Sample liquid transfer means in an automatic chemical testing apparatus

Means for reducing intersample contamination in an automatic chemical testing apparatus, in which liquid from a sample is aspirated from a sample source into a reservoir, and aliquots of the sample are each dispensed into individual reaction containers for analysis by well-known means. A cylindrical reservoir is utilized with a piston therein shaped for pushing out virtually all of the remaining sample from the cylinder after dispensing the sample liquid through a hollow needle, communicating with the cylinder. A solid pin coaxially mounted within the piston is projected through the needle and has minimum clearance therewith, for pushing remaining sample out of the needle. The portion of the pin projecting through the needle is retracted into the piston prior to aspiration of liquid from a next sample.

BACKGROUND OF THE INVENTION 
The present invention relates to automated apparatus for chemical testing 
of liquid samples to determine concentrations of substances therein, and 
more particularly to an improvement in liquid transfer means included 
therein. 
The present invention is an improvement in chemical analyzers of the type 
in which sample liquid is taken from a sample container and aliquots 
thereof are each placed in one or more reaction containers. Reagents are 
added to each reaction container. A resulting reaction mixture is 
incubated, and then spectrophotometrically measured to indicate 
concentrations of substances in the samples for which the analysis is 
being conducted. In the preferred form, the present invention is included 
in a blood serum analyzer. An example of an automatic chemical testing 
apparatus of the sort contemplated by the present invention, is shown in 
U.S. Pat. Nos. 3,622,279 and 3,716,338, both to John J. Moran, and 
respectively issued on Nov. 23, 1971 and Feb. 13, 1973. These patents are 
commonly assigned to the assignee herein, and their disclosures are 
incorporated herein by reference. 
In such chemical analyzers, sample liquid such as blood serum is provided 
in a source, such as a sample cup, and must be transferred to reaction 
containers. The same transfer means are used to transfer an amount of 
sample liquid from each of a number of successive samples to respective 
successive sets of reaction containers. If liquid remaining in the 
transfer means from a first sample is mixed with a next sample, 
intersample contamination, commonly referred to as carryover, may result. 
Various prior art schemes have provided for transfer means which are 
subject to carryover. Common prior arrangements utilize pumping of sample 
liquid through tubes extending from a sample station to a reaction 
station. The transfer means in the above-cited patents to Moran is an 
improvement over those earlier forms of transfer means in that sample 
liquid is aspirated into a reservoir, and the reservoir is moved to 
reaction containers and becomes the dispensing means. The hydraulic 
pathlength through which the sample must travel is thus reduced, and far 
less surface area on the interior of conduits is provided on which sample 
liquid may remain. Further, efficient washing means are provided in the 
aspiration-dispensing means to guard against carryover. 
The present invention comprehends further improvements in the transfer 
means for further improved reduction of carryover by positive displacement 
of sample liquid from the transfer means. 
SUMMARY OF THE INVENTION 
It is therefore an object of the present invention to provide liquid 
transfer means in an automatic chemical testing apparatus of the type in 
which liquid sample is aspirated into a reservoir and dispensed therefrom 
in which mechanical means for reducing carryover are provided. 
It is a further object of the present invention to provide a transfer means 
of the type described in which a conduit having a first end at a reservoir 
and a second end comprising an aspiration-dispense inlet-outlet is cleared 
by moving a solid member therethrough between successive transfer cycles. 
It is also an object of the present invention to provide a transfer means 
of the type described wherein said reservoir comprises a cylinder in which 
a piston is operated to displace substantially all fluid from the 
reservoir during the transfer cycle. 
It is a further object in one form of the present invention to provide a 
transfer means of the type described in which said solid displacement 
means is incorporated in an operating mechanism with the piston. 
It is also a general object of the present invention to provide a transfer 
station of the type described in which the ability to eliminate the step 
of washing for eliminating carryover is facilitated. 
Briefly stated, in accordance with the present invention, there is provided 
in an automatic chemical testing apparatus a sample liquid transfer 
station comprising a reservoir and liquid pumping means, preferably a 
cylinder and a piston. A conduit, preferably in the form of a hollow 
needle, has a first end communicating with the reservoir and an opposite 
end serving as an inlet-outlet. A liquid displacement means is mounted for 
movement preferably through the pumping means, and is operated between 
transfers of liquid from successive samples to project to displace fluid 
from the conduit. Preferably, the pumping means is operated to displace 
all fluid from the reservoir.

DESCRIPTION OF THE PREFERRED EMBODIMENT 
Referring to FIG. 1, there is illustrated an automatic chemical testing 
apparatus 1 such as that described in the above-cited patents to Moran. 
The apparatus 1 is briefly described, prior to a detailed description of 
the subject sample liquid transfer means. Samples are provided in 
individual containers in a sample conveyor 2 to an aspiration station 3. 
The analyzer 1 and sample conveyor 2 are further illustrated in commonly 
assigned U.S. Pat. No. 4,039,288 issued Aug. 2, 1977 to John J. Moran, the 
disclosure of which is incorporated herein by reference. A sample liquid 
transfer means 4 (also called the transfer means 4 for conciseness in 
description), such as that of the present invention, operates to withdraw 
a preselected amount of sample liquid from a sample at the aspiration 
station 3. At a serum dispensing station 5, aliquots of the sample liquid 
are dispensed to rows 6 of reaction containers from the transfer means 4. 
The rows 6 are indexed through a reaction means 7. The reaction means 7 
includes means for incubation and reagent dispensing means which add 
reagent to the sample aliquots. The reagents react with each sample 
aliquot to form reaction mixtures. The reaction mixtures are analyzed, 
preferably spectrophotometrically, at an analysis station 8. Reagents are 
supplied to the reaction means 7, from reagent bottles in a reagent source 
system 9. Chemical tests may be selected by a control means 10, and test 
results may be provided at a terminal 11 which may include a CRT display 
and additionally or alternatively may include means for providing hard 
copy printouts. 
FIG. 2 is a partial side elevation of the apparatus of FIG. 1 illustrating 
the aspiration station 3, the sample liquid transfer means 4 of the 
present invention, dispensing station 5, and partially illustrating the 
sample conveyor 2 and one row 6 of reaction containers positioned at the 
dispensing station 5. 
In the embodiment of FIG. 2, the transfer means 4 comprises a housing 17, 
illustrated partially broken away, supported on an arm 15 including motive 
means for transporting the transfer means 4 from the position in which the 
transfer means 4 is shown in dotted lines at the aspiration station 3 and 
through a path for dispensing aliquots of a sample. The area 16 in FIG. 2 
in dotted lines indicates the extent of travel of the transfer means 4 at 
the dispensing station 5. Operation of the apparatus and the dispensing 
station 5 is further described in commonly assigned patent application 
Ser. No. 725,270 filed Sept. 21, 1976 by John J. Moran, the disclosure of 
which is also incorporated by reference herein. 
The sample conveyor 2 includes a plurality of sample container holders 18, 
linked together to form the sample conveyor 2 and each holding a sample 
container 19. Each row 6 comprises a slat 20 holding a plurality of 
reaction containers 21. A plurality of slats 20 are preferably provided in 
a loop conveyor such as that disclosed in commonly assigned U.S. Pat. No. 
4,039,287 issued Aug. 2, 1977 to John J. Moran, the disclosure of which is 
also incorporated by reference herein. In such an embodiment, the slats 20 
are indexed to successive positions to carry reaction containers 21 from 
the dispensing station 5 through the reaction means 7 to the analysis 
station 8. 
A sample container displacement unit 23 is provided for periodically moving 
successive ones of the sample containers 19 in registration with the 
transfer means 4 for aspiration of sample liquid therefrom. In the present 
embodiment, the transfer means 4 remains vertically fixed, and is 
horizontally movable. Therefore, to provide relative motion between a 
sample container 19 and the transfer means 4, the sample container 
displacement means 23 includes a vertically movable rod 24 for projecting 
through an opening in a sample container holder 18 for providing relative 
motion between the transfer means 4 and the sample container 19 in 
registration therewith. 
The transfer means 4 is further described with respect to FIG. 2, with 
respect to FIG. 3, which is an exploded view of components within the 
transfer means 4, and with respect to FIG. 4 which is an axonometric view 
illustrating in further detail the structure of the transfer means 4. 
A cylinder 30 serves as a reservoir for sample liquid, and is mounted to 
the housing 17. The cylinder 30 may take many different shapes, but is 
most conveniently a right circular cylinder and may be made of glass or of 
a polymer. The cylinder 30 has an opening 31 at an upper end thereof and 
seating means 32 closing a lower end thereof. It should be remembered that 
the terms upper and lower are used for defining relative spatial 
relationships. While it is certainly preferable that the cylinder 30 be 
vertically disposed, it is not an absolute necessity. The seating means 32 
includes an aperture 33 for communication of the interior of the cylinder 
30 with a fluid path. A conduit is provided in the form of a hollow needle 
36 having an upper end received in the aperture 33 and a lower, open end 
for intake of sample liquid during aspiration and for expelling sample 
liquid during dispensing. 
In order to provide for aspiration and dispensing of sample liquid into and 
out of the cylinder 30, pumping means are provided in the form of a piston 
38. The piston 38 has an upper end 39 and a lower end 40. The piston 38 is 
received into the cylinder 30 through the opening 31. The lower end 40 is 
shaped to mate with the seating means 32. Preferably, the piston 38 is 
stainless steel, and the lower end 40 comprises a separate, lower 
polymeric member 41 having an annular recess 42 on its periphery and a 
conical projection 43 at its lower end. Preferably the seating-means 32 
comprises a conical seat for receiving the lower end 40. The purpose of 
this construction is to provide for substantial total elimination of dead 
volume, i.e. volume of sample remaining in the cylinder 30 at the 
completion of downward travel of the piston 38. The annular recess 42 
provides for improved fit of the member 41 in the cylinder 30, reduces 
friction and improves sealing. The lower member 41 has an aperture 44 
formed in registration with the aperture 33 in the seating means 32. The 
aperture 44 extends axially through the lower member 41 to communicate 
with the interior of the piston 38, which is hollow and has an inner 
diameter sufficient for receiving components described below. 
It is also desired to provide for elimination of dead volume in the needle 
36. To this end, a rod 46 is provided for reception into the interior of 
the piston 38 having an elongated pin 47 extending in an axial direction 
from the lower end 48 thereof. The pin 47, aperture 44, aperture 33, and 
the needle 36 are dimensioned with respect to each other such that the pin 
47 may project through the apertures 41 and 33 and into the interior of 
the needle 36. The outer diameter of the pin 47 and the inner diameter of 
the needle 36 are preferably dimensioned for a minimal clearance 
therebetween which still allows movement of the pin 47. Since the pin 47 
is used to move sample liquid out of the interior of the needle 36, the 
pin 47 may be said to be displacement means or clearing means. 
In the preferred form, a collar 51 is provided coaxially mounted with the 
rod 46 at the lower end 48 thereof. The collar 51 is dimensioned so that 
an upper portion of collar 51 receives the rod 46, and a lower portion of 
the rod 51 receives an end of the pin 47. Radially extending set screws 52 
extend through the collar 51 for fastening the rod 46, collar 51 and pin 
47 in this relationship. This construction provides for easy 
replaceability of the pin 47. A coupling member 55 retains the rod 46 in 
operative engagement with the piston 38. An aperture 56 at an upper end of 
the member 55 has a larger diameter than the rod 46 and a smaller diameter 
than the collar 51. The coupling member 55 is placed so that the aperture 
56 surrounds a portion of the rod 46, and is provided with a thread 57 on 
its inner diameter for fastening to the upper end 39 of the piston 38. 
Spring biasing means preferably in the form of a spring 59 are provided for 
insertion in the interior of the piston 38. The spring 59 surrounds the 
pin 47 and rests between the lower end 40 in the piston 38 and the collar 
51, as retained in the piston 38 by the coupling member 55. 
Means are provided for coupling vertical force to the rod 46. In the 
preferred form a rack 61 of teeth is provided extending longitudinally 
along the rod 46 on the outer surface thereof and parallel to the axis 
thereof. A pinion 63 is mounted to the housing 17 for coupling motive 
force to the rod 46. The pinion is driven by a motor 65, mounted on a 
plate 66 secured to the housing 17, which is operated by control means 
(not shown). The control means may be operated as described in the 
above-cited patents to Moran. 
When the motor 65 rotates in a first direction, the rod 46 is pulled 
upwardly. The collar 51 engages the coupling member 55 which pulls the 
cylinder 38 upwardly. When the motor 65 rotates in the opposite direction, 
the collar 51 applies force to the spring 59 which is transmitted to the 
lower end 40 of the cylinder 38. The spring 59 is selected to provide a 
tensile force such that it does not compress unless the cylinder 38 
engages a stop means, e.g. the seating means 32. Therefore, the piston 38 
moves down until its lower end 40 engages the stop means. Thereafter, the 
spring 59 is compressed by the rod 46, and the pin 47 continues its 
downward travel. Operation is further described below. 
In FIG. 4, further details of mounting of the above-described components to 
the housing 17 are shown. The cylinder 30 is mounted in a block assembly 
70 having upper and lower plates 71 and 72, which each have seats formed 
therein for fixed retaining of the cylinder 30. The lower plate 70 has an 
aperture therein for permitting communication for an upper end of the 
needle 36 with the aperture 33 in the lower end of the cylinder 30. 
Mounting members 75 and 76 are placed on either side of the cylinder 30 
and have the plates 71 and 72 mounted thereto for maintaining the cylinder 
30 in place. The mounting members 75 and 76 are positioned with respect to 
the plate 66 to which the motor 65 is mounted so that the axes of the rod 
46, pin 47 piston 38, cylinder 30 lie in one line. 
OPERATION 
Operation of the transfer means 4 is described with respect to FIGS. 4 
through 7. FIGS. 5, 6 and 7 are also axonometric views of the transfer 
means 4 having the housing 17 broken away to show further details. In 
FIGS. 5 to 7, the same reference numerals are used to denote elements 
corresponding to those of FIGS. 1 to 4. 
FIGS. 5-7 illustrate a fluid transfer cycle comprising the steps of 
aspirating sample liquid from one sample container 19, dispensing sample 
liquid, clearing the cylinder 30 and the needle 36 and preparing for 
aspirating from a next sample container 19. 
Referring now to FIG. 4, at the beginning of an operating cycle, a sample 
container 19 in the sample conveyor 2 is indexed to the aspiration station 
3. The transfer means 4 is moved to the position shown in dotted lines at 
the right side of FIG. 2. Relative motion is provided between the sample 
container 19 and the needle 36 so that the lower end of the needle 36 is 
in communication with sample liquid. In the present embodiment, the drive 
means 23 drives the rod 24 to push the sample container 19 up so that the 
sample fluid surrounds the lower end of the needle 36. Prior to projection 
of the needle 36 into the sample liquid, the pinion 63 may be rotated to 
lift the rod 46 and piston 38 from a home position in which the lower end 
40 of the pistion 38 abuts the seating means 32 of the cylinder 30. 
Once the sample liquid is in communication with the lower end of the needle 
36, as the piston 38 is raised, sample liquid is drawn into the cylinder 
30. The control means (not shown) rotates the pinion 63 until the piston 
38 reaches a position of upward travel corresponding to a preselected 
amount of liquid having been drawn into the cylinder 30. At that point, as 
seen in FIG. 5, the motor 65 and consequently the pinion 63, is commanded 
to stop. The transfer means 4 begins movement through the path indicated 
by area 16 in FIG. 2, and the motor 65 is commanded to rotate in the 
opposite direction. The piston 38 is moved downwardly as the transfer 
means 4 moves over the particular slat 20 for dispensing aliquots of 
liquid to reaction containers 21 therein. During this portion of an 
operating cycle, the transfer means 4 moves from right to left as seen in 
FIG. 2 and then from left to right. Dispensing may take place during 
travel of the transfer means 4 in either or both directions. 
After the dispensing operation, the transfer means 4 returns to the 
aspiration station 3 and is preferably placed over the same reaction 
container 19 again (FIG. 6). At this time, the motor 65 is rotated to 
drive the rod 46 and piston 38 to force all remaining liquid out of the 
cylinder 30. The lower end 40 of the piston 38 presses against the seating 
means 32 to flush out substantially all remaining liquid from the cylinder 
30. The pinion 63 continues rotation. The lower end 40 of the piston 38 is 
abutting stop means in the form of the seating means 32. The pin 47 
therefore continues its travel through the aperture 41 in the lower end 40 
of the piston 38 and through the aperture 33 at the lower end of the 
cylinder 30 through the interior of the needle 36. Virtually all liquid 
remaining in the needle 36 is forced out. A bead of liquid may form at the 
lower end of the needle 36 and pin 47. The drive means 23 may be again 
operated to raise and lower the sample container 19 so that the drop 
remaining at the lower end of the pin 47 and needle 36 is drawn into the 
remaining liquid in the sample container 19. The sample container 19 is 
then lowered to a position in which it is free of engagement with, i.e. no 
longer surrounding, the needle 36. Liquid remaining on the exterior of the 
needle 36 will be cleared onto the meniscus of a sample in a next sample 
container 19 from which sample is aspirated in a next cycle. Since the 
needle 36 aspirates liquid from a point below the meniscus, carryover will 
not result from this clearing. 
After this portion of the operating cycle, the pinion 53 is again rotated 
to draw up the rod 46 such that the pin 47 is drawn back into the piston 
38. The transfer means 4 is thus enabled to aspirate from a next sample 
container 12 and resume the operation as illustrated in FIG. 7. 
What is thus provided is an improved fluid transfer means in an automatic 
chemical testing apparatus in which a conduit and reservoir for 
intermediate storage of sample liquid being transferred from a sample 
source to reaction containers are cleared by displacement of a solid 
object therethrough. The ability to prevent carryover without the need for 
provision of a washing step in which liquid is pumped through the 
reservoir and conduit is facilitated. This results in simplification of 
manufacture of the testing apparatus and also avoids the possibility of 
washing liquid diluting a next sample. The specification has been written 
with a view toward enabling those skilled in the art to make many 
modifications from the specific embodiment shown, provide a transfer means 
in an automatic chemical testing apparatus in accordance with the present 
invention.