Biochip Material Classification and Surface Modification

The core of biochip technology lies in the integration of a miniature biochemical analysis system onto the surface of a chip to achieve efficient and precise detection of biological components such as cells, tissues, proteins, nucleic acids and sugars.

This technology originated in the late 1980s and became an important frontier in the life sciences.

It integrates molecular biology, biomaterials, microelectronics, micromechanics, microprocessing technology, chemistry, physics and computer technology, and represents the deep intersection and integration of biology and other disciplines.

1. Classification of biochip substrates

A biochip matrix is the material used to make a biochip, usually a solid surface, which is used to adsorb and immobilize biomolecules to facilitate their detection or analysis.

Key requirements for biochip substrates include good biocompatibility, large surface area, strong adsorption capacity, uniform surface properties, and ease of processing and preparation.

1) Slide Biochip

The use of slides in biochips has several advantages.

First, the high flatness of the slide surface helps the uniform adsorption and immobilization of biomolecules, thus improving the accuracy of the experimental results.

Secondly, the slide material is easy to obtain and low cost, which makes it one of the commonly used materials in biochip preparation.

Slide matrices also have good sensitivity to biochemical reactions and are able to conduct heat and charge quickly, facilitating processes such as enzyme reactions and cell cultures, improving reaction efficiency and accuracy.

Due to the high temperature stability of the slide, it maintains structural stability at higher temperatures, ensuring experimental reliability.

The transparency of the slide is also well suited for fluorescence imaging, and by observing samples labeled with fluorescent dyes, it is possible to obtain important information about biological processes and interactions, thus enhancing imaging quality and resolution.

2) Silicon Biochips

Silicon wafers, because of their superior process controllability, can be accurately fabricated in micron-sized chips by micromachining technology, facilitating the construction of complex microfluidic systems, microarrays and microstructures, and supporting a high degree of integration and automated operation.

Compared to glass, silicon wafers have higher mechanical strength and hardness and are more resistant to breakage.

Silicon wafers have good transparency in certain wavelength ranges, especially in the near-infrared spectral region, making them suitable for fluorescence imaging and analytical applications.

The excellent thermal conductivity of silicon wafers helps to disperse heat quickly and evenly, ensuring reaction stability and accuracy, making them particularly suitable for thermally controlled experiments or high-temperature reactions.

The excellent electrical conductivity of silicon wafers gives them a distinct advantage in electrochemical experiments.

3) Gold-surfaced or gold-coated biochips

Gold surfaces have a plasmon resonance (SPR) effect that can be used to study biomolecular recognition and interactions.

Gold-surfaced or gold-coated biochips analyze the interaction of bioactive molecules to be detected with the chip surface by monitoring changes in the SPR effect.

When a biomolecule binds to the chip surface, the resonant coupling of photons and free electrons leads to a change in the angle of incidence, which in turn causes a change in reflectance.

This signal change can be used as a biosensor for analyzing biological signals.

Gold materials also have excellent corrosion resistance and can resist the effects of chemical reactions such as strong acids or bases, making them suitable for some special biological experiments.

4) Polymer matrix biochips

Polymer matrix microarrays use polymers as the carrier material and are biocompatible and do not cause toxicity or damage to biological samples.

By adjusting the formulation, changing the preparation conditions or adding functional monomers, polymer matrix chips can be customized to meet the performance and functional requirements of different experiments.

In addition, polymer matrix chips have the advantages of excellent optical transparency, degradability, low cost and easy mass production.

Polymeric materials such as polymethylmethacrylate (PMMA), polystyrene (PS), polycarbonate (PC) and polydimethylsiloxane (PDMS) have been widely used for high-throughput detection of bioactive molecules over the past two decades.

5) Nanomaterial matrix biochips

Biochips using nanomaterials as matrix carriers combine nanotechnology and bioanalytical technology and offer significant advantages.

Nanomaterials possess a large specific surface area and unique optoelectronic properties, which can improve the immobilization and detection sensitivity of biomolecules, thus enhancing the precision of detection of biomolecules at low concentrations.

By adjusting the type, morphology and surface modification of nanomaterials, nanomaterial matrix biochips can be multifunctionalized to meet the needs of different biomolecule detection.

Due to the special nature of nanomaterials, this chip also has the advantage of rapid detection, which can analyze a large number of samples in a short period of time and significantly improve the experimental efficiency.

2. Biochip surface modification tools

Biochip surface modification is the introduction of specific functional groups or biomolecules on the chip surface to achieve specific recognition, capture and detection of target molecules or cells.

1) Physical adsorption

Physical adsorption method is to drop the functional molecule or biomolecule solution directly on the chip surface, without the use of special chemical reagents or equipment, easy to operate and easy to control.

In this process, the target molecules are adsorbed on the chip surface by physical forces such as van der Waals forces and electrostatic interaction. Advantages include short processing time, ease of operation and low cost.

The problem is that the physical adsorption method is less stable and easily affected by environmental factors such as temperature, humidity and pH, thus affecting the adsorption effect.

In this way the adsorption effect may gradually weaken during long-term storage and use, leading to increased uncertainty in the measurement results.

2) Covalent binding method

Covalent binding is a commonly used method to achieve immobilization by introducing reactive functional groups on the chip surface to react with functional molecules or biomolecules to form covalent bonds.

The method, which is usually divided into two steps and requires precise control of the reaction conditions and the selection of modification reagents, is relatively complex to operate, but can provide highly stable modification effects.

First, reactive groups need to be introduced on the chip surface, commonly including amino groups and carboxyl groups.

These reactive groups provide reaction sites for subsequent covalent reactions.

Through appropriate surface modification techniques, these groups can be introduced into specific regions of the chip in a targeted manner for the purpose of spatial modification.

The reactive group then reacts with the chemical modifier, and common covalent binding reactions include amine-based reactions, anhydride activation reactions, and thiol reactions.

For example, in an amine-based reaction, a compound containing a reactive ester or anhydride group is used to react with an amino group on the surface of the chip to form a stable amide bond.

In this way, the modifier is firmly fixed on the chip surface and is not easily disturbed by solution conditions or the external environment.

3) Biotin-affinity binding method

Specific binding between biotin and affinities is one of the commonly used biochip modification methods.

First, in order to realize the binding of biotin to affinities, affinity compounds need to be introduced on the surface of the chip, commonly including affinity proteins, affinity ligands, or other molecules with affinity activity.

After the introduction of affinities, a solution of biomolecules or compounds labeled with biotin is applied to the chip surface. Biotin is a small molecule that forms a highly specific non-covalent binding to the affinity pigment.

Biotin is usually labeled with a target biomolecule (e.g., antibody, oligonucleotide, ligand, etc.) either by chemical reaction or biosynthesis.

When a biomolecule labeled with biotin comes into contact with the surface of the chip modified with affinity pigments, the specific binding between the biotin and affinity pigments immobilizes the biomolecule on the surface of the chip, resulting in highly sensitive and selective detection and analysis.