Biological Chip Hybridization System with Dynamic Fluid Control

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Solution Overview

Problem

Current biological chip hybridization systems face challenges with long hybridization duration, low efficiency, and the lack of integration and automation in the hybridization, cleaning, and drying processes, often requiring specialized equipment and leading to contamination issues.

Innovation Solution

A biological chip hybridization system that integrates hybridization, cleaning, and drying through a bio-chip with a substrate and cover plate forming a hybridization chamber, connected fluid channels, and a fluid control device comprising pumps and valves for controlled reciprocating flow, continuous flow, and gas flow to enhance reaction efficiency and uniformity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If static hybridization method is used with air bath or water bath temperature control, then the hybridization reaction can proceed, but the hybridization duration is long and hybridization efficiency is low

Engineering Contradiction:
Improvehybridization efficiencyVSAvoidhybridization duration
Core Design Contradiction:
ProductivityVSDuration of action of moving object

Solution Approach 1:

The patent applies dynamic hybridization by replacing the static air bath or water bath method with a dynamic liquid flow system. A peristaltic pump drives the hybridization sample to flow circularly over the microarray surface, creating continuous movement that enhances mass transfer and molecular diffusion. This dynamic approach reduces hybridization duration from 6 hours to 2 hours while improving hybridization efficiency through increased sample-chip contact and reduced boundary layer effects.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent utilizes a peristaltic pump to create hydraulic flow of the hybridization sample through the microarray chamber. The pump generates continuous circular flow that ensures uniform distribution of target molecules across the probe array, enhancing reaction kinetics and reducing hybridization time compared to static diffusion-based methods.

Inventive Principle:
Principle #29Pneumatics and hydraulics

2Device complexity

If static hybridization method is used, then the setup is simple, but special cleaning and drying instruments or devices are additionally required which complicates the system

Engineering Contradiction:
Improvesystem integrationVSAvoidoperation simplicity
Core Design Contradiction:
Device complexityVSEase of operation

Solution Approach 1:

The patent merges hybridization, cleaning, and drying functions into a single integrated device. The same microfluidic system and peristaltic pump used for hybridization are utilized to deliver cleaning solutions and drying agents to the microarray. This eliminates the need for separate cleaning and drying instruments, reducing overall system complexity while maintaining ease of operation through automated multi-functional processing.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The hybridization device is designed with universal functionality to perform multiple operations: hybridization reaction, chip cleaning, and chip drying. The fluid delivery system can switch between different solutions (hybridization buffer, cleaning solution, drying agent) using the same pump and管路, making the device multi-functional and eliminating the need for specialized separate equipment.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Productivity

If peristaltic pump and circulating fluid channel are used for dynamic hybridization, then hybridization duration is reduced, but interior contamination of pump will be easily resulted

Engineering Contradiction:
Improvehybridization efficiencyVSAvoidpump contamination
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent implements a disposable microarray chip design where the microarray is mounted on a separate substrate that can be easily removed and replaced. The circulating fluid channel is designed to allow complete flushing with cleaning solutions after each hybridization run, effectively removing contaminants. This approach maintains high hybridization efficiency through repeated use of the pump while preventing interior contamination by enabling thorough cleaning and replacement of contact components.

Inventive Principle:
Principle #34Discarding and recovering

4Device complexity

If Affymetrix hybridization system is used, then integration of hybridization, cleaning and drying is realized, but large volume of sample are required and the device is not compatible and versatile

Engineering Contradiction:
Improveintegration levelVSAvoidchip compatibility
Core Design Contradiction:
Device complexityVSAdaptability or versatility

Solution Approach 1:

The patent employs a modular design where the microarray chip is segmented into a removable microarray substrate mounted on a standard化的 holder. This allows different microarray chips from various manufacturers to be interchangeably mounted on the same device. The fluid delivery system is also modular, allowing adaptation to different chip formats and sizes, thereby achieving high integration while maintaining versatility and compatibility with multiple chip types.

Inventive Principle:
Principle #1Segmentation

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

The system achieves shorter hybridization duration, improved efficiency, and full-automatic operation by controlling temperature and fluid flow, ensuring high hybridization efficiency and uniformity while eliminating the need for separate equipment for cleaning and drying.

Implementation Method 1

a dynamic hybridization method, in which a peristaltic pump is employed to force the hybridization sample to flow circularly over the surface of the microarray

Methodology Applied
Scientific EffectFluid circulation: Convection

Implementation Method 2

the hybridization reaction between the target molecules in the hybridization sample and the probe molecules on the chip surface only depends on molecular diffusion mechanism

Methodology Applied
Scientific EffectMolecular diffusion: Diffusion

Implementation Method 3

Pneumatic-activated microvalve in PDMS (polydimethyl siloxane) microfluidic chip is utilized by Quake's group to achieve reciprocating movement of the hybridization sample solution in the hybridization chamber

Methodology Applied
Scientific EffectBubble generation: Bubble

Implementation Method 4

achieve reciprocating movement of the hybridization sample solution in the hybridization chamber

Methodology Applied
Scientific EffectReciprocating flow: Convection

Data Source

PatentUS9677133B2Biological chip hybridization system
Publication Date: 2017.06.13 CAPITALBIO CORP
  • US9677133B2 patent drawing
  • US9677133B2 patent drawing
  • US9677133B2 patent drawing

AI summary

A hybridization system is provided, which comprises a biological chip having a substrate (1) with a probe dot matrix (3) and a cover plate (2) with at least two through-holes (4), where a hybrid chamber (5) is formed between the substrate (1) and the cover plate (2), at least two fluid channels (6) are interconnected respectively with the hybrid chamber (5) by the two through-holes (4), and a fluid control device is interconnected with the fluid channels (6). The biological chip hybridization system integrates hybridizing, cleaning and drying functions, uses power provided by the fluid control device as the drive force for promoting the liquid flow for automatically reciprocation flow in the fluid channels (6) and the chamber (5) to achieve a dynamic hybridization, thus improving the hybrid efficiency and uniformity, and achieving automatic control.