Optics: measuring and testing – By particle light scattering
Reexamination Certificate
2000-10-11
2003-02-11
Stafira, Michael P. (Department: 2877)
Optics: measuring and testing
By particle light scattering
C356S246000
Reexamination Certificate
active
06519032
ABSTRACT:
BACKGROUND OF INVENTION
The present invention generally relates to the characterization of liquid samples by optical techniques, and in preferred embodiments, characterization of polymer samples and non-polymer samples by light-scattering techniques. In particular, the invention relates to methods and apparatus for characterizing liquid samples (e.g. solutions, emulsions, suspensions and/or dispersions) by serial or parallel analysis to determine commercially important properties of the samples or components thereof, such as particle size or particle size distribution. In preferred embodiments, the characterization of the liquid samples or of components thereof is effected in parallel with a probe head comprising an array fiber optic probes suitable for static light scattering and/or dynamic light scattering. The methods and devices disclosed herein are applicable, inter alia, to high-throughput characterization of liquid samples, and especially samples prepared by combinatorial materials science techniques.
Currently, there is substantial research activity directed toward the discovery and optimization of polymeric materials and other materials for a wide range of applications. Although the chemistry of many materials (e.g. polymers) and synthesis reactions (e.g. polymerization) has been extensively studied, it is, nonetheless, rarely possible to predict a priori the physical or chemical properties a particular material will possess or the precise composition and architecture that will result from any particular synthesis scheme. Thus, characterization techniques to determine such properties are an essential part of the discovery process.
Combinatorial chemistry, also referred to as combinatorial materials science and/or high-throughput experimentation, refers generally to methods for synthesizing a collection of chemically diverse materials and to methods for rapidly testing or screening this collection of materials for desirable performance characteristics and properties. Combinatorial chemistry approaches have greatly improved the efficiency of discovery of useful materials. For example, material scientists have developed and applied combinatorial chemistry approaches to discover a variety of novel materials, including for example, high temperature superconductors, magnetoresistors, phosphors and catalysts. See, for example, U.S. Pat. No. 5,776,359 to Schultz et al., U.S. Pat. No. 5,985,356 to Schultz et al., U.S. Pat. No. 6,004,617 to Schultz et al., and U.S. Pat. No. 6,030,917 to Weinberg et al. In comparison to traditional materials science research, combinatorial materials research can effectively evaluate much larger numbers of diverse compounds in a much shorter period of time. Although such high-throughput synthesis and screening methodologies are conceptually promising, substantial technical challenges exist for application thereof to specific research and commercial goals.
Methods have been developed for the combinatorial (e.g., rapid-serial or parallel) synthesis and screening of libraries of small molecules of pharmaceutical interest, and of biological polymers such as polypeptides, proteins, oligonucleotides and deoxyribonucleic acid (DNA) polymers. However, there have been few reports of the application of combinatorial techniques to the field of polymer science for the discovery of new polymeric materials or polymerization catalysts or new synthesis or processing conditions. Brocchini et al. describe the preparation of a polymer library for selecting biomedical implant materials. See S. Brocchini et al.,
A Combinatorial Approach for Polymer Design, J. Am. Chem. Soc
. 119, 4553-4554 (1997). However, Brocchini et al. reported that each synthesized candidate material was individually precipitated, purified, and then characterized according to “routine analysis” that included gel permeation chromatography to measure molecular weight and polydispersities. As such, Brocchini et al. did not address the need for efficient and rapid characterization of polymers.
High-throughput screening approaches have also been developed for a number of combinatorial material science applications, including applications directed toward polymer characterization and toward the identification of useful catalysts. Exemplary approaches are disclosed, for example, in the aforementioned related patent applications, as well as in the following published applications and/or patents: PCT application WO 97/32208 of Willson; U.S. Pat. No. 5,959,297 to Weinberg et al.; PCT application WO 99/64160 of Guan et al.; PCT application WO 00/09255 of Turner et al.; and PCT application WO 00/51720 of Bergh et al.
Light scattering techniques, both static and dynamic, are known in the art for characterizing particle size and shape, and particle size distribution of micron and submicron size materials, among them colloidal dispersions, emulsions, suspensions and/or solutions of inorganic molecules, biological macromolecules or polymers, and/or non-biological polymers.
Dynamic light scattering (DLS) or quasielastic light scattering (QELS) measures the fluctuation of scattered light intensity of suspended fluids or particles exhibiting Brownian motion. For example, and without being bound by theory not specifically recited in the claims, measurement of such intensity fluctuations and autocorrelation techniques can yield the normalized intensity-intensity autocorrelation function g
2
(t) that allows measurement of the particle diffusion coefficient D:
g
2
(
t
)=&bgr;exp(−2
q
2
Dt
) (1),
where &bgr; is an instrument parameter (0<&bgr;<1), and the scattering vector q is related to the scattering angle &thgr;, the incident laser wavelength &lgr;, and the refractive index n of the fluid medium by
q
=
4
π
n
λ
sin
(
θ
2
)
.
(
2
)
The diffusion coefficient D is related to the hydrodynamic radius R
h
of the particle as:
D
=
kT
6
π
η
R
h
(
3
)
where T is the temperature in Kelvin, k is the Boltzman constant, &eegr; is the viscosity of the fluid medium. Although often the primary quantity of interest is the particle size, other quantities of interest like diffusion coefficient may be probed with tracer particles of a defined hydrodynamic radius. Further details of the technique of dynamic light scattering and autocorrelation is described for example in various patents such as U.S. Pat. No. 4,975,237 to Brown, U.S. Pat. No. 4,983,040 to Chu et al., and U.S. Pat. No. 5,011,279 to Autweter et al., and in monographs such as Chu, “
Laser light scattering: basic principles and practice
”, Academic Press 1991; Berne, “
Dynamic light scattering: with applications to chemistry, biology, and physics
”, Wiley 1976. Dynamic light scattering methods may also be used to determine the average molar mass and molar mass distribution of a polymer. See, for example, Burchard, “
Light Scattering Principles and Development
”, Ed. by W. Brown, Clarendon Press 1996.
Static light scattering (SLS) techniques are also well known, and can be used for example, to measure M
w
and the radii of gyration (R
g
) of a polymer in a dilute solution of known concentration. Apparatus and methods suitable for static light scattering are described in the references mentioned in the immediately preceding paragraph.
With the development of combinatorial techniques that allow for the parallel synthesis of arrays comprising a vast number of diverse industrially relevant polymeric and non-polymeric materials, there is a need for methods, devices and systems to rapidly characterize the properties of the synthesized polymer and non-polymer samples.
SUMMARY OF INVENTION
It is therefore an object of the present invention to provide systems and protocols for characterizing combinatorial libraries of polymer samples and non-polymer samples, and particularly, libraries of or derived from synthesis reactions such as polymerization product mixtures, or libraries of or derived from formulations (e.g., of nanodispersion formulat
Bennett James
Kuebler Sigrid C.
Stafira Michael P.
Symyx Technologies Inc.
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