Nano-Scale Flow Sensing Apparatus for HPLC Split Ratio Control
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Solution Overview
Problem
Current flow sensing technologies, such as plunger displacement pumping systems and thermal flow sensors, struggle to deliver stable and accurate nano-scale flow rates in high-performance liquid chromatography (HPLC) due to unpredictable split ratio variations and sensitivity to fluid composition changes, requiring complex calibration routines.
Innovation Solution
A method and apparatus that utilize a main flow sensor and a secondary flow sensor in either the waste or operating path to measure and control nano-scale flow rates independently of solvent composition, using thermal or pressure sensors, with a divider circuit to calculate an empirical split ratio, allowing for precise adjustment of flow rates without elaborate calibration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If a split-flow pumping system is used to deliver nano-scale flow rates, then the pump can operate at normal or micro-scale flow rates, but the split ratio varies unpredictably due to permeability changes
Solution Approach 1:
The patent implements a feedback control system using flow sensors to monitor the actual flow rate through the chromatographic column and adjust the pump flow rate accordingly. This closed-loop control compensates for split ratio variations caused by permeability changes, maintaining stable nano-scale flow delivery without requiring the split ratio to be perfectly stable.
Solution Approach 2:
The system dynamically adjusts the pump flow rate parameter based on real-time feedback from flow sensors. By changing the pump flow rate in response to measured conditions, the system maintains the desired column flow rate despite variations in split restrictor or column permeability over time.
2Measurement precision
If pressure transducers are used to measure flow rate through a restrictor, then flow can be monitored, but the system requires calibration for different fluid viscosities
Solution Approach 1:
The patent replaces pressure-based flow measurement with thermal flow sensing technology. Thermal flow sensors measure flow rate based on heat transfer characteristics rather than pressure differential, eliminating the need for viscosity-based calibration while maintaining measurement precision across different mobile phase compositions.
Solution Approach 2:
The system changes the measurement parameter from pressure differential (which depends on viscosity) to thermal characteristics (which are less sensitive to viscosity changes). This parameter change allows flow measurement without elaborate calibration routines for different fluid compositions.
3Measurement precision
If thermal flow sensors are used to measure nano-scale flow rates, then accurate measurement is achieved, but the sensors are sensitive to ambient temperature variations
Solution Approach 1:
The patent introduces temperature compensation mechanisms as intermediaries between the thermal flow sensor and the environment. By measuring ambient temperature and applying compensation algorithms, the system eliminates temperature variations as a source of measurement error while preserving the sensor's ability to accurately measure nano-scale flow rates.
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 accurate and precise monitoring and control of nano-scale flow rates in HPLC systems, minimizing the need for complex calibration and reducing sensitivity to fluid composition changes, thereby stabilizing flow rates and improving measurement precision.
Implementation Method 1
If the liquid in the tube is permitted to flow, the fluid temperatures at P1 and P2 will depend upon the rate of liquid flux and the resulting heat convection.
Implementation Method 2
Heat introduced into a liquid filled tube/channel will disperse in both the upstream and downstream directions (i.e. due to thermal conduction or diffusion respectively).
Implementation Method 3
Fluid flow rates can be determined by measuring the pressure of a liquid flowing through a restrictor. Assuming a constant viscosity, the back pressure of liquid flowing through a restrictor will scale linearly with the flow rate of the liquid.
Data Source
AI summary
A method and apparatus for monitoring and controlling the nano-scale flow rate of fluid in the operating flow path of a HPLC system without relying on a nano-scale sensor in the operating flow path. A main flow sensor is disposed in the main flow path between the pump and a flow-divider. A waste flow sensor is disposed in the waste flow path downstream of the splitter. The output signal of the waste flow sensor is subtracted from the output signal of the main flow sensor in a difference circuit. The difference signal is divided by the output signal from the main flow sensor in a divider circuit. The output of the divider circuit represents an empirical split ratio of the flow-divider and is independent of media composition.


