Compact Dynamic Multistation Photometer Utilizing Disposable Cuvette Rotor

Abstract

A compact analytical photometer of the rotary cuvette type designed to use small disposable cuvette rotors. A power driven cuvette rotor holder having a generally flat, circular configuration is provided with an integral, upstanding, annular lip for receiving, in an easily insertable and removable fashion, small disposable cuvette rotors. A series of axially extending apertures are disposed in a circular array through the rotor holder in axial alignment with respective cuvettes in the rotor to permit light to be transmitted through the cuvettes as the rotor holder and cuvette rotor rotate between a stationary light source and photodetector. Additional apertures extend through the rotor holder near its periphery to permit light passage through the rotor holder for rotor and cuvette synchronization purposes. Movable rotor and cuvette synchronization detectors are positioned along the periphery of the rotor holder for generating signals which are used to synchronize the photometer output with a computer and to provide rotor speed control. Rapid deceleration of the rotor holder and rotor for sample mixing purposes is accomplished by braking means engaging the rotor holder drive shaft.

Description

BACKGROUND OF THE INVENTION

The invention described herein relates generally to photometers of the rotary cuvette type and more particularly to a compact photometer utilizing disposable cuvette rotors. It was made in the course of, or under, a contract with the U. S. Atomic Energy Commission.

A representative fast photometric analyzer of the rotary cuvette type is described in U. S. Pat. No. 3,555,284, issued to common assignee on Jan. 12, 1971. In the fast analyzer described in that patent, centrifugal force is used to transfer and mix samples and reagents in a multi-cuvette rotor. A stationary photometer scans the cuvettes during rotation. The signals thus generated are evaluated by a computer, allowing the reactions taking place in the respective cuvettes to be observed as they occur. Since all reactions are initiated simultaneously and are coupled with the continuous referencing of the spectrophotometric system of the analyzer, errors due to the electronic, mechanical, or chemical drift are minimized.

Although analyzers built in accordance with the aforementioned patent have been highly successful in that they operate with relatively low sample and reagent volume requirements, have demonstrated a high sample analysis rate, and are subject to automated operation, further improvement is desirable. For example, the cuvette rotor described in that patent is a relatively large and complex structure of glass and polytetrafluorethylene rings sandwiched together and secured between a steel rotor body and bolted flange ring. Such rotors are expensive and must be cleaned between analytical runs to avoid contamination of subsequent samples. Correspondingly large cabinetry, drive motors, etc., must be used with the rotor with the result that the fast analyzer is not truly portable and requires a relatively large amount of valuable laboratory space.

A further reduction in sample and reagent volume requirements is also desirable. Savings of expensive reagents would result from such a reduction in volume requirements. Also, the analyzer could be used in testing applications where it is difficult to obtain a sufficient volume of sample for analysis. For example, a greatly reduced sample volume requirement would facilitate operation in a pediatric laboratory where several analyses could be performed on the small volume of blood obtained from the finger or toe-prick of a newborn infant.

It is also desirable to make the cuvette rotors disposable to avoid the possibility of sample contamination and to permit preloading of standardized reagents. Such disposability would require the cuvette rotor to be simple and inexpensive to construct and easily inserted and removed from the analyzer following an analytical run.

It is, accordingly, a general object of the invention to provide a compact analytical photometer of the rotary cuvette type.

Another, more particular, object of the invention is to provide a compact analytical photometer of the rotary cuvette type which uses small disposable cuvette rotors.

Other objects of the invention will be apparent upon examination of the following description of the invention and the appended drawings.

SUMMARY OF THE INVENTION

In accordance with the invention, a compact analytical photometer of the rotary cuvette type is provided which is especially designed to use small disposable cuvette rotors. A power driven cuvette rotor holder having a generally flat, circular configuration is provided with an integral, upstanding, annular lip for receiving, in an easily insertable and removable fashion, small disposable cuvette rotors. A circular array of axially extending apertures extend through the rotor holder in axial alignment with respective cuvettes in the rotor to permit light to be transmitted axially through the cuvettes as the cuvette rotor and rotor holder rotate between a stationary light source and photodetector. Synchronization apertures extend through the rotor holder near its periphery to permit light passage through the rotor holder for rotor and cuvette synchronication purposes. Rotor and cuvette synchronization detectors are positioned along the periphery of the rotor holder for generating signals which are used to synchronize the photometer output with a computer and to provide rotor speed control. Rapid deceleration of the rotor holder and rotor for sample mixing purposes is accomplished by braking means engaging the rotor holder drive shaft.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a top plan view, partially cut away, of a photometer made in accordance wtih the invention.

FIG. 2 is a vertical section view of the photometer of FIG. 1.

FIG. 3 is an enlarged plan view showing the static loading side of a disposable cuvette rotor for use in the photometer of FIGS. 1 and 2.

FIG. 4 is an enlarged isometric view, sectioned and partially cut away, further illustrating the static loading side of the cuvette rotor of FIG. 3.

FIG. 5 is an enlarged plan view, showing the dynamic loading side of the cuvette rotor of FIGS. 3 and 4.

FIG. 6 is an enlarged isometric view, sectioned and partially cut away, further illustrating the dynamic loading side of the cuvette rotor of FIGS. 3 to 5.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENT

Referring now to the drawings, initially to FIGS. 1 and 2, a compact photometric analyzer is shown in a top plan view and in vertical section, respectively. Rotatably mounted on top of a small, generally rectangular, sheet metal cabinet 1 is a power-driven cuvette rotor holder 2 having a flat, plate-like, circular base 3 with an integral, upstanding, annular lip or rim 4 for receiving and retaining a disposable cuvette rotor 5. Two or more retaining pins 6 (only one shown) are fixed to rotor holder 2 within the confines of lip 4 and engage mating recesses in cuvette rotor 5. Pins 6 prevent relative rotation of the cuvette rotor and rotor holder during operation of the analyzer under conditions of high rotary acceleration, while permitting relatively effortless manual insertion or removal of the cuvette rotor under static conditions. A circular array of apertures 7 extends through base 3 of the rotor holder in axial register with respective sample analysis cuvettes 8 within cuvette rotor 5.

A movable photometric light source 9 provides a light beam of constant intensity interesecting rotor 5 at a point corresponding to the radial positions of sample analysis cuvettes 8. The light beam from source 9, indicated by a broken line in FIG. 2, is aligned in such a manner so as to be transmitted through each aperture 7 and cuvette 8 as they are rotated through the beam. Light source 9 includes a quartz-iodine incandescent lamp 10, a finned lamp housing 11, and a set of focusing lenses 12. Knob 14 is attached to housing 11 to facilitate positioning of the lamp housing during or immediately following analyzer operation when the housing is at an elevated temperature due to the heat generated by lamp 10.

An electronic photodetector 15 is disposed below rotor holder 2 and the top of cabinet 1 where it is positioned to receive light transmitted through sample analysis cuvettes 8 as they pass between the photodetector and light source 9. Photodetector 15 comprises a photomultiplier tube which provides an output signal proportional to the intensity of the light which it receives.

Interposed between photodetector 15 and rotor holder 2 is a movable filter holder 16 which permits the selective positioning of one of a plurality of interference filters 17 in the path of the light transmitted through cuvettes 8. Filter holder 16 is fixed, by means of a set screw, to vertically extending shaft 18 which is rotatably supported by a roller thrust bearing 19 fixed within the base of fixture 20. Fixture 20, which is rigidly fixed to cabinet 1, is slotted to permit angular displacement of filter holder 16 within the limits necessary to align any of filters 17 above photodetector 15. A filter selector knob 22 is fixed to the top end of shaft 18 to enable an operator to manually select the filter desired.

As shown in FIG. 2, a thin-walled tube 23 serve as a mounting post for movable light source 9. Tube 23 is attached to and supported within fixture 20 by means of a set screw and extends coaxially with shaft 18. Rotatably engaging tube 23 immediately above fixture 20 is a first sleeve 24. A second sleeve 25, which serves as a mounting fixture for lamp housing 11, is fixed to first sleeve 24 by set screw means and is rotatable therewith. First sleeve 24 is provided with depressions 26 (only one shown) which are engaged by spring loaded detent 27 when the light source is in operating position as shown or swung away 90.degree. for rotor replacement as indicated in phantom in FIG. 1. Radial adjustment of the light source to align it with the cuvettes is accomplished by loosening set screw 28 and sliding adjustment sleeve 29 within opening 30 in second sleeve 25. An indicator plate 32, which together with filter selector knob 22 shows the position of filter holder 16, is fixed to the top of tube 23 by set screw means. A spring loaded detent in knob 22 engages depressions in indicator plate 32 to provide positive positioning of the filter holder.

Fixed to the bottom of shaft 18 is an index wheel 33 engaging a micro switch 34. Rotation of shaft 13 during a filter selection operation causes a corresponding rotation of the index wheel and activation of the micro switch. This causes a different preset potentiometer to be connected into the photodetector high voltage supply circuit in order to maintain a constant signal from a reference cuvette filled with a water blank. A different preset potentiometer is used for each interference filter 17 in filter holder 16.

An alternative method for maintaining a constant output from the photodetector is described in copending application of common assignee Ser. No. 289,906 filed Sept. 18, 1972. According to that method, the signal level from the reference cuvette is compared with a preset desired level and adjustments to the high voltage photodetector supply made as needed by appropriate control circuitry to maintain the desired output. Drift in the photomultiplier tube and associated circuitry is also compensated for.

The rotor holder and cuvette rotor are rotatably driven by a combination servomotor-tachometer generator 35. A magnetic brake 36 acts on the rotor holder drive shaft 37 to provide rapid braking action to the cuvette rotor to enhance sample and reagent mixing in the cuvettes. Braking from a rotor speed of about 2,000 rpm to a standstill in less than 1 second has been achieved using magnetic brake 36.

Synchronization signals are provided by rotor and cuvette synchronization detectors 38 and 39, respectively. A similarly constructed detector 40 provides a signal for activating the automatic photomultiplier voltage control (not shown). Signals are generated when appropriately spaced apertures in the rotor holder pass through the detectors and allow light from a small tungsten incandescent lamp 41 disposed in the detector above the rotor holder to reach a photodiode 42 disposed in the detector below the cuvette holder. Detector 39, shown in section in FIG. 2, is representative of all three detectors. A circular track 44 for positioning the detectors partially encircles cuvette holder 2. Synchronization may be adjusted by moving the detectors along track 44 until proper synchronization is obtained and then securing them to the cabinet with locking screws.

As shown in FIG. 1, a circular array of synchronization apertures 45 is provided in rotor holder 2 to generate a signal in detector 39 just after each cuvette passes between light source 9 and photodetector 15. Single apertures 46 and 47 cause signals to be generated in detectors 38 and 40, respectively, on each revolution of the rotor holder.

The temperature of cuvette rotor 5 is monitored by means of a thermistor within retaining pin 6 which is positioned to extend between two cuvettes on a common radius with the circular array of cuvettes. The thermistor is further positioned within pin 6 so as to be axially centered within rotor 5. Such positioning provides a close correlation between the output of the thermistor and the temperature of the cuvettes. Slip rings 48 in electrical communication with the thermistor are provided on the rotor holder for reading the signal from the thermistor. The rotor temperature and speed are both read from one meter 49 mounted on top of the analyzer cabinet.

Referring now to FIGS. 3 and 4, the static loading side of the disposable cuvette rotor 5 used in the analyzer of FIGS. 1 and 2 is illustrated in plan and sectioned isometric views, respectively. In construction, the rotor is of laminated design with a central, preferably opaque, plastic disk 51 sandwiched between outer transparent disks 52 and 53. A circular array of axially extending apertures are provided in disk 51 to serve as sample analysis cuvettes 8. Concentric annular arrays of sample and reagent loading cavities 54 and 55 are disposed on a one-to-one basis along radii passing through each cuvette. As shown in FIG. 4, loading cavities 54 and 55 are formed from depressions in central disk 51 and are closed by outer disk 52. Loading apertures 56 and 57 are provided in disk 52 in register with each cavity in the respective arrays of loading cavities. Static loading of reagents and samples through the loading apertures is possible using a hypodermic syringe or automated dispensing equipment. Radial liquid communication is provided by means of small connecting passageways 58 and 59 between respective sets of loading cavities and cuvettes. A central loading port 60 extends through disks 51 and 52 to permit dynamic loading of liquids using the dynamic loading side of the rotor described below in reference to FIGS. 5 and 6.

Plan and perspective views of the dynamic loading side of rotor 5 are shown in FIGS. 5 and 6, respectively. Loading port 60 terminates in a distribution chamber 61 which communicates with cuvettes 8 through radially extending distribution passageways 62 which are of capillary size to retain liquids in the cuvette when the rotor is not spinning. The intersection of passageways 62 creates a saw-tooth or serrated edge effect which provides a substantially equal distribution of liquid into the respective passageways when rotor 5 is rotating and liquid is injected through port 60 into the distribution chamber.

Several methods of loading sample and reagent liquids in rotor 5 are possible. One method involves static loading of individual samples and reagents in respective loading cavities 54 and 55. This is accomplished by inserting the sample and reagent volumes through respective loading apertures 56 and 57. Great flexibility is possible using this method since different combinations of samples and reagents are possible in each set of loading cavities. Rotation of the rotor following static loading effects transfer of the sample and reagent liquids into respective cuvettes for photometric analysis.

Another method of loading may be used where it is desired to either react a plurality of reagents with a single sample or a single reagent with a plurality of samples. In that case, the single sample or reagent is injected through loading port 60 into the spinning rotor and distributed equally to the cuvettes. The rotor is then brought to a standstill and individual sample or reagent loadings are made from the static loading side of the rotor.

Still another method of loading involves the preloading and lyophilization of different reagents in the respective cuvettes. When a photometric analysis is to be made, the lyophilized reagents are solubilized by injecting water or buffer into the spinning rotor in the manner described above. Sample fluid may be likewise dynamically loaded to obtain multiple chemical analyses on a single blood sample.

The above description of one embodiment of the invention should not be interpreted in a limiting sense. For example, the rotor may have a different number of sample analysis cuvettes than the 17 shown. Also, the particular arrangement of passageways for static and dynamic loading could be modified and/or omitted in part so that only static or dynamic loading would be possible. It is intended, rather, that the invention be limited only by the scope of the appended claims.

Claims

What is claimed is:

1. A compact fast analyzer of the rotory cuvette type comprising:

a. a power-driven cuvette rotor holder comprising a flat circular base, an annular, upstanding retaining rim integrally fixed to said base, and an axially extending upstanding pin fixed to said base within the radial confine of said rim; said base defining:

i. a first series of axially extending apertures disposed in a circular array through said base within the radial confine of said rim.

ii. a second series of axially extending apertures disposed in a circular array through said base without the radial confine of said rim, said apertures in said second series of apertures being equal in number to said apertures in said first series of apertures;

b. a removable cuvette rotor having a circular plate-like configuration disposed on said base within the confine of said rim, said rotor having an opening for receiving said pin and, defining a circular array of sample analysis cuvettes in axial register with respective apertures in said first series of apertures;

c. a adjustable light source disposed above said cuvette rotor for providing a beam of light incident on said rotor assembly at a point corresponding to the radial position of said sample analysis cuvettes;

d. means for detecting light from said light source after it has passed through said sample analysis cuvettes, said means for detecting light generating an output signal proportional to the intensity of light detected; and

e. signal generating means disposed adjacent said rotor holder for detecting the passage of apertures in said second series of apertures.

2. The fast analyzer of claim 1 wherein an adjustable filter holder containing a plurality of absorbance filters extends between said base and said means for detecting light from said light source after it has passed through said sample analysis cuvettes.

3. The fast analyzer of claim 1 further including means for rapidly braking rotation of said rotor holder and rotor.

4. The fast analyzer of claim 1 further including a thermistor mounted within said upstanding pin for measuring the temperature of said cuvette rotor, and electrical slip rings in electrical communication with said thermistor affixed to said rotor holder.

5. The fast analyzer of claim 4 wherein said upstanding pin is located at a radial position corresponding to the radius of said first series of axially extending apertures and said sample analysis cuvettes, and wherein said thermistor is within said pin so as to be axially centered within said removable cuvette rotor when said rotor is disposed on said base within the confine of said rim.

6. The fast analyzer of claim 1 wherein said removable cuvette rotor defines:

a. first and second sets of radially oriented loading cavities disposed in concentric annular arrays; and

b. means for effecting centrifugal passage of fluid from said first and second sets of loading cavities to respective cuvettes in said circular array of sample analysis cuvettes.

7. The fast analyzer of claim 6 wherein said cuvette rotor is of laminated construction with a central opaque disk sandwiched between first and second transparent disks, said sets of first and second cavities comprising depressions in said opaque disk, and loading apertures being provided through said first transparent disk in axial register with respective cavities in said first and second sets of loading cavities.

8. The fast analyzer of claim 6 wherein said cuvette rotor further defines a central distribution chamber and a plurality of distribution passageways communicating between said distribution chamber and respective cuvettes in said circular array of sample analysis cuvettes.

9. The fast analyzer of claim 8 wherein each of said distribution passageways intersects with adjacent distribution passageways at an acute angle so as to form a serrated periphery about said distribution chamber.