Liquid purification or separation – Processes – Chromatography
Reexamination Certificate
2001-01-24
2002-05-28
Therkorn, Ernest G. (Department: 1723)
Liquid purification or separation
Processes
Chromatography
C210S198200, C141S012000, C141S080000
Reexamination Certificate
active
06395183
ABSTRACT:
This invention pertains to a method for preparing packed capillary columns. More particularly, the invention pertains to a multi-step method of packing capillary tubes to form packed capillary columns wherein a pre-pack column packed with particulate materials is first prepared by the slurry packing method, and then the packing is transferred from the pre-pack column to a second capillary tube to form a final packed capillary column.
BACKGROUND OF THE INVENTION
Capillary columns are capillary channels which have been packed with a packing material. Suitable channels may be fabricated from hollow tubing of appropriate diameter or formed in planer substrates through a variety of processes.
There are a variety of methods currently in use for packing capillary channels to form packed capillary columns, such as those columns used in the fields of chromatography and electrospray ionization mass spectrometry (ESI-MS).
One method for packing capillary tubes is known as the “Dry Packing Method”. In accordance with this method, dry packing material, such as glass, silica, polymeric powder or metallic powder, is forced into one end of capillary tube. In a particularly advantages aspect of this method, the particulate materials are rapidly vibrated as they are loaded into the tube through a funnel.
Narrow-bore columns, which are being found useful for an expanding variety of technological applications, have inside diameters which are generally <300 &mgr;m, and typically constructed of steel, polymer or fused-silica. Especially narrow columns will be required for the so-called “lab on a chip devices” which are now in their early stages of development, in which capillary channels are fabricated in planar substrates, such as glass or silicon wafers. The “Dry Packing Method” is unsatisfactory for loading such columns, because the small diameters involved do not allow for the free flow of dry powdered material.
A second method for packing capillary tubes is known as the “Slurry Packing Method”. In accordance with this method, a slurry, i.e., a liquid comprising suspended particles of packing material, is forced under pressure into the proximal end of the tube, and pumped until the slurry reaches a frit at the distal end of the tube. The frit serves to “filter” the particulate packing material from the liquid, also known as the “mobile” phase. The mobile phase thus passes through the frit and out of the tube, while the solid packing particles remain behind the frit. As the tube begins to thus become packed, the back-pressure on the system increases due to viscous flow. The packing rate, and the flow rate of the mobile phase through the tube, thus decreases as packing progresses and the amount of packing built-up behind the frit increases. In order to compensate for the increased back-pressure, and maintain a constant flow rate, the pressure of the slurry entering the tube has to be increased.
Slurry packing normally requires the use of high pressures (>1000 psi) in order to generate a high flow rate of mobile phase and resultant high “impact velocity” of the incoming particles. This high velocity forces the incoming particles into intimate contact with the bed. In this way, a tightly packed bed is formed. A tightly packed bed is important for good, reproducible chromatographic performance. This is especially important for column-to-column reproducibility. Slurry packing can be utilized to form columns in capillary channels that are frbricated in tubular or planar substrates.
The “Slurry Packing Method”, while useful, generally requires the use of expensive instrumentation capable of generating and withstanding high operating pressures. This becomes much more the case as the trend towards columns having smaller and smaller inside diameters continues.
In yet a third method, the channel is filled with a monomer solution or a gel, and then the monomer is caused to polymerize inside the tube, to form a continuous porous bed through which gas or liquid may then flow. No solid material is initially introduced into the channel, and this method is based on a change in the state of the initial material charged into the channel from a liquid or gel into a porous solid.
Other known methods involve electroosmotic packing, centrifugal packing and evaporative packing.
None of the foregoing methods offer the economy and ease of use of the method we have now discovered.
SUMMARY OF THE INVENTION
We have now discovered a method for column packing based on the traditional slurry method, which is compatible with low packing pressures (≦1000 psi) and narrow bore columns (<300 &mgr;m inside diameter). This method utilizes a multi-step approach that is analogous to an “annealing” or condensation process. In “annealing”, residual stress or defects in a system are removed through the application of energy.
In accordance with the method, a pre-pack channel is packed with a packing material by the slurry method to form a pre-pack column. The frit is then removed from the pre-pack column, and the pre-pack column is then joined with the final channel to be packed. A fluid, such as that used as the mobile phase for the slurry packing of the pre-pack column, is then forced through the pre-pack column and into the final channel, whereby the packed material in the pre-pack column flows into the final channel to form a packed bed in the final channel, thereby forming a final packed column.
DETAILED DESCRIPTION
In accordance with the method of the present invention, a channel having a proximal end and a distal end, with a porous frit at the distal end, is first pre-packed by forcing a slurry of packing material packing into the proximal end of the channel at a slurry pressure in the range of from about 100 to about 1,000 psi. A loosely-packed bed is thereby formed in the channel, to form a pre-pack column. This loosely-packed bed, however, typically has a plurality of packing defects. Such packing defects are characterized as undesirably large void spaces within the bed. The presence of such large voids in a packed bed would cause the bed to perform poorly in chromatography service.
The frit is then removed from the distal end of the pre-pack column and the pre-pack column, or a portion thereof, is joined to the proximal end of a second channel, void of any mobile phase, having a proximal end and a distal end and having a porous frit at the distal end. The distal end of the pre-pack column is preferably secured to the proximal end of the second channel by a liquid-tight, zero dead volume, seal using a “union”; although any of the other types of devices known in the art for securing one channel to another or any other method of joining one tube to another may also be used for this purpose.
The second channel initially is empty of any liquid, although the presence of a gas, such as air, nitrogen, helium, argon or the like may be desirable. It is especially desirable to have Helium present in the second channel, as Helium is highly compressible and leads to faster travel of the slurry through the channel.
A liquid, such as the mobile phase liquid used in the slurry, is then forced through the proximal end of the pre-pack column, to force the bed of packing material out of the pre-pack column and into the second channel. As the bed flows into the second tube and flows from the proximal end of the second tube to the distal end, kinetic energy from the flowing liquid phase induces transient contact of the particles making up the bed with each other, and induces a uniform distribution of the particles within the bed. As the bed of packing material reaches the frit at the distal end of the second channel, a re-packing of the bed takes place. The re-packing takes place much more quickly than did the pre-packing, because the packing velocities of the individual particles are more uniform; that is to say, that the velocity of each individual particle will be close to the velocity of each of the other particles, so that there will be a uniform velocity profile of the particles as they move through the channel towards the frit. T
Ehrenfeld Emily E.
Valaskovic Gary
New Objectives, Inc.
Norris & McLaughlin & Marcus
Therkorn Ernest G.
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