Lensless Microscopy for Confluent Cell Imaging

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Solution Overview

Problem

Conventional optical microscopes with bulky optics are expensive, difficult to miniaturize, and ineffective for imaging confluent cell cultures or samples with contiguously connected cells, as they face limitations in field of view and image quality due to phase information loss and coherence-based noise sources.

Innovation Solution

The development of e-Petri and SPLM systems that use a scanning projective lensless microscopy methodology, employing a CMOS imaging sensor and a scanning illumination source to capture sub-pixel shifted projection images, allowing for high-resolution imaging of confluent specimens over a wide field of view without mechanical scanning or microfluidic flow.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional optical microscopes with bulky optics are used, then image quality can be maintained, but the system becomes expensive and difficult to miniaturize

Engineering Contradiction:
Improveimage qualityVSAvoidsystem miniaturization
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts and removes the bulky optical lens component from the microscopy system, replacing it with a lensless imaging approach using a CMOS sensor. This extraction eliminates the primary source of system bulk and complexity while maintaining imaging functionality through computational methods and direct sensor placement near the specimen.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the mechanical optical lens system with an electronic/imaging-based solution using a CMOS sensor and computational algorithms. This substitution transitions from a mechanical optical path to an electronic detection and processing system, enabling miniaturization while preserving measurement precision.

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

2Measurement precision

If conventional optical microscopes are used, then detailed cell imaging is possible, but they are ineffective for imaging confluent cell cultures due to field of view limitations

Engineering Contradiction:
Improvecell imaging detailVSAvoidfield of view
Core Design Contradiction:
Measurement precisionVSArea of stationary object

Solution Approach 1:

The patent merges multiple imaging capabilities into a single lensless platform that can simultaneously capture wide-field views and provide detailed cell imagery. By combining a large-area CMOS sensor with computational imaging techniques, the system integrates both broad coverage and fine detail resolution in one unified system.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent transitions from traditional optical focusing in three-dimensional space to a two-dimensional sensor plane imaging approach. By placing the sensor directly near the specimen and using computational methods to reconstruct images, the system achieves wide field of view while maintaining detail through mathematical processing rather than optical focusing.

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

3Measurement precision

If conventional optical microscopes are used, then imaging can be performed, but phase information is lost and coherence-based noise sources affect image quality

Engineering Contradiction:
Improveimage qualityVSAvoidphase information loss
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The patent introduces computational algorithms as an intermediary between light interaction with the specimen and final image formation. These computational methods serve as a mediator that can recover phase information from intensity measurements alone, eliminating the need for complex optical phase-contrast apparatus while restoring lost phase data through mathematical reconstruction.

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentUS9569664B2Methods for rapid distinction between debris and growing cells
Publication Date: 2017.02.14 CALIFORNIA INST OF TECH
  • US9569664B2 patent drawing
  • US9569664B2 patent drawing
  • US9569664B2 patent drawing

AI summary

Methods of rapid distinction between growing cells and debris, which determine a time-lapse movie of specimen images, track features of each entity, and categorize each entity as growing cells or debris.