Chemistry: electrical and wave energy – Processes and products – Electrophoresis or electro-osmosis processes and electrolyte...
Reexamination Certificate
2000-11-14
2004-08-03
Nguyen, Nam (Department: 1753)
Chemistry: electrical and wave energy
Processes and products
Electrophoresis or electro-osmosis processes and electrolyte...
C204S450000, C204S451000, C204S454000
Reexamination Certificate
active
06770182
ABSTRACT:
BACKGROUND OF THE INVENTION
Microchannel devices are finding increased use in the identification and synthesis of chemical and biological species. Employing transverse channel dimensions from a few microns to about one millimeter, such systems may permit the miniaturization and large-scale integration of many chemical processes in a manner analogous to that already achieved in microelectronics. Applications for microchannel devices now under development include such diverse processes as DNA sequencing, immunoassay, the identification of explosives, identification of chemical and biological warfare agents, and the synthesis of chemicals and drugs.
Most microchannel systems for chemical and biological analysis employ some variant of electrochromatographic or electrophoretic separation. In chromatographic processes, bulk electroosmotic motion of a fluid is induced by applying an electric field along the length of the separation column. Individual species move through the column at various speeds due to preferential adsorption on stationary surfaces such as the channel walls or an internal porous packing. In contrast, electrophoretic processes involve little or no bulk fluid motion. Here the applied electric field instead produces motion of ionic species through a stationary or nearly stationary transport medium that may be either a fluid or a gel. Species separation in electrophoretic processes occurs as a result of differing ratios of the ion charge to the ion mobility and consequent differing ion speeds.
Electroosmotic flows offer two important benefits over pressure-driven flows for transport processes in microchannel devices. First, transport speeds in electroosmotic flow are independent of the width and depth of a channel cross-section over a wide range of conditions, making this technique for driving fluid motion extensible to extremely small physical scales. In contrast, pressure-driven flows require a pressure gradient that increases inversely with the square of the minimum transverse dimension to maintain a given fluid speed. Second, the profile of the fluid velocity across the cross-section of a long straight channel is essentially flat in electroosmotic flows, again over a wide range of conditions. All transverse variation in the axial speed is confined to a small region adjacent to the channel walls and comparable in thickness to the electric Debye layer. The benefit of this flat velocity profile is that samples may be transported over long ranges with very little hydrodynamic dispersion due to nonuniform fluid speeds.
Electrophoretic processes offer somewhat different benefits in microchannel devices. Because the overall dimensions of microchannel devices tend to be only a few centimeters, very large electric fields may be produced by relatively small electric potentials. This permits larger ion speeds and reduces the overall time for separation processes. Electrophoretic motion is also easy to produce in microchannel systems since, like electroosmotic flow, only electrodes and a power supply are required to produce the phenomenon. Mechanical pumps are unnecessary. Also like electroosmotic flows, this method of producing species motion introduces little extraneous spreading of a sample band as it moves along the separation column since the electric field in a long straight channel is spatially uniform.
Despite these benefits in long-range transport, electrokinetic mechanisms are not particularly well suited to producing a thin sample band for subsequent processing in a separation or other process channel. The reason for this is that species motion in both electroosmotic and electrophoretic transport processes is governed by the highly-diffusive Laplace equation, and the region over which motion is induced usually occupies at least one channel width. As a result, the thickness of a sample band produced by such motion will usually exceed the channel width; this is not acceptable for many processes of practical interest.
For electrochromatographic and electrophoretic separation processes, the thickness of the initial sample band measured in the direction of the sample motion may need to be small compared to the channel width. Separation columns in microchannel systems are typically not very long, so final spacings between constituent bands may span only a channel width or so. To resolve these bands requires that the thickness of the sample band initially injected into the column is much smaller than the band spacing or, equivalently, much smaller than the channel width. In addition to separation processes, small sample sizes and sharp definition of species interfaces are also desirable during routine sample transport. These desired characteristics allow more precise control over processes such as mixing, dilution and synthesis.
The invention described here provides a method and apparatus for producing a sample band for subsequent processing wherein the thickness of the band in the direction of sample motion is small compared to the channel width. Further, the thickness of the band may be controlled to provide a desired sample volume or size. This method can even produce sample bands having an overall thickness an order of magnitude or so smaller than the channel width. The method can be implemented using conventional channel geometries and conventional electrical hardware. Additional benefits can be obtained by using these new methods in conjunction with improved channel geometries. Such improved geometries are also disclosed here.
Prior Art
FIG. 1
schematically illustrates a very simple microchannel system
100
for chemical analysis. Here, the channels are fabricated on a planar substrate
101
. Reservoirs
102
-
105
have access ports (not shown) that permit introducing and extracting fluid through the top or bottom faces of the substrate. Channels
112
-
115
are filled with a fluid or gel-material hereinafter referred to as a “transport medium,” which supports migration of ions or charged particles of a sample material either through or with the transport medium under the influence of an applied electrical field. The process channels
112
-
115
may also contain a separation matrix comprising a porous or granular material, a microfabricated pattern of obstacles, or a plurality of protrusions that promote species separation. The reservoir access ports (not shown) may also be used to control the hydrostatic pressures in the reservoirs or they may be left open to maintain reservoir pressures equal to the atmospheric pressure. Similar access holes (not shown) are used to insert electrodes
106
-
109
that are connected to power supply
110
through leads
106
′-
109
′ respectively.
Power supply
110
is used to apply electric fields along one or more of channels
112
-
115
emanating from junction
111
. The electric field is the negative of the gradient of the electric potential. The overall electric field is applied by controlling the differences in electric potential between the reservoir electrodes or, equivalently, by controlling the electric current flow to the individual electrodes. Although the electric field within the junction region is generally multidimensional, the electric field and induced sample transport is nearly one dimensional and uniform along straight channel segments, provided that the Debye layer thickness is small compared to the transverse channel dimensions. Under this restriction, easily met by most practical systems, the electrokinetic transport speed is simply proportional to the electric field at any point within the channels or junction. Thus, control of the electric field is equivalent to controlling the sample transport speed.
In a separation process, different species within a sample band (not shown) move along process channel
112
(or separation column) at different speeds due to differences in surface adsorption or differences in ion charge and mobility. As a result, the sample separates into a series of constituent bands that are detected as they pass through a detection device
120
, located toward the end of proces
Griffiths Stewart K.
Nilson Robert H.
Evans Timothy P.
Mutschler Brian L
Nguyen Nam
Sandia National Laboratories
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