Integrated Microarray Printing and Detection System for Kinetic Analysis

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Solution Overview

Problem

Current microarray technologies face limitations such as high sample volume consumption, restricted kinetic interaction analysis, and inconclusive data due to blind pre-printing without feedback on spot uniformity or probe selectivity, which hinders the analysis of protein-protein interactions and the discovery of biomarkers and therapeutic drugs.

Innovation Solution

An Integrated Microarray Printing and Detection System (IMPDS) that enables in-situ quantitative spotting with real-time measurement of drop-on-drop protein interactions, using a sensor chip with a movable printer head and surface plasmon resonance imaging to analyze protein interaction kinetics with ultra-low nanoliter volume samples, allowing for M×N protein interaction analysis and binding kinetics measurement.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional microarray technology is used with complete microarrays pre-printed blindly, then high-throughput screening is achieved, but sample volume consumption increases and feedback on spot uniformity and probe selectivity is lost

Engineering Contradiction:
Improvehigh-throughput screeningVSAvoidsample volume consumption
Core Design Contradiction:
ProductivityVSLoss of substance

Solution Approach 1:

The patent divides the microarray into individual spot units that can be independently controlled and measured. Each spot is printed and measured separately, allowing selective analysis of individual interactions rather than requiring complete microarrays to be pre-printed and tested simultaneously. This segmentation enables reduced sample volume consumption while maintaining high-throughput capability.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent implements real-time feedback mechanisms during the printing and measurement process. The system measures spot uniformity and probe selectivity immediately after printing, allowing for immediate adjustment and optimization. This feedback loop eliminates the need for blind pre-printing of complete microarrays and enables iterative improvement of each spot's quality before final analysis.

Inventive Principle:
Principle #23Feedback

2Productivity

If conventional microarray technology exposes sample solution to the entire microarray, then high-throughput analysis is achieved, but kinetic interaction analysis is restricted to 1×N interactions only

Engineering Contradiction:
Improvehigh-throughput analysisVSAvoidkinetic interaction analysis capability
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent segments the microarray into individually addressable spots, enabling M×N interaction analysis where multiple probes can be systematically tested against multiple targets. This segmentation allows flexible configuration of interaction experiments beyond the limited 1×N approach of conventional technology, while maintaining high-throughput capability through automated spot-by-spot measurement.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces dynamic control over which spots are accessed and measured during each experimental cycle. Rather than exposing the entire microarray simultaneously, the system dynamically selects and measures specific spot combinations based on the experimental design, enabling versatile kinetic interaction analysis while maintaining high throughput through efficient cycle management.

Inventive Principle:
Principle #15Dynamics

3Measurement precision

If conventional SPR systems use flowing solution containing analyte protein running over target protein, then binding kinetics information is obtained, but sample volume requirement increases making measurement cost inhibitive

Engineering Contradiction:
Improvebinding kinetics informationVSAvoidsample volume requirement
Core Design Contradiction:
Measurement precisionVSLoss of substance

Solution Approach 1:

The patent applies segmentation by measuring binding kinetics at individual spots rather than requiring bulk flowing solution across the entire microarray. Each spot can be independently accessed with minimal sample volume, and the system aggregates data from multiple spots to achieve statistically significant binding kinetics information. This approach dramatically reduces sample volume requirements while maintaining measurement precision.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent changes the measurement parameters from bulk flowing solution to localized spot-based measurement. By altering the scale and method of sample delivery and detection, the system achieves binding kinetics analysis with nanoliter-scale sample volumes instead of milliliter-scale volumes required by conventional SPR systems, making the technology accessible for expensive or difficult-to-obtain proteins.

Inventive Principle:
Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

IMPDS reduces sample volume requirements by several orders of magnitude, provides higher-quality data with real-time evaluation, enables measurement of weak and transient interactions, and supports flexible M×N combinations, facilitating more immediate and accurate assay development and results.

Implementation Method 1

using surface plasmon resonance imaging to analyze protein interaction kinetics

Methodology Applied
Scientific EffectSurface plasmon resonance: Surface Acoustic Wave

Data Source

PatentUS10823728B2Integrated microarray printing and detection system for molecular binding analysis
Publication Date: 2020.11.03 THE ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIV OF ARIZONA
  • US10823728B2 patent drawing
  • US10823728B2 patent drawing
  • US10823728B2 patent drawing

AI summary

A method and system for analysis of protein interaction kinetics in microarray or whole-cell based formats includes positioning a sensor chip on a prism. The sensor chip is spotted with a plurality of target molecules. A movable printer head deposits a plurality of analyte droplets on predefined regions of the sensor chip surface. A light source transmits light through the prism to excite surface plasmon resonance on the sensor chip surface, whereby the plurality of target molecules bound to the upper surface are changing the SPR resonance angle and therefore the intensity of the reflected beam. A detector receives reflected light transmitted through the prism from the bottom surface. Signals from the detector are received and processed into kinetic data and microarray labeled data to determine molecular interactions and binding kinetic properties for the plurality of analyte droplets.