Single Particle Deposition via Sedimentation Imaging
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Solution Overview
Problem
Conventional single-cell printing techniques have low yield and limited applicability, as they rely on specific dispenser types and operation conditions, and struggle to consistently deposit single cells due to the hydrodynamic response of cells in piezoelectric nozzles.
Innovation Solution
A method and apparatus using a Piezo Dispense Capillary (PDC) with an optically transparent nozzle section, where particles are detected and the single particle condition is tested by analyzing both the ejection and sedimentation regions, ensuring accurate dispensing of single particles onto a target, and incorporating optical feedback for improved yield and reproducibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional single-cell printing techniques are used with imaging systems and object recognition algorithms, then single-cell isolation capability is achieved, but yield is low (only 80-85% of droplets include single cells)
Solution Approach 1:
The patent applies preliminary action by analyzing particle positions in the sedimentation region before droplet ejection occurs. The system determines whether a droplet will contain a single particle based on particle positions upstream of the ejection region, allowing early classification and deflection decisions. This prevents the need to rely solely on post-ejection imaging analysis, thereby improving yield by capturing droplets that would otherwise be missed.
Solution Approach 2:
The system implements feedback by using imaging data from the sedimentation region to control droplet deflection in real-time. The imaging system detects particle positions, the control system processes this information to determine single-particle conditions, and the deflection mechanism adjusts droplet trajectories accordingly. This closed-loop feedback enables higher accuracy in single-cell isolation compared to conventional open-loop imaging-only approaches.
2Measurement precision
If conventional controlling techniques with imaging systems are applied, then single-cell detection is possible, but applicability is restricted to particular dispenser types and operation conditions
Solution Approach 1:
The patent transitions from analyzing only the ejection region (one dimension) to including the sedimentation region upstream (adding spatial dimension). By imaging particle positions in the sedimentation region before ejection, the system creates an additional observational dimension that provides earlier and more reliable single-particle information. This dimensional expansion makes the technique applicable to various dispenser types and conditions.
Solution Approach 2:
The system achieves universality by implementing a multi-functional approach: the imaging system serves both for detecting particle positions in the sedimentation region and for monitoring ejection characteristics; the control system handles both classification and deflection control; and the deflection mechanism works across different dispenser types. This multi-functional design enables broad applicability while maintaining detection precision.
3Reliability
If droplets are deflected in flight towards waste container by vacuum suction, then multi-cell droplets are removed, but control complexity increases
Solution Approach 1:
The patent extracts the classification function from the ejection moment and performs it earlier in the sedimentation region. By determining single-particle conditions based on particle positions upstream of ejection, the system separates the classification decision-making process from the physical ejection and deflection processes. This extraction simplifies control complexity by making classification decisions based on earlier, more stable particle position data rather than complex post-ejection analysis.
4Manufacturing precision
If a volume at the dispenser orifice equal to droplet volume includes one single cell, then single particle condition is fulfilled, but false positives occur due to hydrodynamic response of cells in piezoelectric nozzles
Solution Approach 1:
The system performs preliminary assessment of single-particle conditions by analyzing particle positions in the sedimentation region before droplet ejection. By determining whether a droplet will contain a single particle based on upstream particle positions rather than waiting for ejection, the system avoids false positives caused by hydrodynamic responses during the ejection process itself.
Solution Approach 2:
The imaging system provides real-time feedback on particle positions in the sedimentation region, allowing the control system to make accurate single-particle condition determinations before ejection occurs. This feedback mechanism eliminates reliance on post-ejection imaging that is susceptible to false positives from hydrodynamic cell responses in piezoelectric nozzles.
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 method achieves near 100% single particle encapsulation rates, enhancing the reliability and flexibility of single-cell deposition across various dispenser types and operation conditions, with improved accuracy and reduced false positives.
Implementation Method 1
droplet dispenser, preferably comprising a Piezo Dispense Capillary (PDC)... and a drive unit... operated for dispensing droplets
Implementation Method 2
An imaging device, preferably a nozzle camera arranged adjacent to the nozzle section, is used for detecting particles in the nozzle section
Implementation Method 3
The ejection region and a sedimentation region (or: sedimentation layer) adjacent to the ejection region are analysed
Data Source
AI summary
A method of depositing single particles onto a target includes loading a particle suspension to a droplet dispenser having a suspension reservoir and a nozzle section, detecting particles in the nozzle section, testing a single particle condition of the droplet dispenser, and determining whether an ejection region of the nozzle section includes one single particle. The method further includes operating the droplet dispenser for dispensing a droplet such that the droplet is dispensed onto the target if the single particle condition is fulfilled, or the droplet is dispensed into a collection reservoir if the single particle condition is not fulfilled. The step of testing the single particle condition further includes determining whether a sedimentation region adjacent to the ejection region is free of particles. A dispenser for performing the method is also provided.