Multi-Well Optical Plate Reader for Electrode-Free Cell Assays

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Solution Overview

Problem

Existing plate imagers and electrophysiology instruments face issues such as cell membrane damage, limited temporal resolution, non-uniform electrical stimulation, and high costs, which hinder complex cellular assays and drug screening.

Innovation Solution

Multi-well plate readers that transmit and detect light at multiple wavelengths, enabling simultaneous optical stimulation and detection across individual wells, using optical actuators and reporters to perform diverse assays with high throughput.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If automated electrophysiology uses physical electrodes for stimulation and recording, then electrical activity of cells can be measured, but cell membranes are damaged and intracellular dialysis occurs

Engineering Contradiction:

Improveelectrical activity measurementVSAvoidcell membrane damage

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent replaces physical electrodes with optical actuators (light-gated ion channels) and optical detectors. Light stimuli activate optogenetic actuators in cells to control electrical activity, and fluorescent reporters detect cellular responses optically, eliminating mechanical penetration and cell membrane damage entirely.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If automated electrophysiology uses physical electrodes, then electrical measurements can be obtained, but dissociated cells are required which damages neurons and limits cell-to-cell communication measurements

Engineering Contradiction:

Improveelectrical activity measurementVSAvoidcellular integrity and communication

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The optical system allows measurement of electrical activity in intact, adherent cells without requiring dissociation. Cells maintain their native architecture and cell-to-cell connections, enabling reliable measurement of network activity and intercellular communication while preserving cellular integrity.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Productivity

If FLIPR instruments use chemical stimulation for voltage-gated channels, then cellular activity can be measured, but the stimuli do not reflect physiological processes and alter pharmacological responses

Engineering Contradiction:

ImprovethroughputVSAvoidphysiological relevance

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The system uses optical parameters (light wavelength, intensity, duration) to control cellular activity instead of chemical parameters. Different wavelengths of light activate specific optogenetic actuators with precise temporal control, mimicking physiological electrical stimuli and producing biologically relevant responses without chemical interference.

Inventive Principle:

Principle #35Parameter changes

4Productivity

If FLIPR-type instruments are used, then cellular activity can be measured, but temporal resolution is insufficient to record important ion channel functions

Engineering Contradiction:

Improvemeasurement capabilityVSAvoidtemporal resolution

Core Design Contradiction:

ProductivityVSSpeed

Solution Approach 1:

The optical detection system uses fast photodetectors and high-speed imaging to capture cellular responses at millisecond timescales, providing sufficient temporal resolution to record rapid ion channel kinetics and action potential dynamics that were previously inaccessible with FLIPR technology.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

5Measurement precision

If electrical field stimulation with fluorescent readout is used, then cellular activity can be measured, but voltage control is limited and field nonuniformities cause overstimulation or electroporation

Engineering Contradiction:

Improvefluorescent readoutVSAvoidstimulation control and cell integrity

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The system uses focused light delivery through objective lenses to stimulate and detect individual wells or specific regions within wells. This provides localized, uniform optical fields with precise spatial control, avoiding the nonuniform electrical fields that cause overstimulation or electroporation in conventional EFS systems.

Inventive Principle:

Principle #3Local quality

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

Achieves five-fold higher throughput than conventional assays, allowing complex optogenetic and cellular measurements without mechanical manipulation, suitable for high-throughput drug screening and disease study.

Implementation Method 1

an objective lens that focuses light to a separate well of a multi-well plate

Methodology Applied

Scientific EffectLight focusing: Focusing

Implementation Method 2

transmit stimulation light to, and detect emission light from, individual wells of a multi-well plate at a plurality of distinct wavelengths

Methodology Applied

Scientific EffectOptical stimulation and detection: Light

Data Source

PatentUS12478971B2Optical plate controller and reader

Publication Date: 2025.11.25 QUIVER HOLDINGS INC

AI summary

The present invention includes multi-well plate readers, and methods of their use. The multi-well plate readers can transmit stimulation light to, and detect emission light from, individual wells of a multi-well plate, simultaneously.