EP0078109B1

EP0078109B1 - Liquid dispenser

Info

Publication number: EP0078109B1
Application number: EP19820305200
Authority: EP
Inventors: Roger Abraham Bunce
Original assignee: University of Birmingham
Current assignee: University of Birmingham
Priority date: 1981-10-23
Filing date: 1982-09-30
Publication date: 1988-06-08
Also published as: EP0078109A1; JPS5880541A; DE3278622D1

Description

This invention relates to liquid dispensers, particularly to liquid dispensers integral with caps and most particularly to those for dispensing blood serum or plasma.
Generally before analysis can be performed on a blood specimen contained in a capped blood tube the serum or plasma must be separated from the red cells. This is usually achieved by centrifugation followed by removal of the blood tube cap and pipetting or pouring of the serum. This may produce dangerous aerosols and pouring from conventional vessels has been declared unsafe in the 'code of practice of the Prevention of infection in clinical Laboratories and Postmortem Rooms" (The Howie report).
The blood tubes have standard dimensions, typically 15 mm diameter and 94 mm length, for mounting in a centrifuge. The centrifuging operation imposes an acceleration of the order of 1500 g on the blood tube and on parts secured thereto. In order to avoid damage to these parts it is therefore necessary that they shall extend substantially parallel to the blood tube axis.
It is known from GB-A-103769 to provide a device for dispensing ink from a container into a vessel, the device having two nozzles, one of which provides for liquid outflow and the other of which provides for venting air into the container, the nozzles being designed so that flow of liquid from the container is stopped when the air vent nozzle is closed by liquid rising in the receiving vessel. In this prior art device the liquid outflow and venting nozzles are of differing shapes and in order to effect pouring through the outflow nozzle the nozzles are bent through substantial angles, so that to start pouring of liquid the container must be tilted in a specific direction about an axis which is substantially perpendicular to the planes of the bent nozzles. The shapes of the nozzles render them unsuitable for use in a centrifuge as above described and the criticality of the direction of tilt would complicate any attempt to use the prior art device in an apparatus for automatic dispensing.
A source of dangerous aerosols, as indicated above, is a web of liquid which may form between the two nozzles of the device and subsequently burst. It is therefore desirable that the nozzles be spaced apart sufficiently to prevent web formation.
FR-A-1380554 shows a device for dispensing a fluid and including two spaced-part identical hollow needles which can pierce the closure of a receiving vessel to allow fluid to flow to that vessel. This reference is intended to stop dispensing of liquid from a container only when that container is empty, and is not capable of dispensing a predetermined quantity of liquid or of repeated dispensing operations.
It is an object of the present invention to provide a dispensing device which can be attached to a blood tube before a centrifuging operation, without risk of damage either to the blood tube or the dispensing device, and which may subsequently be used to dispense measured quantities of separated blood serum safely into an associated receiving vessel.
According to the invention a device for dispensing serum from a cylindrical container comprises a cap sealingly engageable with an open end of said container and two passages passing through said cap so as to open into said container, said passages terminating in nozzles which extend for substantially equal distances in a direction away from said container, and a vessel for receiving said serum, said container and said cap being, in use, inverted over said vessel, the open ends of the nozzles outwardly of the container being spaced from the base of said vessel by a predetermined amount which determines the volume of serum dispensed, said passages comprising substantially identical straight bores which extend substantially parallel to the axis of said cap and either extend from said cap in a direction inwardly of said container by substantially equal distances or do not extend inwardly of said cap into said container, characterised in that said passages have internal dimensions which combine with the surface tension of the serum to prevent flow from said container through one of said passages in the absence of an airflow into said container through the other passage, said passages comprising substantially identical straight bores which extend substantially parallel to the axis of said cap and extend from said cap in a direction inwardly of said container by substantially equal distances, adjacent outer surfaces of said nozzles being spaced by not less than 2.24 mm.
The invention also relates to a method of dispensing a predetermined amount of serum from a container, as set forth in the appended Claim 12.
The invention will now be described by way of example only and with reference to the accompanying drawings:-

Figure 1 is a cross-sectional side elevation of a liquid dispenser;
Figure 2 is a cross-sectional side elevation of a centrifuged blood tube fitted with a liquid dispenser;
Figure 3 is a cross-sectional side elevation of a liquid dispenser having wholly protruding nozzles with a sample container in position;
Figure 4 is a cross-sectional side elevation of a blood tube and liquid dispenser having partially protruding nozzles;
Figure 5 is a cross-sectional side elevation of a blood tube and liquid dispenser having partially protruding tapered nozzles;
Figure 6 is a cross-sectional side elevation of a blood tube and liquid dispenser having three partially protruding nozzles;
Figure 7 is a cross-sectional side elevation of a wadded two piece liquid dispenser;
Figure 8 is a cross-sectional side elevation of a wadless two piece liquid dispenser;
Figure 9 is a diagrammatic cross-section of a blood tube and liquid dispenser assembly before nozzle severance;
Figure 10 is a diagrammatic cross-section of an assembly after nozzle tip severance;
Figure 11 is a diagrammatic cross-section of an assembly with a sample container in position;
Figure 12 is a diagrammatic cross-section of an inverted assembly and sample container before flow commencement;
Figure 13 is a diagrammatic cross-section of an inverted assembly and sample container immediately before release of the first air bubble;
Figure 14 is a diagrammatic cross-section of an inverted assembly and sample container during flow;
Figure 15 is a diagrammatic cross-section of an inverted assembly and sample container after flow cessation;
Figure 16 is a diagrammatic cross-section of an inverted assembly removed from a sample container after flow cessation;
Figure 17 is a diagrammatic cross-section of an upright assembly after flow cessation;
Figure 18 is a diagrammatic cross-section of an assembly after nozzle clearance; (one tube might still be full);
Figure 19 is an isometric view of an assembly showing a wedge system;
Figure 20 is a diagrammatic cross-section of an assembly and sample container before flow commencement in wetted nozzle condition;
Figure 21 is a diagrammatic cross-section of an assembly and sample container after serum has run into nozzles in wetted nozzle condition;
Figure 22 is a diagrammatic cross-section of an assembly and sample container after serum in nozzles has unbalanced and flowed to end of one nozzle; and
Figure 23 illustrates an optional means for supporting a liquid dispenser while dispehsing.

Figure 1 shows a liquid dispenser in the form of a cap of resilient plastics material provided with a first nozzle 1 and a second nozzle 2 the distal ends 3 of the nozzles 1 and 2 are closed and the basal ends 4 are open. An annular lip 5 projects upward from the base 6 and a second annular lip of smaller radius 7 projects co-axially in a like manner.
A third annular lip 8 projects downward from the base 6 and a fourth annular lip of larger radius 9 projects in a like manner. The fourth annular lip 9 has a fast multistart femal thread moulded in its inner surface. Before the first dispensing the cap is cut with scissors, or a cutter like a cigar cutter, along a line indicated by 10 and the severed tip portion 11 discarded.
Figure 2 shows a cap 20 such as that described above with reference to Figure 1 fitted to a blood tube 21, i.e. the first vessel, containing serum 22, a separating gel 23, and coagulated.red cells 24 the remaining volume in the blood tube 21 being occupied by a volume of air 25.
Figure 3 shows in more detail how the third annular lip 8 forms a seal with the blood tube 21, the lengths of lips 8 and 9 are such that the cap 20 may be partially unscrewed without breaking the seal. A sample container 30 is located with its rim between annular lips 5 and 7. In this embodiment the nozzles 1 and 2 are flush with the base 6 and are identically dimensioned.
Figure 4 shows a second embodiment having two nozzles 40 and 41 of identical dimensions which protrude both above and below a base 42.
Figure 5 shows a fourth embodiment having two nozzles 60 and 61 of identical lengths protruding both above and below a base 62. The nozzles are frusto-conical having their larger diameter ends below the base 62.
Figure 6 shows a fifth embodiment having three nozzles 70, 71 and 72 of identical lengths and diameters protruding both above and below a base 73 the nozzles are arranged so that their axes do not fall in a single plane.
It will be appreciated that these embodiments are only examples of the many different combinations of nozzle geometries which fall within the scope of this invention and that features of different embodiments may readily be combined to produce further variations.
Figure 7 shows a modification to the invention in which the dispensing cap is constructed from two parts. A screw cap 100 having an axial orifice through which a resilient member 101 protrudes, being an interference fit with cap 100, and having two nozzles formed within itself as two cylindrical ducts 102. The resilient member broadens out below the cap 100 to form a wad 103 which is seated on the neck 104 of the blood tube 21 upon tightening of the screw cap 100.
Figure 8 shows another modification of the invention in which a screw cap 110 screws directly onto the blood tube 21; formed in the centre of the screw cap 110 is a deep recess 111 which may have weaknesses built into it at 112, for example a frangible membrane. A cylindrical member 113 having two nozzles 114 and 115 is a close fit in the recess 111. Downward pressure on the cylindrical member 113 causes the recess 111 to rupture at weakness 112 and, the cylinder 113 to move from the broken line to the continuous line position and the nozzles to connect the inside of the blood tube 21 and the environment.
It will be obvious to one skilled in the art that although the invention has been described with reference to a screw cap, it is equally possible to use a push-fit cap or a snap-fit cap.
The invention is utilized in a sequence of operations hereinafter described: a blood sample is taken from a patient in a conventional manner and subsequently transferred to a blood tube containing a silica gel. The blood tube is then sealed with a screw cap containing two nozzles and spun in a centrifuge to separate the red cells from the serum.
Figure 9 is a diagrammatic representation of such a spun blood tube 120, with a cap 121, and containing red cells 122 which have migrated to the bottom of the blood tube, separating the red cells from the less dense serum 123 is a separating gel 124 which forms a barrier between the red cells 122 and the serum 123. The cap 121 has two nozzles 125 and 126 protruding therefrom, terminally sealed by tips 127 and 128.
Typically the blood tube 120 is 14.5 mm diameter and 94 mm long. The depth of the red cells 122 is 32 mm, the separating gel 124 is 14 mm and the serum is 32 mm. Thus the air space above the serum has an initial depth of 16 mm.
After centrifugation the tips 127 and 128 of the nozzles 125 and 126 are cut off with scissors, or cigar type of cutter. The scissors may be of the type which retain the severed portion. This type of scissor minimises the risk of contamination of the human operator. Either cutting device could have a stop to gauge the length of nozzles.
An alternative, and at present less conventional, system is able to sample the patient's blood directly. The blood tube containing gel 124 and having a resilient cap 121 affixed, is supplied with its contents at a partial vacuum. A double ended needle is inserted into the patient and then through the resilient cap 121 whereupon the partial vacuum causes a sample of blood to be drawn into the blood tube 120. Thereafter the needle is removed from the patient and cap and the cap and blood tube is centrifuged in the same manner as has been described above.
Figure 10 shows the blood tube 120 and cap 121 with unused, dry, open nozzles 125 and 126 after the nozzle tips have been removed.
Figure 11 shows a sample container 140 emplaced over the nozzles 125 and 126. The blood tube and sample container assembly is subsequently manually inverted to the position shown in Figure 12.
The serum 123 flows to the capped end of the blood tube 120 under the action of gravity. The gel 124 is sufficiently viscous to stay in place and thereby retain the red blood cells 122 at the end of the blood tube . 120 remote from the cap 121.
The probable mechanism of flow will now be described using the nomenclature tabulated below:
The mechanism of flow of serum 123 into the nozzles 125 and 126 depends upon whether the nozzles have previously been used, hereinafter referred to as the wet condition, or are unused, hereinafter referred to as the dry condition.
The mechanism for flow in the dry condition may be explained with reference to Figure 13. Initially the serum 123 flows down only one nozzle 125 and an air bubble 160 is formed at the blood tube end of the other nozzle 126.
Consider the equilibrium at the bubble surface 161, here surface tension forces are resisting the differential pressure across the surface 161. In the extreme case the differential pressure is equal to the surface tension forces, e.g. when the bubble is about to break free from the nozzle. So, as shown in "Intermediate Physics" by C. J. Smith.
P_sis assumed to be the pressure acting at the base of the air bubble 160. Additionally, as the movement of serum 123 down the nozzle 125 takes place quickly, heat transfer is negligible so the expansion of gas in volume 162 may be assumed to be adiabatic. So:
therefore:

Also from static pressure head considerations ignoring surface tension effects in the nozzle containing serum, as for an unwetted nozzle the meniscus is flat, i.e. infinite radius, then:
As the serum 123 is substantially incompressible then from volume considerations:
also
and
Now substituting equation 3 into equation 1
and substituting equation 2 into equation 7
substituting equations 5 and 6 into equation 8
simplifying
For a graphical solution,
and
Now considering the equilibrium of the air bubble 160. It is assumed that the bubble is spherical. This is a valid assumption if the nozzle radius is small and the angle of contact between the serum 123 and the nozzle 126 is zero.

For equilibrium the upward force=weight of serum displaced
For the bubble 160 to detach from the end of the nozzle 126 the upward force must overcome the surface tension force. The bubble may be experimentally determined to be attached to the nozzle at its internal diameter, so the surface tension force is given by: 2π r_nσ. So for detachment to occur
therefore
After the first air bubble 160 has detached, serum 123 flows down the nozzle 125, thereby filling it, and continues to flow out of the nozzle and into the sample container 140 as shown in Figure 14.
Serum continues to flow into the sample container 140 and air bubbles 170 continue to be formed and released from the nozzle 126 until the level of serum 123 in the sample container 140 reaches the lower end of the nozzle 126, whereafter serum is drawn into the nozzle 126 as shown in Figure 15. This action prevents further bubbling and hence stops further flow of serum 123.
The blood tube and cap assembly are gently removed as shown in Figure 16. Surface tension between the serum 123 and the ends of the nozzles 125 and 126 is sufficient to prevent the serum flow out of the nozzles.
It is found experimentally that as the bore of the two nozzles increases the liquid equilibrium becomes more susceptible to mechanical shock. The variation in pressure P_s which causes the effect of surface tension to be overcome and the liquid to run out is due to two main effects. First, the differential pressure head due to a sideways acceleration or retardation temporarily imposing a greater head of liquid above one nozzle than the other, and secondly, a pressure change due to the inertia of the column of liquid in the blood tube acted upon by a vertical acceleration or retardation; that is the effect of a temporarily increased or decreased head of liquid above both nozzles. Also the change in volume of air above the serum in the inverted blood tube, and hence the distortion of the free liquid surfaces at the end of the nozzles depends upon the initial volume of said air. Thus prediction of the stability of the said free liquid surfaces under mechanical shock is complex; especially when the shock is produced by human handling, in which the accelerations applied to a blood tube cannot be standardised. However, with a nozzle diameter of 2 millimetre spillage is avoided readily. The blood tube and cap assembly when righted is shown in Figure 17. The serum 123 falls to be immediately above the gel 124, with the exception of that serum which remains in the nozzles 125 and 126. This serum may be removed, as shown in Figure 18, by unscrewing the cap 121 slightly in order to reduce the air pressure 210 and therefore cause the serum in at least one nozzle to be drawn into the blood tube. The assembly is now ready to dispense a further volume of serum if required. Even if only one nozzle is cleared this nevertheless prevents serum from being undesirably expelled due to a change ambient temperature or pressure. Change in temperature of any gas contained in the blood tube should be avoided as far as possible by eliminating unnecessary handling of the blood tube. in use, so conducting heat to the contents and expelling serum to the environment.
In order to prevent the cap 121 being inadvertently removed during the nozzle clearing operation a wedge form 220, as shown in Figure 19, is moulded or glued to the outside of the blood tube 120 and a tab 221 extends from the cap 121. The orientation of the wedge 220 allows the tab 221 to ride up its inclined surface during screwing on, but to be prevented from being completely removed accidentally. The tab and wedge may be regarded as specific examples of coacting projecting members of a safety catch device.
Further serum samples may be dispensed by repeating the operational sequence. Figure 20 shows a blood tube and sample container assembly which has been inverted. The following is an example of a practical design using blood serum and the following data.
L_d is to be calculated
First calculating the nozzle length for dry dispensing using equation 13: the radius of the air bubble R=2.₃₆8.
Now if Ah_d ranges from 0.038 to 0.039 mm by increments of 0.0001 mm and _Y2 may be calculated from each value of Ah_d using equations 10 and 11. From a graph Ah_d=0.03867 mm is where y,=y₂ so substituting in equation 4 and dividing by an
So then the length of the nozzle for the dry condition must be greater than this i.e. L_d>8.7702 mm.
For the example given, the calculations have been based on a liquid dispenser with dry nozzles. However, a second dispensing is equally satisfactory, i.e. with wet nozzles, with the same predeterminable termination. If the nozzles have previously been treated internally with a wetting agent a different calculation would have to be made, because the equilibrium position of the liquid may be different; that is, the liquid would enter the nozzles by a small distance.
In practice the nozzles have to be longer than the theoretical predictions to overcome the wettability forces between the liquid to be dispensed and the material of the dispenser. These are very difficult to predict and are dependent upon molecular cleanliness. This is well illustrated by the way rain drops follow irregular patterns down a window pane and is probably the main cause of any inconsistency in dispensing especially with small diameter nozzles.
For use in dispensing serum the optimum internal diameter of the nozzles should be between 3.0 and 3.4 mm. This is based on experimental evidence using standard nylon tubing. If 2.0 mm diameter was used dispensing was inconsistent and sometimes the dispenser had to be tapped on the bench to initiate pouring.
The theory predicts the minimum overall length of the nozzles from hydraulic considerations. The distance the nozzle projects from the outer end face of the cap in relation to the receiving vessel determines the volume dispensed. To adjust the sample volume independently of the overall length of the nozzle the nozzle may be sunk into the cap (Figure 4); however, for a given size of the dispensing vessel, this reduces the volume available for dispensing. In this example the delivery volume was 2 ml and the nozzles were made 20 mm long overall.
When designing a serum dispenser it should be made compatible with centrifuge technology. Some types of centrifuge do not allow their buckets to swing freely, e.g. the tubes are retained at 45°. In this case, long nozzles can undergo a permanent bending during centrifugation and need to be more solidly constructed than short nozzles. It is therefore desirable to minimise the length of the nozzles by using design techniques described.
The minimum spacing between the nozzle centres was found to be 7 mm for 4.76 mm 0/D 3.00 mm I/D nozzles. When dispensing, at a shallow angle to the horizontal, liquid moves down one tube and up the other. If the nozzles are too close together liquid is sucked up with the air and pouring stops. Also, if the spacing is made smaller a web of serum forms between the tubes and when the dispenser is removed from the dispensing vessel which can be a source of contamination.
The material used in the construction of the Liquid Dispenser is not critical. Nylon and PTFE have been used to make the nozzles, polythene for the cap and glass or plastic for the vessel. Five liquids have been dispensed: human blood serum, reconstituted equine serum, water, methanol and oil. All worked well, but the oil was obviously dispensed much slower because of the greater viscosity. Varying the amount of liquid in the dispenser did not appear to affect dispensing.
The invention has been described so far in relation to an arrangement in which when liquid is dispensed from a blood tube 21 into a sample container 30 the blood tube is located on the lip of the container to determine the depth of sample dispensed. For use with any other size of sample container 30A the blood tube may be provided with a depth gauge in the form of rods 260 arranged in the same direction as the nozzles, as shown in Figure 23 to locate the nozzles a required distance from the bottom of container 30A. The blood tube may be supported in relation to the rods 260 by a clamp 262.
If it is important to minimise the size of the nozzles pouring can be made more consistent by coating the inside of the nozzles with a dried film of wetting agent such as BRIJ 35 (R.T.M.) (30% solution) having a dilution of 1000:1. If the diameter is increased above 3.4 mm there is a danger that the dispenser may continue to pour after it is lifted clear of the receiving vessel.
The foregoing assumes that liquid dispensing will, in the main, be conducted at a substantially constant temperature of 22°C. However, it is usual to store blood specimens, before test, at a temperature of 4°C, and it should be stated that a liquid dispenser according to the invention also operates satisfactorily at the latter temperature in terminating dispensing predeterminably.

Claims

1. A device for dispensing serum from a cylindrical container (21), comprising a cap_.(20) sealingly engageable with an open end of said container (21) and two passages passing through said cap (20) so as to open into said container (21), said passages terminating in nozzles (1, 2) which extend for substantially equal distances in a direction away from said container (21), and a vessel (30 or 30A or 140) for receiving said serum, said container (21) and said cap (20) being, in use, inverted over said vessel (30 or 30A or 140), the open ends of the nozzles (1, 2) outwardly of the container (21) being spaced from the base of said vessel (30 or 30A or 140) by a predetermined amount which determines the volume of serum dispensed, said passages comprising substantially identical straight bores which extend substantially parallel to the axis of said cap (20) and either extend from said cap (20) in a direction inwardly of said container (21) by substantially equal distances or do not extend inwardly of said cap (20) into said container (21), characterised in that said passages have internal dimensions which combine with the surface tension of the serum to prevent flow from said container (21) through one of said passages in the absence of an air flow into said container (21) through the other passage, said passages comprising substantially identical straight bores which extend substantially parallel to the axis of said cap (20) and extend from said cap (20) in a direction inwardly of said container (21) by substantially equal distances, adjacent outer surfaces of said nozzles (1, 2) being spaced by not less than 2.24 mm.

2. A device as claimed in claim 1 in which said passages have internal diameters between 2.5 and 3.5 millimetres.

3. A device as claimed in claim 2 in which said passages have internal diameters between 3.0 and 3.4 millimetres.

4. A device as claimed in any preceding claim in which said cap (20) is provided with a means (5) for sealingly engaging said vessel (30).

5. A device as claimed in any preceding claim in which said cap (20) has an outer annular lip (9) for mechanical engagement with an outer surface of said container (21) and an inner annular lip (8) sealingly engageable with an inner surface of said container (21) so that said cap (20) may be withdrawn from the open end of said container (21) by a distance less than the axial dimension of said inner lip (8) with affecting said sealing engagement.

6. A device as claimed in any preceding claim which includes a third passage (71) substantially identical with said two passages, the three passages being arranged so that their axes do not lie in a single plane.

7. A device as claimed in any preceding claim in which said cap comprises an inner portion (113) from which said nozzles (114, 115) extend and a concentric separate outer portion (110) sealingly engageable with said container (21).

8. A device as claimed in claim 7 in which said outer portion (110) has a transverse membrane (112) for isolating said passages (114, 115) from said container (21), said membrane (112) being breakable by relative displacement of said inner and outer portions (113, 110).

9. A device as claimed in any preceding claim in which said cap is provided with a projection (221) for latching engagement with a part of said container (120).

10. A device as claimed in any preceding claim in which the internal length of each of said passages is not less than 8.8 millimetres.

11. A device as claimed in any of claims 1 to 7 in which said nozzles are of a relatively soft plastics material and are terminally sealed.

12. A method of dispensing a predetermined amount of a serum from a container (21), comprising sealingly fitting to the container (21) a cap (20) having two tubular passages (1, 2) which have substantially identical straight bores extending substantially parallel to the axis of said cap (20) and which either extend from said cap (20) inwardly of said container (21) by substantially equal distances or do not extend from said cap (20) into said container (21), inverting said container (21) over a vessel (30) so that said vessel (30) sealingly engages said cap (20) and said passages (1, 2) extend within said vessel (30), the open ends of said passages (1, 2) being spaced from the bottom of said vessel (30) by a predetermined distance which determines the volume of the serum dispensed, characterised in that zhe internal dimensions of said passages (1, 2) are such that when a serum level in said vessel (30) reaches the ends of said passages (1, 2) serum is drawn into one of said passages and outflow of serum through the other passage is prevented, adjacent outer surfaces of said passages (1, 2) being spaced by not less than 2.24 mm.

13. A method as claimed in claim 12 in which after dispensing said predetermined amount of serum said cap (20) is partly withdrawn from said container (21) while remaining in sealing engagement therewith, whereby a reduced pressure is provided within said container (21), to draw into said container (21) serum remaining in at least one of said passages (1, 2).