Chemistry: analytical and immunological testing – Optical result – With fluorescence or luminescence
Reexamination Certificate
2002-02-19
2004-09-14
Snay, Jeffrey R. (Department: 1743)
Chemistry: analytical and immunological testing
Optical result
With fluorescence or luminescence
C422S082070
Reexamination Certificate
active
06790672
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Technical Field of the Invention
The present invention relates to the use of encoded molecular sieve particles in an optical sensor analytical system.
2. Description of the Prior Art
The use of optical fibers and optical fiber strands in combination with light absorbing dyes for chemical analytical determinations has undergone rapid development, particularly within the last two decades. Many of the recent improvements employing optical fiber sensors in both qualitative and quantitative analytical determinations concern the desirability of depositing and/or immobilizing various light absorbing dyes at the distal end of the optical fiber. In this manner, a variety of different optical fiber chemical sensors and methods have been reported for specific analytical determinations and applications such as pH measurement, oxygen detection, and carbon dioxide analyses.
Fiber optic sensors have been constructed that permit the use of multiple dyes with a single, discrete fiber optic bundle. U.S. Pat. Nos. 5,244,636 and 5,250,264 to Walt et al. disclose systems for affixing multiple, different dyes on the distal end of the bundle, the teachings of each of these patents being incorporated herein by this reference. The innovation of these patents is the placement of multiple chemical functionalities at the end of a single optical fiber bundle sensor. This configuration yields an analytic chemistry sensor that can be remotely monitored via the typically small bundle. The drawback, however, is the difficulty in applying the various chemistries associated with the chemical functionalities at the sensor's end; and, the functionalities are built on the sensor's end in a serial fashion. Not only is this a slow process, but in practice, only tens of functionalities can be applied.
U.S. Pat. No. 6,023,540 by Walt et al. discloses a microsphere-based analytic chemistry system and method for making the same is disclosed in which microspheres or particles carrying bioactive agents are combined randomly or in ordered fashion and dispersed on a substrate to form an array while maintaining the ability to identify the location of bioactive agents and particles within the array using an optically interrogatable, optical signature encoding scheme. As a preferred embodiment, U.S. Pat. No. 6,023,540 teaches the use of a modified fiber optic bundle or array as a substrate to produce a high density array. The disclosed system and method have utility for detecting target analytes and screening large libraries of bioactive agents. The teachings of U.S. Pat. No. 6,023,540 are fully incorporated by reference herein.
In brief, the main limitation to present state-of-the-art technology whether it be through the use of microspheres, microbeads or particles, is the limited number of methods available to encode the array. Currently, polymeric-based microbeads are encoded by immobilized luminescent dyes only. In addition, there is a physical limitation to how many ultraviolet, visible, and near-infrared dyes can be used simultaneously to encode an array since the emission spectra of luminescence dyes are broad. Furthermore, present state-of-the-art technology utilizes only spherical microbeads. While an optional encoding avenue would be the use of microbeads with different diameters, this approach is limited by the difficulty in fabricating a large-scale batch of microbeads with a tight and uniform bead diameter distribution (which is the only way a plurality of spherical microbeads with different diameters could be employed in a reliable optical size-encoding scheme). In other words, present state-of-the-art microparticle-based analytical systems focus on the microparticle's chemical functionality and luminescent signature only. Therefore, while a small variety of silica-based and polymeric microspheres materials have been utilized, none of these microspheres offer size and shape selectivity.
The present invention represents an improvement over U.S. Pat. No. 6,023,540 as well as other comparable flow cytometric and fiber-optic sensor systems using microbeads, microspheres and/or microparticles. The key feature of the improvement is the added analytical performance features provided by shaped molecular sieve particles, namely optical encoding based on the molecular sieve particles' macroscopic geometric shapes and increased selectivity based on the molecular sieves particles' molecular-sized pore diameters i.e., pore sizes. Such encoded molecular sieve particles can provide at least a five-fold enhancement in tunable parameters for increasing the encoding possibilities of high throughput screening assays relative to the present dye-modified polymeric microsphere, microbead or microparticle standards.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a molecular sieve particle-based fiber-optic microwell array sensor, wherein a microwell array is etched onto an optical fiber bundle that is filled with molecular sieve particles having specific morphologies and pore sizes. The molecular sieve particles can be further modified with guest molecules including but not limited to, dyes, peptides, proteins, enzymes, antigens, antibodies, receptors, ligands, catalysts, nucleic acids, and oligonucleotides to form the basis of an optical chemical sensor or biosensor. These molecular sieve particle-based fiber-optic microwell array sensors also form the basis for combinatorial encoding and/or analysis. It is another object of the present invention to provide methods for synthesizing said molecular sieve particle-based fiber-optic microwell array sensors.
A key feature of the invention is the added analytical performance features provided to the microwell sensors by the shaped molecular sieve particles—namely optical encoding based on the molecular sieve particles' macroscopic geometric shapes and increased selectivity based on the molecular sieves particles' molecular-sized pore diameters. The term “shaped molecular sieve particles” as used herein encompasses the macroscopic geometric shapes of the particles as well as their molecular-sized pore diameters. In addition to the ability to control and tune molecular sieve particle porosity, molecular sieve particles can be molecularly imprinted to further enhance selectivity to include the detection of analytes such as chiral/optically active molecules.
One key feature of the encoded molecular sieve particle-based optical sensor analytical system is the added optical encoding possibilities resulting from the plurality of the molecular sieve particle macroscopic geometric shapes that can be synthesized. In addition to spheres, molecular sieve particles can be synthesized with distinct gyroidal, discoidal, and hexagonal cylindrical shapes to increase the parameters by which optical shape-based encoding can be performed. Furthermore, the high surface area of the shaped molecular sieve particles enables encoding and detection in single microwells that is not possible with plastic beads or amphorous silica.
Perhaps the most intriguing aspect of the molecular sieve particle-based fiber-optic microwell array sensor approach is the differences in the atomic compositions of molecular sieve materials in comparison to silica-based and polymeric microsphere materials. Specifically, silica-based and polymeric microspheres materials are comprised mainly of low atomic weight atoms such as carbon, hydrogen, nitrogen, oxygen, and silicon. Conversely, molecular sieve materials can be synthesized with a variety of atoms such as aluminum, titanium, iron, nickel, cobalt, germanium, gallium, boron, tin, selenium and other metals, metalloids, and non-metals. A variety of atoms can permit a number of new and alternative methods to be utilized for array encoding such as optical encoding by spectroscopic absorption techniques and/or energy dispersive and wavelength dispersive x-ray fluorescence techniques. Such approaches have the advantage of allowing the same limited number of luminescent dyes and the same number of m
Balkus, Jr. Kenneth J.
Coutinho Decio H.
Meek Claudia C.
Pantano Paul
Board of Regents the University of Texas System
Jenkens & Gilchrist P.C.
Snay Jeffrey R.
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