Handheld Microfluidic Cell Lysis Device with Nanoblades

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Solution Overview

Problem

Existing mechanical cell lysis equipment lacks single cell resolution, which is necessary for single cell biological studies due to the intrinsic heterogeneity in cell populations, and requires high operating pressures that can lead to biomolecule denaturation and is not suitable for portable devices.

Innovation Solution

A mechanical cell lysing apparatus with single cell resolution that includes an inlet port, a trap structure, a stress raiser to apply mechanical stress, and an outlet port, allowing for low-pressure lysis of cells using hydrodynamic trapping and nanoblades to concentrate force, enabling efficient lysis of mammalian, yeast, and bacterial cells without external power.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional high-shear mechanical lysis equipment is used, then cell lysis efficiency is improved, but operating pressure becomes extremely high (up to 40,000 psi) and biomolecules may denature

Engineering Contradiction:
Improvecell lysis efficiencyVSAvoidoperating pressure
Core Design Contradiction:
ProductivityVSStress or pressure

Solution Approach 1:

The device segments the cell lysis process into two stages: first trapping individual cells in microfluidic chambers, then applying controlled mechanical stress via nanoblades. This segmentation allows single-cell resolution while maintaining low overall pressure requirements, avoiding the need for extreme pressures used in traditional bulk lysis equipment.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent implements local quality by concentrating mechanical stress at specific locations where nanoblades contact trapped cells. Instead of applying high pressure uniformly across a bulk sample, the stress is localized to the cell membrane at the nanoblade contact point, enabling efficient lysis at low applied pressure (less than 5 psi for mammalian cells, less than 40 psi for yeast cells).

Inventive Principle:
Principle #3Local quality

2Productivity

If traditional mechanical lysis equipment is used, then cell lysis is achieved, but the equipment becomes bulky and unsuitable for portable devices

Engineering Contradiction:
Improvecell lysis capabilityVSAvoiddevice portability
Core Design Contradiction:
ProductivityVSWeight of moving object

Solution Approach 1:

The patent replaces traditional high-pressure mechanical systems with a microfluidic system that uses hydrodynamic flow and localized nanoscale structures. This substitution eliminates the need for bulky high-pressure pumps and mechanical presses, enabling a handheld device design that maintains effective cell lysis capability while achieving portability.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The invention transitions from macro-scale mechanical lysis to micro-scale and nano-scale operations within microfluidic channels. By moving to smaller dimensions, the device achieves equivalent or superior lysis performance in a compact form factor suitable for portable applications.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Productivity

If traditional mechanical lysis equipment is used, then bulk cell lysis is achieved, but single cell resolution is not obtained

Engineering Contradiction:
Improvebulk cell lysis capabilityVSAvoidsingle cell resolution
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The device segments the bulk cell sample into individual cells, each trapped in separate microfluidic chambers. This segmentation enables single-cell resolution by isolating individual cells for targeted lysis, while still allowing processing of multiple cells through the system. The trap structure with controlled flow paths ensures one cell per trap, achieving the required single-cell precision.

Inventive Principle:
Principle #1Segmentation

4Speed

If high pressure is applied for cell lysis, then lysis speed is improved, but heating occurs and biomolecules denature

Engineering Contradiction:
Improvelysis speedVSAvoidheating from power dissipation
Core Design Contradiction:
SpeedVSTemperature

Solution Approach 1:

The patent replaces high-power mechanical pressure systems with a low-power microfluidic system using nanoblades. This substitution dramatically reduces power dissipation and associated heating, maintaining rapid lysis speed through efficient mechanical leverage at the nanoscale while avoiding the thermal damage that plagues traditional high-pressure systems.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 apparatus achieves efficient and controlled lysis of individual cells with low applied pressure, suitable for point-of-care diagnostics and small sample volumes, preserving biomolecules for analysis.

Implementation Method 1

a stress raiser configured to raise a mechanical stress on a membrane of the cell of interest

Methodology Applied
Scientific EffectStress concentration:

Implementation Method 2

allowing for low-pressure lysis of cells using hydrodynamic trapping

Methodology Applied
Scientific EffectHydrodynamic trapping:

Data Source

PatentUS9365816B2Handheld low pressure mechanical cell lysis device with single cell resolution
Publication Date: 2016.06.14 CALIFORNIA INST OF TECH
  • US9365816B2 patent drawing
  • US9365816B2 patent drawing
  • US9365816B2 patent drawing

AI summary

Apparatus and methods for mechanical cell lysis with single cell resolution which requires very low applied pressure. The device can be handheld, simple to operate, requires no external power except for hand-applied pressure via a syringe, and is applicable to all cell types including yeast and bacterial cells. The device is also capable of mechanically lysing a single cell. A single cell is selected from a biological sample of interest. The single cell is lysed by application of mechanical stress in a single cell lysing apparatus having a trap structure for deterministically capturing the cell and a stress raiser that cooperates with a source of mechanical stress so as to apply sufficient force to rupture a cell. The stress raiser can be a properly designed edge of the trap or it can be a lithographically produced structure such as a nanoblade or a nanopillar.