Micro-fluidic Device Assaying Biological Activity

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Solution Overview

Problem

Current methods for assaying biological activity in micro-fluidic devices are limited in their ability to efficiently culture biological cells, introduce capture micro-objects, and assess bound biological materials, particularly in isolating and tracking specific biological materials of interest produced by clonal cell colonies.

Innovation Solution

The process involves culturing biological cells in holding pens of a micro-fluidic device, introducing capture micro-objects with specific binding substances, allowing binding of biological materials of interest, removing and tracking these objects, and assessing them for bound materials using techniques like dielectrophoresis or magnetic fields, allowing for precise measurement and correlation with their origin.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If capture micro-objects are introduced into holding pens to assay biological activity, then measurement precision is improved, but device complexity increases due to the need for multiple regions and manipulation mechanisms

Engineering Contradiction:
Improveassay precisionVSAvoiddevice complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The micro-fluidic device is divided into distinct functional regions: a holding pen region for cell culture and a separate assay region for detection. This segmentation allows capture micro-objects to be introduced into the holding pen, perform their binding function, and then be moved to the assay region for precise measurement, thereby improving assay precision while managing device complexity through functional zoning

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Capture micro-objects serve as intermediary elements that mediate between the biological cells in the holding pen and the detection system in the assay region. These micro-objects bind to biological materials of interest and can be selectively manipulated and transferred, enabling precise measurement without requiring direct integration of all device functions in one complex structure

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If multiple capture micro-objects are manipulated and moved between regions, then productivity is improved, but loss of time increases due to manipulation steps

Engineering Contradiction:
Improveassay throughputVSAvoidmanipulation time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The manipulation of capture micro-objects between the holding pen and assay region is performed through periodic flow cycles. Fluid flow is alternately directed to move capture micro-objects from the holding pen to the assay region and back, enabling batch processing of multiple micro-objects without requiring continuous complex manipulation, thus improving productivity while minimizing time loss through efficient cyclic operation

Inventive Principle:
Principle #19Periodic action

3Reliability

If biological cells are cultured in holding pens with isolation regions, then reliability is improved by maintaining clonality, but device complexity increases due to enclosure structures

Engineering Contradiction:
Improveclonality maintenanceVSAvoidstructure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The holding pen is designed with an isolation region that is partially enclosed by barriers, extracting the cell culture environment from the main fluidic channel. This allows biological cells to be cultured in an isolated compartment that maintains clonality and prevents contamination, while the partial enclosure structure minimizes added complexity compared to fully enclosed systems

Inventive Principle:
Principle #2Taking out (Extraction)

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 enables efficient and precise assay of biological activity, maintaining clonality of cell colonies and allowing for the assessment of biological materials with high affinity, facilitating the identification of cell colonies producing specific materials of interest.

Implementation Method 1

The light trap can include a light pattern, projected onto an inner surface of the micro-fluidic device, that surrounds the at least one capture micro-object and activates electrodes, such as dielectrophoresis (DEP) electrodes, within the micro-fluidic device.

Methodology Applied
Scientific EffectDielectrophoresis: Dielectric

Implementation Method 2

The one or more capture micro-objects are magnetic. In related examples, removing the one or more capture micro-objects can involve applying a magnetic field to the micro-fluidic device.

Methodology Applied
Scientific EffectMagnetic field: Magnetic Field

Implementation Method 3

The capture micro-objects can include, for example, a binding substance that specifically binds said biological material of interest.

Methodology Applied
Scientific EffectSpecific binding: Adsorption

Data Source

PatentEP3783094B1Micro-fluidic devices for assaying biological activity
Publication Date: 2023.10.11 BERKELEY LIGHTS INC
  • EP3783094B1 patent drawingFigure 1
  • EP3783094B1 patent drawingFigure 2A
  • EP3783094B1 patent drawingFigure 2B~2C

AI summary

Biological activity in holding pens in a micro-fluidic device can be assayed by placing in the holding pens capture objects that bind a particular material of interest produced by the biological activity. The biological material of interest that binds to each capture object can then be assessed, either in the micro-fluidic device or after exporting the capture object from the micro-fluidic device. The assessment can be utilized to characterize the biological activity in each holding pen. The biological activity can be production of the biological material of interest. Thus, the biological activity can correspond to or arise from one or more biological cells. Biological cells within a holding pen can be clonal cell colonies. The biological activity of each clonal cell colony can be assayed while maintaining the clonal status of each colony.