Microfluidic Sample Staining With Precise Reagent Control
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Solution Overview
Problem
Current automated staining technologies for biological samples face challenges in conserving precious reagents, maintaining reagent concentration control, and reducing waste generation, particularly in advanced staining protocols like immunohistochemistry and in-situ hybridization, while ensuring consistent staining results and preserving tissue morphology.
Innovation Solution
An integrated system and method utilizing microfluidic reagent applicators, bulk fluid applicators, and fluid aspirators, combined into a single unit, with controlled relative motion and imaging, to precisely apply and remove reagents, forming wells on samples for efficient reagent use and waste reduction, and enabling simultaneous deposition of incompatible reagents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If dip and dunk stainers are used for high-throughput production, then productivity is improved, but reagent concentration control deteriorates and waste increases
Solution Approach 1:
The system divides the staining process into discrete, localized droplet applications rather than bulk immersion. Each droplet is precisely deposited at specific locations on the sample, allowing individual control over reagent concentration and placement. This segmentation enables high-throughput processing while maintaining precise concentration control for each staining step.
Solution Approach 2:
The microfluidic system applies different reagent concentrations to different locations on the sample based on specific requirements. Each droplet can have tailored composition and concentration, allowing optimal staining conditions for different tissue regions while minimizing overall reagent consumption and waste.
2Area of stationary object
If puddle staining is used to cover samples, then staining coverage is improved, but reagent volume increases and waste is generated
Solution Approach 1:
Instead of applying uniform reagent coverage across the entire sample area, the system deposits reagents only at specific locations where staining is needed. Each droplet is precisely positioned and sized to cover only the necessary tissue regions, eliminating waste from excessive reagent application while maintaining adequate coverage for diagnostic purposes.
Solution Approach 2:
The system applies reagents in controlled, partial amounts rather than excessive bulk volumes. By using minimal droplet sizes that just suffice for staining the required sample areas, the system achieves effective coverage without the reagent waste characteristic of puddle staining methods.
3Manufacturing precision
If multiple rinses are performed to remove reagents, then staining consistency is improved, but processing time increases and waste is generated
Solution Approach 1:
The system extracts and removes excess reagents immediately after deposition using aspirators positioned near the droplet application sites. This active removal eliminates the need for multiple prolonged rinse steps, achieving staining consistency through controlled reagent presence rather than extensive washing, thereby reducing processing time and waste.
Solution Approach 2:
The system rapidly completes the reagent application and removal cycle, skipping the time-consuming multiple rinse steps of traditional methods. By using precisely controlled droplet deposition followed by immediate aspiration of excess reagent, the system achieves consistent staining results in a fraction of the time required for conventional rinsing protocols.
Data Source
AI summary
A system and method for treatment of biological samples is disclosed. In some embodiments, an automated biological sample staining system (100), comprising at least one microfluidic reagent applicator (118); at least one bulk fluid applicator (116); at least one fluid aspirator; at least one sample substrate holder; at least one relative motion system; and a control system (102) that is programmed to execute at least one staining protocol on a sample mounted on a substrate that is held in the at least one sample substrate holder.