U.S. patent number 4,265,855 [Application Number 05/957,091] was granted by the patent office on 1981-05-05 for system for performing immunochemical and other analyses involving phase separation.
This patent grant is currently assigned to Electro-Nucleonics, Inc.. Invention is credited to Frank Karsai, Raymond S. Krautheim, Richard M. Mandle.
United States Patent |
4,265,855 |
Mandle , et al. |
May 5, 1981 |
System for performing immunochemical and other analyses involving
phase separation
Abstract
A system for automatically processing liquids in open-ended
containers. The containers are moved past a plurality of operating
stations that carry out the following operations: washing,
reagent-adding, incubation, detection, and storage. The operating
stations for washing and reagent-addition include vertically and
horizontally movable assemblies for operating upon the containers.
The containers are carried in groups in individual carrying blocks
which are moved throughout the system.
Inventors: |
Mandle; Richard M. (Pompton
Lakes, NJ), Karsai; Frank (Dover, NJ), Krautheim; Raymond
S. (Nutley, NJ) |
Assignee: |
Electro-Nucleonics, Inc.
(Essex, NJ)
|
Family
ID: |
25499054 |
Appl.
No.: |
05/957,091 |
Filed: |
November 3, 1978 |
Current U.S.
Class: |
422/65; 141/130;
422/63 |
Current CPC
Class: |
G01N
35/00732 (20130101); G01N 35/026 (20130101); G01N
35/0098 (20130101); G01N 2035/1025 (20130101); G01N
2035/00762 (20130101) |
Current International
Class: |
G01N
35/02 (20060101); G01N 35/10 (20060101); G01N
35/00 (20060101); G01N 001/14 () |
Field of
Search: |
;422/65,102,71,103,101
;73/423A,425.6 ;141/130 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Serwin; R. E.
Claims
We claim:
1. A system for automatically processing liquids in open-ended
containers comprising conveyor means for conveying said containers
past a plurality of operating stations, one of said operating
stations comprising a station for adding and removing a liquid
respectively to and from said containers, said station comprising a
head assembly engageable with at least one of said containers and
including at least one liquid supply tube and at least one
aspirating tube, said head assembly including means for positioning
only one of said tubes within the open end of one of said
containers at any time.
2. A system according to claim 1, in which said head assembly
comprises a liquid supply head for supplying liquid to said liquid
supply tube and an aspirating head for applying a vacuum to said
aspirating tube.
3. A system according to claim 1, in which another of said
operating stations comprises a reagent adding station for adding a
reagent to said containers, said reagent adding station comprising
a reagent dispensing head mounted for vertical and horizontal
movement, for moving said reagent adding head to a first position
in which reagent is supplied to said reagent adding head and
thereafter to at least one dispensing position in which said
reagent adding head is moved vertically successively to add reagent
to a plurality of said containers, a washing tray, and means for
moving said tray into a washing position beneath said supply and
aspirating heads for washing said aspirating tube.
4. A system according to claim 2, in which said aspirating head is
positioned over said supply head, and including means for causing
relative vertical movement between said supply and aspirating heads
to cause said aspirating tube to pass through said supply head.
5. A system according to claim 4, in which said supply head
includes a container-engaging portion in the lower part thereof for
engaging the open ends of said containers.
6. A system according to claim 5, in which said container-engaging
portion is movable vertically within said supply head and is
yieldably biased to a lower position, said container-engaging
portion being movable upwardly upon engagement of said supply head
with said containers.
7. A system according to claim 6, in which said container-engaging
portion includes at least one passage therein in which said supply
tube is positioned, said passage terminating in a frusto-conical
opening of increasing diameter to facilitate the positioning of the
open-ended containers therein.
8. A system according to claim 7, in which said containers are
carried loosely in a carrying block to facilitate entry into said
frusto-conical opening.
9. A system according to claim 8, in which said containers are
carried by a card, the lower portions of said containers extending
below said card, said card being carried on said block with said
lower portions of said containers extending loosely into openings
in said block.
10. A system according to claim 9, in which said card is light
reflecting, and a least one of said heads includes light generating
and detecting means positioned so as to be adjacent a card when
said head is operative and, by the detection of reflected light
from said card, generates a signal indicating the presence of said
card with containers thereon in operative position with respect to
said last-mentioned head.
11. A system according to claim 1, in which said supply tube is
positioned at an angle with respect to the vertical to direct said
liquid against the sides of said containers.
12. A system according to claim 1, including a reagent adding head
which comprises at least one syringe having a piston member therein
which is movable in a drawing direction to draw liquid into the
syringe and in a dispensing direction to dispense liquid from the
syringe, and including drive means for driving said piston in said
drawing and dispensing directions, and control means controlling
said drive means so as to cause said piston member to be driven
slightly in the drawing direction following each movement of the
piston in the dispensing direction to prevent droplet leakage from
said syringe.
13. A system according to claim 1, including inspection means for
inspecting said containers after they have moved past said
operating stations.
14. In a system for automatically processing liquids in open-ended
containers, a washing assembly for adding and removing a washing
liquid respectively to and from said containers, said washing
assembly comprising supply and aspirating heads positioned above
said containers and movable vertically thereover, said supply head
including at least one liquid supply tube communicating with a
liquid supply manifold within said head, said aspirating head
including at least one aspirating tube communicating with a vacuum
chamber within said aspirating head, said aspirating and supply
heads being movable vertically with respect to each other, said
supply tube extending at an angle with respect to the vertical and
terminating within said supply head, and said aspirating head being
movable to move said aspirating tube to a position in which it
extends through and below said supply head.
15. A system according to claim 14, in which said supply head
includes a container-engaging portion in the lower part thereof for
engaging the open ends of said containers, said container-engaging
portion being movable vertically within said supply head and
yieldably biased to a lower position within said head, said
container-engaging portion being movable upwardly upon engagement
of said supply head with said containers.
16. A system according to claim 15, in which said supply tube
terminates at its lower portion within the container-engaging
portion of said supply head, said container-engaging portion being
movable with respect to said supply tube so that, when said
container-engaging portion is moved upwardly upon engagement of
said supply head with said containers, said lower end of said
supply tube extends below said container-engaging portion.
Description
BACKGROUND AND BRIEF DESCRIPTION OF THE INVENTION
This invention relates to the automatic processing of liquids in
open-ended containers for testing purposes, and more particularly
provides an automated system for detecting Hepatitis B. Surface
antigen (HB.sub.s AG) in human serum or plasma.
Many immunochemical reactions are performed by using what is known
as a solid phase or phase separation system. Such analyses place
one of the components on a solid support so it may readily be
removed from the system during analysis. An example is the
detection of HB.sub.s AG, wherein the antibody to HB.sub.s AG is
affixed to solid controlled pore glass particles (CPG). Such CPG is
mixed in a test tube with a patient's serum. The serum in a
diseased patient contains antigen to hepatitis, and under proper
conditions the antigen may be made to react with the antibody on
the CPG. A typical operation includes the removal of other serum
proteins from those hepatitis associated proteins which adhere
biologically to the CPG. This separation involves the use of
aqueous washes, such as saline or phosphate buffers which allow the
extraneous proteins to be removed without disturbing the chemical
bond between the antigen and the hepatitis-associated proteins on
the CPG. Identification markers or labels are also added in this
analysis, but the excess quantity of these reagents usually must be
removed also by washing or other phase separation techniques.
In performing a typical hepatitis assay, a patient's serum is
incubated or mixed with CPG so that the required chemical reaction
takes place. Next, buffer is added to and agitated with the
patient's sample, and following agitation the CPG settles to the
bottom of the test tube. Following settling, the liquid in the tube
is aspirated or otherwise withdrawn, with the CPG remaining in the
tube. Such buffer addition-agitation-removal may be repeated a
number of times to remove most of the extraneous proteins. To
verify the presence of an antigen adhering to the CPG, a label is
added to the test tube which may be identified as, for example, by
a coloring agent, an enzyme multiplication agent, or radioactive
tag or a fluorescent agent incubation of the tagged label with the
antibody antigen complex on the CPG forms a "sandwich". After a
suitable incubation period, the excess label is removed by a wash
in generally a number of washing steps. The material adhering to
the CPG in the tube, as a sandwich, yields an indication which may
be compared to known positive or negative controls to identify the
patient's serum.
The operations outlined above are described in the brochure
RIAUSURE.sup..RTM. II published by Electro-Nucleonics Laboratories,
Inc. These operations are tedious and require manual dexterity and
continued operator attention to be properly carried out. The danger
from operator fatigue and mistake, leading to false identification
of a sample, is always present. In addition, variations in test
parameters can occur from one test to another, leading to varying
results.
It is desirable to optimize any immunochemical analysis by choosing
proper conditions. While generally it is desirable to decrease the
size of the CPG and the serum-carrying container (because the
kinetics of the reactions will be faster and more reliable), the
reduction of size creates problems in the manual handling of the
tests, leading to errors.
The present invention provides for the automating of the HB.sub.s
AG test procedure. It proceeds from the RIAUSURE.RTM. procedure of
Electro-Nucleonics Laboratories, Inc. That procedure provides
agitation and settling according to a programmed time schedule
using small ferrite magnets placed inside each of the assay tubes.
The test tubes are placed on an electro-magnetic assembly
containing field coils energized by a digital counter, producing a
varying field causing the magnets to move within the test tube and
thereby agitate the serum-buffer-glass system within each tube. At
an appropriate time, the magnetic field is deenergized, allowing
the magnets to rest at the bottom of the test tubes, leaving a
clear, supernatant liquid thereabove. A multiple head aspirater is
employed to withdraw the supernatant liquid from the test tubes; a
separate multiple head dispenser is used to introduce liquid along
the wall of each test tube. The above cycle is completed manually
and repeated until the tubes are properly washed. An appropriate
label is added manually to each tube.
In the present invention, a card is utilized to hold a number of
test tubes (e.g., twenty test tubes). The tubes are open-ended at
the top thereof, and are carried by the card so that the bottom
portions thereof extend below the card. The card rests on a
carrying block, and the lower portions of the containers extend
loosely into openings in the block. In this fashion, the test tubes
are carried loosely by the block, facilitating later operations, as
described below. A number of such blocks are positioned on a
support table and are moved thereon in step-wise fashion around the
table. Each tube contains a sample of a patient's serum along with
magnetic particles, and underlying the table is a series of coils,
the magnetic fields from which cause agitation of the magnetic
particles and an appropriate mixing of the liquids within the test
tubes. The test tube-containing blocks are caused to move in a
rectangular pattern around the table in step-wise fashion by moving
pins. The positions on the table provide for incubation, washing,
label addition, detection, storage, and instrument cleansing. The
washing assembly for adding a washing liquid to the test tubes and
removing that liquid therefrom utilizes supply and aspirating heads
positioned above the test tubes and movable vertically thereover.
To process a number of test tubes simultaneously, the supply head
includes a number of liquid supply tubes that communicate with a
liquid supply manifold within the head. The aspirating head
includes a plurality of aspirating tubes communicating with a
vacuum chamber within the aspirating head. The aspirating and
supply heads are movable vertically with respect to each other.
Preferably, the supply tubes extend at an angle with respect to the
vertical so as to wash the sides of the test tubes, and terminate
within the supply head. The aspirating head is movable to move the
aspirating tubes to positions in which they extend through and
below the supply head and into the test tubes for aspirating liquid
therefrom. To facilitate holding the test tubes, the supply head
includes a test tube engaging portion in the lower part thereof for
engaging the open ends of the test tubes. That lower portion of the
supply head is movable vertically within the supply head and is
yieldably biased to a lower position, moving upwardly upon
engagement of the supply head with the test tubes. The supply head
includes passages therein in which the supply tubes are positioned,
and other passages for containing the aspirating tubes from the
aspirating head thereabove. These passages terminate in a
frusto-conical opening of increasing diameter to facilitate the
positioning of the open-ended test tubes therein, facilitated by
the loose holding of the test tubes in each carrying block.
Provision is made for washing the aspirating tubes to avoid
carryover of contaminants.
Label addition is carried out by a label adding head preferably
carrying two syringes, one for each of two rows of test tubes
carried in a card. This head is moved vertically and horizontally
to receive label and to dispense that label into the test tubes.
The syringes are driven so that there is a slight drawing motion
after each dispensing operation to prevent droplet leakage from the
syringes.
Following passage of the test tubes through the system, the tubes
are inspected, for example, by an appropriate radiometric or
colorometric test.
The invention will be more completely understood by reference to
the following detailed description which is to be read in
conjunction with the attached drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a plan view of a presently preferred system embodying the
invention.
FIG. 2 is a perspective view of a test tube carrying card and block
assembly useful in practicing the invention.
FIG. 3 is a sectional view of the block of FIG. 2, with test tubes
and card in position thereon, illustrating the inspection of two
test tubes by appropriate light emitting and detecting cells.
FIG. 4 is a side view of a washing station in the assembly of FIG.
1.
FIG. 5 is a sectional view taken along the section 5--5 in FIG.
4.
FIG. 6 is a sectional view (to an enlarged scale) of part of the
assembly shown in FIG. 5, along section 6--6.
FIG. 7 is a sectional view (to an enlarged scale) of the assembly
of FIG. 6, taken along the section 7--7.
FIG. 8 is a side view of a label addition station in the system of
FIG. 1.
FIG. 9 is a sectional view (to an enlarged scale) taken along the
section 9--9 in FIG. 8.
FIG. 10 is a plan view of a portion of one of the test tube
carrying cards, showing an identifying magnetic card thereon.
FIG. 11 is a perspective view of the magnetic card shown in FIG.
10.
DETAILED DESCRIPTION
Referring to FIG. 1, a system for automatically carrying out the
various steps of a HB.sub.s AG test is shown. A number of test tube
carrying blocks 20 are positioned upon a support surface 22 for
movement in step-wise fashion in a rectilinear pattern as guided by
rails 24. Pusher pins 26a, 26b, 26c and 26d are employed, operated
in appropriate sequence to move the blocks 20. The movement of the
blocks is rectilinear, generally counterclockwise as viewed in FIG.
1. After each movement of the blocks, they all remain at rest for
approximately 7.5 minutes and then are moved to the next position.
Typically, the sequence of pin movement is the withdrawal of pins
26a and 26c (respectively moved to the right and to the left in
FIG. 1), followed by the extension of pins 26b and 26d
(respectively downwardly and upwardly as viewed in FIG. 1). In this
fashion, the block designated 20a in the lower right-hand portion
of FIG. 1 is moved from the forward row to the rear row, while the
test tube carrying block designated 20b in the upper left-hand
portion of FIG. 1 is moved from the rear row to the forward row.
Following this movement of these two blocks at the ends of the
respective rows, the pins 26a and 26c are extended respectively to
move all the blocks 20 in the forward row at the lower portion of
FIG. 1 to the right and all the blocks in the rear row in the upper
portion of FIG. 1 to the left. The next movement of pins occurs
approximately 7.5 minutes later, for example, allowing sufficient
time for the various operations to be performed during the at rest
positions of the test tube carrying blocks.
In FIG. 1, the various operations carried out in the system, to be
described below, are indicated generally. It will be noted that the
test tubes carried in the blocks generally undergo incubation
during the eight positions of movement in the rear row of FIG. 1.
It is assumed that each of the test tubes is filled with
appropriate serum, in the case of the HB.sub.s AG test, and that
appropriate negative and positive controls are included. As shown
by the notations in FIG. 1, washing follows incubation, followed
thereafter by label addition, followed thereafter by further
incubation, followed thereafter by further washing, with a
completion of these procedures at the time the block 20 reaches the
position of the block 20b in FIG. 1. In this position of the block,
appropriate detection of the test tubes may follow to characterize
the serum under tests in each test tube. The front row of
tube-carrying blocks is designated "storage"; no operations on the
test tubes are carried out in these positions.
As noted above, the table includes coils 28 positioned thereunder
which carry out the appropriate agitation of the contents of the
test tubes, which include magnetic particles therein. Additionally,
in FIG. 1, a wash tray 30 is included for washing aspirator needles
used in the washing of the test tubes prior to label addition, as
will be explained below.
Referring to FIG. 2, a typical test tube carrying block 20 is
shown, along with a card 32 that carries test tubes 34. The card 32
carries two rows of ten test tubes each, but this number is simply
representative. The card normally snuggly receives the test tubes
34, with their open ends 34a extending above the card and their
closed, lower ends extending below the card and loosely into holes
36 in the block 20. As will be noted from FIG. 3, there is adequate
space between the walls of the test tubes and the walls of the
openings 36 in the block to permit movement of the card and test
tubes. This movement facilitates in the registry of the test tubes
with respect to the washing thereof, as will be explained in more
detail below. As shown in FIG. 3, the block 20 is arch shaped in
its lower portion, as at 38. This permits the entire block to pass
over a detection station, which may include light emitting diodes
40 and photoelectric detectors 42, as shown in FIG. 3, which are
mounted on the table of FIG. 1 in the detection station positioned
under the block 20 in the position of the block 20b as shown in
FIG. 1. Thus, a colorometric test may be utilized, e.g., for enzyme
amplification, in which case, the test tubes 34 would be of clear
material. Other detection systems could be utilized, e.g.,
radiometric involving the counting of radioactivity as is typically
used in the HB.sub.s AG test procedure. In such case, the test
tubes 34 could be opaque or clear.
FIG. 4 shows a washing station, such as the washing station prior
to the label addition station in the system of FIG. 1. That station
includes a supply head 44 and an aspirating head 46 positioned
above the test tubes 34 in a carrying block 20. The supply head 44
is for supplying a washing liquid to the test tubes, while the
aspirating head 46 is for the purpose of aspirating from the test
tubes the washing liquid. Referring to FIGS. 4 and 5 together, the
heads 44 and 46 are carried in tongue and groove rail mountings 48
and 50, which permit the removal of these heads for cleansing,
replacement, etc. The rails 48 and 50 are mounted for vertical
movement in rails 52 and 54. A motor 56 drives the rail 50 up and
down by virtue of a threaded drive shaft 58 which passes through
the rail 48 and threadedly engages the rail 50. In similar fashion,
a drive motor 60 drives the rail 48 upwardly and downwardly through
use of a threaded drive shaft 62 which passes through the rail 50
and threadedly engages the rail 48. Appropriate timed vertical
movement of the rails 48 and 50 is achieved through suitable
control of the drive motors 56 and 60.
As noted above, prior to the washing operation, eight positions of
incubation of the contents of the test tube take place, involving
approximately one hour of incubation. During this time of
incubation, the antigen to hepatitis contained in a diseased
patient's serum contained in one of the test tubes reacts with the
antibody of the CPG particles within the test tube. In the washing
station, two separate washes with an appropriate buffer solution
take place. The wash solution is supplied to the supply head 44
through an appropriate line 64. During the washing cycle, the motor
60 is energized to lower the supply head 44 downwardly. Before the
washing solution is dispensed from the head 44, the detection of
test tubes in position beneath the supply head is completed by a
light generating and detecting unit 66 carried by the supply head
44. To this end, the cards 32 carrying the test tubes are typically
colored white or light reflective, while the blocks 20 on their
upper surface are colored black or light absorptive. If a card 32
is in place upon the block 20, light will be reflected sufficiently
and detected by the unit 66, indicating the positioning of the test
tubes in place to receive the wash solution. If a card 32 is not in
position, indicating the absence of test tubes, then the light
absorptive coating on the block 20 would absorb sufficient light so
that no detection of light by the unit 66 would take place,
indicating an absence of test tubes and ceasing further operation
in the washing cycle, specifically preventing the supply of wash
fluid from the supply head 44.
The supply head 44 is shown in more detail in FIG. 7. It includes a
lower test tube-engaging portion 44a which is slidable vertically
and which is yieldably biased by a spring 70. The lower portion of
the supply head 44 is frusto-conical, as at 44b, to facilitate in
the positioning of the test tubes 34 properly in position with
respect to the supply head. As that supply head is lowered, the
test tubes bear against the head portion 44a, causing it to move
upwardly against the biasing action of the spring 70.
When the supply head 44 has engaged the test tubes 34, each test
tube has positioned in the upper, open end thereof a liquid supply
tube 72. That supply tube is angled with respect to the vertical
(typically an angle of four degrees) so that the wash liquid
impinges against the sides of the test tubes 34. The washing action
is enhanced by such side impingement of liquid on the test tubes.
The liquid supply tubes 72 loop upwardly and downwardly, as at 72a.
It has been found that by so looping the liquid supply tubes,
problems of dripping can be avoided. The supply tubes 72 are
supplied with liquid from a chamber within the supply head 44 that
is supplied with liquid from the liquid supply line 64. O-rings 74
may be used to provide an appropriate seal between the supply head
44 and the tubes 72 where the latter enter into the liquid supply
chamber within the head 44 (FIG. 6).
During the washing operation, the aspirating head 46 is moved
downwardly by appropriate energization of the motor 56 so that
aspirating tubes 76 carried thereby extend downwardly through and
below the supply head (through passages 78 in the supply head 44)
to the positions shown in FIG. 7 in dashed lines. In these
positions of the aspirating tubes 76, the tubes exhaust the liquid
within the test tubes 34. The movement of the aspirating head 46 is
such that the lower tips of the aspirating tubes 76 are just above
the settled CPG in the test tubes 34. The aspirating of liquid
takes place only after sufficient settling time has occurred so
that the CPG and the magnets in the test tubes 34 have settled,
preventing the aspiration of the CPG and magnets through the
aspirating tubes. The aspirating tubes 76 communicate with a vacuum
chamber within the aspirating head 46, which in turn communicates
with an exhaust line 80 shown in FIG. 4.
In a typical HB.sub.s AG test, 200 microliters of serum and 3
microliters by volume of CPG and 10 microliters by volume of
magnets may be included in each of the test tubes 34. 1,000
microliters of washing solution may be used in each of two separate
washes while the test tubes are in the washing station. Following
the washing and aspiration of washing solution from the test tubes,
the block 20 is moved to the next station in FIG. 1, which is for
label addition. Prior to the next washing of a succeeding block 20,
wash tray 30 shown in FIG. 1 is moved into position beneath the
supply head 44 and aspirating head 46. The washing tray 30 contains
two channels 30a and 30b which are supplied with liquid via supply
and exhaust lines 82. Typically, liquid is pumped into the channels
30a and 30b in intermittent fashion so that a wave type movement of
liquid within the channels occurs. The lower ends of the aspirating
tubes 76 extend into these channels 30a and 30b and are completely
washed thereby. During the washing of the aspirating tubes 76,
vacuum is applied by the line 80 so as to aspirate liquid through
the tubes 76 to ensure a complete cleaning thereof. This washing of
the aspirating tubes removes all contamination, so that material
from one test cannot contaminate another. Detection of the complete
washing of the aspirating tubes 76 may be achieved by use of a
probe 88 positioned in the aspirating head 46 within the vacuum
chamber thereof opposite the end of each of the aspirating tubes
76. The spraying of cleansing fluid onto the probe 88 may complete
an electrical circuit so that the passage of cleansing fluid is
sensed. Failure to sense the flow of cleansing fluid can actuate a
suitable alarm. The probe 88 may be used to sense the flow of
washing liquid through the aspirating tubes during the washing of
the test tubes as well as the washing of the aspirating tubes.
The wash tray 30 is movable horizontally back and forth by a drive
motor (not shown) which moves the wash tray along a support rail
90.
FIG. 8 shows the details of the label addition station of FIG. 1. A
label dispensing head 92 is carried by a mounting member 94 for
horizontal movement along a rail 96. A motor 98 is mounted on the
rail 96, and includes a threaded drive shaft 100 which threadedly
engages the mounting member 94. Suitable energization of the motor
98 causes the mounting member 94 to move horizontally back and
forth along the rail 96.
The label dispensing head 92 is also mounted for vertical movement
through the mounting of the rail 96 on a vertical post 102 for
vertical movement on that post. A motor 104 mounted on the post 102
drives a threaded drive shaft 106 which threadedly engages the rail
96. Suitable energization of the motor 104 moves the rail 96
vertically.
The label dispensing head 92 includes a pair of syringes 108 having
piston members 110 therein. The piston members 110 are driven by a
suitable drive motor 112 acting through drive shaft 114 that
threadedly engages coupling 116 that joins together the two
pistons.
In operation, the motor 98 is first energized to move the label
dispensing head 92 to the dashed line position shown at the right
of FIG. 8. In this position, that label dispensing head is
positioned over liquid label supply container 118. Next the drive
motor 104 is energized, lowering the rail 96 and the dispensing
head 92 so that syringe tubes 120 extend into the label supply
container 118. Next the motor 112 is energized to move the pistons
110 to the left in FIG. 9, drawing label solution from the
container 118 into the syringes 108 and thereby filling the
syringes. Next the motor 104 is energized to raise the rail 96 and
to remove the syringe tubes 120 from the supply solution. To avoid
dripping, the motor 112 may be energized to drive the syringe
pistons 110 slightly to the right (the dispensing direction) in
FIG. 9 and then slightly to the left (the drawing direction in FIG.
9) to suck in liquid droplets at the end of the syringe tubes 120
to prevent droplet leakage from the ends of the syringe tubes. Next
the motor 98 is energized to move the label dispensing head 92 in
position above the first two test tubes 34 on the block 20 (the
right most test tubes in FIG. 8). The motor 104 is next energized
to lower the rail 96 so that the syringe tubes 120 are positioned
appropriately within the test tubes 34. The motor 112 is then
driven so that the syringe pistons 110 move to the right a measured
distance to dispense a measured amount of label solution (typically
100 microliters). Following the dispensing operation, the motor 112
is energized to draw the syringe pistons 110 slightly to the left
so as to suck in any droplets at the ends of the syringe tubes 120
and to prevent droplet leakage from those tubes. The motor 104 is
energized to raise the head 92, the motor 98 is then energized to
move the label dispensing head 92 to the next pair of test tubes
34, and the operation just described repeats.
Following the addition of label solution to all the test tubes, the
block 20 moves through the incubation positions shown in FIG. 1.
Following incubation, during which the labelled antibody added to
each test tube undergoes reaction with the contents of the tube,
the contents of each tube are again washed with a buffer solution
as in the washing that took place following the first incubation as
described above. The washing apparatus may be the same as that
described above in connection with the washing following first
incubation. Cleansing of the aspirating tubes through use of a wash
tray may or may not take place, as desired. Typically, in the
HB.sub.s AG test, elaborate cleaning of the aspirating tubes is not
necessary, because contamination is not present within the test
tubes as it is during the first washing operation described above.
Following the final washing, which takes place at two washing
stations, the CPG within the test tubes is ready for examination to
determine the results of the test. Detection may take place when
the test tube carrying block 20 is in the position of the blok 20b
shown in FIG. 1, as described above. With reference to FIG. 10, the
block 20 may include a tag 122 thereon which is magnetized, e.g.,
as at 124 as shown in FIGS. 10 and 11, for suitable detection of
the test tube carrying block as it passes through the various
stations within the system.
A presently preferred embodiment of the invention has been
described above. Obviously, modifications could be made. Electrical
coils beneath the test tube support table have been shown, in
conjunction with magnetic particles within the test tubes. The
coils could be replaced with an oscillating magnetic mat, if
desired. Cooling coils could also be added, as well as
thermastatically controlled heating elements. Controls for the
detection of low level of reagents, washing solutions, and
overfilling of various reservoirs can be utilized, as desired.
Beginning of test and end of test detections may be used, as well
as optical/electrical devices at the various liquid dispensing
stations to sense liquid levels, liquid presence, and the like.
Further, while the device has been described in connection with a
hepatitis test, any immunological test may be performed involving
some or all of the various operations described above.
Accordingly, the invention should be taken to be defined by the
following claims.
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