Chemical apparatus and process disinfecting – deodorizing – preser – Analyzer – structured indicator – or manipulative laboratory... – Means for analyzing liquid or solid sample
Reexamination Certificate
1999-07-26
2002-01-29
Snay, Jeffrey (Department: 1743)
Chemical apparatus and process disinfecting, deodorizing, preser
Analyzer, structured indicator, or manipulative laboratory...
Means for analyzing liquid or solid sample
C422S082000, C422S105000, C422S110000
Reexamination Certificate
active
06342184
ABSTRACT:
The present invention relates to an improved means for managing liquid flow in small bore tubes or channels. More particularly it relates to apparatus for managing liquid flow in microanalytical and micro-preparative procedures such as capillary electrophoresis and high performance liquid chromatography and electrochromatography.
The techniques of micro high performance liquid chromatography, electrochromatography and/or capillary electrophoresis involve the flow of a liquid phase through capillary tubing which typically has an internal diameter within the range of 2 &mgr;m to about 1000 &mgr;m e.g. 50 &mgr;m. In many of the applications of these micro- analytical and micro preparative techniques it is necessary to provide means for stopping the flow of one liquid phase in the column or tubing and introducing another liquid phase at a selected point in the capillary tubing and/or alternatively providing means for diversion of the liquid phase flow by means of additional inlets and outlets as and when required. To date such management of the flow of liquid phase through the column or tubing is achieved by means of specifically engineered switching valves with capillary tubes connected by means of sleeve connectors or unions into which the capillary tubes are located. These valves which have to be custom built to exacting specifications are very expensive and there are several operational disadvantages associated with their use. Thus the mechanical valves must be chemically inert so that the mobile phase remains uncontaminated by residues from the valve and this requirement limits the choice of the material and lubricants for the valves construction and maintenance. The feting of the valves to the column and the construction of the additional inlets and outlets in the capillary tubing must be achieved with ideally zero dead volume couplings and unions. Further the flow through the valve should not be turbulent so that the analyte peak of interest remains narrow in order to achieve the required degree of resolution.
The problem that arises with use of sleeve connectors or unions is the generation of dead volume between the ends of each capillary. The size of the dead volume may be reduced by the careful positioning of the capillaries and ensuring clean cut ends but it is not possible to reduce the dead volume to zero or to be sufficiently small so as to be insignificant on the scale of operation of an analytical technique such as multi-dimensional electrophoresis. Thus for example simple solid geometry calculations show in a conventional Y piece sleeve connector for capillary tubing of 50 &mgr;m internal diameter and 375 &mgr;m outer diameter the minimum dead volume will be at least 23 nL and in practice it will be significantly larger. This dead volume is too large for micro-analytical techniques such as capillary electrophoresis which use injection volumes in the order of 5 nL. In these circumstances the resolution of closely spaced peaks can be compromised by convective and eddy current induced mixing which will take place in the dead volume region.
We have now found that the disadvantageous problems associated with the use of mechanical switching valves in capillary tube liquid flow systems can be avoided by the use of rapid freeze and rapid thaw of the liquid phase at appropriate segments of the capillary system. The flow of the liquid phase through the capillary tubing can be stopped if a small segment of the column is rapidly cooled so as to freeze the liquid phase in that segment. Further the thermal capacity of the small segment of the column to be frozen is very small and this allows for rapid freezing and rapid thawing as required.
The disadvantages associated with the sleeve connectors and unions can be overcome by use of micro-channel pathways to connect the various capillary tubes and the present invention provides a means for achieving this.
The present invention therefore provides a means for managing liquid flow through small bore tubing or channels which comprises a means for freezing the liquid in a small segment of the tube or channel. Preferably the means for freezing the liquid phase is a jet of cold gas directed onto the required section of the tube. Conveniently the cooling gas is provided from a liquefied source of the gas under pressure such as liquid carbon dioxide or liquid nitrogen.
Alternative means for rapidly freezing the liquid phase includes the use of a thermo electronic arrangement such as a Peltier cooling arrangement or a cold finger. A separate means such as a jet of warm air for rapidly thawing the frozen segment of the column may also be provided but this may not be necessary if the normal temperature of the environment is sufficiently high.
In a further aspect of the invention there is provided a microanalytical or micro-preparative apparatus comprising one or more inlet pathways connected to one or more outlet pathways, the pathways comprising small bore tubing or channels and means for freezing of the liquid phase in a small segment of each of the inlet or outlet pathways. Preferably said means for rapidly freezing the liquid phase is a finely directed jet of cold gas. If necessary the apparatus may also be provided with means such as a jet of warm air so as to rapidly thaw the frozen segment of the column as and when required.
Preferably the inlet and outlet pathways comprise capillary tubes. The capillary tubes may be connected by means of a rigid body in which the ends of the capillary tubes to be connected are held and micro-channels in said body providing a connection with the bores of the said capillary tubing within the rigid body. Each micro-channel connecting two capillary tubes conveniently has a cross sectional area of a similar order of magnitude to that of the internal bore of the capillary tube, but may be considerably smaller. Typically the micro-channels will have a cross sectional area of up to 2 times that of the internal bore of the capillary tube. It will be appreciated however that for a given capillary tube connecting means the shape (cross-sectional area and length) of each micro-channel may be selected on the basis of the micro-analytical procedure with which it is to be used and the physical constraints of the particular connecting means.
For use in micro-preparative procedures including micro-analytical procedures wherein it is required to prepare in situ a derivative of the analyte at least two of the micro-channels in the connecting means according to the invention, are arranged so that they form a reaction cell, or connect to or intersect at a reaction cell within the rigid body or connect with a reaction cell outside the body, for example one of the capillary tubes connected thereto.
In one embodiment of the invention the rigid body comprises a lower body member, with a flat upper surface, into which the capillary tubes to be connected are held with one end of each said capillary tube flush with the flat upper surface of the lower body member; an upper body member which has a flat lower surface; micro-channels in the flat surface of the lower and/or upper body members positioned to connect the bores of the appropriate capillary tubes; and means for securing the upper and lower body members together.
In a preferred embodiment of the invention the rigid body comprises a lower body member, with a flat upper surface, in which the capillary tubes to be connected are held with one open end of the said capillary tube flush with the flat upper surface of the body member; an upper body member which has a flat lower surface containing micro-channels such that when the lower surface is located on the upper surface of the lower body member the micro-channels therein connect the openings in the appropriate capillary tubes, and means for securing the upper and lower body members together.
In a further embodiment of the invention the rigid body comprises a lower body member, with a flat upper surface into which the capillary tubes to be connected are held with one open end of the said capillary tube flush with the flat u
Bevan Christopher David
Mutton Ian Martin
Bacon & Thomas
Glaxo Group Limited
Snay Jeffrey
LandOfFree
Liquid flow management means does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Liquid flow management means, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Liquid flow management means will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2817888