Multichannel TDI Biochemical Array Imaging Alignment

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Solution Overview

Problem

High-density biochemical arrays require advanced imaging systems for efficient data acquisition, but increased array density complicates image acquisition due to challenges in tracking experiment identity and maintaining alignment, leading to issues with image smearing and alignment errors.

Innovation Solution

A multichannel biochemical array imaging system with independent adjustments for each channel, including rotation, x and y offset, and scale, utilizing time delay integration (TDI) cameras and a combination of beam splitters and filters to collect data in multiple wavelength bins simultaneously, along with precise zoom lens systems and dynamic adjustments via TDI pulse timing and galvo-controlled offset plates for accurate image alignment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If array density is increased to perform more biochemical experiments in parallel, then productivity is improved, but measurement precision deteriorates due to alignment errors and image smearing

Engineering Contradiction:
Improvenumber of biochemical experiments per unit timeVSAvoidalignment accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent applies dynamics by making the imaging system adaptable to different scanning speeds through variable TDI delay timing. The system dynamically adjusts the TDI delay to match the scanning speed, allowing high-speed scanning of dense arrays while maintaining alignment precision. This resolves the contradiction by enabling the system to operate at high productivity speeds without sacrificing measurement precision.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent changes the TDI delay parameter to optimize performance for different array densities and scanning speeds. By adjusting the TDI delay timing parameter, the system maintains sub-pixel alignment accuracy even when scanning high-density arrays at high speeds. This parameter adjustment allows the system to achieve both high productivity and high measurement precision simultaneously.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If scanning speed is increased to improve data acquisition rate, then productivity is improved, but measurement precision deteriorates due to alignment errors

Engineering Contradiction:
Improvedata acquisition rateVSAvoidalignment accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The system dynamically adjusts the TDI delay timing to match the scanning speed. As the scanning speed increases, the TDI delay is adjusted accordingly to maintain proper synchronization between the scanning motion and image integration. This dynamic adjustment enables high-speed scanning while preserving sub-pixel alignment accuracy, resolving the contradiction between productivity and measurement precision.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent implements feedback through alignment detection and correction mechanisms that monitor and adjust for scanning speed variations. The system detects alignment errors and compensates for them by adjusting the TDI delay timing, ensuring that measurement precision is maintained even at high scanning speeds. This feedback loop resolves the contradiction by continuously optimizing the system performance.

Inventive Principle:
Principle #23Feedback

3Measurement precision

If TDI camera is used to increase photon integration time and signal-to-noise ratio, then measurement precision is improved, but device complexity increases due to synchronization requirements

Engineering Contradiction:
Improvesignal-to-noise ratioVSAvoidsynchronization system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical synchronization systems with electronic timing control. Instead of using mechanical linkages or optical choppers to synchronize the TDI camera with the scanning system, the invention uses electronic timing signals to coordinate the TDI delay with the scanning speed. This substitution reduces device complexity while maintaining the high signal-to-noise ratio benefits of TDI imaging.

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

4Productivity

If multiple wavelength bins are imaged simultaneously to increase data throughput, then productivity is improved, but device complexity increases due to multichannel requirements

Engineering Contradiction:
Improvedata throughput rateVSAvoidmultichannel system complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent merges multiple imaging channels into a single TDI camera system by using beam splitters to direct different wavelengths to different regions of the same sensor array. This combining approach allows simultaneous imaging of multiple wavelength bins, increasing data throughput while reducing the complexity associated with multiple separate camera systems. The merged system maintains high productivity while simplifying the overall device architecture.

Inventive Principle:
Principle #5Merging (Combining)

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

The system achieves high precision and throughput by maintaining alignment to better than 20 nm accuracy while scanning millions of data spots per second, enabling efficient data collection from high-density arrays with improved signal-to-noise ratio and reduced image smearing.

Implementation Method 1

utilizing time delay integration (TDI) cameras

Methodology Applied
Scientific EffectTime Delayed Integration (TDI):

Implementation Method 2

a combination of beam splitters and filters to collect data in multiple wavelength bins simultaneously

Methodology Applied
Scientific EffectOptical filtering: Filter (optical)

Implementation Method 3

precise zoom lens systems

Methodology Applied
Scientific EffectOptical focusing: Lens

Implementation Method 4

imaging system for capturing a sequence of images from a target at ultra-high framing rates... imaging system with independent adjustments for each channel... to collect data in multiple wavelength bins simultaneously

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP2633359B1Method and system for imaging high density biochemical arrays with sub-pixel alignment
Publication Date: 2021.11.17 COMPLETE GENOMICS INC
  • EP2633359B1 patent drawingFigure 1A
  • EP2633359B1 patent drawingFigure 1B
  • EP2633359B1 patent drawingFigure 1C

AI summary

A system and associated method for imaging high density biochemical arrays comprises one or more imaging channels that share a common objective lens and a corresponding one or more time delay integration-type imaging cameras with optical alignment mechanisms that permit independent inter-channel and intra-channel adjustment of each of four degrees: X, Y, rotation and scale. The imaging channels are configured to independently examine different spectra of the image of the biochemical arrays.