Serial Nucleic Acid Processing via Microfluidic Segmentation
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Solution Overview
Problem
Existing nucleic acid assay systems operate in batch mode, making them time-consuming and labor-intensive for processing multiple samples, as they require manual preparation and processing of each sample separately, lacking the capability for rapid serial multiplex assays.
Innovation Solution
A system comprising a microfluidic cartridge with flow-through channels, an optical system for fluorescence imaging, temperature and pressure control, and a liquid handling system with a robotic pipettor for automated processing and mixing of reagents, enabling real-time processing of multiple nucleic acid assays simultaneously.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If batch mode processing is used for nucleic acid assays, then sample preparation and analysis can be performed with simple equipment, but processing time and labor intensity increase significantly when handling multiple samples
Solution Approach 1:
The system divides the processing into discrete temporal segments, where each sample is processed sequentially through the same microfluidic channel. The robotic pipettor delivers samples one at a time, and the temperature control system cycles through denaturation, annealing, and extension phases for each sample before moving to the next, enabling high-throughput processing without requiring parallel hardware channels
Solution Approach 2:
A single microfluidic channel and temperature control system perform multiple functions by sequentially processing different samples. The same physical infrastructure (channel, heaters, sensors) is reused for each assay, eliminating the need for dedicated hardware per sample while maintaining full analytical capability for each nucleic acid detection task
2Productivity
If manual preparation and processing of each sample is performed separately, then equipment complexity remains low, but labor intensity and processing time increase
Solution Approach 1:
The robotic pipettor autonomously performs sample delivery, reagent addition, and waste removal without human intervention. The system self-regulates fluid flow through the microfluidic channel and automatically cycles temperature phases, reducing labor intensity while the added automation components increase device complexity in a controlled manner
Solution Approach 2:
Manual mechanical operations (pipetting, mixing, temperature cycling) are replaced with automated systems. The robotic pipettor uses motorized positioning and pneumatic control instead of manual manipulation, and the temperature control system uses electronic feedback loops instead of manual heating/cooling adjustments, increasing automation while managing system complexity
3Productivity
If rapid serial processing of multiple samples is implemented, then productivity increases, but the system requires automated liquid handling and microfluidic control mechanisms
Solution Approach 1:
The system processes multiple samples in the temporal dimension rather than requiring parallel spatial channels. By sequencing sample introduction and processing in time, the system achieves multiplexing capability without increasing the number of physical microfluidic channels, thus improving productivity while limiting the growth of device complexity
Solution Approach 2:
The microfluidic channel acts as an intermediary between the robotic pipettor and the detection system. It provides a controlled environment for nucleic acid amplification and serves as the interface where automated fluid delivery meets thermal cycling and optical detection, enabling rapid serial processing while managing the complexity of coordinating multiple automated subsystems
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 rapid serial processing of multiple nucleic acid assays, significantly reducing processing time and labor by automating the handling and analysis of multiple samples concurrently, enhancing efficiency and throughput in nucleic acid detection and analysis.
Implementation Method 1
an optical system, which provides information on the position of material within a microfluidic channel
Implementation Method 2
The PCR process phases of denaturing, annealing, and extension occur at different temperatures and cause target DNA molecule samples to replicate themselves. Temperature cycling (thermocyling) requirements vary with particular nucleic acid samples and assays
Implementation Method 3
a pressure measurement and control system for applying variable pneumatic pressures to the microfluidic cartridge
Implementation Method 4
a liquid handling system comprising at least one robotic pipettor for aspirating, mixing, and dispensing reagent mixtures to the microfluidic cartridge
Implementation Method 5
a microfluidic cartridge having at least one flow-through channel
Data Source
AI summary
The present invention relates to systems and methods for the real time processing of nucleic acid during polymerase chain reaction (PCR) and thermal melt applications. According to an aspect of the invention, a system for the rapid serial processing of multiple nucleic acid assays is provided. In one embodiment, the system includes, but is not limited to: a microfluidic cartridge having microfluidic (flow-through) channels, a fluorescence imaging system, a temperature measurement and control system; a pressure measurement and control system for applying variable pneumatic pressures to the microfluidic cartridge; a storage device for holding multiple reagents (e.g., a well-plate); a liquid handling system comprising at least one robotic pipettor for aspirating, mixing, and dispensing reagent mixtures to the microfluidic cartridge; systems for data storage, processing, and output; and a system controller to coordinate the various devices and functions.