EWOD Droplet Washing via Shape Control

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Solution Overview

Problem

Current immunoassay techniques, particularly those using electrowetting on dielectric (EWOD) systems, face inefficiencies in bead washing due to low dilution factors, leading to increased assay time and reagent usage, as they rely on simple mixing of antibody droplets with buffer, resulting in falsely elevated signals and prolonged testing times.

Innovation Solution

The method involves controlling droplet shape to minimize the area of contact between droplets, using non-circular cross-sections such as triangular or hexagonal shapes to restrict fluid mixing, allowing for efficient transfer of beads while minimizing fluid transfer, thereby enhancing washing efficiency and achieving high dilution factors with fewer wash steps.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If simple mixing of antibody droplet and buffer is used for washing, then the washing process is simple to implement, but the dilution factor is low and washing efficiency is poor

Engineering Contradiction:
Improveease of washing implementationVSAvoidwashing efficiency
Core Design Contradiction:
Ease of manufactureVSProductivity

Solution Approach 1:

The washing process is segmented into multiple sequential wash cycles, where each cycle consists of buffer addition, mixing, and removal steps. This segmentation allows each individual wash step to be optimized and repeated to achieve cumulative dilution effects, transforming a single inefficient mixing operation into multiple controlled washing stages that collectively achieve high dilution factors

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The washing process employs periodic action through repeated cycles of buffer addition, mixing, and removal. Each cycle temporarily introduces fresh buffer to dilute unbound antibodies, then removes the diluted mixture. This periodic repetition of the wash cycle progressively reduces the concentration of unbound antibodies, achieving high dilution factors that would be impossible in a single mixing step

Inventive Principle:
Principle #19Periodic action

2Measurement precision

If multiple wash cycles are performed to achieve sufficient dilution, then the dilution factor increases, but the assay time and reagent usage increase

Engineering Contradiction:
Improvesignal accuracyVSAvoidassay time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The system changes key parameters of the washing process: using magnetically responsive beads allows for rapid magnetic separation that eliminates lengthy centrifugation or filtration steps; optimizing buffer volume ratios and mixing intensities maximizes dilution efficiency per cycle; adjusting the number and duration of wash cycles based on required precision levels allows flexible optimization between speed and accuracy

Inventive Principle:
Principle #35Parameter changes

3Reliability

If beads are immobilized using magnetic field for washing separation, then the separation is effective, but the device complexity increases due to magnet and droplet control system

Engineering Contradiction:
Improveseparation effectivenessVSAvoiddevice complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The magnetic field system serves multiple functions: it immobilizes beads during washing to enable separation, it can be used to concentrate beads for detection, and it facilitates rapid washing cycles. The EWOD system similarly performs multiple roles including droplet transport, mixing, and volume control. This multi-functionality reduces the need for separate dedicated components for each operation, thereby managing device complexity while maintaining reliability

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

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 significantly reduces assay time, reagent usage, and device complexity, improving accuracy by minimizing false positives and enabling Point of Care applications, while being applicable to various droplet and bead control mechanisms.

Implementation Method 1

Electrowetting on dielectric (EWOD) is a well-known technique for manipulating discrete droplets of fluid by application of an electric field

Methodology Applied
Scientific EffectElectrowetting on dielectric: Electrowetting

Implementation Method 2

A common means of carrying out the separation illustrated in Figure 1c is to employ beads that are paramagnetic or ferromagnetic, for example by having a ferrite core. In this case the beads may be immobilized in the presence of a magnetic field

Methodology Applied
Scientific EffectMagnetic field: Magnetic Field

Data Source

PatentEP2756885B1Efficient dilution method, including washing method for immunoassay
Publication Date: 2019.05.22 SHARP LIFE SCI EU LTD
  • EP2756885B1 patent drawingFigure 1(a)~1(d)
  • EP2756885B1 patent drawingFigure 2(a)~2(b)
  • EP2756885B1 patent drawingFigure 3(a)~3(h)

AI summary

A method of droplet manipulation utilizing a droplet manipulation device activating elements (138) of the device to bring a first droplet (2) into proximity of a second droplet (16), controlling the elements of the device to alter the shape of at least one of the first and second droplets, and further controlling the elements of the device to move at least one of the first or second droplets until the droplets are in contact about an aggregate area (40). The elements are controlled in a manner so as to control the area of contact and the degree of mixing of the fluid between the first and second droplets. The method may be employed to move particles of a particulate suspension from the first droplet to the second droplet. The droplet manipulation device may be an electrowetting on dielectric (EWOD) device, which includes shaping electrodes (60, 62) activated to shape droplets, and a bridging electrode (64) activated to join the droplets to transfer fluid between the shaped droplets.