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Bioanalysis systems including optical integrated circuit

a bioanalysis and integrated circuit technology, applied in the field of bioanalysis systems and methods, can solve the problems of inhibiting its wide spread use, difficult and inefficient current methods used in the identification and validation of “targets” and the optimization of drug structure in the pharmaceutical industry, and requiring vast sums of money and inordinate amounts of time, so as to achieve high throughput, and reduce the effect of drug discovery and developmen

Inactive Publication Date: 2006-09-14
LACKRITZ HILARY S +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides systems and methods for improving the management of light in conventional SPR systems. It uses OICs to enhance the throughput and sensitivity of SPR, making it more attractive for drug discovery. The invention also allows for faster and simpler discovery of new targets for drugs, identification of such targets, and screening of candidate entities as directed to the targets. It also enables the identification of receptors for targets of unknown function. The invention includes a bioanalysis system containing a light source, metallic support, light detector, and OICs. A disposable microwell array is also provided for the system. The invention also describes a method for analyzing distribution in a Z direction and orientation of mass relative to a SPR surface using multiple wavelengths, physical surface modification, depth profiling, and polarization analysis. Overall, the invention improves the efficiency and accuracy of SPR systems for drug discovery.

Problems solved by technology

Drug discovery and development requires vast sums of money and inordinate amounts of time.
Specifically, current methods used to identify and validate “targets” and to optimize drug structures in the pharmaceutical industry are particularly difficult and inefficient in large measure due to deficiencies in analytical techniques.
While SPR is a promising technology, there are concerns associated with SPR that inhibit its wide spread use.
One problem is that conventional methods for SPR lead to less sensitive results than fluorescence results.
Another problem is that SPR has not been capable of high-throughput in terms of assays / unit time.
Yet another limiting factor is non-specific binding to the sensing surface, a problem common to all types of direct-measuring sensors, i.e. where no labelled reagent, such as an enzyme or a fluorophore, is used to provide the detected signal.

Method used

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  • Bioanalysis systems including optical integrated circuit
  • Bioanalysis systems including optical integrated circuit
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Examples

Experimental program
Comparison scheme
Effect test

example 1

Preparation of Receptor Coated Gold Surface

[0152] Gold surfaces are prepared and washed using (1) water, (2) ethanol. The gold surfaces are then exposed to at least 5 μL / mm2 of 10 mM 11-mercaptoundecanoic acid (MUA) dissolved in ethanol overnight at RT. The surfaces are then washed using (1) ethanol, (2) 50% ethanol / water, (3) 25% ethanol / water, (4) water then dried. The MUA treated gold surface is then exposed to at least 5 μL / mm2 of 100 mM N-ethyl-N1-(dimethylaminopropyl)carbodiimide (EDCI) and 40 mM N-Hydroxysuccinimide (NHS) in 50 mM MES-Na, at pH 5.0 at RT for 30 min to form an NHS-ester of the MUA. The NHS-ester surfaces are washed with PBS (Phosphate buffered saline) then exposed to streptavidin (10 μg / mL) in PBS for 30 min at RT. Finally the gold surface linked to streptavidin is washed with PBS.

example 2

Incorporation of a Receptor into a Microwell Array

[0153] The gold surfaces of the microwell array are coupled to streptavidin according to the procedure of Example 1.

example 3

Incorporation of a Receptor into a 2 Dimensional Array

[0154] Streptavidin is coupled to the gold surface of a 2 dimensional array constructed using the method of Example 1. A set of biotinylated receptors (prepared by literature methods) is bound to the streptavidin coated surface by “printing” small volumes of receptor solutions (0.5 μL of each at 10 μg / mL in PBS) at known locations on the surface spaced apart by more than 2 mm. After a brief incubation (2 min), unbound receptors are removed by washing the array with PBS.

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Abstract

Optical Integrated Circuits (OIC) in Surface Plasmon Resonance (SPR) Analysis Systems combined with micorarray or microwell plates to provide enhanced sensitivity, stability, speed of analysis and reduced size are disclosed. Using the OIC with other optical analysis methods to provide enhance analysis systems is also disclosed.

Description

RELATED APPLICATIONS [0001] This application claims priority to provisional application Ser. No. 60 / 408,821 filed Sep. 7, 2002, the contents of which are incorporated herein.FIELD OF THE INVENTION [0002] The present invention generally relates to bioanalysis systems and methods, such as Surface Plasmon Resonance systems, involving optical circuits. In particular, the present invention relates to using optical circuits to improve management of light in bioanalysis systems such as Surface Plasmon Resonance and providing improved sample arrays. BACKGROUND OF THE INVENTION [0003] The pharmaceutical industry is involved in the discovery and development of medicines that improve our health. Drug discovery and development requires vast sums of money and inordinate amounts of time. Specifically, current methods used to identify and validate “targets” and to optimize drug structures in the pharmaceutical industry are particularly difficult and inefficient in large measure due to deficiencies...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): G01N33/553G01N21/25G01N21/55G01N33/543
CPCG01N21/253G01N21/553G01N33/54373G01N2201/0612G01N2201/0627
Inventor LACKRITZ, HILARY S.KENNEY, JOHNGIBBONS, IANTICKNOR, ANTHONY J.
Owner LACKRITZ HILARY S
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