U.S. patent number 3,767,364 [Application Number 05/167,379] was granted by the patent office on 1973-10-23 for reagent pipette system.
This patent grant is currently assigned to Sherwood Medical Industries. Invention is credited to David Scott Beckham, David Alan Ritchie.
United States Patent |
3,767,364 |
Ritchie , et al. |
October 23, 1973 |
REAGENT PIPETTE SYSTEM
Abstract
A testing apparatus for automatically determining prothrombin
times and other similar factor assays. A turntable conveyor moves
successive blood plasma samples in containers to a test station
where each sample is tested, pertinent information sensed and fed
to a printer for readout. Preliminary to the testing station is a
first reagent dispenser where a reagent is dispensed to each sample
and a second reagent dispenser is located at the testing station
for adding a second reagent. Intermediate the two reagent
dispensers is a sample incubation device which intimately contacts
each container to apply heat thereto to incubate the sample
contained therein. Each reagent dispenser is provided with a
reagent reservoir and associated magnetic stirring system. A unique
system for decoupling the magnetic stirring system from a magnetic
stirrer and moving the magnetic stirrer out of the path of a
pipette forming part of each reagent dispenser is provided. At the
testing station, a unique photosensitive detection device is
provided for sensing the formation of clots after the second
reagent is added.
Inventors: |
Ritchie; David Alan (St. Louis,
MO), Beckham; David Scott (St. Louis, MO) |
Assignee: |
Sherwood Medical Industries
(St. Louis, MO)
|
Family
ID: |
22607136 |
Appl.
No.: |
05/167,379 |
Filed: |
July 30, 1971 |
Current U.S.
Class: |
422/50; 422/561;
141/130; 422/64 |
Current CPC
Class: |
G01N
35/025 (20130101); G01N 2035/00534 (20130101); G01N
2035/00376 (20130101) |
Current International
Class: |
G01N
35/02 (20060101); G01N 35/00 (20060101); B01l
003/02 (); G01n 001/14 () |
Field of
Search: |
;23/253R,253A,259
;141/130 ;73/425.6 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Wolk; Morris O.
Assistant Examiner: Marantz; Sidney
Claims
We claim:
1. A reagent pipette system for withdrawing a reagent from a
reservoir and conveying the reagent to a point of use comprising: a
pipette; means mounting said pipette for movement between a first
position whereat the pipette is at a point of reagent use, a second
position whereat the pipette overlies a reagent reservoir, and a
third position wherein said pipette is within a reagent reservoir;
a pump operatively associated with said pipette for drawing a
predetermined quantity of reagent into said pipette when said
pipette is in said third position and for discharging the reagent
from said pipette when said pipette is in said first position; and
a common operator for said pipette and said pump comprising a
single cam, a first cam follower associated with said cam for
operating said pump, and a second cam follower associated with said
cam and coupled to said pipette for moving said pipette between
said positions.
2. The reagent pipette system of claim 1 wherein said cam includes
a first cam surface defined by a cam track engageable with said
second cam follower, and a second cam surface defined by the
periphery of the cam which is engageable with said first cam
follower.
3. The reagent pipette system of claim 2 wherein said cam is a
barrel cam and said second cam surface defined by the periphery of
the cam is located on one end of said barrel cam.
4. The reagent pipette system of claim 1 further including a lever;
means pivotally mounting said lever; means securing said lever to
said pipette; said second cam follower being secured to said lever
and responsive to said cam for pivoting said lever about a
substantially horizontal axis; and means associated with said
pipette and responsive to up and down movement of the same for
pivoting said pipette about a substantially vertical axis between
said first and second positions.
5. The reagent pipette system of claim 4 wherein said last-named
means comprises a pivotal shaft mounting said pipette and including
an outwardly extending pin comprising a third cam follower, and a
fixed cam for said third cam follower including a vertical cam
surface terminating in an angularly directed cam surface whereby as
said shaft is moved upwardly or downwardly, said angularly directed
cam surface will pivot said pipette between said first and second
positions.
6. A reagent pipette system for delivering a reagent from a
reservoir to a point of use comprising: stationary mounting means;
a pipette; a shaft connected to said pipette, means for mounting
said pipette and said shaft to said mounting means for movement
relative thereto, said shaft being mounted for pivotal movement
between a first position whereat said pipette overlies a point of
use and a second position whereat said pipette overlies a reagent
reservoir, said shaft further being mounted for reciprocating
movement to move said pipette from said second position to a third
position into the reservoir; pump means stationarily mounted to
said mounting means and connected in fluid communication with said
pipette; pump operating means operative when said pipette is in the
reservoir for drawing a reagent into the pipette and operative when
said pipette is in said first position for discharging the reagent
contained therein; first cam means for reciprocating said shaft;
and second cam means responsive to reciprocation of said shaft for
effecting said pivotal movement of said shaft between said first
and second positions.
7. The reagent pipette system of claim 6 wherein said first cam
means comprise a cam operated lever secured to said shaft.
8. The reagent pipette system of claim 6 wherein said second cam
means comprise a cam follower and a cam track, said cam track being
vertically arranged and having an angular extension at its upper
end, said cam follower engaging said cam track, one of said cam
track and said cam follower being mounted on said shaft and the
other of said cam track and said cam follower being stationarily
mounted adjacent said shaft.
9. A reagent pipette system for delivering a reagent from a
reservoir to a point of use comprising: a main shaft coupled to
said pipette for rotating said pipette about the axis of said shaft
between a first position wherein said pipette overlies a point of
use and a second position wherein said pipette overlies a reagent
reservoir, and for moving said pipette axially between said second
position and a third position wherein said pipette is within said
reservoir; means for operating said shaft comprising first cam
means, motor means coupled to said first cam means for rotating
said first cam means, said first cam means having a cam surface
thereon, a cam follower engaged with said cam surface and coupled
to said shaft for moving said shaft axially and effecting movement
of said pipette between said second and third positions in response
to rotation of said first cam means, and second cam means coupled
to said shaft for effecting rotational movement of said pipette
between said first and second positions in response to
predetermined axial movement of said shaft, fluid pump means
connected in fluid communication with said pipette, and third cam
means coupled between said pump means and said first cam means for
operating said pump means in response to predetermined rotation of
said first cam means to draw reagent into said pipette from said
reservoir when said pipette is in said third position, and to
discharge reagent from said pipette when said pipette is in said
first position.
10. The reagent pipette system of claim 9 wherein said pump means
is a piston pump which includes a pump shaft, and said third cam
means includes a second cam surface on said first cam means, and a
second cam follower connected to said pump shaft and engaged with
said second cam surface to effect reciprocal movement of said pump
shaft and operation of said piston pump in response to rotation of
said first cam means.
11. The reagent pipette system of claim 10 further including
stationary mounting means supporting said pipette and said pump
means, means mounting said pipette for rotary movement relative to
said mounting means and said pump means, and wherein said second
cam means comprises a third cam follower and a cam track engageable
with said third cam follower, one of said third cam follower and
said cam track is mounted to said mounting means and the other of
said third cam follower and said cam track is connected to said
main shaft.
Description
BACKGROUND OF THE INVENTION
This invention relates to medical testing devices and more
particularly, to medical testing devices wherein a change in an
optical characteristic of a sample is sensed, for example, in the
determination of prothrombin times.
Increasingly, the population has relied upon competent medical
assistance to solve individual medical problems to a greater and
greater extent. This factor, coupled with the ever-growing wealth
of medical knowledge, has resulted in a vast upsurge in the number
of tests of various types performed as part of the diagnosis or
health monitoring process and an increasing unavailability of
competent personnel to perform such tests. As a result of the
increase in demand for such services, the cost of performing the
same has gone up as well. Thus, not only can it be difficult to
obtain qualified personnel to perform such tests, but the costs of
such services are oftentimes prohibitive and, even under the best
of conditions, the human factor is generally present thereby
raising the possibility the test will be improperly conducted or
its results improperly determined.
As a result, there is an increasing need for apparatus for
performing such tests in an inexpensive fashion, which apparatus
can be operated by relatively unskilled personnel and which will
eliminate most opportunities for unreliability of results due to
human error.
SUMMARY OF THE INVENTION
The principal object of the invention is to provide a new and
improved testing device for automatically performing tests on
samples for the medical field. More particularly, it is an object
of the invention to provide a testing apparatus that is
particularly suited for automatically determining prothrombin times
and other similar tests.
A further object of the invention is to provide a new and improved
optical detection system for detecting an optical change in a
sample; a new and improved sample incubation mechanism; a new and
improved automatic reagent pipetting system; and a new and improved
reagent reservoir and stirring system, all for use in various forms
of testing apparatus.
The exemplary embodiment achieves the foregoing objects with a
construction employing a sample conveyor in the form of a turntable
which may receive a plurality of sample-holding containers and
stepwise convey the same through a first reagent dispensing
station, a sample incubation station; and a combined second reagent
dispensing station and testing station. At the testing station, an
optical detecting system is employed to determine optical changes
in the sample as, for example, clot detection in a prothrombin
test. The time required for such clotting after dispensing of a
second reagent into the sample is then recorded and printed out on
a printer.
The optical system at the testing station employs a light source on
one side of the path of movement of the samples and a
photosensitive element on the opposite side of the path. On the
light source side there is provided a high-pass, red filter for the
purpose of eliminating the effects of variations in optical
absorption from one plasma sample to another. On the photosensitive
element side of the path, there is provided a collimated hole
structure to serve as a mask for light passing through the sample
and a diffuser in the form of an elongated light pipe. The
photosensitive element is arranged transverse to the direction of
elongation of the light pipe and the system is generally
insensitive to optical noise for increased reliability in accurate
detection of optical changes.
The unique incubation means employed comprise an arcuate,
heat-conductive block, formed of a material such as aluminum which
is mounted for movement into and out of the path of movement of the
sample containers. The block includes a plurality of recesses for
receiving individual sample containers and has an electric heater
associated with the same. A solenoid is employed to move the block
into and out of the path of movement of the containers and is
operated conjointly with an operating means for the turntable so
that when the turntable operates to index the next sample to the
testing station, the block is drawn out of the path until such
indexing is completed whereupon it is permitted to move back into
the path. In the path, the sample containers are received within
the recesses in the block and uniformly incubated to a desired
temperature.
The reagent pipetting system involves a pipette mounted on a rotary
and reciprocating shaft for (1) rotational movement between a
position overlying a sample container in the turntable and a
position overlying a reagent reservoir, and (2) reciprocable
movement between the last-named position and a position within the
reservoir at which the reagent may be drawn into the pipette for
subsequent dispensing into the sample. A piston pump is associated
with the pipette and is operated by a cam to cause reagent to be
drawn into the pipette when the pipette is in the reservoir and
dispensed from the pipette when the pipette overlies a sample. The
same cam is also operative to control movement of the pipette
between the three above-mentioned positions by means of a follower
connected to a lever which in turn is connected to the shaft
mounting the pipette to reciprocate the shaft. Another cam
arrangement including a cam follower affixed to the shaft mounting
the pipette and a stationary cam is responsive to reciprocation of
the shaft to impart rotation thereto to ultimately move the pipette
between the first two positions mentioned above.
The magnetic stirring system is particularly suited for operation
in conjunction with the reagent type pipetting system. A reservoir
in the form of an inverted, truncated cone is employed and beneath
the bottom thereof, a movable magnet for establishing a movable
magnetic field is provided so that a magnetic stirring bar within
the reservoir will be moved to stir the contents of the same. Means
are provided for disabling the moving magnetic field establishing
means and for moving the magnetic stirring bar out of the path of
the pipette as it descends into the reservoir and comprise a lever
including a magnetic shield interposable between the movable magnet
and the bottom of the reservoir to break the magnetic coupling
between the movable magnet and the magnetic stirring bar. The lever
also mounts a generally upright magnet which is moved to a position
adjacent the reservoir to draw the magnetic stirring bar to the one
side thereof. The lever is operated by a cam follower adapted to be
engaged by an element movable with the shaft mounting the pipette
as mentioned in the preceding paragraph.
Other objects and advantages of the invention will become apparent
from the following specification taken in conjunction with the
accompanying drawings.
DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective of a testing device made according to the
invention contained generally within a housing;
FIG. 2 is a plan view of the sample conveyor, two pipetting
systems, two magnetic stirring systems and the incubator block with
parts broken away for clarity;
FIG. 3 is a vertical section taken of the sample conveyor;
FIG. 4 is a vertical section taken approximately along the line
4--4 of FIG. 2;
FIG. 5 is a side elevation of a reagent pipetting system;
FIG. 6 is a side elevation of the reagent pipetting system taken at
approximately 90.degree. to the showing in FIG. 5;
FIG. 7 is a vertical section taken approximately along the line
7--7 of FIG. 2;
FIG. 8 is a vertical section taken approximately along the line
8--8 of FIG. 2; and
FIG. 9 is a block diagram of one form of a control system that may
be employed in the invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
GENERAL DESCRIPTION
As generally alluded to previously, a testing device made according
to the invention is ideally suited for performing and recording
results of prothrombin tests or other similar tests, although it
will be recognized by those skilled in the art that a goodly number
of the various mechanisms and structures hereinafter described are
susceptible to use in other testing devices or systems which
perform tests totally different from prothrombin or related tests
and, for that matter, with the non-chemical tests. Thus, while the
invention will be described in conjunction with the prothrombin
time test, it is to be understood that the same is not to be
considered to be so limited except as expressly stated in the
appended claims.
Prothrombin time tests measure the clotting time of blood plasma
and may be of either the one reagent or two reagent variety.
Specifically, in performing prothrombin time tests, a plasma sample
has both calcium chloride solution and thromboplastin introduced
into the same. In a one reagent test, the calcium chloride and
thromboplastin are combined and a desired amount of the combined
mixture is introduced into the sample. For many purposes, a single
reagent test is sufficient but where stability of the
thromboplastin is of concern, as when the tests are performed
relatively infrequently, or in large batches, it is desirable to
maintain the thromboplastin and the calcium chloride solution
separate to prolong the stable life of the thromboplastin.
As will be seen, the apparatus is ideally suited for either type of
test but will be specifically described in conjunction with the two
regent test which requires a greater number of systems than does
the single reagent test.
In particular, a conveyor is loaded with cuvettes containing the
plasma samples to be tested and the conveyor is stepwise advanced
automatically from a starting point to a first regaent dispensing
station where the first reagent, at room temperature, is forcibly
added to and thereby mixed with the sample. As the conveyor is
stepwise advanced, each succeeding sample receives the first
reagent at the reagent dispensing station while those samples
having already received the first reagent are advanced to an
incubating station where each sample is heated to a predetermined
temperature prior to being advanced to a second reagent dispensing
station which coincides with a testing station. As each sample
reaches the second reagent dispensing station, the second reagent,
heated to the desired incubation temperature, is forcibly added to
and thereby mixed with that sample and a clock started. Upon a
change in the optical density of the sample due to the formation of
fibrin strands, an optical detecting system detects the change and
stops the timing device whereupon the results are printed out and
the turntable indexed for testing of the next succeeding sample.
The optical detecting system is disabled for an initial period so
as to overlook optical turbulence created by forcible injection of
the reagent.
DETAILED DESCRIPTION
Housing Structure
An exemplary embodiment of a testing device made according to the
invention is illustrated in FIG. 1 and is seen to comprise a
housing, generally designated 20, having a control panel 22. A
turntable conveyor 24 is generally flush with the upper side of the
housing 20 and is employed to advance a series of samples through
the various stages mentioned previously in a stepwise fashion as
will be seen. The upper side of the housing 20 also mounts a pair
of reservoirs 26 and 28, each of which is adapted to receive a
different one of the reagents employed in a two reagent test.
Associated with each reservoir is a corresponding reagent pipetting
system, generally designated 30 and 32, respectively, each
including a volume adjustment knob 33 and a pipette 34.
The housing 20 is completed by a cutout 36, in a pivotal door 41
from which a results tape bearing the printed results of tests may
emerge. A manual operator 40 for the tape 38 is also provided. The
door 41 may be opened for replacement of the tape 38.
CONVEYING SYSTEM
Referring now to FIGS. 2 and 3, the turntable 24 is formed of a
disc 42 having a plurality of apertures 44 about all but about 60
degrees of its periphery. According to one embodiment of the
invention, sixty of the apertures 44 are provided and the disc 42
is provided with indicia 46 indentifying each aperture 44. The
apertures received cuvettes containing the sample to be tested.
The disc 42 is secured by means of screws 48 to a mounting plate 50
underlying the disc 42 and is provided with a cap 52 for covering
the screws 48. The resulting assemblage is secured to a shaft 54
which is journalled in bearings 56 and mounts a large, driven gear
58 in engagement with a small, drive gear 60 (FIG. 2) mounted on
the output shaft 62 of an electric motor 64 having a built-in gear
reduction system. The arrangement is such that energization of the
motor 64 will ultimately cause the disc 42 to be rotated in a
counterclockwise direction as viewed in FIG. 2.
The bearings 56 are mounted in the central aperture of a mounting
platform 66 which is elevated above the bottom of the housing 20 by
posts 68. A portion of the shaft 54 extends through the lowermost
one of the bearings 56 and provides a shaft extension 70 of reduced
diameter. The reduced diameter shaft 70 has secured thereto, a hub
72 which in turn mounts an encoder plate 74 having printed circuit
segments 76 (FIG. 2) on its upper surface. The encoder plate 74
rotates with the turntable 24 and by configuring the printed
circuit segments 76 in a manner known in various arts, a binary
coded signal may be obtained from the same which is indicative of
the particular one of the apertures 44 located at the testing
station for correlation of sample number with test times. To this
end, the underside of the platform 66 mounts an insulating bracket
78 which, in turn, mounts a plurality of depending electrical
brushes 80 which engage the printed circuit segments 76 for picking
off sample position information for employment elsewhere in the
system to correlate the results with sample number.
In addition to the drive gear 60, the motor shaft 62 mounts a
timing cam 82 configured substantially as shown in FIG. 2 and which
is in engagement with switch operators 84 and 86 of microswitches
88 and 90 respectively. The microswitch 88 may be employed in a
conventional motor control system for maintaining energization of
the motor 64 when its operation has been initiated by the
completion of a test, or by manual means, and for terminating
energization of the motor 64 when the next cuvette has been moved
to the testing station. Microswitch 90 may be employed in a
conventional motor control system for initiating pipette operation
as sample cuvettes move beneath pipette stations.
REAGENT RESERVOIR AND MAGNETIC STIRRING SYSTEM
A preferred form of reagent reservoir and magnetic stirring system
is illustrated in FIGS. 2 and 4 and will now be described. As
stated previously, two such systems 26 and 28 are employed and the
two are identical with the exception that one is the mirror image
of the other and the reagent reservoir 26 is equipped with a
heating element and control therefor (not shown) for maintaining
the contents of the reservoir at a desired temperature.
More particularly, the reagent reservoir and magnetic stirring
system 26 includes a reservoir block 100 having an inverted,
frustoconical recess 102 in its upper surface. The recess 102 is
adapted to receive a similarly configured reagent cup 104 which may
contain a reagent and which, in turn, may receive a magnetic
stirring bar 106 which may be coated with Teflon or the like to
insure inertness with respect to a reagent within the
reservoir.
Mounted on the underside of the block 100 by means of cap screws
108 and a mounting bracket 110 is an electrical motor 112 having a
rotary output shaft 114 which mounts a permanent magnet 116 for
rotation just below the bottom of the recess 102. As is well-known,
when the motor 112 is energized, the resulting rotation of the
magnet 116 will establish a moving magnetic field within the recess
102 which, in turn, will cause the magnetic stirring bar 106 to
rotate to stir the contents of the same.
As mentioned generally previously, the pipettes 34 are adapted to
be moved into the respective one of the reservoirs 26 and 28 for
the purpose of withdrawing reagent from the same and conveying the
reagent to a point of use whereat it may be discharged into a
sample-containing cuvette in the turntable 24. In order to minimize
the amount of reagent required in a reservoir sufficient to permit
automatic operation of the pipetting systems, and to promote
maximum stirring efficiency, the reservoir recesses 102 are
frusto-conical as mentioned previously. However, the presence of
the magnetic stirring bar 106 in the reservoir will not permit the
pipette 24 to fully move to the bottom of the reservoir without
interference that could possibly damage the pipette. While the
possibility of such interference could be precluded by limiting the
downward movement of a pipette 34 into the reservoir, such would
require the use of more reagent than necessary in order to maintain
the level in the reservoir at a sufficient height so as to be
reachable by the pipette 34.
Accordingly, means are provided for simultaneously decoupling the
movable magnet 116 and the stirring bar 106 while drawing the
latter to a position adjacent the side of the reservoir when the
pipette 34 is entering the latter. As viewed in FIGS. 2 and 4, a
pivot stud 118 is received in a bore 120 in the block 100 and
mounts a lever 122 for pivotal movement about a vertical axis at a
height wherein a magnetic shield 124 integral with the lever 122
may be interposed between the bottom of the reservoir and the
movable magnet 116. The shield 124 breaks the magnetic coupling
between the magnet 116 and the magnetic stirring bar 106 so that
the latter will cease to rotate with the magnet 116.
The lever 122 also mounts a generally upstanding magnet 126 by
means of a bracket 128 and a screw 130 for movement to a position
in a notch 132 adjacent one side of the recess 102. Thus, when the
magnetic coupling between the magnet 116 and the magnetic stirring
bar 106 is broken by the interposition of the shield 124, the
magnet 126 will simultaneously establish a stationary magnetic
field within the reservoir 102 which will draw the magnetic
stirring bar to the side of the reservoir and hold the same
stationary so that a pipette 34 may move into the reservoir to the
bottom thereof during the reagent withdrawing process.
Control of the position of the lever 122 is obtained by means of a
cam follower extension 134 mounting a wear piece 136 which may be
engaged by a cam element movable with the pipette as will be
described in greater detail hereinafter. With reference
specifically to FIG. 2, and particularly to the system 26, when the
pipette system 30 is activated to move its respective pipette 34 to
a position overlying the reservoir 26, a cam associated therewith
will engage the wear piece 136 to cause the lever 122 to pivot in a
clockwise direction to interpose the shield 124 between the magnet
116 and the magnetic stirring bar 106 and simultaneously position
the magnet 126 to pull the stirring bar 106 to the side of the
reservoir. When the pipetting system 30 has withdrawn a reagent
from the reservoir and returned to the position illustrated in FIG.
2, a spring 138 returns the lever 122 to the position illustrated
in FIG. 2 with the result that stirring will once again be
resumed.
REAGENT DISPENSERS
The reagent dispensing system may best be understood with reference
to FIGS. 2, 5 and 6. As mentioned previously, two such systems 30
and 32 are provided and each is identical to the other with the
exception that one is a mirror image of the other. With reference
specifically to FIGS. 5 and 6, each reagent dispenser is seen to
comprise a base 150 mounted an elevated mounting plate 152 by means
of spacing posts 154. The mounting plate 152, in turn, mounts an
electric motor 156 having a reduction gear train 158 operatively
associated with its output shaft. An output shaft 160 of the
reduction gear train 158 extends through a bore 162 in the plate
152 downwardly to a cam shaft 164. The cam shaft 164 is journalled
for rotation between the base 150 and the mounting plate 152 by
means of bearings 166 and mounts a barrel cam 168.
The barrel cam 168 includes two cam surfaces for operating a pump
for the reagent dispenser and for moving a pipette associated
therewith between a first position wherein the same overlies a
sample-holding container or cuvette in the turntable, a second
position wherein the pipette overlies the associated reservoir, and
a third position wherein the pipette is within the reservoir. More
particularly, the barrel cam 168 is generally cylindrical and
includes a peripheral, first cam surface 170 on its upper end which
is adapted to cooperate with a cam follower 172 mounted on the
lower end of a shaft 174 of a piston pump 176.
The piston pump 176 may be of conventional construction and of the
type wherein the shaft 174 is spring-urged downwardly so that when
the shaft 174 is moved upwardly by the cam surface 170, material in
the system will be expelled while when the shaft 174 is permitted
to move downwardly by reason of the biasing of the internal spring,
material may be drawn into the pipetting system.
To the foregoing end, the upper end of the pump 176 is in fluid
communication with a flexible tubing 178 which may be formed of
polyvinyl chloride or the like and which passes through a grommet
180 into an inverted can-like structure 182. Near the upper end of
the canlike structure 182 there is provided an outwardly extending
arm 184 terminating in a downturned connector 186 to which one of
the pipette tips 34 may be secured. Within the arm 184 is a conduit
188 which, by means of a connector 190 provides for fluid
communication between connector 186 and the tubing 178. Thus, when
a pipette associated with the arm 188 is within the reservoir and
the pump shaft 174 moves downwardly, reagent will be drawn into the
same while when a pipette associated with the arm 188 is overlying
a sample-containing cuvette on the turntable 24 and the pump shaft
174 is moved upwardly, reagent within the pipette will be expelled
into the cuvette.
In order to insure that a proper quantity of reagent is accurately
delivered, adjustment means for controlling the permissible stroke
of the pump shaft 174 are provided. Since prothrombin tests may
frequently be performed employing 0.1 ml of reagent or 0.2 ml of
reagent, means are provided for independently adjusting the stroke
of the pump shaft 174 between two positions for the two
corresponding quantities.
More specifically, an L-shaped bracket 192 is secured to the upper
surface of the mounting plate 152 and includes a keyhole slot 194
which receives the pump 176. To tightly secure the pump at a
desired attitude with respect to the bracket 192, a cap screw 196
may be employed to tightly close the confines of the slot 194 about
the periphery of the pump 176 to hold the same in position.
Mounted on the shaft 174 of the pump 176 intermediate the cam
follower 172 and the lower end 198 of the pump is an adjustable
collar 200. The collar may be secured at a desired location on the
shaft 174 by means not shown.
The L-shaped bracket 192, in addition to the pump 176, mounts a
rotatable shaft 202 on which the volume control knob 33 may be
received. The lower end of the shaft 202 extends through an
appropriate bore in the mounting plate 152 and mounts a laterally
projecting stop arm 204. The arrangement is such that for one
position of rotation of the shaft 202, the arm 204 will be in the
path of the collar 200 to restrict downward movement of the shaft
174 under influence of the internal spring of the pump 176. Thus,
for purposes of securing a 0.1 ml delivery of reagent, the collar
200 may be so located on the shaft 174 that the stroke applied to
the shaft 174 by the cam surface 170 will deliver the appropriate
volume.
For another position of rotation of the shaft 202, the stop arm 204
will not interfere with downward movement of the collar 200 to
permit a delivery of a greater volume of reagent, as for example,
the previous mentioned 0.2 ml. To control the precise volume of
such a larger delivery, a second adjustable mechanism is provided.
Specifically, to one side of the shaft 174, there is provided a
threaded bore in the plate 152 which may receive a cap screw 206.
Near the lower end of the cap screw 206, there is provided a nut
208 mounting a stop disc 210 having a diameter sufficiently great
that it will interfere with downward movement of the collar 200 as
best illustrated in FIG. 5. Thus, by appropriately adjusting the
cap screw 206 and thus the position of the stop disc 210, a second,
greater delivery may be precisely controlled.
Returning to the barrel cam 168, the same includes a second cam
surface in the form of a cam track 220 receiving a cam follower
222. The cam follower 222 is secured to a lever 224 intermediate
its ends. As best viewed in FIG. 5, the left-hand end of the lever
224 is pivotally mounted by means of a pin 226 in an upstanding
yoke 228 secured to the base plate 150. The opposite end of the
lever 224 terminates in a yoke 230 having inwardly projecting pins
232 (only one of which is shown) received in a groove 234 in a
spool-like structure 236. The spool-like structure 236 is, in turn,
secured to the lower end of a shaft 238 which passes upwardly
through a bore in the plate 152 to be slidably received in an
upstanding sleeve 240 secured to the mounting plate 152. The upper
end of the shaft 238 extends through the sleeve 240 to be received
in a mounting bracket 242 secured within the can-like structure
182. Bracket 242 is secured to pipette arm 188 and is vertically
and angularly adjustable on shaft 238 to accurately position the
pipette with respect to the reagent reservoirs and sample cuvettes.
As a result, rotation of the barrel cam 168 will impart oscillatory
movement to the lever 224 about the pivot 226 which will result in
reciprocation of the shaft 238 within the sleeve 240 to ultimately
move a pipette 34 secured to the arm 188 upwardly and downwardly
as, for example, into and out of a reagent reservoir.
To cause movement of the pipette from a position overlying a
cuvette on a turntable to the position overlying the reservoir, a
cam system including the sleeve 240 is provided to be responsive to
the reciprocatory motion of the shaft 238. As seen in FIGS. 5 and
6, an outwardly extending pin 244 is secured to the shaft 238 and
is received in a generally vertically arranged slot 246 in the
sleeve 240. The upper end of the slot 246 terminates in an angular
extension 248 with the result that when the pin 244 is moved
upwardly into the extension 248, the shaft 240, and thus the arm
188 will pivot from a position overlying the reservoir to a
position overlying a cuvette. Of course, when the pin 240 moved
downwardly in the slot, the pivoting action will be the
reverse.
To insure cooperation of the reagent dispensers and the reagent
reservoir and stirring system, an outwardly extending arm 250 is
secured to the shaft 238 for rotation therewith. Extending upwardly
from the arm 250 is a cam arm 252 which is adapted to abut the wear
piece 136 on the lever 122 controlling the magnetic stirrer. The
arrangement is such that during initial downward movement of the
pin 244 within the slot 248 as the pipette moves from the first
position overlying the cuvette to the second position overlying the
reagent reservoir, the simultaneous pivoting of arm 250 will cause
the cam arm 252 to engage the lever 122 and pivot the same to a
position wherein the magnetic stirrer is rendered inoperable and
the stirring bar is drawn to the side of the reservoir.
The dispensing system is completed by a pair of cams 254 and 256 on
the cylindrical periphery of the barrel cam 168 which are adapted
to respectively engage the actuators of microswitches 258 and 260
respectively. Microswitch 258 is part of a conventional control
circuit for the motor 156. That is, once the motor 156 is energized
by the remainder of the system, and assuming that a cuvette is
present at a dispensing station, the microswitch 258 may be
employed to maintain energization of the motor after once being
initially energized and for terminating operation of the motor 156,
respectively, once the same has caused the barrel cam 168 to rotate
through a complete revolution. Microswitch 260 provides an
electrical pulse to signal completion of the pipetting cycle and
start of the test counter as it operates on cam 256.
INCUBATING SYSTEM
The incubation system may be understood with reference to FIGS. 2,
7 and 8 and is seen to include an elongated, heat-conductive block
270 which may be formed of a material such as aluminum. Because of
the circular nature of the path through which the sample-holding
cuvettes are moved, the block 270 is arcuate as best seen in FIG. 2
and as illustrated in FIG. 7, includes a plurality of upwardly
opening recesses 272 underlying the disc 42 comprising the
turntable 24. The recesses are configured to snugly receive the
lower end of a sample-containing cuvette and to insure easy
register, are provided with outwardly flared upper ends 274.
The block 270 is received in a channel-like casting 276 for up and
down movement therein. That is, during rotation of the turntable
24, the block 270 is moved downwardly within the channel so that
sample-containing cuvettes may freely pass over the upper surface
of the block 270 while when the turntable 24 is motionless, the
block 270 is moved upwardly so that cuvettes are received within
the recesses 272 for incubation. To achieve such movement, the
center of the block 270 includes a downwardly extending shaft 278
which passes through a bushing 280 to be connected to the armature
282 of a solenoid 284. The arrangement is such that when the
solenoid 284 is operated, its armature 282 will be moved downwardly
from the position illustrated in FIG. 7 to move the block 270
downwardly. To return the block 270 to its elevated position, a
coil spring 286 surrounds the armature 282 to provide an upward
biasing force against the shaft 278.
Accurate adjustment of block 270 to its proper elevated position is
accomplished through movement of an adjustable stop collar 271 on
shaft extension 290. Stop collar 271 is of large enough diameter to
prevent its passage through the hole of bushing 273 on solenoid
284. Thus when stop collar 271 is fixed to shaft extension 290 with
a set screw, upward travel of block 270, when returned by spring
286, is limited by stop collar 271 as it comes into contact with
bushing 273. With block 270 adjusted to its proper elevated
position, recess 272 at test location 322 is positioned so that
when a sample cuvette is contained therein, that sample cuvette is
slightly lifted off the surface of disc 42. For this purpose, the
recess 272 at test location 322 is not as deep as the remaining
recesses to lift the cuvette off of turntable 42 only at station
322.
Lifting the sample cuvette off the surface of disc 42 mechanically
isolates the cuvette from the disc 42 and prevents movement or
mechanical shock transmitted to the disc 42 from being conveyed to
the sample cuvette, which may cause optical density variations in
the detection system.
When the block 270 is to moved downwardly and out of the path of
movement of the cuvette, it is desirable that such action be
accomplished rapidly while when movement in the opposite direction
to engage cuvettes is desired, it is preferable that such movement
occur at a significantly lesser rate so that upward movement of the
block 270 will not cuase the same to slam against the undersides of
cuvettes supported by the turntable 24. To this end, any suitable
linkage such as that illustrated schematically at 288 connects the
lower end of an extension 290 of the solenoid armature 282 to a
one-way dashpot 292 of conventional construction. That is, the
dashpot 292 will conventionally include a check valve operatively
associated with a compression chamber while the linkage 288 will be
connected to a piston of the dashpot so that upon downward movement
of the piston within the chamber, gas will not be compressed, but
rather, will be permitted to freely exit the chamber through the
check valve. However, during upward movement of the piston by
reason of the biasing of the spring 286, the check valve will close
and gas flow into the chamber will be restricted by a bleeder line,
generally adjustable, so that a partial vacuum will exist to retard
the rate of upward movement. The slower rate of upward movement
precludes slamming as mentioned previously and insures accurate
registry of the bottoms of each cuvette with the respective
recesses 272.
To impart heat to the samples via the block 270, silicone rubber
strip heating elements 294 are secured to the underside of the
block 270 and are provided with electrical current by leads 296
(only one of which is shown) extending upwardly to the heaters 294
through a bore 298 electrically isolated by a grommet 300. Sponge
pads 299 are interposed between heaters 294 and casting 276 to
thermally insulate the casting and provide additional damping when
the block 270 contacts casting 276.
To accurately control the temperature of the block 270 so that the
samples may be incubated to a predetermined desired temperature, a
typical temperature sensing element such as a thermistor 302 is
mounted in the block 270. Extending downwardly from the block 270
is a lead protecting tube 304 which slidably passes through a bore
306 in the casting 276 and which houses electrical leads 308 for
connection to a control circuit for the strip heaters 294.
As illustrated in FIG. 7, a plurality of the recesses 272 are
provided with the number being sufficient in conjunction with the
residence time of a particular sample at any one of the points to
which it may be moved by the turntable 24 to insure that each
sample is brought up to the desired incubation temperature before
it is advanced to the testing station.
TESTING STATION AND CUVETTE SENSORS
The nature of the testing station as well as cuvette sensors may be
ascertained from FIGS. 2 and 8. With regard first to the cuvette
sensors, it should be noted that at two stations designated 320 and
322 respectively in FIG. 2, reagents may be added to cuvettes. Of
course, if a cuvette is not present, the reagent should not be
dispensed and to this end, each of those stations is provided with
a cuvette sensor. As illustrated in FIG. 8, each cuvette sensor
includes a light source 324 received in a horizontally extending
bore 326 in the casting 276 which terminates in a small,
horizontally directed opening 328 confronting the channel defined
by the casting 276. Aligned with the opening 328, but on the
opposite side of the channel therefrom is a similar opening 330
confronting a bore 322 which is closed by a photosensitive element
such as a photosensitive resistor 334. Interposed between the
aperture 330 and the photosensitive element 334 is a collimated
hole structure 336 (commercially available from the Brunswick
Corporation) which is held in place against the end of the bore 332
by a small coil spring 338 interposed between the photosensitive
element 334 and the collimated hole structure 336.
The collimated hole structure 336 is a small cylindrical disc
having a plurality of very small openings passing through the same
in a direction generally parallel to its cylindrical axis. For
example, a disc a quarter inch in diameter may have as many as
5,000 such passages extending through the same. The purpose of the
same is to serve as a mask for the photosensitive element 334 so
that the same will not improperly sense a change in light condition
due to changes in ambient light. That is, the collimated hole
structure 336 will preclude light rays not nearly parallel such as
those emanating from substantially any source but the lamp 324 from
passing to the photosensitive element 334. To further insure
accurate detection, the lamp 324 may be of the type having a lens
340 integral with its envelope for insuring that substantially
parallel rays of light are directed toward the collimated hole
structure 336 and the photosensitive element 334.
To provide for cuvette detection, the upper ends of the cuvettes
may be frosted so as to scatter light emanating from the source 324
and preclude its passage to the photosensitive element 334. Thus, a
condition of low illumination of the latter will be indicative of
the presence of a cuvette. On the other hand, when no cuvette is
present, light will freely pass to the same and substantial
illumination of the photosensitive element 334 will be taken as an
indication that no reagent should be dispensed. Through appropriate
interlock control circuitry of a conventional nature, the
indications of the photosenstive elements 334 may be taken to
inhibit operation of their associated reagent dispenser.
With regard to the testing station, the same exists only at the
point 322 and is also illustrated in detail in FIG. 8. In
particular, at the point 322, the casting 276 is provided with a
second light source receiving bore 350 which may receive a light
bulb 352 again of the type having a lens 354 integral with its
envelope for providing a source generating substantially parallel
rays of light in the beam emanating therefrom. The bore 350
terminates in an opening 356 of slightly decreased diameter and
interposed between the opening 356 and the light bulb 352 is a
high-pass filter 358. In the case of prothrombin time tests, the
filter 358 will typically be red and of a type that will not permit
the passage of wave lengths below 600 nanometers so as to eliminate
in results, the effects of variations in individual blood
plasma.
Aligned with the opening 356 but on the opposite side of the
channel is a similar opening 360 and a second collimated hole
structure 362. The collimated hole structure 362 is received in a
bore 364 which is plugged at one end as at 366 and which includes a
diffuser in the form of a section of light pipe 368. The function
of the collimated hole structure once again is to prevent improper
detection of a change in light condition due to changes in ambient
light. A photosensitive element 370 again, preferably a
photosensitive resistor, is received in a bore 372 that is
transverse to the bore 364 so that the photosensitive element 370
is exposed to a side of the light pipe 368. The purpose of the
foregoing arrangement is to preclude localized variations in the
total beam of light passing through a sample from resulting in an
erroneous judgment of clotting. For example, a photosensitive
resistor such as at 370 will typically have a light sensitive
surface made up in the form of a gridwork. If a particle within the
sample were to become interposed between the light source and a
line on the gridwork of the photosensitive element 370, a much
larger variation in the electrical output characteristics of the
element 370 would result than if the same were subjected to a
diffused beam when the light sensed would be the average of that
passing through the sample, as provided by the light pipe 368.
CONTROL SYSTEM
The control system for the testing device is illustrated in
simplified block form in FIG. 9 as illustrative of one type of
control system that may be employed. The same employs basic logic
techniques known in a variety of electronic arts and therefore will
only be functionally described, it being within the skill of the
art to provide actual circuitry to perform the specific functions
noted.
A conventional divide by six circuit 390 receives a conventional 60
Hertz line signal to provide a ten pulse per second output to both
a counter 392 and a clock gate 394. In addition, the signal taken
as, for example, from one of the microswitches associated with the
first pipette system 26 is provided to the counter 392 for reset
purposes. That is, the arrangement is such that when the first
pipette system 26, which, it will be recalled, is at the testing
station, delivers reagent to a sample, the counter 392 will be
reset. At this time the pulses provided by the divide by six
circuit 390 will cause the counter to begin to count until such
time as it may be halted whereupon the count contained therein will
be indicative of the clotting time of a sample in tenths of a
second. The count from the counter 392 is loaded into a shift
register 396 which is shifted by pulses passed by the clock gate
394 when enabled to in turn load a decoder driver 398 of
conventional construction which, in turn, drives a printer 400 for
printing the results on the tape 38.
While not illustrated in FIG. 9, the brushes 80 associated with the
printed circuit segments 76 may also provide an input to the shift
register 396 for indicating sample number so that results may be
correlated with the sample number and printed out.
According to one embodiment, the counter 392 comprises a four
decade binary coded decimal counter providing a count of up to
999.9 seconds although significantly less capacity will normally be
the maximum required. The shift register 398 may comprise
thirty-two bits in all with the first eight bits being employed for
sample number information, the next four bits employed to provide a
space in the printed results between sample number and clotting
time, the next sixteen bits for the clotting time and the last four
bits to provide a print command.
As a result, when clotting has occurred, the shift register will
already contain clotting time information as well as sample number
and upon the clotting, the enabling of clock gate 394 will result
in the shifting of the contents of the shift register 396 into the
decoder driver with the last four bits of information providing a
print command to the printer 400.
The clock gate 394 is enabled by the output of a comparator 402.
The comparator 402 is provided with enabling input from an enabling
gate 404 as well as a reference signal on a line 406 and a testing
input signal from a differentiating circuit 409. The
differentiating circuit receives its input from an amplifier 410
which, in turn, is driven by the photo-sensitive element 370 (FIG.
8). As a result of the foregoing, it will be appreciated that the
comparator 402 will compare an input voltage proportional to the
rate of change of the output signal from the photocell 370 to the
reference signal with the result that when the total change is
greater than the reference voltage, the readout process will begin.
Because the system looks at the rate of change rather than a change
from one level to another, variations from one plasma to another as
well as possible variations in line voltage are minimized to
provide more consistent results.
The counter 392 also provides an output signal to a time decoder
412. The latter includes one output to the enabled gate 404 to
cause the latter to enable the comparator approximately nine
seconds after a reagent has been dispensed into a sample at the
testing station. The purpose of this arrangement is to preclude the
comparator from reacting to changes or turbulence caused when the
reagent is introduced into the cuvette at the testing station.
In addition, the time decoder provides at least two different time
outputs including a thirty second output to an automatic indexing
control circuit 414. The latter also receives an input signal from
the comparator 402 and the arrangement is such that the indexing
circuit 414 will cause indexing of the turntable every thirty
seconds or whenever a clot is detected, whichever takes longer. To
this end, the indexing circuit includes an output to a turntable
drive circuit 416 to initiate operation of the same whereafter it
is controlled by the microswitches previously described; and to a
block drive system 418 for controlling the position of the
incubation block relative to the path in which the cuvettes move.
In addition, the indexing circuit 414 provides signals to the
pipette systems 26 and 28 to enable the same to dispense reagent to
a cuvette when movement of the turntable has ceased. Such a
dispensing command from the indexing circuit 414 may be overridden
if associated cuvette sensing circuits 420 fail to detect the
presence of the cuvette in the manner mentioned previously.
Finally, the system is completed by a reservoir heater 422 for the
dispensing system 26 and a block heater 424 for the incubation
block as generally mentioned previously.
From the foregoing, it will be appreciated that a testing device
made according to the invention provides for virtual full
automation of certain types of medical tests and minimized the need
for trained personnel to run such tests. Additionally, the system
provides for accurate testing along with increased reproducibility
of results.
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