Single Photon Counting Flow Cytometer with Si SPAD Array
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Solution Overview
Problem
Current photon detection systems in flow cytometry and spectroscopy lack the sensitivity and dynamic range to effectively capture conjugated fluorescence signals, particularly due to high dark count rates and limited dynamic range, which restricts the ability to detect low-level fluorescence and perform hyperspectral analysis.
Innovation Solution
A silicon (Si)-based photon sensor using a differential Geiger-mode photon detector with a wide dynamic range, capable of detecting single photons and providing high sensitivity through advanced signal processing techniques such as differential signal processing and adaptive pedestal clamping, allowing for the detection of multiple photons during the quenching time of the sensor.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional photon detection systems are used in flow cytometry, then the system structure is simple, but the sensitivity and dynamic range are insufficient to detect low-level fluorescence signals
Solution Approach 1:
The detection system is divided into multiple independent single-photon avalanche diodes (SPADs) arranged in an array, where each SPAD element independently detects photons. This segmentation enables parallel detection across multiple channels, significantly improving sensitivity and dynamic range while maintaining manageable system complexity through modular architecture
Solution Approach 2:
The patent transitions from conventional single-point or limited-channel detection to a two-dimensional array of SPAD elements, adding spatial dimensionality to the detection system. This dimensional expansion enables simultaneous multi-wavelength detection and hyperspectral analysis, dramatically enhancing measurement precision without proportionally increasing complexity
2Reliability
If conventional photodetectors with limited dynamic range are used, then the device complexity is low, but the ability to detect multiple photons during quenching time is restricted
Solution Approach 1:
The system implements feedback mechanisms where each SPAD element provides individual photon detection signals that are fed into coincidence logic circuits. These circuits use temporal correlation feedback to distinguish true multi-photon events from noise, enabling reliable detection of multiple photons during the detector quenching period while maintaining high dynamic range
Solution Approach 2:
The patent employs preliminary discrimination of photon arrival times through time-correlated single-photon counting (TCSPC) methodology. By pre-processing and timestamping individual photon events before final analysis, the system prepares data in a format that enables accurate multi-photon detection and fluorescence lifetime measurement, expanding reliable detection capability
3Measurement precision
If high dark count rates occur in photon detectors, then the detection of low-level fluorescence is hindered, but reducing dark count requires advanced detector technology
Solution Approach 1:
The patent extracts and removes dark count signals from the detection process through multiple mechanisms: individual SPAD elements are thermally managed to minimize intrinsic dark counts, electronic filtering extracts true photon signals from noise based on temporal characteristics, and statistical methods separate dark count events from genuine fluorescence photons, thereby improving signal-to-noise ratio
Solution Approach 2:
The system converts the challenge of dark count noise into a beneficial feature by using time-correlated single-photon counting to distinguish between random dark count events and genuine fluorescence photons based on their temporal patterns. Fluorescence lifetime information, which would normally be lost, is extracted from the timing data, turning noise characterization into a useful measurement dimension
4Measurement precision
If conventional detection systems are used for hyperspectral analysis, then the system is simpler, but spectral resolution and fluorescence characterization are limited
Solution Approach 1:
The detector array is segmented into multiple SPAD elements, each potentially sensitive to different wavelength ranges or positioned to collect different spectral components. This spatial segmentation of the detection function enables simultaneous multi-wavelength detection, providing high spectral resolution for fluorescence characterization without requiring complex sequential scanning
Solution Approach 2:
The patent adds a temporal dimension to spectral analysis through time-correlated single-photon counting, creating a four-dimensional data space (spatial position, wavelength, intensity, and time). This dimensional expansion enables fluorescence lifetime imaging and spectral unmixing, providing enhanced spectral resolution and material characterization capability
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 solution enables the detection of low-level fluorescence with improved sensitivity and dynamic range, enabling next-generation cellular analysis and material characterization with high spectral resolution and reduced dark count rates.
Implementation Method 1
A silicon (Si)-based photon sensor using a differential Geiger-mode photon detector with a wide dynamic range, capable of detecting single photons
Implementation Method 2
differential Geiger-mode photon detector with a wide dynamic range, capable of detecting single photons and providing high sensitivity
Data Source
AI summary
A measurement system is disclosed which includes a flow chamber configured to propagate a sample in a flow stream, one or more optical sources configured to irradiate the sample in the flow stream, one or more detector systems each configured to receive resultant light from the sample and, in response, generate a photon signal, the one or more detector systems each including one or more photon sensors each adapted to generate an electronic pulse in response to receiving a photon and a circuit operating in the giga hertz supporting the one or more photon sensors thus configured to count each individual photon in the resultant light from the sample.