Automated Nucleic Acid Assays With User-Defined Protocol Control
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Solution Overview
Problem
Existing molecular assays, particularly lab-developed tests (LDTs), lack robust quantitative analytical methods that are easily automated and minimize false-positive and false-negative determinations, and require custom protocols that cannot be easily implemented in existing automated systems designed for standardized IVD assays.
Innovation Solution
A software tool enables users to define user-defined parameters for assay protocols, allowing for the development and optimization of LDTs through interactive interfaces, and a controller to process and modify data sets to determine optimized parameters for LDTs, which can be finalized and locked for automated nucleic acid amplification assays.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If custom protocols are used for LDTs, then assay flexibility and user-defined parameters are improved, but system complexity and difficulty of implementation in automated systems worsen
Solution Approach 1:
The automated analyzer is designed with a universal protocol engine that can execute both standardized IVD assays and custom LDT protocols through a common architecture. The system accepts different protocol types (standardized and custom) through a unified interface, allowing one system to perform multiple assay types without requiring separate dedicated systems for each assay category.
Solution Approach 2:
The assay protocol is divided into discrete, modular steps that can be independently configured and executed. Custom LDT protocols are broken down into sequential operations (sample preparation, reagent addition, thermal cycling parameters, detection settings) that can be individually defined and combined, making complex custom assays manageable through systematic segmentation of the overall protocol into controllable modules.
2Productivity
If batch mode processing is used, then system simplicity is maintained, but productivity and throughput worsen
Solution Approach 1:
The system enables continuous processing by allowing overlapping execution of different assay types. While one assay is undergoing amplification, the system can simultaneously prepare reagents for the next assay, transfer samples, or configure protocols. This continuous utilization of system resources eliminates idle time between batch completions and maintains high throughput without requiring parallel independent systems.
Solution Approach 2:
Reagents and samples are prepared in advance before the actual amplification and detection phases. The system pre-configures protocol parameters, pre-cools reagents to required temperatures, and pre-positions samples in reaction vessels before initiating the assay sequence. This preliminary preparation reduces active processing time and enables faster turnover between assays.
3Measurement precision
If quantitative methods are improved, then measurement precision is improved, but risk of false-positive and false-negative determinations worsens
Solution Approach 1:
The system incorporates real-time monitoring and feedback mechanisms during the amplification process. Detection signals are continuously measured and compared against threshold values and reference curves. The system automatically adjusts acquisition parameters and analyzes amplification kinetics in real-time to distinguish true positive signals from background noise, reducing false determinations while maintaining quantitative precision.
Solution Approach 2:
The system implements built-in quality controls and validation checks before final result reporting. Reference standards and control samples are processed alongside test samples to establish baseline expectations. The system pre-validates protocol parameters, checks reagent integrity, and verifies instrument performance before running assays, cushioning against conditions that could lead to false results while preserving measurement accuracy.
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
Enables the automation of LDTs with user-defined parameters, improving quantitative accuracy and minimizing false results, while allowing for flexible and optimized assay protocols in an automated analyzer.
Implementation Method 1
exposing each of the first and second samples to reagents and conditions adapted to isolate and purify a first analyte and a second analyte
Implementation Method 2
PCR employs thermal cycling, which consists of repeated cycles of heating and cooling of a reaction mixture
Implementation Method 3
the target nucleic acid may be amplified by a nucleic acid amplification reaction, such as, for example, Polymerase Chain Reaction ("PCR")
Implementation Method 4
The growth of the amplicon may be detected using signal detecting devices (e.g., fluorescence detection devices) that measure signal emissions (e.g., level of fluorescence at a predetermined wavelength or range of wavelengths, etc.) indicative of the amplicon
Data Source
Figure 1A
Figure 1B
Figure 2A
AI summary
A system, method, computer, and computer readable medium enabling a user to quantify a target nucleic acid analyte.