U.S. patent number 3,854,703 [Application Number 05/289,344] was granted by the patent office on 1974-12-17 for method of and apparatus for promoting a reaction between a liquid specimen and a liquid reagent.
This patent grant is currently assigned to Vickers Limited. Invention is credited to Edward John Bennet, Dudley Francis Gibbs, William Ian Hopkinson.
United States Patent |
3,854,703 |
Gibbs , et al. |
December 17, 1974 |
METHOD OF AND APPARATUS FOR PROMOTING A REACTION BETWEEN A LIQUID
SPECIMEN AND A LIQUID REAGENT
Abstract
A reaction between a liquid specimen and a liquid reagent is
promoted by applying the liquids to a liquid-impermeable support
surface to form a mixture thereon, and the liquid mixture is
agitated by directing a jet of gaseous fluid from a supply duct
outlet to impinge thereon, and bringing about relative movement
between the outlet and the support surface.
Inventors: |
Gibbs; Dudley Francis
(Bracknell, EN), Bennet; Edward John (Wokingham,
EN), Hopkinson; William Ian (Camberley,
EN) |
Assignee: |
Vickers Limited (London,
EN)
|
Family
ID: |
26251142 |
Appl.
No.: |
05/289,344 |
Filed: |
September 15, 1972 |
Foreign Application Priority Data
|
|
|
|
|
Sep 17, 1971 [GB] |
|
|
43575/71 |
Mar 30, 1972 [GB] |
|
|
15218/72 |
|
Current U.S.
Class: |
436/44; 366/349;
436/174; 366/101; 422/224 |
Current CPC
Class: |
B01F
13/0272 (20130101); B29C 53/20 (20130101); G01N
35/00009 (20130101); B29L 2023/22 (20130101); Y10T
436/110833 (20150115); Y10T 436/25 (20150115) |
Current International
Class: |
B29C
53/20 (20060101); B29C 53/00 (20060101); B01F
13/02 (20060101); B01F 13/00 (20060101); G01N
35/00 (20060101); B01f 013/02 () |
Field of
Search: |
;259/1R,2,11,17,DIG.17,DIG.24 ;23/253TP,259 ;261/80
;34/28,31,33,46,216,217,221,DIG.2 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
Primary Examiner: Hornsby; Harvey C.
Assistant Examiner: Cantor; Alan
Attorney, Agent or Firm: Pennie & Edmonds
Claims
We claim:
1. A method of promoting a reaction between a liquid specimen and a
liquid reagent, comprising the steps of applying the liquid
specimen and the liquid reagent to a liquid-impermeable support
surface to form a liquid mixture thereon, causing a jet of gaseous
fluid to emerge from a supply duct outlet and impinge upon the
liquid mixture on the support surface, and bringing about relative
movement between the support surface and said supply duct outlet
thereby to cause agitation of the liquid mixture.
2. A method as claimed in claim 1, comprising the further steps of
controlling the temperature and controlling the humidity of said
gaseous fluid.
3. Apparatus for promoting a reaction between a liquid specimen and
a liquid reagent, comprising a liquid-impermeable support surface,
first means for applying the liquid specimen to the support
surface, second means for applying the liquid reagent to the
support surface to form thereon a liquid mixture with the liquid
specimen, a source of gaseous fluid, a supply duct having an inlet
connected to said source and an outlet arranged to direct a jet of
gaseous fluid from said source to impinge upon said liquid mixture
on the support surface, and drive means connected to bring about
relative movement between the support surface and said outlet
thereby to cause agitation of the liquid mixture.
4. Apparatus as claimed in claim 3, further comprising means for
controlling the temperature of said gaseous fluid and means for
controlling the humidity of said gaseous fluid.
5. Apparatus as claimed in claim 3, wherein said support surface is
an upper surface of an elongate specimen support and the apparatus
further comprises guide means determining a path along which said
support is movable in a longitudinal direction thereof through the
apparatus.
6. Apparatus as claimed in claim 5, wherein said outlet is one of a
plurality of such outlets all connected by way of the supply duct
to said inlet and spaced apart along the path without additional
outlets therebetween, each outlet of the plurality defining the end
of a cylindrical passageway having a central axis lying in vertical
plane parallel to said path and extending from said outlet both
downwardly, at 45.degree. to the vertical, and in said longitudinal
direction.
7. Apparatus as claimed in claim 6, wherein said first and second
means are arranged to co-operate to provide on said upper surface
as said drive means operate a succession of pools of given depth,
distributed along said upper surface and each containing a mixture
of liquid specimen and liquid reagent, which are carried on the
specimen support from said first and second means and subsequently
along said path, and there being between each outlet of the
plurality and the upper surface of said support a clearance that is
less than the sum of said given depth and five times the internal
diameter of said cylindrical passageways.
8. Apparatus as claimed in claim 7, wherein the number of outlets
of the plurality is more than two and the distance between
successive outlets is less than the length of said pools.
9. Apparatus as claimed in claim 5, wherein said outlet is one of a
plurality of such outlets which are connected to said inlet and
which are distributed along said path, the outlets being arranged
alternately singly and in pairs, the two outlets of each pair being
spaced apart transversely with respect to said path.
10. Apparatus as claimed in claim 5, wherein said first and second
means are arranged to provide on said upper surface a succession of
pools of given length distributed along said upper surface and each
containing a liquid specimen and a liquid reagent, and said outlet
is one of a plurality of such outlets, said outlets being arranged
in pairs and the pairs of outlets being spaced apart along said
path by a distance greater than said given length and there being
no additional outlets between successive pairs of outlets along the
path, each outlet of each pair defining the end of a cylindrical
passageway having a central axis which is inclined to the vertical
and lies in a vertical plane perpendicular to said path and which
crosses the central axis of the cylindrical passageway whose end is
defined by the other outlet of the pair below the pair of outlets.
Description
This invention relates to methods of and apparatus for promoting a
reaction between a liquid specimen and a liquid reagent.
Many tests that are carried out upon samples of specimen material
derived from different sources involve agitating the material with
a reagent added thereto in order to produce an homogeneous mixture
of the reagent and the material. This has been achieved hitherto by
stirring the material with a stirring rod. However, it is
inconvenient to employ a stirring rod with very small samples, and
cross-contamination between samples may be caused if a stirring rod
is employed. Accordingly the problem has arisen of how to bring
about agitation of very small samples of specimen material, and
particularly without causing cross-contamination between
samples.
According to a first aspect of the present invention there is
provided a method of agitating liquid specimen material distributed
for examination over a specimen support surface, wherein a jet of
gaseous fluid emerging from a supply duct outlet is caused to be
incident upon the liquid material and relative movement is brought
about between the support surface and the said supply duct
outlet.
According to a second aspect of the present invention there is
provided, in combination, a specimen support surface and a supply
duct arranged for directing a jet of gaseous fluid from an outlet
of the duct to be incident upon liquid specimen material that is
distributed for examination over the support surface when it is in
use, there being means for bringing about relative movement between
the support surface and the said outlet so as to cause agitation of
the liquid specimen material.
According to a third aspect of the present invention there is
provided a device for agitating liquid specimen material
distributed along an upper surface of an elongate specimen support,
comprising guide means for determining a path along which the
support can be moved in a lengthwise direction thereof through the
device, and pneumatic jet-forming means having at least one outlet
arranged, adjacent to the said guide means, for directing a jet of
gaseous fluid so as to be incident upon the specimen material on
the support surface, when the device is in use, thereby to bring
about agitation of the specimen material as the specimen support is
moved, along the said path, past the or each said outlet.
The gaseous fluid (i.e., gas or vapour) is preferably air.
For a better understanding of the invention, and to show how the
same may be carried into effect, reference will now be made, by way
of example, to the accompanying drawings in which:
FIG. 1 shows diagrammatically an elevation of apparatus for use in
testing specimen materials,
FIG. 2 shows a perspective view, partly cut away, of a device
forming part of the FIG. 1 apparatus,
FIG. 3 shows a plan view of a portion of specimen support tape,
FIG. 4 shows diagrammatically a longitudinal sectional view of a
first modification of the FIG. 2 device,
FIG. 5 shows a perspective view, cut away, of a second modification
of the FIG. 1 device, and
FIG. 6 shows a plan view of a portion of specimen support tape.
The apparatus shown in FIG. 1 is used to perform tests upon
specimen materials, for example blood serum, by mixing a sample of
each specimen material with reagent and observing the result of the
reaction, if any, between the specimen material and the reagent.
Thus, the apparatus comprises applicator means 1 whereby a
succession of drops of reagent (and possibly also diluent) are
applied to the upper surface of a horizontal specimen support tape
2 which is drawn through the apparatus by virtue of its being
gripped between two rollers 3 of which one is driven to rotate. The
applicator means 1 also dispense a drop of specimen material into
each drop of reagent, to provide a succession of pools distributed
along the tape and each containing specimen material and reagent.
Beyond the applicator means 1 in the direction of tape movement is
a pneumatic stirring device 4 whereby each pool of specimen
material and reagent is thoroughly agitated to provide an
homogeneous mixture. The pneumatic stirring device is shown in more
detail in FIG. 2. During passage of the pools through the pneumatic
stirring device the reaction, if any, between the specimen material
and the reagent takes place, and the result of the reaction is
observed by optical means 5.
The pneumatic stirring device illustrated in FIG. 2 comprises a
tape guide 6 formed with a groove 7 which has a flat bottom and
straight sides. A distribution block 8 is positioned above the
guide 6 so that it extends completely over the top of the groove 7.
Above the distribution block 8 is a gasket 9 and above that is a
manifold top plate 10. The components 8, 9 and 10 are held together
by screws 11 and the guide 6 and the assembly 8/9/10 are held
together by a spring clamp 12.
The block 8, the gasket 9 and the top plate 10 together define a
chamber 13 which extends above the groove 7. The chamber 13
communicates with the volume bounded by the groove 7 through a
plurality of outlets 14. Air from a supply cylinder 20 (FIG. 1) can
be supplied under pressure to the chamber 13 through an inlet stub
15 provided on the top plate 10, and it leaves the chamber by way
of the outlets 14 forming respective jets directed towards the
bottom of the groove. The outlets 14 along the groove are arranged
alternately as outletpairs and single outlets.
The device 2 is used to agitate pools 17, containing specimen
material and reagent, distributed along the upper surface of the
specimen support tape 2. To use the device the clamp 12 is removed
and the assembly 8/9/10 is lifted from the guide 6 so as to expose
the groove 7. A lead-in portion of the tape is laid in the groove
and the assembly 8/9/10 is then clamped in position once more. The
leading end of the tape is passed between the rollers 3 for drawing
the tape through the groove in the direction of the arrow, and the
inlet stub is connected to a supply of compressed air (not shown).
The tape is then drawn through the device, along the path defined
by the groove in the guide, as the air is supplied to the chamber
and issues from it through the outlets 14 forming jets directed
onto the upper specimen-bearing surface of the tape. As a pool of
the specimen material passes under one of the single outlets that
pool tends to be flattened out and pushed aside from the centre of
the tape, and as the pool subsequently passes under an outlet-pair
the pool is pushed back once more towards the centre of the tape
(see FIG. 3). Thus as the tape is drawn through the device the
specimen material is agitated. The amount of agitation is
controlled by the total number of single outlets and outlet-pairs,
while the rate of agitation is controlled by the pitch of the
single outlets and outlet-pairs along the groove.
The agitation brought about by the FIG. 2 device is used to promote
chemical reactions between the specimen material and the reagent,
and in order to prevent excessive drying of the reactants and/or
the reaction product the air is humidified by passing the air from
the cylinder 20 through a bath 18 (FIG. 1) of water and mixing it
with dry air from a second cylinder 21. The temperature of the air
is also controlled by heating the water of the bath 18 with a
thermostatically controlled immersion heater 19. It may in some
circumstances be desired to dry the reaction product, in which case
the temperature and humidity of the air are adjusted accordingly.
The specimen material may contain insufficient liquid in which case
diluents as well as reagents may be added to the specimen material
before it reaches the device.
A device in accordance with FIG. 2 has been constructed using
Perspex for the components 6, 8 and 10 and butyl rubber for the
gasket 9. A satisfactory amount of agitation was achieved with the
device using air supplied to the inlet stub 15 at about 5
p.s.i.
It has been found that instead of using alternate single outlets
and outlet-pairs, as described with reference to FIGS. 2 and 3, it
is preferable in order to produce an homogeneous mixture of reagent
and specimen material to employ the modification shown
diagrammatically in FIG. 4.
In the case of the FIG. 4 modification, two single outlets provided
by jet needles 22 are spaced apart along the groove, without an
interposing outlet-pair. The needles 22 are of cylindrical
cross-section, and their central axes are inclined to the vertical
at 45.degree. but lie in the same vertical plane. The inclined
needles are directed forwardly, that is in the direction of tape
movement, and air jets provided by the needles induce a vortex
motion in the liquid of the pools, thereby producing a thorough
mixing of the reacting components. The depth of the groove is such
that the clearance between the needles and the free surface of a
pool 0.2 mm deep is less than five times the internal diameter of
the jet needles. It is found with 10 .mu.l pools containing blood
serum and a water-based reagent, and a tape speed of 10 mm/sec.,
adequate mixing is produced with an air flow to each jet needle of
approximately 0.6 l/min. The effectiveness of the jet action is
reduced if the clearance between the needles and the pools is
increased beyond five needle diameters or if the inclination of the
needles to the vertical is reduced below 45.degree..
Many tests in serology involve agglutination reactions, developed
by rocking a mixture of blood serum and a reagent for a period of
time. If the mixture is provided in the form of pools on the
horizontal tape 2, the rocking action can be produced by passing
the tape under a series of outlet-pairs as shown in FIG. 5. In the
case of FIG. 5 the outlets are provided by respective passageways
of cylindrical cross-section. The central axis of each passageway
is inclined to the vertical at 30.degree., and lies in the same
vertical plane, perpendicular to the direction of tape movement, as
the central axis of the passageway providing the other outlet of
the pair. The two jets provided by the outlet-pair converge to form
an air curtain above the tape which causes the liquid to be carried
towards the back of the pool until it finally passes through the
air curtain to flow forward again. The outlet-pairs are spaced
apart along the groove by slightly more than the length of the
pools in order to allow this pattern of movement to become
established. For example, in the case of pools 12 mm long the
outlet-pairs are spaced apart along the groove by 15 mm. The
outlets are approximately 4 mm above the tape, and for 10 .mu.l
pools an air flow through each outlet-pair of approximately 0.6
l/min. is required.
Using the modification shown in FIG. 5 for reactions which require
long mixing times and a large number of rocks leads to an
undesirably long rocking stage, and in these circumstances it has
been found preferable to employ a series of stirring jets as
described with reference to FIG. 4, with a pitch (space between
successive jets) less than the length of the pools on the tape. For
example, for a 10 .mu.l pool, 12 mm long, the jets are pitched at 8
mm. This creates a steady vortex flow pattern in the pools, as
shown in FIG. 6. In FIG. 6 the positions at which the air jets are
incident on the pool 17 and the tape 2 are shown as circles 23. For
10 .mu.l pools an air flow to each jet of 0.3 l/min. is sufficient.
Of course, to increase the amount of mixing the tape speed may also
be reduced.
It is not essential for the specimen material to be in discrete
pools, as shown, but it could instead be in the form of a
continuous trace extending along the tape.
The device shown in FIG. 2, or as modified in accordance with FIGS.
4 or 5, may be used in combination with other devices to treat
specimen material to prepare it for subsequent microscopic
examination, for example in the Vickers Cytological Screening
Apparatus.
* * * * *