Self-Resetting Integrator-Differentiator for High-Speed Molecular Diagnostics

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Solution Overview

Problem

Current molecular diagnostics face challenges with poor signal-to-noise ratios and limited temporal resolution due to noise constraints in electronic platforms, which hinder high-speed and high-dynamic-range measurements of single biomolecules.

Innovation Solution

The integration of resettable capacitors in a self-resetting continuous-time integrator-differentiator system, utilizing non-overlapping clock phases to manage charge balancing and prevent saturation, allowing for high-bandwidth and low-noise measurements.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional electronic acquisition circuits are used, then measurement bandwidth is maintained, but noise amplitude increases and signal-to-noise ratio deteriorates

Engineering Contradiction:
Improvesignal-to-noise ratioVSAvoidtemporal resolution
Core Design Contradiction:
Measurement precisionVSSpeed

Solution Approach 1:

The patent segments the acquisition circuit into multiple parallel integrator channels, each handling a specific frequency band or time window. This segmentation allows independent optimization of each channel's integration time and noise filtering parameters, enabling high temporal resolution in some channels while maintaining low noise in others, thus resolving the contradiction between speed and measurement precision.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent implements periodic sampling and integration windows that synchronize with the expected signal characteristics. By using periodic action, the system can accumulate signal energy over multiple periods while rejecting aperiodic noise, achieving both high temporal resolution for event detection and low noise for precise measurement.

Inventive Principle:
Principle #19Periodic action

2Measurement precision

If integration time is increased to reduce noise, then noise amplitude decreases, but temporal resolution is sacrificed

Engineering Contradiction:
Improvenoise amplitudeVSAvoidtemporal resolution
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent employs dynamic integration time adjustment where the integration window adapts based on signal characteristics and detection requirements. For transient events, shorter integration times preserve temporal resolution, while for steady-state signals, longer integration times reduce noise. This dynamic adaptation resolves the fixed trade-off between noise reduction and temporal resolution.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The system changes integration parameters (time constant, sampling rate, number of averages) based on the specific measurement conditions and signal type. By dynamically adjusting these parameters, the system can optimize for either low noise or high temporal resolution depending on the experimental requirements, eliminating the need to permanently sacrifice one for the other.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If discrete-time systems are used, then measurement performance improves, but bandwidth is reduced

Engineering Contradiction:
Improvemeasurement performanceVSAvoidbandwidth
Core Design Contradiction:
Measurement precisionVSSpeed

Solution Approach 1:

The patent merges continuous-time filtering stages with discrete-time processing stages in a hybrid architecture. The continuous-time portion maintains high bandwidth by operating at the full signal rate, while the discrete-time portion provides precise measurement and noise reduction. This combination allows the system to achieve both high bandwidth and high measurement performance simultaneously.

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

This approach enables faster, cheaper, and higher-fidelity diagnostics by eliminating transient reset glitches, maintaining low noise levels, and preventing saturation, thus enabling sub-microsecond real-time tracking of single molecules and facilitating large-scale parallel sensing arrays for applications like DNA sequencing.

Implementation Method 1

integrating charge stored thereby on a first resettable capacitor of an integrator

Methodology Applied
Scientific EffectCapacitance: Capacitance

Implementation Method 2

The first resettable capacitor is shorted with a first switch controlled by the first one of the plurality of clock phases to equalize the first integrated charge stored on the first resettable capacitor

Methodology Applied
Scientific EffectCharge redistribution: Electrical Accumulator

Data Source

PatentUS10274477B2High-speed molecular diagnostics
Publication Date: 2019.04.30 BROWN UNIVERSITY
  • US10274477B2 patent drawing
  • US10274477B2 patent drawing
  • US10274477B2 patent drawing

AI summary

A system for high-speed molecular diagnostics includes a self-resetting continuous-time integrator configured to integrate an input current on one of a plurality of integration capacitors to generate an integrated voltage. A self-resetting continuous-time differentiator is configured to differentiate the integrated voltage on one of a plurality of differentiating capacitors to generate an output voltage proportional to the input current. A fixed-threshold window comparator is configured to reset one of the plurality of integration capacitors, reset one of the plurality of differentiating capacitors, open a second one of the plurality of integration capacitors and open a second one of the plurality of differentiating capacitors in response to the integrated voltage exceeding a voltage range.