Chemical apparatus and process disinfecting – deodorizing – preser – Control element responsive to a sensed operating condition
Reexamination Certificate
2000-11-13
2004-03-30
Warden, Jill (Department: 1743)
Chemical apparatus and process disinfecting, deodorizing, preser
Control element responsive to a sensed operating condition
C422S105000, C436S180000, C073S863320, C073S863710, C073S864000, C073S864010, C073S864020, C073S864110, C073S864130, C073S864340, C251S129080, C251S129180, C137S487500
Reexamination Certificate
active
06713021
ABSTRACT:
The present invention relates to a dispensing assembly for liquid droplets of the type comprising a dispenser, having a main bore communicating with the nozzle having a nozzle bore terminating in a dispensing tip and delivery means for moving liquid to the dispenser and from there through the bore to form a droplet on the exterior of the tip and then to cause a droplet to fall off therefrom. The invention is further concerned with a method of dispensing a droplet from a pressurised liquid delivery source through a metering valve dispenser comprising an elongate body member having a main bore communicating through a valve seat with a nozzle having a nozzle bore terminating in a dispensing tip, a separate floating valve boss of magnetic material housed in the body member, the cross sectional area of which is sufficiently less than that of the main bore to permit the free passage of liquid therebetween thus by passing the valve boss; and a separate valve boss actuating coil assembly surrounding the body member.
The present invention is generally related to liquid handling systems and in particular to systems for dispensing and aspirating of small volumes of reagents. It is particularly directed to a high throughput screening, polymerase chain reaction (PCR), combinatorial chemistry, microarraying, medical diagnostics and others. In the area of high throughput screening, PCR and combinatorial chemistry, the typical application for such a fluid handling system is in dispensing small volumes of the reagents, e.g. 1 ml and smaller and in particular volumes around 1 microliter and smaller. It is also directed to the aspiration of volumes from sample wells so that the reagents can be transported between the wells. The invention relates also to microarray technology, a recent advance in the field of high throughput screening. Microarray technology is being used for applications such as DNA arrays. In this technology the arrays are created on glass or polymer slides. The fluid handling system for this technology is directed to dispensing consistent droplets of reagents of submicrolitre volume.
Development of instrumentation for dispensing of minute volumes of liquids has been an important area of technological progress for some time. Numerous devices for controlled dispensing of small volumes of liquids (in the range of 1 &mgr;l and smaller) for ink jet printing application have been developed over the past twenty five years. More recently, a wide range of new areas of applications has emerged for devices handling liquids in the low microlitre range. These are discussed for example in “analytical chemistry” [A. J. Bard, Integrated chemical systems, Wiley-Interscience Pbl, 1994], and “biomedical applications [A. G. Graig, J. D. Hoheeisel, Automation, Series Methods in Microbiology, vol 28, Academic Press, 1999].
The present invention is also directed to medical diagnostics e.g. for printing reagents on a substrate covered with bodily fluids for subsequent analysis or alternatively for printing bodily fluids on substrates.
The requirements of a dispensing system vary significantly depending on the application. For example, the main requirement of a dispensing system for the ink jet applications is to deliver droplets of a fixed volume with a high repetition rate. The separation between individual nozzles should be as small as possible so that many nozzles can be accommodated on a single printing cartridge. On the other hand in t his application the task is simplified by th e fact that the mechanical properties of the liquid dispensed namely ink are well defined and consistent. Also in most cases the device used in the ink jet applications does not need to aspire the liquid through the nozzle for the cartridge refill.
For biomedical applications such as High Throughput Screening (HTS) the requirements imposed on a dispensing system are completely different. The system should be capable of handling a variety of reagents with different mechanical properties e.g. viscosity. Usually these systems should also be capable of aspiring the reagents through the nozzle from a well. On the other hand there is no such a demanding requirement for the high repetition rate of drops as in ink jet applications. Another requirement in the HTS applications is that cross contamination between different wells served by th e same dispensing device be avoided as much as possible.
The most common method of liquid handling for the HTS applications is based on a positive displacement pump such as described in U.S. Patent Specification No. U.S. Pat. No. 5,744,099 (Chase et al). The pump consists of a syringe with a plunger driven by a motor , usually a stepper or servo-motor. The syringe is usually connected to the nozzle of the liquid handling system by means of a flexible polymer tubing The nozzle is typically attached to an arm of a robotic system which carries it between different wells for aspiring and dispensing the liquids. The syringe is filled with a liquid such as water. The water continuously extends through the flexible tubing into the nozzle down towards the tip. The liquid reagent which needs to be dispensed, fills up into the nozzle from the tip. In order to avoid mixing of the water and the reagent and therefore cross-contamination, an air bubble or bubble of another gas is usually left between them. In order to dispense the reagent from the nozzle, the plunger of the syringe is displaced. Suppose this displacement expels the volume &Dgr;V of the water from the syringe. The front end of the water filling the nozzle is displaced along with it. The water is virtually incompressible. If the inner volume within the flexible tubing remains unchanged, then the volume &Dgr;V displaced from the syringe equals the volume displaced by the moving front of the water in the nozzle. If the volume of the air bubble is small it is possible to ignore the variations of the bubble's volume as the plunger of the syringe moves. Thus the back end of the reagent is displaced by the same volume &Dgr;V in the nozzle, and therefore the volume ejected from the tip is the same &Dgr;V. This is the principle of operation of such a pump. The pump works accurately if the volume &Dgr;V is much greater than the volume of the air bubble. In practice the volume of the air bubble changes as the plunger of the syringe moves. Indeed in order to eject a drop from the tip, the pressure in the tubing should exceed the atmospheric pressure by an amount determined by the surface tension acting on the drop before it detaches from the nozzle. Therefore at the moment of ejection the pressure in the tubing increases and after the ejection, it decreases. As common gasses are compressible, the volume of the air or gas bubble changes during the ejection of the droplet and this adds to the error of the accuracy of the system. The smaller the volume of the air bubble, the smaller is the expected error. In other words the accuracy is determined significantly by the ratio of the volumes of the air bubble and the liquid droplet. The smaller this ratio is the better the accuracy. For practical reasons it is difficult to reduce the volume of the air or gas bubble to below some one or two microlitres and usually it is considerably greater than this. Therefore, this method with two liquids separated by an air or gas bubble and based on a positive displacement pump is not well suited for dispensing volume as low as 1 microlitre or lower. There are also additional limitations on accuracy when sub-microlitre volumes need to be dispensed. For example, as the arm of the robotic system moves over the target wells, the flexible tubing filled with the water bends and consequently its inner volume changes. Therefore, as the arm moves, the front end of the water in the nozzle moves to some extent even if the plunger of the syringe does not. This adds to the error of the volume dispensed. Other limitations are discussed in Graig et al referred to above. Examples of such positive displacement pumps are shown in U.S. Pat. Specification No. 5,744,09
Makarov Sergei
Osing Juergen
Shvets Igor
Gordon B. R
The Provost Fellows and Scholars of the College of the Holy and
Warden Jill
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