Digital Microfluidics Cartridge for NGS Flow Cell Liquid Handling

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Solution Overview

Problem

Current liquid-handling systems for next-generation sequencing (NGS) are inefficient due to dead volumes and reliance on mechanical pumps and valves, which are unreliable and difficult to maintain, leading to suboptimal reagent utilization and longer processing times.

Innovation Solution

A digital microfluidic liquid handling system with a droplet actuator that includes a substrate gap filled with a filler fluid, electrode arrangements for precise liquid control, and a gravity-driven dispenser, enabling efficient and rapid switching of liquids to a flow cell without mechanical parts.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If mechanical pumps and valves are used for liquid handling, then liquid switching capability is achieved, but system reliability decreases and maintenance difficulty increases

Engineering Contradiction:

Improvesystem reliabilityVSAvoidmechanical parts complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces mechanical pumps and valves with a digital microfluidic system that uses electrode arrays to control liquid flow. The droplet actuator employs electrowetting-on-dielectric (EWOD) technology where voltage applied to electrodes manipulates droplet position and flow direction, eliminating all mechanical moving parts while achieving precise liquid handling and rapid switching capability

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent introduces an immiscible filler fluid as an intermediary medium in the droplet actuator chamber. This filler fluid provides a hydrophobic environment that enables electrowetting control of aqueous reagent droplets, allowing electrical fields to manipulate liquid flow without mechanical components. The filler fluid acts as a mediator between the electrical control system and the reagent liquids

Inventive Principle:

Principle #24Intermediary (Mediator)

2Loss of substance

If dead volume is present between liquid sources and flow cell, then liquid storage is enabled, but reagent utilization efficiency decreases

Engineering Contradiction:

Improvereagent utilization efficiencyVSAvoiddead volume

Core Design Contradiction:

Loss of substanceVSVolume of stationary object

Solution Approach 1:

The patent extracts and eliminates the dead volume problem by integrating liquid sources directly into the droplet actuator chip. Reagent reservoirs are fabricated as micro-wells on the chip substrate, positioned immediately adjacent to the reaction chamber. This direct integration removes the intermediate tubing and valve connections that create dead volume, ensuring complete reagent transfer and maximum utilization efficiency

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent merges the liquid storage function and liquid delivery function into a single integrated microfluidic structure. The reagent reservoirs, droplet actuator chamber, and flow cell are combined in one continuous microfluidic pathway without dead zones, allowing seamless transition from storage to reaction and eliminating reagent waste in intermediate volumes

Inventive Principle:

Principle #5Merging (Combining)

3Productivity

If mechanical valves are used for liquid switching, then liquid routing is achieved, but processing time increases

Engineering Contradiction:

Improveprocessing speedVSAvoidliquid switching time

Core Design Contradiction:

ProductivityVSLoss of time

Solution Approach 1:

The patent replaces mechanical valve switching with electrical control of electrowetting electrodes. Liquid routing is achieved by applying voltage patterns to electrode arrays that create electrostatic forces, rapidly moving droplets from one location to another. This electrical control mechanism operates on microsecond timescales, eliminating the mechanical inertia and wear limitations of valve-based systems

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent employs periodic voltage cycling to the electrode arrays to achieve rapid, repetitive liquid switching. By applying alternating voltage sequences to different electrode groups, the system can quickly route different reagents to the flow cell in a cyclic manner, enabling high-speed multiplexed liquid handling without mechanical movement limitations

Inventive Principle:

Principle #19Periodic action

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 system enhances reagent utilization efficiency, reduces processing time, and provides a more reliable and cost-effective method for liquid handling in NGS by eliminating dead volumes and simplifying the system architecture.

Implementation Method 1

A digital microfluidic liquid handling system with a droplet actuator that includes a substrate gap filled with a filler fluid, electrode arrangements for precise liquid control

Methodology Applied

Scientific EffectElectrowetting: Electrowetting

Implementation Method 2

Methodology Applied

Scientific EffectGravitation: Gravitation

Data Source

PatentUS9863913B2Digital microfluidics cartridge and system for operating a flow cell

Publication Date: 2018.01.09 ADVANCED LIQUID LOGIC INC

AI summary

A liquid handling system for supplying liquids to a flow cell (FC). The system may include a droplet actuator cartridge, wherein the droplet actuator and a flow cell are fluidly coupled to, or situated within, a droplet operations gap of the droplet actuator.