Composite Biosensor with In-Line Desalting Membrane

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Solution Overview

Problem

Existing nanostructured sensor arrays, such as field effect transistors (FET), face inefficiencies in detecting bio-molecules in high ionic strength solutions due to the screening effect, where the Debye screening length is reduced, making it difficult to detect binding events beyond the shielding layer, especially at physiological salt concentrations.

Innovation Solution

A composite detection device with in-line desalting capabilities, featuring a porous silicon membrane for desalting an analyte stream and a silicon nanosensor for detecting bio-molecules, allowing for continuous desalting and detection in a microfluidic device, enabling effective detection of bio-molecules by reducing ion interference.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If nanostructured sensor arrays are used for detecting bio-molecules, then detection sensitivity is improved, but detection capability deteriorates in high ionic strength solutions due to screening effect

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddetection capability in high ionic strength solutions
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The device is segmented into two functional zones: a desalting zone with porous membrane structure that removes ions, and a sensing zone with nanostructured FET that detects biomolecules. This spatial segmentation allows the sample to be desalted before reaching the sensitive detection region, resolving the contradiction between maintaining high detection sensitivity and operating in physiological salt conditions.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

A porous membrane acts as an intermediary component between the sample inlet and the FET sensor. This membrane mediates the transition from high ionic strength physiological samples to low ionic strength detection conditions by selectively removing ions while allowing biomolecules to pass through to the sensing region.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If offline desalting methods are used, then ion interference is reduced, but device complexity and processing time increase

Engineering Contradiction:
Improvedetection accuracyVSAvoidimplementation complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The desalting function and detection function are merged into a single integrated device structure. The porous membrane is incorporated directly into the microfluidic channel leading to the FET sensor, combining what were previously separate offline operations into one continuous in-line process, thereby reducing device complexity and processing time.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

Desalting is performed as a preliminary action before the sample reaches the detection zone. The porous membrane pre-treats the sample by removing ions upstream of the FET sensor, ensuring that detection occurs under optimal low ionic strength conditions without requiring complex offline desalting equipment.

Inventive Principle:
Principle #10Preliminary action

3Quantity of substance

If Debye screening length is reduced in high ionic strength solutions, then screening effect increases, but binding event detection beyond shielding layer becomes impossible

Engineering Contradiction:
Improveionic strengthVSAvoidbinding event detection
Core Design Contradiction:
Quantity of substanceVSDifficulty of detecting and measuring

Solution Approach 1:

The ionic strength parameter of the sample is changed from high (physiological) to low through the desalting process. By reducing ion concentration, the Debye screening length increases, allowing the electric field from the FET sensor to extend far enough to detect binding events on the sensor surface despite the presence of biomolecules.

Inventive Principle:
Principle #35Parameter changes

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

The in-line desalting system enhances the detection sensitivity and specificity of bio-molecules by reducing ion interference, allowing for the detection of binding events that would otherwise be obscured, thereby improving the performance of nano-FET biosensors in high ionic strength solutions.

Implementation Method 1

The device 10 includes a porous membrane 24 configured to desalt the analyte stream by diffusion

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

a porous silicon membrane for desalting an analyte stream

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Implementation Method 3

The binding of protein or other biomolecules induces net charge change, or change in dipole moment and binding-induced dipoles or modification of energy distribution and/or density of surface states. These binding events can change surface potential of the FET device and therefore modulate the conductance of the semiconductor channel.

Methodology Applied
Scientific EffectField effect transistor conduction modulation: Conduction (electrical)

Implementation Method 4

When the device channel is reduced to nanoscale, the detection limit can be significantly reduced due to increased surface-to-volume ratio

Methodology Applied
Scientific EffectSurface potential change: Electric Field

Data Source

PatentUS8940521B2Composite detection devices having in-line desalting and methods of making the same
Publication Date: 2015.01.27 CYTIVA SWEDEN AB
  • US8940521B2 patent drawing
  • US8940521B2 patent drawing
  • US8940521B2 patent drawing

AI summary

A composite detection device having in-line desalting is provided. The composite detection device comprises a membrane configured for desalting at least a portion of an analyte stream, and a nanostructure for detecting a bio-molecule or a bio-molecule interaction, wherein the nanostructure and the membrane are arranged such that an analyte stream desalted at least in part by the membrane is detected by the nanostructure. A bio-sending detection system having the composite detection device and method of fabrication of the composite detection device are also provided.