Chemical apparatus and process disinfecting – deodorizing – preser – Analyzer – structured indicator – or manipulative laboratory... – Means for analyzing liquid or solid sample
Reexamination Certificate
2000-01-11
2001-07-24
Tung, T. (Department: 1743)
Chemical apparatus and process disinfecting, deodorizing, preser
Analyzer, structured indicator, or manipulative laboratory...
Means for analyzing liquid or solid sample
C422S070000, C422S091000, C422S105000, C422S105000, C435S287200, C435S288600, C435S288700, C204S450000, C204S451000, C204S600000, C204S601000
Reexamination Certificate
active
06264892
ABSTRACT:
TECHNICAL FIELD
The present invention relates generally to miniaturized planar column technology for liquid phase analysis, and more particularly to fabrication of microstructures in novel separation support media using laser ablation techniques. The microstructures find use in any analysis system which may be performed on small and/or macromolecular solutes in the liquid phase and which may employ chromatographic or electrophoretic means of separation.
BACKGROUND OF THE INVENTION
In sample analysis instrumentation, and especially in separation systems such as liquid chromatography and capillary electrophoresis systems, smaller dimensions generally result in improved performance characteristics and at the same time result in reduced production and analysis costs. Miniaturized separation systems provide more effective system design, result in lower overhead, and enable increased speed of analysis, decreased sample and solvent consumption and the possibility of increased detection efficiency.
Accordingly, several approaches towards miniaturization for liquid phase analysis have developed in the art; the conventional approach using drawn fused-silica capillary, and an evolving approach using silicon micromachining.
In conventional miniaturized technology the instrumentation has not been reduced in size, rather, it is the separation compartment size which has been significantly reduced. As an example, micro-column liquid chromatography (&mgr;LC) has been described wherein columns with diameters of 100-200 &mgr;m are employed as compared to prior column diameters of around 4.6 mm.
Another approach towards miniaturization has been the use of capillary electrophoresis (CE), which entails a separation technique carried out in capillaries 25-100 &mgr;m in diameter. CE has been demonstrated to be useful as a method for the separation of a variety of large and small solutes.
J. Chromatog.
218:209 (1981);
Analytical Chemistry
53:1298 (1981).
A major drawback of the above approaches to miniaturization involves the chemical activity and chemical instability of silicon dioxide (SiO
2
) substrates, such as silica, quartz or glass, which are commonly used in both CE and &mgr;LC systems. More particularly, silicon dioxide substrates are characterized as high energy surfaces and strongly adsorb many compounds, most notably bases. The use of silicon dioxide materials in separation systems is further restricted due to the chemical instability of those substrates, as the dissolution of SiO
2
materials increases in basic conditions (at pHs greater than 7.0).
In order to avoid some of the substantial limitations of conventional &mgr;LC and CE techniques, and in order to enable even greater reduction in separation system sizes, there has been a trend towards providing planarized systems having capillary separation microstructures. In this regard, production of miniaturized separation systems involving fabrication of microstructures in silicon by micromachining or microlithographic techniques has been described. See, e.g.: Fan et al.,
Anal Chem.
66(1):177-184 (1994); Manz et al.,
Adv. in Chrom.
33:1-66 (1993); Harrison et al.,
Sens. Actuators, B
B10(2):107-116 (1993); Manz et al.,
Trends Anal. Chem.
10(5):144-149 (1991); and Manz et al.,
Sensors and Actuators B
(
Chemical
) B1(1-6): 249-255 (1990).
The use of micromachining techniques to fabricate separation systems in silicon provides the practical benefit of enabling mass production of such systems. In this regard, a number of established techniques developed by the microelectronics industry involving micromachining of planar materials, such as silicon, exist and provide a useful and well accepted approach to miniaturization. Examples of the use of such micromachining techniques to produce miniaturized separation devices on silicon or borosilicate glass chips can be found in U.S. Pat. No. 5,194,133 to Clark et al., U.S. Pat. No. 5,132,012 to Miura et al., in U.S. Pat. No. 4,908,112 to Pace, and in U.S. Pat. No. 4,891,120 to Sethi et al.
Although silicon micromachining has been useful in the fabrication of miniaturized systems on a single surface, there are significant disadvantages to the use of this approach in creating the analysis device portion of a miniaturized separation system.
Silicon micromachining is not amenable to producing a high degree of alignment between two etched or machined pieces. This has a negative impact on the symmetry and shape of a separation channel formed by micromachining, which in turn may impact separation efficiency. Also, sealing of micromachined silicon surfaces is generally carried out using adhesives which may be prone to attack by separation conditions imposed by liquid phase analyses. Furthermore, under oxidizing conditions, a silica surface is formed on the silicon chip substrate. Thus, silicon micromachining is fundamentally limited by the chemistry of SiO
2
. Accordingly, there has remained a need for an improved miniaturized separation system which is able to avoid the inherent shortcomings of conventional miniaturization and silicon micromachining techniques.
SUMMARY OF THE INVENTION
The present invention relates to a miniaturized planar column device for use in a liquid phase separation apparatus.
It is a primary object of the invention to provide a miniaturized column device laser-ablated in a substantially planar substrate, wherein the substrate is of a material selected to avoid the inherent chemical activity and pH instability encountered with silicon and silicon dioxide-based substrates.
It is another object of the invention to provide an on-device reservoir or makeup flow compartment in a miniaturized planar column device, enabling enhanced on-column analysis or detection of components in a liquid sample. It is a related object of the invention to provide a column device for liquid phase analysis having an optional detection means in compact form.
It is yet a further related object of the invention to provide a liquid phase separation apparatus that is capable of performing complex sample handling, separation, and detection methods with reduced technician manipulation or interaction. Thus, the subject invention finds potential application in monitoring and/or analysis of components in industrial chemical, biological, biochemical and medical processes and the like.
The miniaturized planar column devices can be used in a liquid phase separation apparatus which features improved means for liquid handling, including various sample injection means. Thus, a miniaturized column device is provided having a means to interface with a variety of external liquid reservoirs. A particular system design is also provided which allows a variety of injection methods to be readily adapted to the planar structure, such as pressure injection, hydrodynamic injection or electrokinetic injection.
Optional keeper means are described herein and are useful for providing structural support to a miniaturized column device disposed therein. Keeper means further enable the interface of a variety of associated conduit or lightguide means with a column device. Additionally, sample eluate droplet generation and expulsion means are provided to assist in the extraction and collection of a sample eluate from a miniaturized column device. Optional post-column collection devices are also described which cooperate with the liquid phase separation apparatus to collect the sample eluate.
A particular advantage provided by the invention is the use of processes other than silicon micromachining techniques or etching techniques to create miniaturized columns in a wide variety of polymeric and ceramic substrates having desirable attributes for an analysis portion of a separation system. A miniaturized planar column device is formed herein by ablating component microstructures in a substrate using laser radiation. Preferably, a miniaturized column device is formed by providing two substantially planar halves having microstructures laser-ablated therein, which, when the two halves are folded upon each other, define a separation comp
Bek Fritz
Kaltenbach Patrick
Mittelstadt Laurie S.
Swedberg Sally A.
Witt Klaus E.
Agilent Technologie,s Inc.
Starsiak Jr. John S.
Tung T.
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