TDI Sensor Segmentation for Multi-Fluorophore Imaging

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Solution Overview

Problem

In time domain multiplexing TDI imaging, switching between imaging modes, such as switching of light sources, can result in the mixing of corresponding images on the sensor, which affects the accuracy of detecting multiple fluorophores simultaneously.

Innovation Solution

The TDI sensor is configured with sensitive and insensitive cells, where charge is transferred in consecutive steps, and illuminated in a periodic manner using alternating light sources, with opaque elements or optical elements to block or focus light only on sensitive cells, allowing for simultaneous detection of different spectra or colors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If light sources are switched in an alternating manner to detect multiple fluorophores, then the number of detectable fluorophores increases, but image mixing occurs on the sensor

Engineering Contradiction:

Improvenumber of detectable fluorophoresVSAvoidimage detection accuracy

Core Design Contradiction:

Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The sensor is divided into multiple TDI channels, each dedicated to detecting a specific fluorophore excited by a particular light source. This segmentation prevents image mixing by assigning separate detection pathways for different fluorophores, allowing simultaneous multi-fluorophore detection without cross-contamination of signals.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies preliminary spectral unmixing or spatial separation before final image reconstruction. By pre-organizing the detection architecture with dedicated TDI channels for each fluorophore, the system prevents mixing artifacts from propagating through the imaging process, thereby maintaining measurement precision while enabling multi-fluorophore versatility.

Inventive Principle:

Principle #10Preliminary action

2Measurement precision

If multiple scans are performed to detect different fluorophores, then detection accuracy improves, but scanning time and overhead increase

Engineering Contradiction:

Improvedetection accuracyVSAvoidscanning time

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

Multiple fluorophore detection channels are merged into a single TDI sensor array, allowing simultaneous acquisition of all fluorophore images during one scan. This combining approach eliminates the need for sequential scanning, reducing overhead time while maintaining detection accuracy through the inherent noise-rejection capabilities of TDI.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The TDI sensor enables continuous accumulation of signal from all fluorophores simultaneously during a single uninterrupted scan. This continuous detection approach eliminates the start-stop nature of sequential scanning, maintaining high detection accuracy while minimizing time loss to scanning overhead and system drift between scans.

Inventive Principle:

Principle #20Continuity of useful action

3Duration of action of moving object

If TDI sensor accumulates charge from multiple fluorophores simultaneously, then integration time increases, but signal from different fluorophores mixes

Engineering Contradiction:

Improveintegration timeVSAvoidsignal separation

Core Design Contradiction:

Duration of action of moving objectVSLoss of information

Solution Approach 1:

The TDI sensor is segmented into multiple independent charge accumulation channels, with each channel dedicated to a specific fluorophore. This segmentation allows simultaneous long-integration-time detection of multiple fluorophores without signal mixing, as each fluorophore's photons are accumulated in separate charge regions that can be independently read out.

Inventive Principle:

Principle #1Segmentation

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 configuration enables the simultaneous and independent detection of multiple images during a single scan, improving the integration time and reducing image mixing, thus enhancing the sensitivity and accuracy of fluorescence imaging.

Implementation Method 1

Time delay and integration (TDI) is an imaging method known to be often faster compared to using a simple line sensor

Methodology Applied

Scientific EffectTime delay and integration:

Implementation Method 2

In fluorescence imaging, there is often a need for detecting the presence of multiple fluorescent labels (fluorophores) in a given sample simultaneously

Methodology Applied

Scientific EffectFluorescence detection: Fluorescence

Data Source

PatentEP2406599B1Time domain multiplexing for imaging using time delay and integration sensors

Publication Date: 2021.05.12 KONINKLIJKE PHILIPS NV

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AI summary

A time delay integration (TDI) sensor (22) comprises a sequence of cells (42, 44, 42, 44) numbered 1 to N. The TDI sensor is configured for transferring a charge from the cell numbered 1 via the cells numbered 2 to N- 1 to the cell numbered N. Each cell (42; 44) in the sequence of cells is either sensitive or insensitive in the sense that when the TDI sensor (22) is evenly illuminated by light (46) having a first spectrum, the intensity of the light (46) incident on any of the insensitive cells (44) is at most 90% of the intensity of the light (46) incident on any of the sensitive cells (42). The sequence of cells (42, 44, 42, 44) comprises, in this order: a first sensitive cell (42), at least one insensitive cell (44), and a second sensitive cell (42). An imaging system comprising a TDI sensor and a method of imaging an object are also disclosed.