Microelectronic Chip for Selecting Lytic Effector Cells

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Solution Overview

Problem

Current methods for isolating and selecting effector cells like CTL and NK cells, which induce lysis in target cells, are complex, lengthy, and expensive, and often ineffective due to the rarity of these cells and unknown target cell characteristics, limiting their therapeutic potential in treating diseases such as cancer.

Innovation Solution

A method for real-time monitoring and quantification of lysis mediated by CTL and NK cells using an innovative analytical assay, allowing for the selection and expansion of highly lytic effector cell clones through interaction with target cells, utilizing miniaturized devices that maintain biological activity, enabling efficient diagnostic and therapeutic applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If pre-purification and clonal selection by dilution are used to isolate CTL and NK cells, then effector cells can be obtained, but the process becomes complex, lengthy, and expensive

Engineering Contradiction:
Improveisolation effectivenessVSAvoidselection process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical and manual selection processes with an automated microelectronic chip system that uses dielectrophoresis and integrated sensors to automatically isolate and select effector cells based on their functional activity, eliminating the need for manual clonal selection by dilution

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

Solution Approach 2:

The microelectronic chip integrates multiple functions including cell manipulation, real-time monitoring of lysis activity, and automated selection into a single device, allowing simultaneous performance of purification, functional assessment, and clone selection without requiring separate complex procedures

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

2Reliability

If clonal selection by dilution is used, then effector cells can be isolated, but the method is not always activatable due to unknown target cell characteristics

Engineering Contradiction:
Improveisolation effectivenessVSAvoidmethod applicability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The system performs preliminary functional testing of effector cells on the microelectronic chip before final selection, allowing identification of active clones based on their actual lysis capability rather than relying on pre-known target cell characteristics, making the method applicable even when target characteristics are unknown

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The effector cells themselves perform the selection function by naturally exhibiting their lytic activity on target cells present in the sample, allowing the system to identify active clones based on their intrinsic functional properties without requiring prior knowledge of target cell markers or characteristics

Inventive Principle:
Principle #25Self-service

3Stability of the object's composition

If rare effector cells are used without stimulation, then the natural state is maintained, but the lytic action is not effective due to cell rarity

Engineering Contradiction:
Improvecell state stabilityVSAvoidlytic effectiveness
Core Design Contradiction:
Stability of the object's compositionVSProductivity

Solution Approach 1:

The system performs preliminary stimulation and activation of rare effector cells on the microelectronic chip before functional assessment, allowing even rare cells to be activated and their lytic potential realized, thereby maintaining cell state stability while enhancing productivity

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The microelectronic chip serves as an intermediary platform that provides controlled stimulation conditions and concentrates rare effector cells with target cells, enabling effective interaction and lysis activity even when effector cells are present at very low frequencies

Inventive Principle:
Principle #24Intermediary (Mediator)

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 the rapid identification and isolation of highly lytic CTL and NK cells, improving diagnostic and therapeutic efficacy by enhancing the selection and expansion of effector cells, reducing the complexity and cost of existing methods, and maintaining the specificity and stability of the immune reaction.

Implementation Method 1

Altomare L. et al. (2003) discloses a printed circuit board device able to generate dielectrophoresis-based, software-controlled cages allowing to move tumour cells 'entrapped' in the cages.

Methodology Applied
Scientific EffectDielectrophoresis: Dielectric

Implementation Method 2

The present invention teaches a method for the functional selection of immune system cells by means of real-time monitoring and quantification of the lysis of target cells

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP2016407B8Diagnostic and therapeutic application of CTL and NK functionally selected cells
Publication Date: 2017.03.15 MENARINI SILICON BIOSYSTEMS SPA
  • EP2016407B8 patent drawing
  • EP2016407B8 patent drawing

AI summary

The invention proposes a novel therapeutic and diagnostic methodology based on the use of effector cells (for example CTL and NK cells) selected for being able to induce lysis in target cells. In particular, the invention teaches how to select strains of effector cells of the immune system according to their lytic properties. It also teaches how diagnostic procedures for checking the activity of therapeutic vaccines can be improved with respect to what shown. Finally, it shows how cell therapies used at present can be improved by using this approach.