Valveless Pressure Chamber Capillary Gap for Sample Dispensing

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Solution Overview

Problem

Existing systems for dispensing biological samples into a buffer liquid are inefficient due to wear and high costs of mechanical valves, large sample volumes, and dilution of samples as they travel through long capillary tubes, which affects the signal-to-noise ratio in mass spectrometry measurements, making them unsuitable for high-throughput screening applications.

Innovation Solution

A system utilizing a pressure chamber with overpressure to facilitate the dispensing of samples directly into a capillary gap between an inlet and outlet capillary, allowing for precise control of liquid bridges and reducing the distance samples travel, thereby minimizing dilution and increasing the signal-to-noise ratio, using a dispenser with a solid pin or pipette for rapid and accurate sample introduction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If mechanical valves (Rheodyne) are used to switch between buffer liquid and liquid sample, then reliable switching capability is achieved, but wear occurs and replacement is required after thousands of switching actions

Engineering Contradiction:
Improveswitching capabilityVSAvoidservice life of valve
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent removes the mechanical valve component entirely from the system. Instead of using a Rheodyne valve for switching, the invention employs a valveless design where the capillary system directly switches between buffer liquid and liquid sample flows, eliminating the wear-prone mechanical switching mechanism while maintaining reliable flow control

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the mechanical valve switching system with a fluid-based switching mechanism using capillary pressure differences and liquid bridges. The mechanical Rheodyne valve is substituted by a valveless liquid handling system that uses pressure chamber control to achieve switching without mechanical moving parts

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Quantity of substance

If long capillary tubes are used to transport liquid sample from HPLC to capillary spray tube, then separation and transport are achieved, but sample dilution occurs reducing signal-to-noise ratio

Engineering Contradiction:
Improvesample concentrationVSAvoidcapillary tube length
Core Design Contradiction:
Quantity of substanceVSLength of moving object

Solution Approach 1:

The patent extracts and removes the long capillary transport section from the system. By eliminating the traditional HPLC-to-spray tube capillary connection, the invention prevents sample dilution that occurs over long transport distances while maintaining effective sample delivery to the electrospray source

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent performs preliminary sample concentration and preparation in the pressure chamber before injection, ensuring the sample is already concentrated and ready for analysis without requiring long transport capillaries that would cause dilution

Inventive Principle:
Principle #10Preliminary action

3Reliability

If large volumes of buffer liquid are supplied continuously to prevent capillary drying, then capillary function is maintained, but sample dilution increases and throughput decreases

Engineering Contradiction:
Improvecapillary functionVSAvoidthroughput
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent implements periodic rather than continuous buffer liquid supply. The system alternates between buffer liquid flow and liquid sample injection cycles, allowing the capillary to be refilled with buffer periodically without continuous flow that would dilute samples and reduce throughput

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The patent uses dynamic pressure chamber control to adjust buffer liquid supply timing and amount. The pressure chamber system dynamically switches between supplying buffer liquid to maintain capillary function and injecting liquid samples, optimizing both reliability and productivity

Inventive Principle:
Principle #15Dynamics

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 system enables efficient, high-throughput dispensing of small sample volumes with reduced dilution and improved signal-to-noise ratios, suitable for biochemical and biological samples, enhancing the performance in mass spectrometry measurements.

Implementation Method 1

A pressure chamber (1) having a pressure supply means (18) for generating an overpressure within the pressure chamber (1) relative to a pressure outside the pressure chamber (1)

Methodology Applied
Scientific EffectOverpressure: Pressure Increase

Implementation Method 2

An inlet capillary (2) for supplying a buffer liquid (9) to an outlet end (6) of the inlet capillary (2)

Methodology Applied
Scientific EffectCapillary flow: Capillary Action

Implementation Method 3

An outlet capillary (3) for discharging the buffer liquid (9) and/or the sample (5) from the pressure chamber (1)

Methodology Applied
Scientific EffectCapillary flow: Capillary Action

Implementation Method 4

The outlet end (6) of the inlet capillary (2) and the inlet end (7) of the outlet capillary (3) are facing each other to form a capillary gap (8)

Methodology Applied
Scientific EffectSurface tension: Surface Tension

Data Source

PatentEP2893357B1System for dispensing a sample into a buffer liquid
Publication Date: 2020.08.12 F HOFFMANN LA ROCHE & CO AG
  • EP2893357B1 patent drawingFigure 1
  • EP2893357B1 patent drawingFigure 2~4
  • EP2893357B1 patent drawingFigure 5~8

AI summary

A system for dispensing a sample (5) into a buffer liquid comprises a pressure chamber (1) having pressure supply means for generating an overpressure within the pressure chamber. An inlet capillary (2) is provided for supplying a buffer liquid (9) to an outlet end (6) arranged in the pressure chamber. Also, an outlet capillary (3) is provided for discharging buffer liquid and/or sample from the pressure chamber. The outlet capillary (3) has an inlet end (7) arranged in the pressure chamber (1) facing the outlet end (6) of the inlet capillary (2) to form a capillary gap (8). A dispenser (4) having a dispensing end (10) is arranged in the pressure chamber (1) at the capillary gap (8) to allow the sample (5) at the dispensing end (10) to be dispensed from the dispensing end (10) into the buffer liquid entering the inlet end (7) of the outlet capillary (3). The pressure chamber (1) comprises a pressure-tight sample port (13) adapted to allow the dispenser (4) with the dispensing end (10) to be moved into and out of the pressure chamber (1), wherein the pressure chamber (1) comprises a pressure-tight sample port adapted to allow the dispenser (4) with the dispensing end (10) to be moved into and out of the pressure chamber ( 1 ).