Time-Gated Fluorescence Detection with Periodic Charge Integration
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Solution Overview
Problem
Conventional time-gated fluorescence (TGF) systems face challenges in speed, low photon emission, and limited multi-color capabilities, requiring complex optics and electronics for high-speed pulsed excitation and detection, which are costly and inefficient for biochemical assays.
Innovation Solution
A high-performance, cost-efficient TGF system using semiconductor biochips with integrated electronic shutters and periodic charge integration (PCI) methods, enabling faster and more efficient detection of analytes by integrating photon signals over multiple excitation pulses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional TGF systems use high-speed pulsed excitation and detection, then signal-to-background ratio is improved, but device complexity and cost increase
Solution Approach 1:
The patent applies periodic pulsed excitation at frequencies between 1-100 MHz, where the excitation source is modulated in a periodic manner to enable time-gated detection. This periodic action allows separation of signal from background by detecting fluorescence only during specific time windows after excitation pulses, achieving high signal-to-background ratios without requiring complex continuous systems
Solution Approach 2:
The patent uses preliminary charge integration during the excitation pulse period, where photo-induced charge is accumulated in the sensor before the excitation pulse ends. This preliminary action prepares the detection system to capture the fluorescence signal efficiently during the subsequent time gate window, reducing the need for complex post-processing electronics
2Speed
If TGF systems integrate charge during excitation pulse, then detection speed is improved, but background noise from excitation signal increases
Solution Approach 1:
The patent employs periodic pulsed excitation with duty cycles less than 10%, where the excitation is applied in brief intervals followed by detection windows. This periodic structure enables the system to integrate charge during excitation while subsequently measuring fluorescence only during time gates when excitation is off, effectively separating signal acquisition from background contamination
Solution Approach 2:
The patent dynamically controls the electronic shutter to open and close at specific times relative to the excitation pulses. The shutter remains closed during excitation integration and opens during fluorescence detection, creating time-dependent dynamic control that allows simultaneous charge integration and background rejection
3Adaptability or versatility
If TGF systems use fast optical excitation switching, then multi-color differentiation capability is improved, but electronics speed and noise performance requirements increase
Solution Approach 1:
The patent uses periodic excitation pulses with frequencies of 1-100 MHz to excite multiple fluorophores with different lifetimes. By applying excitation periodically and using time-gated detection at different phases of the periodic cycle, the system can differentiate between multiple colors based on their distinct fluorescence decay characteristics without requiring extremely fast electronics
Solution Approach 2:
The patent performs preliminary charge integration during the excitation pulse for multiple fluorophores simultaneously. This preliminary integration captures the combined signal from all excited fluorophores, and subsequent time-gated measurement separates them based on decay kinetics, reducing the need for complex high-speed electronics to differentiate colors in real-time
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 higher signal-to-background ratios and reduces background noise, allowing for faster and more reliable detection of analytes with improved multi-color differentiation capabilities, suitable for massively parallel biochemical assays.
Implementation Method 1
the sensor is configured to (i) collect a signal from the solution generated upon exposure of the solution to an excitation pulse within a first time period
Implementation Method 2
with aid of the electronic shutter, remove photo-induced charge generated within a second time period in the sensor by the excitation pulse
Implementation Method 3
integrating photon signals over multiple excitation pulses
Implementation Method 4
the analyte may contain a fluorophore construct, which may emit light when excited by an optical excitation source. The emission may occur at a longer wavelength than the excitation source
Data Source
AI summary
The present disclosure provides methods, apparatus and systems for time-gated fluorescent-based detection. Time-based fluorescence analysis can be used in certain biochemical assays by measuring the emitted photon flux from fluorophores after an individual excitation pulse.