to be able to swing free thereof in an arcuate path.

Between the time and position that the aliquot is dispensed and the first reagent is dispensed there is 4 a distance along the path of the cuvettes during which measurement of the transmittance of the aliquot with its diluent and the cuvette walls can be accomplished. Just prior to the point that each cuvetteis again being positioned beneath the aliquot 70 dispenser mechanism 36 there is a laundry station 48 having probes and mechanisms for removing the reactants, if any, from the cuvette, washing the cuvette and making it usable for receipt of a new aliquot.

The data-generating means 34 are characterized by the presence of a plurality of photodetectors radially arranged around a rotor 56 and comprising a source of radiation such as a lamp 50 and individual radiation detectors 52 which can be photoelectric cells, photomulti pliers orthe like. Each detector 52 can have its own light source 50 as shown in the embodiments of Figures 2 and 3 or there can be a single light source such as the lamp 50 in the embod- iment of Figure 4. (The same reference numerals are 85 applied to the same or equivalent components in the two embodiments).

In the first embodiment the individual lamps 50 are located outboard of the path followed by the cir- cular array of cuvettes, while in the second embodiment the single lamp 50 is located at the axis of the rotor 56.

In both embodiments the photodetector means are wholly carried by the rotor 56. The radiation paths 54 in all events are at most about the radius of 95 the rotor 56 and usually, as for example in the embodiment of Figures 2 and 3, a fraction of the rotor radius. Thus, the path is a few centimeters long and has very few optical elements in the train.

Advantages are principally derived where there is a plurality of photometers mounted on the rotor 56 but some advantages are available if only one photometer is utilized; hence reference to -photometer means" is intended to encompass both con- cepts. It is clear that in a single photometer as compared with a rotor having eight photometers the rate at which data can be gathered would be less forthe single photometerthan for the multiple photometer device, assuming that the number of cuvettes in the turntable and the speed of rotation of the rotor are the same in both cases. A single photometer apparatus can have its rate of data generation increased by increasing its speed of rotation. The capacity of data handling, storage and so on of the data processing means will be dependent upon the amount of data being generated. Likewise the complexity of the data processing means will be related to the variety of data generated. All of these factors and more come into play in the choice of the number of photometers, the speed of the rotor, the wavelengths at which measurements are made, and the chemical reactions which can be handled by the apparatus.

For comparison purposes it is pointed out that the scale of the drawings in Figures 2 to 4 is such that the diameter of the rotor 56 is measured below the location of the lamps 50 in Figure 3 is approximately 30 centimeters so that the total optical path from lamp 50 to the photoresponsive device is less than about 2 centimeters in the embodiments of Figures 2 and 3 GB 2 083 616 A 4 and less than about 8 centimeters in the embodiment of Figure 4.

The circle of cuvettes 32 carried on the disc or turntable 74 rotates on the axis 58 which is also the axis of rotation of the rotor 56. Thus, the cuvette array and the photometers are concentric. The mounting and driving means for the rotor 56 and the turntable 74 will be detailed with reference to Figures 2 to 4; however operational, timing and position relationships can be considered with reference to Figure 1. As mentioned above, the rotor 56 in Figures 2 to 4 may be considered to have a diameter of about 30 centimeters which indicates a scale of roughly half- size in those Figures. Figure 1 is illus- trated at about one-fifth full size. In neither case is this intended to be limiting since the invention has broad application to.many different forms and sizes of apparatus.

It will be apparentfrom the foregoing that during its complete circuit of movementfor a single revolution of the turntable 74 any given cuvette 32 will have had its aliquot subjected to fluid processing, chemical reaction and measurement, and as well will be prepared to receive a new aliquot for the repeti- tion of the cycle. The path of the cuvettes is a circle in the apparatus which has been illustrated and will be described as such, but modified forms are possible.

The turntable 74 is indexed at a relatively slow rate, making a total of about five to twenty revolutions per hour, with the periods of dwell somewhat longer than the periods of movement. This speed is said to be relatively slow in contrast to the speed of the rotor 56 with its photometers which will be normally rotating at a speed of as much as several hundred revolutions per minute. Thus, for each dwell period, at which time the measurements are preferably programmed to be taken, there can be many rotations of the rotor taking place with the corresponding number of measurements being made by all photometers of all cuvettes. Preferably there should be a minimum of one revolution of rotor 56 per dwell period.

In this way, many time spaced photometric measurements of the reaction in any specific cuvette can be made, recorded andlor stored for data processing in a single circuit of the cuvette path, that is, during one revolution of the turntable 74. The described mode of processing and endpoint determination can readily be effected in this period of time, not only for the aliquot in the single cuvette 32 but for a continuous number of aliquots being added to and removed from the cuvettes 32 of the turntable 74.

If there are 120 cuvettes 32 mounted on the turntable 74 and the turntable is indexed once every six seconds, one full circuit is achieved as a single revolution of the turntable 74 relative to the housing carrying the data generating components 34 every twelve minutes. If the rotor 56 and its eight photometers rotate arcund the axis 58 at a speed of one revolution every six seconds, this is a relatively slow speed of ten revolutions per minute or 120 revolutions of the rotor 56 for each revolution of the turntable 74. if we assume that measurements are being made at ail times, each cuvette 32 of the array on the turntable 74 will be scanned photometrically 960 times in a complete circuit relative to the housing carrying the data generating components, for exam ple, relative to the point where the aliquot has been inserted. If the speed of the rotor 56 is doubled the number of measurements will increase to 1920 times, but it should be appreciated that since this is for only one cuvette and its aliquot, the total number of measurements made in a single revolution of the turntable 74 is of the order of 18,000 forthe slower speed of the rotor 56 and 36,000 forthe double 75 speed mentioned.

Since some of the positions where cuvettes 32 will be located are employed for laundering the cuvettes, some are employed for injecting the aliquot and car rying the same to the reagent insertion location and some can even be employed for agitation, the total number of cuvette positions around the circular path where the measurement or monitoring is taking place is less than the total number of cuvettes. Thus the total number of measurements mentioned above is less than stated by an amount which takes into account the locations needed forthe above mentioned functions. It might be mentioned that monitoring can be continued at every position, if desired, leaving the data processing control means to discard readings which have no significance.

Readings made during periods where laundering is taking place could be equated to blank measure ments and even some information can be acquired from the aliquot in non-reactive condition before the introduction of reagents. Forthe purposes of the dis cussion which follows, it will be assumed that 800 separate photometric measurements can be made on each aliquot where the rotor is rotating at ten revolutions per minute, there are 120 cuvettes, the indexing is taking place at a rate of one revolution of the turntable 74 in twelve minutes, each step of the indexing occurs every 6 seconds and there are sev eral stations along the path of the cuvette array which are occupied by functions that are not con cerned with photometric monitoring.

Since 800 measurement points of a reaction, each measurement being three-fourths of a second apart during ten minutes, may not be required and since certain chemical tests can be monitored better at a specific wavelength, each of the photometers can be provided with a specific filter 60 so that each photo meter can produce radiation and make measure ments at its own wavelength. Assuming that each of the filters 60 is different and information from a specific aliquot in a specific cuvette most valuably can be obtained from only one of the eight photo meters, then there can be obtained from such one photometer one hundred measurements of the reac tion of that one aliquot during the ten minute cycle because there is one measurement every six sec onds. Certainly, if it is desired that a reaction be mon itored more often than once every six seconds, more than one of the photometers can be constructed to operate at the same wavelength.

It is pointed out that the photometers which are illustrated in the drawings are equally spaced around the rotor 56, but other arrangements where the photometers are grouped or spaced unequally are possible. Bichromatic determinations may be GB 2 083 616 A 5 desirable in pairs of photometers very closely spaced.

As known, with the proper choice of reagents, several different reactions can be monitored at the same wavelength; hence, with a capability of several different wavelengths and suitable reagent selection, numerous different tests can be processed by the apparatus. Since all of thecuvettes are being scanned by each of the photometers, the availability of different photometers monitoring at different wavelengths permits aliquot alone as well as a reaction in a cuvette to be monitored by more than one photometer and therefore at more than one wavelength, with the separation of time between monitoring at different wavelengths being threefourths of a second in the illustrated embodiment. It will of course vary pursuant to construction and requirements. Each aliquot need not be monitored at all wavelengths, nor does each sample have to pro- vide aliquots for all tests capable of being achieved by use of the apparatus. The data into the input means 18 and the master control unit 20 can be controlled and programmed in such a manner as to command the execution of only those tests requested for each sample and will employ euvettes only as needed, thereby reducing the total amount required of sample and reagent volumes and making good use of the cuvette positions and the photometer means to increase sample throughput of the apparatus.

The apparatus does not require a fixed set of several tests for each sample even if different ones of the set of tests would not be requested for certain of the samples nor, as is also well known in the prior art, does the apparatus cause empty cuvettes representing "skipped" tests to occupy space in the rotating array on the turntable 74. The just mentioned and other sample processing control functions by the master control unit are carried on a func- 105tion control bus 62, shown in Figure 5.

It will be mentioned at this piont by way of recapitulation and emphasis that the apparatus has great flexibility in being applicable to many choices of testing but without sacrificing economy or th roughput. As mentioned above, each aliquot need not be monitored on all wave-lengths. In addition to this, each sample does not have to provide aliquots for all tests capable of being accompished by the apparatus. Test selection is here achieved without loss of analytical capacity, without wasting any of the aliquots or reagents, without carrying out any unnecessary tests whose data are useless and without skipping any cuvettes. On this account it can be appreciated that the throughput of the apparatus is also not affected by the great versatility of the device.

It may be said of this apparatus that it has true test selectivity without the equivocation of prior automatic chemistry devices in that if a test is not performed in a given cuvette that same cuvette is available for anothertest.

Next, with reference to Figures 2 and 3, the details of the data generating component assembly 34 will be discussed. with some reference also to Figure 4.

As shown, each radiation source 50 and its associ- 6 ated detector 52 are relatively close together and on a line and securely mounted to the rotor 56 and thereby define therebetween the short radiation path 54 of fixed length which lies on a radius from the axis 58. The rotor 56 is arranged to rotate on the axis 58 and is provided with a depending rotary sleeve 64 which is journalled on bearings 66 mounted to the housing base members 68 and 70. Suitable drive means 72 can be coupled to the sleeve 64 to apply the rotational movement to the rotor 56 and its photometers, two of which are illustrated in Figure 3. The photometer components and the short radiation paths 54 therebetween are thus held in fixed orientation with respect to each other and their radial orien- tation with respect to the axis 58. The journalled mounting of the support 56 provides a precision orientation of the radiation path 54 with respect to its distance from the axis 58, such distance remaining substantially constant as the rotor 56 is rotated.

The bearings 66 are of any suitable conventional design and construction. The criteria for such bearings are accuracy, smoothness, reliability, in addition to providing the thrust support needed in view of the weight of the rotor 56 and its components.

Radial support requirements in view of the weight and forces generated during rotation of the rotor 56 must also be taken into consideration in choosing the bearings 66.

The construction described together with a judici- ous choice of high quality bearings 66 will result in accurate tracking of the photometers during rotation of the rotor 56 thereby enabling accurate and repetitively identical photometric measurements to be taken during operation of the apparatus. Nothwith- standing precautions taken to assure accurate tracking and elimination of any eccentricity during rotation, some eccentricity during this rotation will not adversely affect accuracy.

The annular array of cuvettes 32 is mounted on the turntable 74 as explained. These can be removable cuvettes orthe turntable can be molded or otherwise formed with the cuvettes 32 permanently attached thereto. The turntable 74 is journalled for rotation on the same axis 58 as that of the rotor 56 and the disposi- tion of the turntable is above the rotor 56 so that access may be had to the entrances to the cuvettes 32 from above, as will be explained. The array of cuvettes extend downwardly from the body of the turntable 74 which is somewhat disc-like or planar in character, defining an annular ring path through which all of the cuvettes travel during rotation of the turntable 74. This ring intersects all of the radiation paths 54 of the photometers mounted on the rotor 56. These paths 54 are radially arranged about the rotor 56 and in the case of the very short paths 54 of the embodiments of Figures 2 and 3 the spaces between the filters 60 and the lamps 50 also define a similar ring that coincides with that formed by the path of cuvettes 32.

The photometers 50-52 are mounted on the upper surface of the rotor 56 in any suitable manner by clamps or brackets or the like or can be mounted on the interior of a thickened disc forming the rotor which can be accurately molded to receive the same.

In such case, a groove or trough or annular config- GB 2 083 616 A 6 uration can be formed in the upper surface of the rotor 56 in annular configuration to receive and clear the depending array of cuvettes during their rotation. The radiation paths can then be arranged to pass through the groove in a radial direction which will enable them to pass unobstructed through the walls of the cuvette where the aliquot being measured is located. The euvettes are made out of some transparent or translucent material and have prop- erly oriented walls that do not refract or scatterthe beam of radiation passing through the same.

The cuvette turntable 74 has a hub with depending collar 76, is centered an the axis 58 and is journalled for rotation by means of bearings 78 thatare mounted between the collar 76 and the sleeve 64, thus permitting the cuvette turntable to be rotated independently of the rotation of the photometer rotor 56. Rotation of the turntable 74 in an indexing mode is effected by conventional means not shown in Figure 3, but illustrated in Figure 4 and discussed with respect thereto. Since the turntable 74 and the photometer rotor 56 are coaxial on the same axis 58, and thecollar 76 of the turntable 74 rotates within the sleeve 64 of the rotor 56, the path of the cuvettes go and the area swept by the photometers are concentric and the cuvettes are caused to intercept the short radiation path 54 of each photometer with highly reproducible positional accuracy thereby promoting accurate photometric measurements without need for complex light guiding arrangements employed in the prior art.

To enhance the continuously smooth rotary motion of the photometer rotor 56 it can be designed with weighted circumferential volume to operate with a flywheel effect. In contrastthe cuvette turntable 74 should be relatively lightweight if the indexing thereof is to be accomplished in steps with dwell periods between steps.

Figure 4 illustrates apparatus including an afterna- tive arrangement of the photometer means 50-52. Such modification and other differences between Figures 3 and 4 will be presented after the discussion of Figure 5, which includes explanation of most of the- operation of the structure.shown in both Figures 3 anc14.

Asshown in Figures 3-5, the electrical outputfrom the radiation detectors 52 is coupled to electrical components for analog to digital conversion and transmission from the data generating component assembly 34to the control console 10 (Figure 1). The electrical components are secured to portions of the rotor 56 and its sleeve 64, by way of circuit components, circuit boardsand connectors such as 80 and 82, so that the electrical components can move along with their associated photometers, during their rotation around the axis 58, without the need for slip rings, commutators orthe like at thesensitive points of the circuit or more complex wiring arrangements. T hie transmission of a large quantity of discrete electrical measurements in the form of analog values ftom a plurality of radiation detectors 52 that is continuously moving presents problems, both mechanical and electrical. It is believed that the need for greater throughput of precise data from many photometers, concerning numerous chemical 7 tests being carried out on a high number of aliquots, is not practically satisfied by the prior technology. The arrangement in Figure 5 provides an efficient, flexible, yet simple and preceise mode of data 5 transmission, Commencing with the top left of Figure 5, there is shown one of the assemblies mounted on the rotor 56 which will be termed a photometer module 84 including radiation source 50 directing its radiation to pass through the walls of one of the cuvettes 32 and strike the sensitive surface of the detector 52, after passing through the filter 60. The detector can be a silicon diode, a photo m u ltiplier, vacuum photodiode or other photoresponsive device. A few mil- liseconds of scanning time by one of the photometers moving-past an effectively stationary cuvette will be sufficient to obtain the required analog measurement of the radiation incident on the detector 52 to enable eventual calculation of absorption and absorbance. The detector 52 responds to the amount of radiation transmitted through the aliquot in the cuvette and the cuvette walls by generating an electric signal proportional to such amountof radiation. An integrator 86 is connected to the detector and converts the generated signal to an output voltage signal which is proportional to the transmittance of the aliquot. A logarithmic analog to digital converter 88 is coupled to the output of the integrator and generates as its output to a line 90 a digital signal which is a function of the absorbance of the aliquot. For ease of illustration, only one of the eight photometer modules 84 is illustrated, but all eight of the photometer output lines 90 are shown.

Since at one instantaneous position of the con- tinuously moving photometer rotor 56 all eight of the detectors 52 could be respectively receiving radiation which has traversed the samples in eight different cuvettes, a digital multiplexer 92 is connected to all of the photometer output lines 90. The multiplexer operates in typical switching manner under the control of a control unit 94, by way of a control line 96, discretely to transferthe data from each of the log A/D converters 88 to the data control unit on a data line 98. Such data can be handled in the form of binary bits, with one binary word representing the absorbance reading from one cuvette. The correlation of each specific absorbence data word with its aliquot or cuvette identification is accomplished by the data control unit. The means for such identification and coupling same to data control unit are not illustrated. Afterthe data word has been transferred to the data control unit 94, that unit generates a reset command on a line 100 to the appropriate log AID converter 88 to enable that con- verter to receive the next analog signal derived from the next cuvette to be scanned by that one photometer 84.

Each integrator 86 is reset by its A/D converter when its digital word is fed into the multiplexer. A reset line 102 carries that command, usually prior to the resetting of the A/D converter by the data control unit 94. To ensure that the radiation through one euvette does not include radiation from an adjacent cuvette as seen by its integrator 86 the integrator is enabled by a start integrate command line 104 which GB 2 083 616 A 7 is triggered in response to one of various conditions, such as: a timing relationship with the rotor drive means 72, or a positioning of the cuvette relative to the radiation path 54, or the shape of the output signal waveform from the detector 52.

The manner of data input-output handling is related to the sophistication of the data control unit 94 and the size of its memory, if any. For example, by employing a simple data control unit, each instance that a digital word is fed into the data control unit it can be transmitted to the master control unit 20 and be processed therein for receipt by the readout unit 22. The master control unit can have a data storage and correlation capacity as well as the earlier men- tioned function control, instruction and command information. On the other hand, if the data control unit has sufficient storage capacity, at least all data words such as the 960 mentioned which are obtained during one or more rotations of the rotor 56 can be stored therein.

Assuming that each of the photometers 52 is operating at a different wavelength and that a specific cuvette 32 is to be monitored by only the one photometer 52 operating at that wavelength which optimizes the measurement of the specific reaction occurring in that cuvette, then of the 960 data words received by the multiplexer 92 during one cycle or revolution of the photometer rotor 56, only one hundred twenty of those words (for the example described) normally would be needed by the master control unit 20. The determination of which data words are to be employed for data processing is developed from the input information which associates specific samples with specific tests. The master control unit 20 then assigns each specific cuvette to a sample and a test and thereby a specific photometer; whereupon, the data word required from that cuvette for each revolution of the rotor 56 can be identified and related to the data words from the same cuvette 32 obtained from each of the next following rotor revolutions, which preferably totals one hundred twenty revolutions of the photometer rotor 56.

Depending upon the desirable extent of communi- cations between the data control unit 94 and the master control unit 20, the sizes of their memories, the speed of operation of the apparatus, etc. , all of which involve cost, throughput and other factors which influence engineering design, the engineering design can cause all ninety six thousand words to be transmitted to the master control unit for its selection of the needed twelve thousand data words; or, the two control units 20 and 94 can communicate such that only the desired twelve thousand words are transmitted from the data control unit to the master control unit.

The engineering design is influenced by the timing of the transmission of the data words from the data control unit to the master control unit. There may be a finite amount of unused time between the scanning of each cuvette, while the rotor 56 is moving into alignment with the next set of eight cuvettes, and also at the end of each revolution, when the cuvette array is indexed one step. Since the apparatus can operate in the continuous mode, as 8 GB 2 083 616 A 8 earlier described, one revolution can be followed by the next without any significant disruption, as contrasted to the batch mode of operation. Hence, data also can be transmitted in a continuous mode and not stored until some latertime and then dumped into a processing unit. This continuous transmission of data from the data generating component assembly 34 to the control console 10 can be with some control by the data control unit 94, rather than exclusively by the master control unit 20, as abovementioned.

In referring to unused time above, that is, time between the scanning of cuvettes or at the end of a revolution, no limitations on the invention are intended. Thus, it is feasible to measure dark current between cuvette scannings to set the photometer scales. The readings can readily be identified by the control unit and processed as desired and programmed.

Although a continuous operation mode has well known advantages over batch operation, there can be conditions which warrant batch handling. The apparatus can be used in batch processing. For example, the entire cuvette turntable 74 could be in the form of a removable disc to be replaced by one or more similar discs having the cuvettes already filled with aliquots and possibly even reagents, each replacement disc being a batch. If the batch consists of only a few aliquots, the cuvette disc can be constructed in segments and then only a segment or portion of the disc be replaced with a prepared segment of cuvettes. Likewise, a stat or urgently needed test could be "inserted" into the apparatus.

Such a structure would have a turntable like that shown at 74 with a thin plastic disc, perhaps formed by vacuum molding a synthetic resin sheet with the depressions forming the cuvettes, capable of being clamped or snapped onto the upper surface of the turntable. The operation of the apparatus would not be too much different, being required only to enable proper orientation of the replaceable disc to provide sample identification and with some modification which starts and stops the apparatus so that the attendant can remove the used disc and replace it with a new one.

In normal operation such a disc or turnable would not be required to rotate and its cuvettes would be scanned by the plurality of photometers during rotation of the rotor 56. Stepping of the disc or turntable 74 would be useful where the apparatus could be alternated between continuous and batch modes. The removability of the disc on the turntable 74 could be of advantage where stat testing is to be done and it is not desired to integrate such tests in with the routine ones being processed. Stepping could also be of advantage along with removability in a batch mode where the steps carry different sets of filters into the radiation paths.

In a batch method device where the rotor carries a plurality of photometers, such photometers could employ individual lamps 50 for each photodetector 62 or a single central source of radiation serving all photometers.

One possible alternative comprises a fixed or single photometer, the rotor also carrying a filter wheel arranged vertically and intercepting the beam of radiation from the photometer before it passes through the curvettes. The rotor in such case is arranged to stop momentarily at each cuvette and automatically rotate the filter wheel to provide several measurements at different wavelengths that are identified by suitable synchronizing means to be sent to the proper address of the storage or record- ing device through data control means. In this way, the effect of plural photometers is achieved without the need for any duplication of photometers.

It is pointed outthatthe reference to the rotation or revolutions of the rotor 56 is not to be considered limited to movement in one direction since it is feasible forthe rotor 56 to oscillate by rotating substantially one revolution and then reversing itself to rotate a revolution in the opposite direction, etc.

Next, with reference to Figure 5, there will be dis- closed both types of data flow and control; first, that which requires two-way communications between the control units 20 and 94; and second, one-way communications. The latter, although simpler than the former, would require more sophistication and also more storage capacity by the master control unit.

Two-way communications between the master control unit and the data control unit can be accomp lished with the aid of a pair of communications logic units 106 and 108, a pair of transmitters 110 and 112, and a pair of receivers 114 and 116. The elements 106, 110 and 114 would be housed in the rotating portion of the data generating component assembly 34. The corresponding elements 108,112 and 116 would be located in the control console 10 andlor a stationary portion of the assembly 34. A control bus 118 and a data bus 120 link the data control unit 94 with its communications logic unit 106.

In like manner, control and data buses 122 and 124 linkthe master control unit 20 with the communications logic unit 108. Typical of the bidirectional control information on the buses 118 and 122 would be the availability of one or more data words to be written into or read from one or the other or both of the memories in the units 20 and 94 and the availability of the associated logic unit 106 and 108 to receive or transmit such data.

Since the now being described embodiment of the electronics there is to be two-way communications between the data control unit in the reaction table and the master control unit in the control console, the control and data buses 118-124 will be bidirectional as indicated by the arrowheads in Figure 5. Also. the communications logic units 106 and 108 will possess two-way capabilities.

The bidirectional data buses 120 and 124 will carry each data word serially in parallel bit order, but the inputs from the receivers 114 and 116 and the outputs to the transmitters 110 and 112 will be serially by bit. The preferred transmitters and receivers, as illustrated in Figures 3 and 5, respectively are photoemissive and photosensitive. Figure 4 employs a slip ring assembly 110-116; however, other forms of transmission and reception are possible, such as of 65 Indexing turntable with cuvettes and a rotor having a 130 the radio frequency type, and are encompassed 9 GB 2 083 616 A 9 within the general terms and are notto be considered limited by the illustration of the preferred embodiments.

Phototransmission, as by a photodiode, is both simple and well suited to the handling of binary serial bit data and is well known to those skilled in the art. Moreover, photoemission and reception are less subject to interference than radio transmission, especially when the elements 110-116 can be closely 10 spaced.

As shown in Figure 3, the transmitter 110 and receiver 114 are housed within the sleeve 64 and rotate therewith close to the axis 58. The associated elements 116 and 112 are stationary and lie close to the projection of the axis 58 and are wired into the logic unit.108 in the control console 10. - Mounted in such a manner close to axis 58, the factthat the transmitter 110 and receiver 114 are rotating will not cause errors in the binary bit data transmission. On the other hand, if the magnitude of 85 a signal, ratherthan presence or absence thereof, were the measure of the test data and the control commands, then relative movement of the transmitters and receivers could produce transmission errors.

From the foregoing it will be appreciated that for economical use of strage capacity in the master control unit 20 only the desired data words should be transmitted from the data control unit 94. To effect such economy the input information from the data input means 18 will enable the master control unit to establish a listing of the aliquots or their cuvettes from which data is desired. As new samples are added to the sample disc 30, associated input infor- mation fed into the master control unit and old samples complete theirtesting the "desired" listing will be updated continuously. As each data word is received by the data control unit 94 from the multiplexer 92 it will, by two-way communications, be checked with the desired data list and only be transmitted to the master control unit after an affirmative comparison. This communication will require the data control unit and its logic unit to have interchanges on the buses 118 and 120 regarding: the fact that a data word has been received from the mu itiplexer, identification of that word and that the logic units 106 and 108 are ready to communicate that identification information to the master control unit.

In like manner, the master control unit and its 115 buses 122 and 124 with its logic unit 108 will: acknowledge availability to communicate, receive the identification data, provide a comparison reply and then either cause the data word to be discarded by the data control unit or cause it to be transmitted for storage by the master control unit. Each communication will require transmission and receipt by one or the other pair of components 110 and 116, or 112 and 114.

In the other embodied form of data communications, all data words are transmitted from the data control unit 94 to the master control unit 20 and the latter then itself will decide which data words to continue to store for ultimate readout purposes.

Because of this simpler form of communications the data buses 120 and 124 need not only feed in the direction toward the master control unit, the communications logic unit 106 will operate only as a sending unit, the communications logic unit 108 will operate only as a receiving unit and the transmitterreceiver pair of elements 112 and 114 will not be required. The bidirectional control buses 118 and 122 between the control units and their respective communications logic units are required for the purposes above-mentioned.

The differences between the embodiments of Figures 3 and 4 will now be described. First, concerning the photometer means, the radiation source 50 of Figure 4 is located at the axis 58 and comprises a single element tungsten lamp rather than a plurality of lamps positioned around the periphery of the photometer rotor 56 as in Figure 3. The source 50 in Figure 4 is connected to the rotor 56 for rotation therewith.

A plurality of lens-containing optical tubes 126 are mounted to the photometer rotor 56 of Figure 4 such that one end of each tube is proximate to the radiation source 50 and the other end of each tube is close to the annular path or pattern traversed by the cuvet- tes and is aligned with a specific one of the radiation or photometric detectors 52. The photometric detectors 52 are also mounted on the rotor 56 substantially as in the Figure 3 embodiment. The paths or patterns swept by the beams of radiation reaching each detector is in effect the same as in Figure 3.

One advantage of employing a single source 50 is that it is easierto dissipate the heat generated thereby and thus easierto regulate the temperature of the cuvettes 32. Note that in the embodiment shown in Figure 3 the individual lamps are located quite close to the annular ring defined by the cuvette path so that the heat of these lamps could be radiated or transmitted to the materials carried by the cuvettes. The nature of many of the reactions whose characteristics are being measured is such that temperature changes are critical. As a matter of fact, means will often be provided for incubation of the cuvettes during their scanning and the arrangement of Figure 4 enables such structure to be easier achieved and more effective in operation because of the absence of heat sources.

Another advantage of a single source such as in Figure 4 is that there is no problem with different intensities, coiors or wavelengths which can be expected in a plurality of different lamps, even where matched. Whatever happens to the single source lamp 50 happens to all readings made so that the effect is not felt where relative measurements are made. The lamp 50 can be cooled very easily by air circulated in its vicinity in a manner which will not cool, for example, the cuvettes. The power supply for a single source 50 is simpler and more economica 1.

In the views described thus far shown there is a single beam 54 which passes through the euvette 32 and thence impinges upon the photodetector 52 after passing through a filter 60 which is usually in close proximity if not incorporated into the photodetector. In the structure of Figure 4it is feasible to focus the light beam into a very fine pencil for pas- GB 2 083 616 A 10 sage through the lower portion of the cuvettes 32 but in addition it is feasible to incorporate beam splitting means into the focussing tube or outside thereof to provide two beams which may be directed in parallel paths through different levels of the cuvettes for investigating different strata of the analyte. Such a structure is shown in Figure 4a to be described in detail below.

In Figure 4a components equivalent to those of Figure 4 carry the same reference numerals primed. The rotor 56' has a focussing tube 126'which directs a beam 54'derived from a source such as 50 (not shown in Figure 4a) to a semisilvered or dichroic mirror 150 arranged at 45'in front of the tube 126'. A part of the beam passes through the mirror 150 and becomes a bottom beam 54% and another is reflected at 90' upward and thence reflected from the 45'angled mirror 152 to become the upper beam 54'u. These beams pass through different levels of the liquid 154 carried in the cuvette 32' mounted in the turntable 74'which is disposed to move in a path which carries it and its companion cuvettes through the groove 156 provided in the rotor 56.

There are two photodetectors at 52'and 52" mounted on the rotor 56 in suitable cavities aligned with the mirrors 150 and 152, respectively, and thus aligned to receive the beams 54'b and 54'u against their sensitive surfaces. Each is provided with a filter 60'and 60% respectively. Openings 158 and 160 respectively enable the beams to pass.

The beam 54'emerging from the focussing tube 126'splits, part going through a lower stratum of the liquid 154 and part going through an upper stratum of the same liquid. The photodetectors 52'and 52--- are independent, each providing a different signal which can be transmitted through suitable connections to data processing equipment to provide additional information concerning the reaction which may be going on in the cuvette 32'.

Figure 4 shows the drive means for the cuvette turntable 74, which was not illustrated in Figure 3, because of drawing space limitations. A motor 128 has its drive shaft 130 coupled by a pinion gear 132 to a suitably mating configuration 134 on the periphery of the turntable 74. If the indexing of the cuvettes is to be in steps, the motor 128 can be a stepping motor, or there can be provided linkage, clutch means, etc., for providing appropriately timed stepping from a continuously driven motor.

As earlier mentioned briefly, a slip ring assembly 110-116 can provide the receiver and transmitter needs of the apparatus and couple data and other communications from and to the reaction table 34 and the master control unit 20.

supplied to the readout unit 22 without any data reduction, conversion or analysis, such being left to the skill of a technician in interpreting the same. In a preferred mode of operation the master control unit would have the capability of associating the data for each test, obtaining mathematic rate andlor end point determination, then converting that information into a reading of the chemistry value in the desired concentration units for the test, thereafter feeding the results into the readout unit.

Although some variations in structure and operation of this chemical reaction monitoring apparatus have been disclosed hereinabove,. other variations are capable of being made. For example, the prefer- red embodiments teach continuous movement of the photometer rotor; however, a stepping device movement can be employed. Also, the photometer means are spaced around the circumference of their support, since such positioning enables a uniform weight distribution around the support; however, the photometer means could be mounted with variable spacing especially if the path of motion is other than circular. It may be desired to employ disposable euvettes. If so, the laundry station 48 would be

Claims (11)

replaced by means for removing used cuvettes and for inserting clean cuvettes into the cuvette turntable 74. At least in such situation, the cuvettes need not move around a closed path. Reagents need not be liquid but may be dispensed dry. Cuvettes may be used in a disposable mode with the reagent already in p!ace, requiring only the additoin of the aliquot and a diluent. CLAIMS

1. Apparatus for monitoring chemical reactions loo occurring in a plurality of liquid orthe like sample substances carried by a plurality of respective sample support members and which produce an optical effect when exposed to radiant energy which comprises, A. a su p po rt structu re, B. a sample support member carrier disposed in a first plane and having a plurality of sample support members disposed thereon in a circular array around the periphery of the carrier and the array hav- ing a central axis normal to said first plane, the sample support member carrier being nonrotatably mounted on the support structure, C. a rotor disposed parallel with the sample support member carrier and mounted for rotation on said axis, D. a plurality of photometers arranged on said rotor and each- including a photoresponsive element and there being radiant energy source means serving all of the photoresponsive elements and direct- From the above, it now should be understood how 120 ing a beam of radiant energy to each of them the entire apparatus operates with its moving photometer means and preferably in a continuous modeto place into the master control unit 20 the digitized values of the readings related to absor- bance from the data generating components assembly 34. Since reaction can be monitored at frequent intervals during a prolonged period of time rather than a small portion thereof, both rate and end point data are obtainable. Once into the master control unit, the raw data can be associated with each test and whereby there is at least one beam for each element, each beam having a fixed orientation relative to its associated photoresponsive element that is maintained at all times during rotation of the rotor, the source means and elements being geometrically arranged in a radial configuration around the rotor, and the beams being so located that each will be intercepted by all the sample support members in sequence during rotation of the rotor, E. means for driving the rotor in a rotary move- 11 GB 2 083 616 A 11 ment, F. the photoresponsive elements being responsive to the beams to produce electrical signals when intercepted by sample support members, the signals being related to the chemical conditions of sample 70 ment.

substances, if any, carried by the respective sample support members, G. means for generating usable data from any such signals associated with said support structure and nonrotatable carrier and nonrotatable carrier 75 and H. means for coupling the signals from the rotor to said last mentioned means.

2. An apparatus as claimed in claim 1 in which the sample support member carrier is wholly removable from the support structure to enable replacement thereof by another such carrier.

3. An apparatus as claimed in claim 1 or2 in which the source means comprise a single lamp in the center of the rotor and each beam emanates from said lamp.

4. An apparatus as claimed in claim 1 or2 in which the source means comprise a lamp associated with each photometer, the movement of the rotor resulting in the sample support members being brought into intercepting relationship between the beam of the lamp and the photoresponsive element of each photometer.

5. An apparatus as claimed in any preceding claim in which an All) converter is mounted on said 95 rotor between each respective photoresponsive element and said coupling means whereby the photoresponsive elements pass analog signals while said coupling means pass digital signals.

6. An apparatus as claimed in any preceding claim 1 in which each sample support member com prises a cuvette having at least one wall which is capable of transmitting radiant energy, said cuvette is adapted to hold a liquid sample and in which each beam of radiant energy is arranged to passthrough said wall and at least through a portion of the liquid sample. if any, in said cuvette and thence to the photoresponsive element associated with said each beam.

7. An apparatus as claimed in any preceding claim in which said first plane is horizontal and said axis is vertical.

8. An apparatus as claimed in claim 6 or claims 6 and 7 in which a second wall of each cuvette oppo site said one wall is also capable of transmitting radiant energy and the photoresponsive element of each beam is arranged to receive the radiant energy from each second wall in sequence as the rotor is rotated.

9. An apparatus as claimed in claim 8 in which each beam, its associated photoresponsive element and the source means serving said photoresponsive element are in rectilinear alignment.

10. An apparatus as claimed in any preceding claim, in which the said carrier is a plurality of open ings arranged in a circle about said axis and said sample support members are removably engaged in said openings to form said circular array.

11. An apparatus as claimed in any preceding claim, in which at least one of said sample support members comprises at least one wall capable of transmission of said radiant energy for impingement of said sample substance and measurement of the resulting interaction by said photoresponsive eie- New claims or amendments to claims filed on 24 Nov 1981 superseded claim 1. New or amended claim:- 1. Apparatus for monitoring chemical reactions occurring in a plurality of sample substances carried by a plurality of respective sample support members and which produce an optical effect when exposed to radiant energy which comprises, A. a support structure, B. a sample support member carrier disposed in a first plane and having a plurality of sample support members disposed thereon in a circular array around the periphery of the carrier and the array having a central axis normal to said first plane, the sample support member carrier being nonrotatably mounted on the support structure and wholly removable from the support structure to enable replacement thereof by another such carrier, C. a rotor disposed parallel with the sample support member carrier and mounted for rotation on said axis, D. a plurality of photometers arranged on said rotor and each including a photoresponsive element and there being radiant energy source means serving all of the photo responsive elements and directing a beam of radiant energy to each of them whereby there is at least one beam for each element, each beam having a fixed orientation relative to its associated photoresponsive element that is maintained at all times during rotation of the rotor, the photoresponsive elements being circularly distri buted around the rotor, and the beams being so located that each will be intercepted by all the sample support members in sequence during rotation of the rotor, E. means for driving the rotor in a rotary move ment, F. the photoresponsive elements being responsive to the beams to produce electrical signals when intercepted by sample support members, the signals being related to the chemical conditions of sample substances, if any, carried by the respective sample support members.

G. means for generating usable data from any such signals associated with said support structure, and H. means for coupling the signals from the rotor to said last mentioned means.

Printed for Her Majesty's Stationery Office by The Tweeddale Press Ltd., Serwick-upon-Tweed, 1982. Published at the Patent Office, 25 Southampton Ruildings, London, WC2A lAY, from which copies maybe obtained.