Piezo Droplet Dispensing for Single Cell Sorting in Microfluidics

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Solution Overview

Problem

Current flow cytometry technologies are unable to handle small sample volumes effectively, such as those from 1 to 10 µl, and cannot deliver a defined number of living cells in volumes below 100 nl due to the requirement for stationary flow conditions, which limits their ability in advanced applications like single cell arrays and cell printing.

Innovation Solution

A piezo-driven on-demand droplet generating device with a branch-less one-way channel and a detection system that directs ejected droplets to specific positions based on detected cell or particle information, allowing for precise dispensing of a defined number of cells or particles in free flying droplets, enabling inkjet-like printing and sorting.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If flow cytometry uses stationary flow conditions inside the flow cell, then cell sorting and separation can be achieved, but the device cannot handle small sample volumes (1-10 µl) and cannot deliver defined numbers of cells in volumes below 100 nl

Engineering Contradiction:
Improvesample volumeVSAvoidcell sorting reliability
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent transitions from stationary flow conditions to dynamic droplet-based flow conditions. Cells are suspended in free-flying droplets that can be generated, manipulated, and sorted dynamically, enabling the system to handle small sample volumes while maintaining reliable cell sorting capability through on-demand droplet generation and sorting.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The continuous liquid stream is segmented into discrete droplets, each containing a defined number of cells. This segmentation allows the system to process small sample volumes by distributing cells across multiple droplets, enabling precise control over cell delivery in minimal liquid volumes.

Inventive Principle:
Principle #1Segmentation

2Speed

If flow cytometry establishes stationary flow conditions, then cell analysis can be performed, but the flow cannot be switched on and off in sufficiently short time for on-demand dispensing

Engineering Contradiction:
Improveflow switching speedVSAvoidcell detection precision
Core Design Contradiction:
SpeedVSMeasurement precision

Solution Approach 1:

The system uses periodic droplet generation and ejection instead of continuous flow. Droplets are generated on-demand at controlled intervals, allowing the flow to be switched on and off rapidly. This periodic action enables precise timing for cell dispensing while maintaining detection precision through synchronized measurement at specific droplet positions.

Inventive Principle:
Principle #19Periodic action

3Manufacturing precision

If conventional inkjet printing is used to deliver living cells, then spatially resolved printing can be achieved, but the number of cells per droplet is generally random

Engineering Contradiction:
Improvespatial printing precisionVSAvoidnumber of cells per droplet
Core Design Contradiction:
Manufacturing precisionVSQuantity of substance

Solution Approach 1:

The system incorporates feedback mechanisms to monitor and control the number of cells in each droplet. By detecting cells in the observation volume and providing feedback to the droplet generation system, the patent enables precise control over cell number per droplet while maintaining spatial printing precision through coordinated droplet ejection and positioning.

Inventive Principle:
Principle #23Feedback

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

This approach allows for reliable dispensing and sorting of single cells or particles in very small volumes, overcoming the limitations of existing technologies by enabling on-demand cell or particle sorting and printing, and producing aliquots smaller than previously achievable, with high reliability and precision.

Implementation Method 1

a piezo-driven on-demand droplet generating device configured to eject out of an orifice a free flying droplet of a suspension of cells or particles

Methodology Applied
Scientific EffectPiezoelectric effect: Piezoelectric Effect

Implementation Method 2

a device for detecting information on cells or particles located in an observation volume of the suspension within the branch-less one-way channel

Methodology Applied
Scientific EffectOptical detection: Light

Data Source

PatentEP2577254B1Apparatus and method for dispensing cells or particles confined in a free flying droplet
Publication Date: 2015.02.25 ALBERT LUDWIGS UNIV FREIBURG
  • EP2577254B1 patent drawingFigure 1
  • EP2577254B1 patent drawingFigure 2
  • EP2577254B1 patent drawingFigure 3

AI summary

An apparatus for dispensing one or more cells or particles confined in a free flying droplet comprises a droplet generating device configured to eject out of an orifice a free flying droplet of a suspension of cells or particles. The droplet generating device comprises a branch-less one-way channel having the orifice at one end thereof. A device for detecting information on cells or particles located in an observation volume of the suspension within the branch-less one-way channel is provided. An ejected droplet is directed to a first position or a second position depending on the detected information.