Movement-Based iSIM Cell Imaging Through Oscillating Beamlets

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Solution Overview

Problem

Existing cell imaging systems face challenges in achieving high throughput and high resolution simultaneously, often requiring multiple imaging systems or large objectives that are costly and complex, while existing super-resolution techniques like iSIM suffer from misalignment and drift due to complex optical elements.

Innovation Solution

The implementation of movement-based iSIM systems that oscillate or rotate beamlet forming elements and optical masks to achieve super-resolution imaging, reducing complexity and cost by minimizing optical components and aligning elements through synchronized motion.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If multiple imaging systems are used to achieve high throughput, then imaging speed is improved, but system cost and complexity increase significantly

Engineering Contradiction:
Improveimaging throughputVSAvoidsystem complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent implements dynamic scanning of the illumination pattern across the sample using a single imaging system. The illumination pattern is scanned in multiple directions and positions to capture multiple images, which are then computationally combined to achieve super-resolution. This dynamic approach allows one system to perform the work of multiple static systems, improving throughput without proportionally increasing complexity.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The illumination pattern is periodically scanned across the sample in multiple passes with different positions and orientations. This periodic scanning allows the system to collect multiple datasets from a single imaging system, which are then processed to achieve both high throughput and super-resolution without requiring multiple parallel imaging systems.

Inventive Principle:
Principle #19Periodic action

2Area of stationary object

If large objectives with large field numbers are used to increase FOV, then imaging area is improved, but system cost increases due to expensive optics and cameras

Engineering Contradiction:
Improvefield of viewVSAvoidsystem cost
Core Design Contradiction:
Area of stationary objectVSDevice complexity

Solution Approach 1:

Instead of using a single large objective with large field number, the patent uses a smaller objective with a standard field number but dynamically scans the illumination pattern across a larger area. This allows the system to achieve a larger effective imaging area by moving the illumination pattern through multiple positions, avoiding the need for expensive large-format optics and cameras.

Inventive Principle:
Principle #15Dynamics

3Measurement precision

If complex optical elements are used in iSIM systems, then super-resolution is achieved, but misalignment and drift occur due to sensitivity to small shifts

Engineering Contradiction:
ImproveresolutionVSAvoidalignment stability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent combines the illumination pattern generation and scanning functions into an integrated system where the pattern is directly scanned across the sample. This merging of functions reduces the number of separate optical elements and their associated alignment requirements, thereby improving reliability while maintaining super-resolution capability.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The system incorporates real-time detection and correction mechanisms that monitor and compensate for alignment shifts and drift during operation. This self-correction capability allows the system to maintain super-resolution accuracy despite small shifts in optical elements, improving reliability without sacrificing measurement precision.

Inventive Principle:
Principle #25Self-service

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

These systems provide high throughput and high resolution imaging with reduced complexity and cost, minimizing misalignment and drift, enabling single cell analytics and subcellular component discrimination.

Implementation Method 1

directing an illumination beam from an illumination source to the sample, wherein the illumination beam passes through a first beamlet forming element

Methodology Applied
Scientific EffectDiffraction: Diffraction

Implementation Method 2

Structure Illumination Microscopy (SIM) is a proven super-resolution microscopy technique that allows a doubling of the resolution of images taken with a microscope objective

Methodology Applied
Scientific EffectStructured Illumination:

Implementation Method 3

SIM allows super resolution by digitally combining many pictures to reconstruct a composite image with improved resolution

Methodology Applied
Scientific EffectSuper-resolution:

Data Source

PatentUS20250283824A1Methods and systems for cell imaging
Publication Date: 2025.09.11 BIFROST BIOSYSTEMS INC
  • US20250283824A1 patent drawing
  • US20250283824A1 patent drawing
  • US20250283824A1 patent drawing

AI summary

The present disclosure relates to imaging systems and methods of use thereof for imaging with simplified structured illumination microscopy (SIM). The present methods may be simpler and less costly to build and maintain that existing SIM systems. The imaging methods may include oscillating a portion of the imaging system to scan an illumination pattern across a field of view of the sample.