Note: Descriptions are shown in the official language in which they were submitted.
2~396~8
-1 - .
7603
AUTOMATED ANALYTICAL INSTRUMENT
This invention relates to an automated analytical instrument
for conducting assays for a component of interest in a fluid sample.
Various types of chemical tests can be performed by
automated test equipment, an example of testing of considerable
5 interest being the assay of biological substances for human health care.
Automated test equipment allows large numbers of test samples to be
processed rapidly. Such equipment is employed in health care
institutions including hospitals and laboratories. Biological fluids, such
as whole blood, plasma or serum are tested to find evidence of disease,
10 to monitor therapeutic drua levels, etc.
In the automated test instrument a sample of the test fluid
is typically provided in a sample cup and all of the process stsps
includin~ pipetting of the sample onto an assay test element, incubation
and readout of the signal obtained are carried out automatically. The
15 test instrument typically includes a series of work stations each of
2Q~9678
-2-
which performs a specific step in the test procedure. The assay element
or cartridge is typically transported from one work station to the next by
means of a conveyor such as a carousel to enablc the test steps to be
accomplished sequentially. The conveyor usuaily carries a plurality of
5 the assay cartrdiges, each secured to a specific location on the upper
surface of the conveyor. In the usual arrangement, the assay cartridges
are spaced apart from each other in berths which are located along the
periphery of the conveyor to facilitate automatic insertion and
extraction .
Various automated analytical instruments for performing
such analyses have been disclosed. However, as the state of the art
advances more demands are made of such instruments and those which
have been previously disclosed are not completely satisfactory in
providing such enhanced capabilities.
1 5 For example, consider the temperature controlled chamber.
The cost of manufacturing the chamber can be advantageously reduced
by constructing at least a part of the chamber from a moldable
polymeric material. Further, it would be advantageous to be able to
dispense the sample fluid to the assay modules while the latter reside in
20 the temperature controlled chamber. However, in providing a
temperature controlled chamber having such features difficulties may be
encountered in maintaining the temperature within the chamber within
the narrow range typically required. For example, 37 i 0.5C.
Another consideration involves the fluid dispensing system.
25 It is preferred in many automated instruments to utilize a pipette in
combination with a disposable pipette tip which is typically used only
one time and discarded so as to eliminate a possible source of
2~ 7g
contamination of fluids and resultant errors in the assay results.
However, it is necessary when dispensing sample fluid and/or test
reagent(s) to the assay element that the orifice of the pipette tip be
located at a predetermined precisely controlled location above the assay
element. Difficulties may be encountered in meeting this requirement
when using disposable pipette tips. Since the disposable tips are
typically made from resilient, moldable polymeric material for each of
manufacture and cost considerations, and because the tip is positioned
on the stem (typically metal) of the pipette by frictionai fit, there may be
some variation from tip to tip as to the distance of the tip orifice from
the stem of the pipette. Since, as mentioned above, it is necessary to
locate the pipette tip orifice at a predetermined, precisely controlled
location above the assay element during the fluid dispense step, any
variation in the positioning of the disposable pipette tip on the pipette
stem can result in an error in the desired positioning of the pipette tip
which can lead to an error in the assay result. Accordingly, it would be
desirable to have ~he capability of determining the spatial location of the
pipette tip during the dispense cycle and to be able to determine
vvhether a disposable tip has been affixed to the pipette stem.
Stiil another factor involves the effect of the relative
humidity level inside the instrument. Since the accuracy of the results
provided by some types of assay elements can vary according to the
relative humidity of the ambient anvironment, it is necessary to have
some technique for compensatin~ for relatlve humidity variatlons.
Also, it is apparent that with a plurality of assays being
carried out concurrently in the automated instrument, whether in a batch
mode where a plurality of assays for the same analyte or component are
2~3~78
being carried out or in a random access mode where a plurality of
assays for different analytes or metabolites are performed, it is
preferable as a safety measure to utilize some form of automatic
identification of the various assay modules to ensure that the desired
5 assay protocols are followed with the individual assay modules.
SUMMARY OF THE !NVENTI(:)N
These and other objects and advantages are accomplished
in accordance with the invention by providing an automated analytical
instrument which includes a temperature controlled chamber, a conveyor
10 for carrying a plurality of assay elements, at least the part of the
conveyor carrying the assay elements being within the temperature
controlled chamber, apparatus for loadins the assay elements onto the
conveyor and for removing the assay elements therefrom, a fluid
dispensing system for delivering fluid to the assay elements while the
15 assay elements reside on the conveyor within the temperature controlled
chamber and optical apparatus for providing optical readout of a signal
generated by an assay element, the signal bein~ a function of the
component of interest in a sample fluid applied to the element.
The instrument includes a microprocessor for controlling
20 and synchronizing the process steps for the assays performed by the
assay elements.
The fluid dispense system, which includes a pipette having
a stem which is adapted to be used with disposable pipette tips, is
operative in conjunction with an optical pipette locator system which
25 utilizes a sensor comprised of a light source and a light beam detector
to measure the location of the pipette tip. The light source is located in
a plane immediately above the assay elements carried on the surface of
2~3~678
-5-
the conveyor. The pipette is initially positioned with some measure of
accuracy by apparatus such as a servo mechanism or a stepper motor
and then final adjustment and precise positioning in the dispense
location is provided by the optical sensor in conjunction with a
5 microprocessor as will be described in detail below herein. After the
fluid is dispensed the pipette is prepared for the next dispense step by
removing the disposable tip and replacing it with a new one.
In accordance with another feature of the invention the
temperature controlled chamber may be constructed partly of polymeric
10 material and includes two heating elements, one arranged above the
conveyor and the other below the conveyor. The heating elememts are
energized with pulses of electrical current which are applied at a rate
preferable at least double the rate at which assay elements can be
loaded onto the conveyor in the temperature controlled chamber. As
15 will be described in detail below, in response to signals provided by a
temperature sensor located in the chamber, the duration of the pulses
is increased or decreased by pulse-width modulation, respectively, to
raise or lower the temperature in the chamber.
In another embodiment of the invention a humidity sensor
20 is provided within the analytical instrument and in combination with the
microporcessor is used to correct the assay result provided by the assay
element for the relative humidity level within the isntrument.
Another feature of the invention resides in the use of a bar
code identification label on the assay module which is read by a bar
25 code reader to provide information to the micro-processor relating to the
specific assay to be conducted with the assay module.
2 ~ 8
BRIEF DESCRIPTION OF THE DRAWINGS
For a better understandin~ of ~he invention as well as other
objects and further features thereof, reference is made to the following
detailed description of various preferred embodiments thereof taken in
5 conjunction with the accompanyin~ drawin~s wherein:
Fig. 1 is a stylized view, partially diagrammatic, of an
analytical instrument employing a cicular conveyor for moving assay
modules among various work stations;
Fig. 2 is a stylized view, partially diagrammatic, of a pipette
10 transport for moving the pipette between a supply of disposable tips,
reagent reservoirs and compartments of an assay module, the figure also
showing an optical detection system for sensing the location of a pipette
tip;
Fig. 3 is an enlarged fragmentary view of a pipette tip
15 within a iight beam of the optical detection system;
Fig. 4 is a block diagram showing a servo control loop of
the pipette transport operative with a microprocessor for positioning the
pipette within the vertical direction;
Fig. 5 is a flow chart showing operation of the
20 mciroprocessor;
Fig. 6 shows details in a block of the chart of Fig. 5 relating
to the computation of additional pipette travel, including a safety check
to insure that a pipette is present on the pipette barrel;
Fig. 7 is a timing diagram showing vertical movement of the
25 pipette;
Fig. 8 is a view of an analytical instrument with portions
thereof indicated diagrammatically, including a perspective view of a
2~9~
-7-
temperature controlled chamber accordin~q to the invention with portions
of the chamber shown cut away to disclose interior components thereof;
Fig. 9 is a sectional view of the temperature controlled
chamber taken along the line 3 - 3 of Fig. 8;
Fig. 10 is a block diagram of a heater control system for
enerqizing top and bottom heaters of the chamber;
Fig. 1 1 is a graphical illustration demonstrating the variation
with relative humidity in the intensity of fluorescent signals obtained as
the result of the presence of an analyte of interest in sample fluids;
Fig. 12 is a block diagram showing the interrelationships
between a microprocessor and elements of the analytical instrument;
and
- Fig. 13 is a flow chart showing the operation of the
microprocessor in the performance of an assay.
DESCRIPTION QE THE PREFERRED EMBODIMENTS
In Fig. 1, there is shown an analytical instrument 20 which
provides automatically a sequence of process steps to accomplish an
assay of a test sample. A plurality of modules 22 are employed within
the instrument 20 to increase the throughput rate, one process step
being carried out with one module concurrently with the performance of
other process steps with other modules. 1 he modules 22 are illustrated
with respect to a preferred embodi nent thereof which includes one or
more chambers in the housing. Such chambers may be configured as
wells, or reservoirs, for the storage and/or mixing of fluids which are
used in the assay procedure or the chambers may culminate in an
openin~q to permit fluids to be provided to a reaction zone within the
module. The chambers are formed integrally within the housing of the
2~3~
-8-
module. The analytical instrument 20 includes a conveyor, or carousel,
24, which is rotated about an axle 26 by a motor 28. By way of
example, the motor 28 may be mechanically coupled to the carousel 24
by a gear 30 or by a belt drive (not shown). The carousel 24 carries the
5 modules 22 from one work station to another work station, two such
work stations 32 and 34 bein~ shown, by way of example, in Fig. 1.
The carousel 24 rotates within a temperature controlled chamber 3~
having a heater 38 for maintaining a desired temperature at the various
work stations so as to allow for a process step of incubation.
Work sl~llon 32 Is ~ pipollin~ stalion whoroat samplo ~luid
and any other required fluid test reagent(s) are delivered to the assay
modules 22. By way of example, there are shown two pipettes 40 and
42. The pipettes, 40 and 42, are positioned and operated by a pipette
mechanism 44 mechanically connected to the pipettes 40 and 42, as
15 indicated by dashed lines.
During the assay procedure, as a result of the reaction(s)
and interaction(s) between the sample fluid and the test reagent(s)
which take place, a detectable change is effected corresponding to the
presence of an analyte or component of interest in the sample fluid. The
detectable change may be a color change which may be read
spectrophotometrically such as with a densitometer or, in an assay
method based on fluorescent-labeled biologically active species or one
which involves the generation of a fluorescent species as a result of a
reaction between test reagents, a fluorescent output signal can be
generated and read spectrofluorometrically. Such detectable changes
may be read from above or below the assay module. At work station
34 there is shown by way of example a fluorometer 46 for irradiating
~9~
g
the reaction zone within the assay module and for measuring the
fluorescence emitted from the fluorescent species present therein.
The carousel 24 may be arranged so as to accommodate
varying numbers of assay modules 22. Each position, or berth 54 for
5 holding an assay module is provided in this embodiment with a small
aperture 56 to allow the irradiatin3 illumination to reach the reaction
zone in the assay module and to permit the fluorescent emissions to be
collected and measured. Also shown in an injector 58 for inserting a
module 22 in an empty berth 54, the injector 58 having an arm 60 for
10 gripping a module 22 during the insertion operation. The injector 58
also serves to extract a module from a berth 54 by use of the arm 60
upon completion of a test procedure. Operation of the motor 28, the
pipette mechanism 44, the fluorometer 46 and the injector 58 are
synchronized by means of a microprocessor unit 62.
Fig. 2 provides detail in the construction of the pipette
mechanism 44 of Fig. 1. To facilitate description of the invention,the
pipette mechanism 44 will be described hereinafter as having a pipette
transport 64 operative with only one of the pipettes, namely, the pipette
40. The transport 64 provides for relative movement, in two
20 dimensions, between the pipette 40 and a set of reservoirs 66 located
at a distance from the module 22, the reservoir 66 serving to store
rea~ents useful in the assays carried out by the instrument 20. The
reservoirs 66 are located on a movable table 68 which also holds a set
of tips 70 which are to be affixed to a stem 72 of the pipette 40. With
25 reference to an X-Y-Z coordinate axes system, the pipette 40 is
translatable in the X direction along a box beam 74 of the transport 64,
and the table 68 is translatable in the Y direction by riding along a rail
2~3~78
-~o-
76 of the transport 64. A vertical drive 78 is located within the beam
74 and serves to raise and to lower the pipette 40 in the Z direction.
A horizontal drive 80 located within the box beam 74 drives
the pipette in the X direction. The vertical drive 78 and the horizontal
drive 80 are of conventional design, and are indicated in simplified
fashion in Fig. 2. In simplified fashion, the vertical drive 78 may be
described as comprising a wheel 82 slidably moun~ed to a spline shaft
84 which, alternatively, may have a square cross section. The shaft 84
is rotated by a motor 86. The horizontal drive 80 includes a base 88
which slides in the X direction alon~ th~ beam 74 in respons~ to rotation
of a motor 90. The motor 90 drives a belt 92 through a pulley 94, the
belt 92 being connected to the base 88 for translating the base 88 upon
rotation of the pulley 94 by the motor 90. A fixture 96 upstanding from
the base 88 slides the wheel 82 along the shaft 84 upon movement of
the base 88 so that the wheel 82 stays in fixed position relative to the
base 88. The pipette 40 passes through the base 88 so as to be
translated in the X direction by the base 88. The wheel 82 is
mechanically connected to the pipette 40, as by gear teeth on the wheel
82, or by means of a belt drive (not shown). The mechanical
connection of the wheel 82 to the pipette 40 provides for a translation
of the pipette 40 in the Z direction upon rotation of the wheel 82 by the
motor 86. The belt drive 98 may be employed, similarly, for driving the
table 68 in the Y direction in response to rotation of a motor 100 affixed
to the rail 76.
As noted above in the description of the analytical
instrument of Fig. 1, the motor 28 is under control of the computer 62.
Similarly, the motor 100, 90, and 86 are also under control of the
2Q39678
computer 62. Connections of the motors 28, 100, 90, and 86 are
indicated in Fig. 2 by terminals A, B. C, and D, respectively. Thereby,
movement of the pipette 40 can be synchronized with a positioning of
the module 22 by the carousel 24 to a location directly beneath the
5 beam 74. In order to provide access to the module 22 by the pipette
44, a slot 102 is provided in a top wall 104 of the temperature
controlled chamber 36. The slot 102 is parallel to the beam 74. The
location of the slot 102 relative to the beam 74 permits the stem 72 of
the pipette 40 to be lowered through the slot 102 selectively above a
10 desired compartment of a plurality of compartments 106 of the module
22. The len~th of the slot 102 is commensurate with the len3th of the
module 22 to permit displacement of the stem 72 in the X direction for
alignment with a selected one of the compartments 106. The slot 102
is relatively narrow, and has a width lar~e enough to clear the stem 72
15 and the tip 70 mounted on the distal end of the stem 72. With respect
to the overall dimension of the chamber 36, the area occupied by the
slot 102 is sufficiently small to preclude any significant amount of air
flow between the interior and the exterior of the chamber 38. Thereby,
the slot 102 has no more than a ne01igible effect in the control of the
20 chamber temperature, which temperature is controlled by the heater 38
(Fig. 1).
In accordance with a feature of the invention, an optical
detection system 108 is provided to signal the microprocessor 62 when
the tip 70 of the pipette 40 has advanced in the downward direction to
25 a predetermined distance from the selected compartment 106. The
detection system 108 comprises a source 110 of light which, by way
of example, may be a semiconductor diode which emits infrared
2~3~78
-12-
radiation. The detection system 108 also comprises a detector 1 12, the
light being indicated by a beam 114. The detector 112, which may
comprise a semiconductor phot~diode, modulates an electric current
along line 1 16 in response to light of the beam 1 14 incident upon the
5 detector 112.
The detection system 108 includes electrical comparison
circuitry 118 for measuring the magnitude of the current on line 116.
By way of example in the construction of the circuitry 118, the circuitry
118 comprises a comparator 120 and a resistive voltage divider 124
10 providing a reference voltage respectively to the comparator 120. The
divider 124 is shown to comprise a potentiometer for allowing manual
adjustment of the reference voltage for initial alignment of the detection
system 108. The alignment provides for selection of comparator
reference voltages in accordance with the degree of optical transparency
15 of the tip 70.
In the operation of the detection system 108, the full
strength of the light beam 1 14 is incident upon the detector 1 12 in the
absence of the pipette 40. By way of example, the pipette 40 may be
at the location of one of the reservoirs 66, as indicated in phantom view
20 of the pipette, During maximum intensity of the received optical signal
at the detector 112, a maximum current and voltage appear on !ine 116.
During descent of the pipette 40, the tip 70 interrupts the light beam
1 14. The line 1 16 is connected to the input terminal of comparator 120
and, accordingly, both of the comparators 120 and 122 output a logic-1
25 signal to the microprocessor 62 under conditions of maximum
illumination of the detector 112, as occurs prior to interruption of the
light beam 114 by the pipette 40. Interruption of the light beam 114
-13- ~ 8
greatly reduces the intensity of light received at the detector 112. The
extent of the interruption of the light depends on the degree of the
transparency of the tip 70. The tip 70 is preferably fabricated of a
polymeric material which is translucent so as to reduce the intensity of
5 the light without casting a complete shadow upon the detector 112.
The voltage reference levels of the divider 124 are set such
that the amount of li~ht transmitted by a tip is sufficient to activate the
comparator 120 to output a logic-1 signal indicating a low, L, level of
light received at the detector 1 12. In the event that the light beam 1 14
10 is interrupted by a tip 70, then the intensity of light received by the
detector 112 is too low to activate the comparator 120 with the result
that the comparator outputs logic-0. Thus, there is a 1-bit outputted by
the comparison circuitry 118 designating the status and location of the
tip 70 as the tip 70 advances along a path of travel in the Z direction to
15 a selected compartment 106 of the module 22.
Fluid reagent is drawn into the pipette tip 70 by vacuum
and expelled from the tip 70 by pressure delivered to the pipette 40 by
a suction tube 126 under control of a control unit 128. The tube 126
is flexible and of sufficient length to connect the control unit 128 with
20 the pipette 40 at all locations of the pipette 40. The control unit 128
is connected to the microprocessor 62 which commands the control unit
128 to apply vacuum for inducting fluid, and for releasing vacuum and
applying positive pressure, if necessary, to expel the fluid reagent.
Aspiration of fluid is done from a selected one of the reservoirs 66.
25 Expelling of the fluid rea~ent is accomplished only when the tip 70 is in
the position for dispensing the fluid to the selected one of the
compartments 106 in the designated module 22. It is noted also that
2~39~78
-14-
aspiration of fluid reagent can be accomplished at one of the
compartments 106 of the module 22 to be dispensed in another of the
compartments 106. In this respect, a reservoir for storage of fluid
reagent can be located directly within the module 22 or remote from the
5 module 22, as at the table 68. The location of the various reservoirs
66 of the table 68 are stored in a memory of the microprocessor 62.
This enables the micro-processor 62 to move the table 68 to a specific
address in the Y direction, and to move the pipette 40 to a specific
address in the X direction, the X and the Y components of the address
10 fully identifying the requisite one of the reservoirs 66. In similar fashion, the microprocessor 62 stores locations of the available tips 70 held by
the table 68 so that successive ones of the tips 70 can be selected for
affixation to the stem 72.
The transport 64 is operative in the process of affixing a tip
15 70 to the stem 72 of a pipette 40, and in the detachment of the tip 70
from the stem 72. The procedure begins by a lifting of the pipette 40
so that the tip 70 clears the slot 102. The pipette 40 is then free to
move along the beam 74 to an extractor 130. The extractor 130 has
a semicircular channel 132 cut out in the edge of a horizontal portion of
20 the extractor 130, the channel 132 having a diameter large enough to
permit clearance of the stem 72 by the channel 132, but small enough
to permit engagement of the channel 132 with the tip 70. Under
commands of the microprocessor 62, the pipette is brought towards the
extractor 130 with the tip 70 being below the channel 132. The stem
25 72 enters the channel 132 after which the pipette 40 is raised to engage
the tip 70 with the extractor 130. The tip 70 remains stationary as the
stem 72 lifts out of the tip 70. Thereupon, the tip 70 falls into a bin
2~9~8
-15-
134 for collection of used tips 70. It is advisable to employ the
extractor 130 at the beginning of operation of the instrument 20 to
ensure that the stem 72 is free for reception of a new tip 70.
After ensuring that the stem 72 is free for reception of a tip
5 70, the pipette 40 is brought, by displacement in the X direction, to a
location above the table 68, whereupon the table 68 is translated in the
Y direction to bring the stem 72 above and in registration with a
selected tip 70 held by the table 68. The pipette 40 then advances
downward to make frictional contact with the interior surface of the tip
10 70. Thereupon, the pipette is raised, and the tip is retained on the distal
end of the stem 72 by friction forces.
With reference also to Fig. 3, the distal end of the stem 72
is shown making frictional contact with the surface of a channel 136 of
the tip 70. The channel 136 extends along a central longitudinal axis of
15 the tip 70 from one end of the tip to the opposite end of the tip. The
channel 136 has a circular cross-sectional shape of varying diameter, the
diameter being larger at the top end 138 than at the bottom end 140.
As the stem 72 advances downwardly into the channel 136,
constriction of the channel 136 produces frictional forces which tighten
20 the tip 70 upon the stem 72. These frictional forces are sufficient to
ensure a secure attachment of the tip 70 to the stem 72 during transfer
of fluid reagent during test procedures of the instrument 20. However,
the frictional forces are sufficiently small to permit the extractor 130 to
slide the tip 70 off of the stem 72 upon completion of a transfer of fluid
25 reagent.
With respect to the practice of the invention, it is noted
that the manner of affixing the stem 72 to the tip 70 provides
-16- 2~3~78
substantial uni~ormity in the locations of successive tips 70 upon the
stem 72. However, in view of the flexibility of the polymeric material
of the tip 70 brought about by contact with the relatively rigid tube of
the stem 72, and in view of some variation in frictional forces among
5 the tips 70, it has been found that there is slight variation among th~
locations of the orlfices 140 of the tlps 7~ relatlve to the dlstal end of
the stem 72. This variation is ~ufficient to serve as a source of
inaccuracy to the dispensin~ of fluid in th~ compartments 106 of the
module 22. The invention automatically corrects for these variations in
10 tip location by sensing the location of the orifice 140 of the tip 70 by
means of the light beam 114. The procedure of the invention for
correcting for the variations in tip location is explained further with
reference ~o the diagram of Fig. 4 and the fiow charts of Figs. 5-6.
Fig.4 shows the feedback circuit 142 for inter-connecting
15 the microprocessor 62 with the servo motor 86 for operation of the
vertical pipette drive 78 disclosed in Fig. 2. As shown in Fig. 4, the
circuit 142 includes a summer 144, a digital-to-analog converter 146,
a filter 148, an amplifier 150, a shaft angle encoder 152, a memory 154
of the microprocessor 62, and an entry device 156, such as a keyboard,
20 for entering data into the memory 154.
In operation, for lowering the pipette 40 towards the
module 22 (Fig. 2), the microprocessor 62 successively enters new
locations on the path of travel of the pipette 40 in the Z direction.
Location signals of the microprocessor 62 are applied to one input
25 terminal of the summer 144. The present location of the tip 70, as
estimated by the encoder 152 is applied to a second input terminal of
the summer 144 to be subtracted from the value input at the first
2~3~78
-17-
terminal of the summer 144. It is noted that the encoder 152 provides
an accurate value of the location of the pipette stem 72, but not of the
tip 70, because the position of the tip 70 relative to the stem 72 varies
from tip to tip because of the frictional fit explained above. Therefore,
5 a value of shaft angle outputted by the encoder 152 can be taken only
as an estimate of the true position of the tip 70.
The signals outputted by the encoder 152 and by the
microprocessor 62 are formatted digitally. The summer 144 forms the
difference of these two signals and applies the difference to the
10 converter 146 for converting the difference from a digitally formatted
signal to an analog signal. The analo~ signal outputted by the converter
146 may be regarded as the loop error signal of the feedback circuit
142. The loop error signal is filtered by the filter 148 which, in
accordance with the usual practice in the construction of the feedback
15 loops, may be a low-pass filter, and may include a lead-lag filter
component. The filter 148 provides stability to the feedback loop. An
output signal of the filter 148 is amplified by the amplifier 150, and is
applied to the servo motor 86. The loop gain and bandwidth, as
established by the amplifier 150 and the filter 148, in conjunction with
20 the motor 86 determines the dynamic response of the loop in a manner
well known in the design of servomechanisms. The motor 86 rotates
towards the rotational position commanded by the microprocessor 62.
As the motor 86 rotates, the vertical drive 78 lowers the pipette 40.
By way of alternative embodiment in the construction of
25 the feedback circuit of Fig. 4, it is noted that the functions of the
summer 144 and the filter 148 can be accomplished directly within the
microprocessor 62 by suitable programming of the microprocessor 62.
-18- 2Q3~
In such a case, the computer 62 outputs the error si~nal via the
converter 146 directly to the amplifier 150 for driving the motor 86.
Also, if desired, the servo motor 86 can be replaced with a stepping
motor (not shown) which operates in response to digital pulses directing
5 incremental rotational displacement of a rotor of the motor. In such a
case, summer 144, converter 146, filter 148, amplifier 150 and shaft
angle decoder 152 would not be re~uired, and the microprocessor 62
would bé programmed to output well-known stepping-motor control
pulses for driving the motor. It is to be understood that any one of these
10 configurations of feedback loop can be employed to opera~e the vertical
pipette drive 78, the configuration of Fig. 4 having been shown to
facilitate the teaching of the practice of the invention.
With respect to the circuit shown in Fig. 4, the
microprocessor 62 continues to input further values of position along the
15 path traveled by the pipette 40 until the light-beam comparison circuit
1 18 signals the microprocessor 62 of a break in the light beam. The
location of the tip 70 is now known accurately by virtue of contact of
the tip 70 with the light beam 114. The pipette 40 now travels through
an additional distance to bring the tip 70 into the dispensing position
20 relative to the module 22. The value of the additional distance of
positional travel is based on data stored in the memory 154. The
microprocessor 62 reads the memory 154 to obtain the travel data. A
person operating the instrument 20 provides the requisite data on
additional travel based on a knowledge of the configuration of the
25 module 22, particularly the height of the module 156 relative to a top
surface 158 of the carousel 24. This height data is entered via the entry
device 156 in the memory 154.
- 19- ~ $ 7 8
The operation of the feedback circuit 142 may be explained
further with reference to Fig. 2 and with reference to the timing diagram
of Fig. 7. Prior to the lowering of th~ pipstte 40, the tip 70 is at a
sufficiently high elevation to permit transporting the pipette 40 in the X
5 direction between the carousel 24 and the table 68. This is referred to
in Fig. 7 as the transport level. The pipette 40 then undergoes its initial
descent during an interval of time identified in Fig. 7. The initial descent
interval ends with the breaking of the light beam 1 14. Thereupon, there
is the final interval of descent in which the pipette 40 descends the
10 additional travel. This brings the pipette tip to the dispense level
indicated in Fig. 7. After completion of a dispensing interval of time, the
feedback circuit 142 raises the pipette 40 back to the transport level
during a retraction interval shown in Fig. 7. Also shown in Fig. 7 is a
safety level which will be described with reference to the flow charts of
15 Figs. 5-6.
With reference to Fig. 5, the inventive feature of lowering
the pipette to the module 22 while compensating for variations in
positions of the tip 70 is explained with reference to a flow chart. The
flow char~ describes operation of the microprocessor 62 of Fig. 2 for
20 operating the vertical pipette drive 78 (Figs. 2 and 4) for lowering the
pipette 40 to dispense fluid reagent in a compartment 106 of the
module 22. Initiation of the pipette descent toward the module 22
occurs at block 160. At block 162, the determination is made as to
whether the light beam 114 (Fig, Z) is present. The microprocessor 62
25 determines the presence of the light beam by examination of the high
and low signals outputted by the ~omparison circuitry 118. Since the
pipette 40 is in an elevated position, there is no blocka~e of the light
2~3~78
-20-
beam 114 and, accordingly, the light beam 114 should be present and
the comparator 120 should be outputting the logic-1 signal indicating
full intensity of the light beam 114. If the beam is not present, then, at
block 164, a person operating the instrument 20 is signaled to correct
5 an apparent fault in the instrument.
if the light beam is present, the procedure advanses to
block 166 wherein the microprocessor 62 directs the lowering of the
pipette 40 in the manner described above with reference to Fig. 4.
Therein, the microprocessor 62 continually inputs new positions along
10 the path of travel of the pipette 40 at a rate commensurate with the
dynamic response of the feedback loop 142. Periodically, during the
lowering of the pipette 40, the microprocessor 62 observes output
signals of the comparison circuitry 118 to determine whether there has
been an interruption of the light beam 114, this determination being
15 performed at block 168.
Assuming that no interruption of the light beam 114 by the
pipette 40 has occurred, then operation proceeds along line 170 to block
172 to determine whether the safety level (shown in Fig. 7), has been
reached. There is the possibility of a sys$em malfunction wherein the
20 stem 72 of the pipette 40 has failed to secure the tip 70 at the table 68.
This could occur for a variety of reasons, such as operator negligence
in filling the table 68 with the set of tips 70, or the possibility of a
cracked tip which fails to provide adequate friction for securing the tip
to the stem 72. Since the shaft angle encoder 152 (Fig. 4) continually
25 outputs position data to the microprocessor 62, the microprocessor 62
has knowledge of the location of the distal end of the stem 72. As the
distal end of the stem 72 approaches the vicinity of the li~ht beam 114,
2~3~
-21 -
there should be an interruption of the beam 1 14 by the tip 70, assuming
the tip 70 is present. The safety level is the lowest point at which the
microprocessor 62 will allow the s~em 72 to drop without interruption
of the beam 114. If the safety level is reached, then the microprocessor
5 62 concludes that the tip 70 is absent, and operation proceeds to block
174 wherein the microprocessor 62 orders retraction of the pipette 40
to the transport level. As noted hereinabove, at the transport level, the
pipette 40 clears the top wall 104 of the temperature controlled
chamber 36 so that the stem 72 is fully visible to an operator for
10 performing remedial action. From block 174, operation proceeds to
block 176 wherein the operator is signaled to take remedial action.
During normal operation of the instrument 20, the tip 70 is
present on the stem 72 and, accordingly, at block 172 the safety level
woul~ not be reached without interruption of the light beam 114.
15 Accordingly, operation proceeds from block 172 along line 178 back to
block 166 wherein the microprocessor 62 continues to lower the pipette
at the preset rate. The operation continues in repetitive fashion through
the blocks 166, 168, and 170 until interruption of the light beam 114
occurs at line 180. The interruption of the light beam 1 14 is signaled
20 to the microprocessor 62 by a change in the output signal of the
comparison circuitry 118 such that signal changes from logic-1 to
logic-0.
Assuming that the tip 70 is present, then, upon the
interruption of the light beam at line 180, the output signal of the
25 comparison circuitry 118 is at logic-0 to indicate to the microprocessor
62 that the tip 70 has reached the position of the light beam 114 along
the path of travel of the tip 70 towards the module 22. Accordingly, at
2~9~8
-22-
block 182, the microprocessor 62 determines the position of the
dispense level (Fig. 7) so as to compute the additional amount of travel
required by the tip 70 to reach the dispense level. The operation within
block 182 will be described in further detail with reference to Fig. 6.
In Fig. 5, the operation proceeds from block 182 via line
186 to block 188 wherein the pipette 40 is lowered further to locate the
tip 70 at the dispense level. This lowering of the pipette is
accomplished, in the manner disclosed hereinabove with reference to the
feedback circuit 142 of Fig. 4, wherein the microprocessor 62 inputs
further locations along the travel path of the pipette to bring the tip 70
to the dispense level. Thereafter, at block 190 the microprocessor 62
commands the suction control unit 128 to dispense fluid to the selected
compartment 106 of the module 22. Thereafter at block 192, the
pipette 40 is retracted back from the module 22 to the transport level.
The system 20 can now initiate other steps in the testing procedures of
the modules 22.
Fig. 6 shows details in the procedure of block 182 (Fig. 5)
for checking the filling of the pipette tip followed by the computation of
the additional travel of the pipette. The procedure at line 180 proceeds
20 to block 194 to check the intensity of the light beam. In the event that,
at block 194, the light is fully obscured, both the H and the L signals of
the comparison circuit 118 are at iogic-0, as was noted hereinabove,
which allows the microprocessor 62 to determine, at block 198, that the
pipette is loaded. Thereupon, at block 200 the microprocessor reads the
25 present pipette position as outputted by the encoder 152 ~Fig. 4) . This
is followed, at block 202, by a reading of the position data of the
module 22, which data has been stored in the memory 154 (Fig. 4).
2~3~7$
-23-
The module position data designates the location of a top
surface of the module 22 relative to the top surface 158 of the carousel
24. Since the distance between the light beam 114 and the carousel
surface 158 is known and fixed, the inputting of this module data is
equivalent to giving the microprocessor the distance between the top
surface of the module 22 and the beam 114. Accordingly, at block
204, the additional distance between the beam 114 and the module 22
is added to the vertical distance already traveled by the pipette 40, the
vertical distance being provided by the encoder 152. This gives the
reading of the encoder 152 which will be obtained when the pipette tip
70 reaches the dispense level. This information is used by the
microprocessor 62 in operating the circuit of Fig. 4 for continued
lowering of the pipette 40. Accordingly, the operation can now proceed
via line 186 to block 188 as has been disclosed above with reference to
Fig. 5.
The timing diagrarn of Fig. 7 has al-ready been referred to
in the description of the circuitry of Fig. 4 and the procedure of Figs. 5
and 6. Briefly, the diagram of Fig. 7 shows the descent of the pipette
tip 70 at a fixed rate during the initial descent interval. This is followed
by a pause in which the condition of the light beam is observed,
followed by the final descent in which the pipette tip 70 is brought to
the dispense level. At the conclusion of the dispense interval, the tip 70
is retracted to the transport level. The safety level is disposed between
the light beam level and the dispense level.
The foregoing description provides for operation of the
instrument 20 in a fashion which allows the pipette to be lowered with
-24-
an accuracy which is independent of the position of the pipette tip 70
on the pipette stem 72.
With reference to Fi~s. 1, 8 and 9, there is provided further
details in the construction of a preferred embodiment of the temperature
5 controlled chamber 36 and its operation with the analytical instrument
20. The preferred embodiment of the temperature controlled chamber
36 has a circular form, and is operative with only a single pipette, for
example, the pipette 40. The pipette mechanism 44 comprises a
transport 64 for moving the pipette 40 in a radial direction tX) of the
10 chamber 36 between the chamber 36 and a selectable reservoir 66 of
a plurality of reservoirs 66. The reservoirs 66 are carried upon a table
68 which may be translated in a direction (Y) perpendicular to the
pipette movement, X, of the transport 64 so as to enable two axes (X
and Y) selection of a reservoir 66 containing a desired reagent.
15 Motorized drives for the transport 64 and the table 68 are available
commercially and, accordingly, need not be described in detail herein.
In these types of analytical instruments, disposable pipette tips are used
typically for the delivery of one fluid only and then discarded so as to
avoid contamination which could lead to errors in the assay result.
20 Accordingly, the table 68 carries a supply of tips 70 to be inserted upon
a stem 72 of the pipette 40. A tip 70 is attached to the stem 72 with
frictional force by pushing the ste:n 72 down into a tip 70 on the table
68. The tip 70 is extracted from the stem 72 by the extractor 130
shown located alongside the table 68, the extractor 130 having a
25 hooked flange 276 with the channel 132 which envelop the tip 70 to
pull off the tip 70 during an upward motion of the tip 70.
~9fi~
-25-
ln accordance with the invention, the temperature
controlled chamber 36 comprises a top wall 104 located above the
carousel 24, a bottom wall which serves as a floor 280 of the
temperature controlled chamber 36 and is located below the carousel
5 24, and two sidewalls whereir~ one of the sidewalls is an outer wall 282
which extends from the top wall 104 to the bottom wall 280 and the
second of the sidewalls is an inner wall 284 which extends from the top
wall 104 toward a central portion of the carousel 24. The top wall 104
has an annular shape. An upper region 286 of the chamber 36 is
10 bounded by the top wall 104, the top surface 158 of the carousel 24,
the outer wall 2~2 and the inner wall 284.
In this preferred embodiment the sample fluid and any other
required fluid reagents are dispensed to the assay modules 22 while the
latter are in the temperature controlled chamber in accordance with the
15 invention. Accordingly, in order to provide access to the module 22 by
the pipette 40, a slot 102 is provided in the top wall 104 of the
chamber 36. The slot 102 extends in a radial direction of the oven 36,
parallel to the X direction. The slot 102 is located relative to the
transport 64 to permit the stem 72 of the pipette 40 to be lowered
20 through the slot 102 selectively above a desired compartment of a
plurality of compartments 106 of the module 22. The length of the slot
102 is commensurate with the length of the module 22 to permit
displacement of the stem 72 in the X direction for alignment with a
selected one of the compartments 106. The slot lQ2 is relatively
25 narrow, and is surrounded by a grommet 294. The slot 102 has a width
large enough to clear the stem 72 and the tip 70 mounted on the distal
end of the stem 72. With respect to the overall dimension of the
2 ~ 7 ~
-26-
chamber 36, the area occupied by the slot 102 is sufficiently small to
preclude any si~nificant amount of air flow between the interior and the
exterior of the temperature controlled chamber 36. Thereby, the slot
102 has no more than a negligible effect in the control of the chamber
5 temperature.
The chamber 36 further comprises two heaters, namely, a
top heater 296 supported by the top wall 104, and a bottom heater 298
supported by the bottom wall 280 for controlling the chamber
temperature. The bottom heater 298 is located in a lower region 300
of the chamber 36, between the carousel 24 and the floor 280. An
injection port 302 is provided in the outer wall 282 facin~ the injector
58 to provide access to the arm 60 for inserting a module 22 in a berth
54 of the carousel 24, and for extracting the module 22 from the berth
54. A frame 304 is located within the upper region 286 for supportin~
sensors useful in the operation of the temperature control system 20,
one such sensor 306 being provided for sensing the chamber
temperature. The frame 304 is secured by a bracket 308 to the outer
wall 282. By way of example in the construction of the frame 304, the
frame 304 may be constructed as a circuit board for supporting
electronic circuitry (not shown in Fi~s. 8 and 9) such as a preamplifier
for amplifyin~ electrical si~nals provided by the sensor 306. Electrical
cables 312. 314, and 316 connect respectively with the top heater 296,
the bottom heater 298, and the sensor 306 for connecting these
components to circuitry outside of the temperature controlled chamber.
To facilitate maintainin~ of a substantially constant
temperature within the chamber 36, it is advisable to minimize any flow
of air between the interior of the temperature controlled chamber 36 and
~!~3~
-27-
the external environ,rnent. Accordin~ly, the inner wall 284 meets the
top surface 158 of the carousel 24 at an airlock 318 which provides
sufficient clearance of space between the inner wall 284 and the
carousel 24 to allow for relative motion between the carousel 24 and
5 the inner wall 284, the clearance space being 'sufficiently narrow to
inhibit flow of air between the interior of the chamber 36 and the
external environment. The airlock 318 comprises an inner circular rib
320 and and an outer circular rib 322 which are spaced apart radially
from each other to form a channel for receiving a lip 324 of the inner
10 wall 284. The axle 26 which supports the carousel 24 passes through
an aperture 326 in the bottom wall 28Q. The aperture 326 provides a
clearance space which permits rotation of the axle 26. The rotation
provided by the motor 28 and gear 30 (Fig. 1) is represented in Fig. 9
by a drive unit 328 connected to the axle 26. The clearance space of
15 the aperture 326 inhibits the flow oF air between the interior oof the
chamber 36 and the external environment. Thus, the bottorn wall 280,
in combination with the clearance space of the aperture 326 rnay be
regarded as an airlock 330.
The remaining openin~s in which air may be exchanged
20 between interior and exterior of the chamber 36 are the injection port
302 and the pipette slot 102. The port 302 is essentially closed off by
the structure of the injector 58 except during passage of a module 22
through the port 302. The slot 102 has dimensions such that no more
than a negligible amount of air is interchanged between the interior of
25 the chamber and the external environment. For example, for a carousel
24 having a diameter of about 13 inches, the slot 102 can have a width
less than about one-quarter inch and a length less than about 1.3
2 ~ 7 ~
-28-
inches. Also, it is noted that the volume of the lower region 300 is
sufficiently small, and a gap 332 between the carousel 24 and the outer
wall 282 is sufficiently sma!l as to minimize airflow between the upper
region 286 and the lower region 300 of the chamber 36. Also, the
5 volume of the upper region 286 is no larger than necessary to
accommodate the physical sizes of the modules 22 and the sensor
assembly 334 comprising the frame 304 and the sensor 306.
Minimizing the interior volume of the upper region 286 increases the
dynamic response of a temperature control system 336 and reduces
10 transients in the response of the temperature control system 336 to be
described below with reference to Fig. 10. The toroidal shape of the
upper region 286 aids in reducing the volume of the upper re~ion 286.
Additionally, to maintain circulation of air from the upper
region 286 and the lower region 300 there are provided a plurality of
15 apertures, or vents, in the carousel 24 together with a fin to direct the
air through the aperture as the carousel is rotated. One such aperture
311 is shown with a fin 313 for purposes of illustration. In a preferred
embodiment eight such apertures, each about one-half by one-quarter
inch are provided in the carousel. Further, since the carousel may be
20 rotated in either direction it is preferred to arrange half of the fins in
each direction to facilitate circulation of air irrespective of the direction
of rotation.
As shown in Fig. 10, the temperature control system 336
comprises the temperature sensor 306 and the heaters 296 and 298
25 disclosed previously in Fig. 9. In addition, the temperature control
system 336 comprises a temperature setting potentiometer 338, a
subtracter 340, a filter 342, a summer 344, a source 346 of a reference
-29- 2 ~ 8
voltage, a pulse width modulator 348, a clock pulse generator 350, and
a power source 352.
In operation, the potentiometer 338 is connected between
a voltage, V, and ground to provide a manually adjustable output voltage
5 at terminal 354 which is applied to a first terminal of the subtracter 340.
An output voltage of the sensor 306 is connected to a second input
terminal of the subtracter 340. The subtracter 340 comprises
well-known circuitry, such as that of an operational amplifier (not
shown), for forming the difference between the voltages of the
10 potentiometer 338 and the sensor 306, and applies the difference to the
filter 342. The heaters 296 and 298 are connected serially between
output terminals of the power source 352, the source 352 applying
electric current to the heaters 296 and 298 for the generation of heat.
The heat is indicated symbolically by waves 356 propagating from the
15 heaters 296 and 298 toward the temperature sensor 306.
The power source 352 is gated on and off by pulses
provided by the generator 350 via the modulator 348. The voltage
reference of the source 346 is applied via the summer 344 to the
modulator 348 to establish a basic width to pulses outputted by the
20 modulator 348 to the power source 352. The repetition frequency of
the pulses is established by the generator 350. The basic pulse width,
in combination with the repetition frequency, establishes a duty cycle for
the administration of energizing current to the heaters 296 and 298
which is approximately correct for maintaining a temperature in the
25 desired range, e.g., 37 i 0.5C in the vicinity of the carousel 24. An
output voltage of the filter 342 is applied to the summer 344 to be
added algebraically with the reference voltage of the source 346 to
2~3~6~8
adjust the pulse width as needed to increase or decrease the amount of
heat produced by the heaters 296 and 298. For example, if the sensor
306, in response to the chamber temperature provided by the heaters
296 and 298, outputs a voltage equal to that of the potentiometer 338,
5 then the error signal outputted by the subtracter 340 is zero, and the
modulator 348 outputs pulses at the basic pulse width.
The circuitry of Fi~. 10 may be viewed as a feedback loop
in which the waves 356 of heat complete the loop by connecting the
heaters 296 and 298 to the temperature sensor 306. If the sensor 306
10 outputs a voltage different from that of the potentiometer 338, a loop
error signal outputted by the subtracter 340 has the proper sense,
positive or negative, and proper amplitude to adjust the width of the
pulses outputted by the modulator 348 for maintaining the desired
chamber ternperature. For example, if the sensed temperature is too
15 iow, the pulse width is increased, and if the sensed temperature is too
high, the pulse width is decreased. The filter 342 may be a low-pass
filter as is customarily employed in feedback circuitry for precise control
of the dynamic response of a feedback loop.
It should be noted here that the system may be controlled
20 entirely by appropria~ely programming the microprocessor software. In
this preferred embodiment the subtracter 340, filter 342, source 344,
pulse width modulator 348 and clock pulse generator 350 are not
necessary.
The main source of interruption of the temperature of the
2~ chamber is the insertion of the module 22 via the port 302 since the
assay modules are typically at room temperature which typically is from
fifteen to twenty degrees less than that of the chamber. In typical
2~39~8
-31 -
automated analytical instruments the introduction of assay modules to
the carousel within the chamber can occur at a rate of one every ten
seconds, the duration of such rate being dependent of course upon the
number of open berths on the carousel. Even though the module 22
5 may be retained within the chamber 36 for a minute or longer prior to
beginning the assay procedure in order to stabilize the module
temperature, attainment of a desired temperature of the module and of
the test material and reagents contained within the module can only be
accomplished adequately by maintaining the chamber temperature in the
10 vicinity of the carousel and the modules within the desired value, e.g.,
37 i 0.5~. Thus, the perturbations in temperature resulting from the
frequent injection of modules and removal of modules may well result
in rapid undulations of chamber temperature which can caus~ the
temperature in the vicinity of the carousel and the assay modules to be
15 outside the desired range.
In order to maintain the desired chamber temperature, and
to prevent excessive undulations due to the introduction of modules, the
pulse repetition frequency provided by the generator 350 is at least
double the rate of introduction of modules, the Nyquist criteria. For
20 example, the current pulses provided by the power source 352 may
occur at a repetition frequency of one pulse every three seconds. The
average duration of a pulse may be two seconds. This provides a
dynamic response to the temperature control system 336 which is
adequately fast to deal with the rate of module introduction. The
25 temperature sensor 306 is placed immediately above a plane containing
the top surfaces of the modules 22 so as to sense the temperature
accurately at the openings of the module compartments 106. Also, as
-32- 2~39~78
has been noted hereinabove, the volume of the upper region 286 is
minimized to reduce the amount of air which must be heated, and to
reduce the amount of air currents which might otherwise flow about
within the chamber 36.
The use of a metallic, thermally-conductive, inner sidewall
284 in conjunction with the use of the metallic, thermally-conductive top
wall 104 extends a region of heating to a major portion of the upper
region 286 for improved thermal response. It is noted that while the
bottom wall 280 and the carousel 24 are formed of polymeric material
having a relatively low conductivity, there are no openings, such as the
injection port 302, in the lower region 300 of the chamber 36 so that
the temperature of the lower region can remain stable by the inclusion
of the bottom heater 298 in the lower region 300. Therefore, it is
possible to construct the bottom wall 280 and the outer sidewall 282
of polymeric material which facilitates and lessens the cost of
manufacture, and that only the annular top wall 78 and the cylindrical
inner sidewall 284 need be formed of metal. Any suitable polymeric
material may be used for the bottom wall and the outer sidewall such as
polyurethane, polycarbonate and the like.
With respect to Fig. 11 it is noted that one aspect of
certain types of assay elements is the dependency of the test results
upon the relative humidity level in the chamber 36. One type of assay
element which exhibits humidity-affected results is the "dry" multilayer
assay element such as is described in commonly assigned, copending
United States patent application Serial No. 382,552 filed July 19,1989.
In one embodiment of such assay elements a fluorescent labeled species
is utilized in the assay method and there is provided a fluorescent
~39~7~
-33-
readout signal which is a function of the analyte or component of
interest in the fluid sample. Typically, the optical readout signal is then
applied to a standard curve developed with fluids having known
concentrations of the analyte or component of interest to obtain the
5 concentration of the sample fluid. Where the signal obtained from the
assay e!ement varies with variations in the relative humidity level within
the temperature controlled chamber, it is apparent that errors can be
introduced in the assay result because of humidity considerations.
Accordingly, it is necessary, for such assay elements, to correct the
10 readout signal such as by the use of a humidity sen~or, which can be
located within the temperature controlled chamber 36 such as on frame
304 or within the instrument 20 but outside the chamber 36. The
humidity value provided by the humidity sensor 310 is supplied to the
microporcessor 62 which is programmed to correct the output signal in
the appropriate manner.
Fig. 12 shows interconnections of the microprocessor 62
with various apparatus and sources of data employed in the instrument
20 of Figs. 1, 2, and 8. In particular, the following connections with the
microprocessor 62 are noted, namely, the temperature sensor 306 (Figs.
20 8 and 9), the humidity sensor 310 ~Figs. 8 and 9), the module ejector
58 (Figs. 1 and 8), the work station 34 (Fig. 1) providing optical
readout, a bar-code reader 358 -(Fig. 8), the mechanism for positioning
the table 68 (Fig. 2), the carousel driver unit 328 (Fig. 9), a shaft-angle
encoder 360 (Fig. 9) connected mechanically to the axle 26 and the
driver unit 328 for providing the carousel position, and the transport 64
for positioning the pipette 40 in the X and the Z directions. The
microprocessor 62 is provic;ed with a memory unit 362 showing values
2~39~78
-34-
of the set of graphs portrayed in Fig. 11. By addressin~ the memory
362 with measured values of the optical readout signal and the
humidity, the memory 362 outputs a value for the analyte or component
of interest.
5With respectto the bar-code reader 358, it is advantageous
to locate a bar code in the form of a label 364 (Fig. 8) on a side of the
module 22 to identify the module. By way of example in the locating of
the reader 358, the reader 358 may be positioned at the injection port
302 alongside a path of travel of the module 22 during insertion of the
10module 22 by the injector 58 into the chamber 36. The bar-code label
62 is placed on the side of the module 22 which faces the reader 358
so that the label 362 can be read as the module 22 passes by the reader
58 during insertion cf the module 22 into the chamber 36. The bar code
signifies to the microprocessor 62 what tests are to be made so as to
15avoid a source of error as might occur were it necessary for the operator
to instruct the instrument.
Fig. 13 is a flow chart which demonstrates use of the
microprocessor 62 in the performance of the assay of a fluid sample.
The procedure begins with injection of the module by the injector 58.
20As the arm 60 moves the module 22 past the head of the reader 358,
the bar code of the label 362 is read by the reader 358. Data read by
the reader 358 is inputted to the microprocessor 62. The module 22
passes through the injection port 302 and sits within a berth 54.
Thereupon, the module is allowed to rotate on the carousel 24 during an
25interval of time sufficiently long to allow the temperature of the module
and its contents to rise from the ambient room temperature to the
warmer temperature within the charnber 36. The specific berth 54
.,~, . .
-35- 2~39~78
which holds the module 22 is identified at the time of insertion of the
module, the identity of the berth being provided by the carousel position
as measured by the shaft-angle encoder 360 (Fig. 9).
Prior to termination of the warm-up time interval, the table
68 (Fig. 2) is positioned so as to allow the pipette 40 to obtain a new
tip 70, and to be filled with a fluid sample in a selected one of the
reservoirs 66. The pipette is loaded with the selected sample, and is
then positioned above a compartment 106 of a module 22, whereupon
the reagent is dispensed by the pipette 40 to the module 22. Data as
to the temperature and humidity of the environment within the chamber
36 is provided by the sensors 306 and 310 to the microprocessor 62.
The fluid sample administered by the pipette is allowed to react with the
reagent in the module compartment 106 for a predetermined interval of
time. The microprocessor outputs a fault signal if the temperature is
incorrect. Subsequently, any other necessary reagents are dispensed to
the module.
At the conclusion of the reagent reaction time, the module
22 is positioned at the optical readout station 34 to allow the module to
be irradiated with the appropriate excitation energy. A reading of the
emitted energy at viewing site 50 is collected and transmitted to the
microprocessor where it is adjusted for the relative humidity as
described above herein. Upon completion of the assay the assay module
is removed from the chamber. Thus, the analytical instrument of the
invention can carry out a plurality of assays in an efficient manner.
It is to be understood that the above described
embodiments of the invention are illustrative only, and that modifications
thereof may occur to those skilled in the art. Accordingly, this invention
-36- 2~39~8
is not to be regarded as limited to the embodiments disclosed herein, but
is to be limited only as defined by the appended claims.
