Droplet Sorting System for High Monoclonality in Biopharmaceuticals
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Solution Overview
Problem
Current techniques face challenges in diagnosing rare biological events and ensuring monoclonality in biopharmaceutical production, particularly in selecting cell populations with high production yield and maintaining viability during processing.
Innovation Solution
A method involving the preparation, sorting, and dispensing of droplets containing biological entities, utilizing fluidic flow paths and pressure control to achieve a high probability of obtaining a single target entity or combination of entities in a single droplet, with sorting and selection stages enhancing monoclonality assurance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional droplet generation and sorting techniques are used, then droplet processing can be performed, but the probability of obtaining a single target entity in a single droplet remains below 99.9%
Solution Approach 1:
The sorting process is divided into multiple sequential stages: initial droplet generation with Poisson statistics, first sorting stage at a junction to remove empty droplets and droplets with multiple entities, and second sorting/selection stage at the point of dispensing. Each stage incrementally increases the probability of obtaining a single target entity, achieving >99.9% purity through cumulative selection.
Solution Approach 2:
The system performs preliminary sorting and selection before final dispensing. Droplets are pre-screened for containing the correct number of target entities during flow through the sorting stages, allowing only qualified droplets to reach the dispensing point. This preliminary action ensures high probability of single entity capture before the final step.
2Reliability
If multiple sorting stages are implemented to increase entity selection probability, then monoclonality assurance improves, but the device complexity and processing time increase
Solution Approach 1:
The sorting stages are arranged in continuous series along the fluid flow path, with droplets progressing through generation, first sorting, and second sorting without interruption. The continuous flow maintains constant processing rate while accumulating selection efficacy across stages, minimizing idle time and maintaining high throughput despite multiple selection steps.
Data Source
AI summary
Instruments and cartridges for processing droplets in emulsions containing biological entities such as cells. A method of such processing comprises providing a plurality of the entities in a fluid; preparing a droplet from the fluid; determining whether the droplet contains one or more entities of said plurality of entities, or whether said droplet does not contain a said entity; sorting said droplet dependent on an outcome of the determination; and dispensing the sorted droplet into a reservoir. The dispensing may comprise identifying and extracting the sorted droplet from a first fluidic flow path of said fluid by transferring the sorted droplet from into a second fluidic flow path and then ejecting the sorted droplet into a reservoir by applying pressure to the second fluidic flow path. The droplet contents may be tracked so that the contents of an individual droplet can be sorted, selectively dispensed, and retrieved.