In biomedical fields such as gene sequencing, disease diagnosis, and drug screening, biochips have achieved breakthroughs in "one drop of sample, multiple detections" with the advantages of "high-throughput, high sensitivity, and miniaturization". The core of all of this lies in the precision processing technology that integrates microelectronics, micromechanics, and biotechnology behind it. From the preparation of chip substrates to the fixation of biomolecules, the processing of biochips requires the construction of complex structures and functions at the micrometer or even nanometer scale. The accuracy and reliability of each step of the process directly determine the detection efficiency and accuracy of biochips.

　　Biochip processing technologyThe core is substrate microfabrication: creating a detection canvas. The substrate of biochips needs to be fabricated through microfabrication processes to create microchannels, microreactors, and other structures, providing miniaturized reaction spaces for biological detection. At present, photolithography and etching techniques are commonly used: photolithography processes use ultraviolet light or electron beams to transfer microchannel patterns onto photoresist on the substrate surface, with a line width accuracy of 1-10 μ m, ensuring the consistency of microchannel size; Dry etching or wet etching removes excess substrate material according to the pattern, forming microchannels with a depth of 10-100 μ m. The roughness of the inner wall of the channel needs to be controlled at the nanometer level to avoid affecting liquid flow and biomolecule adsorption. For example, in the substrate processing of gene chips, it is necessary to create microarray grooves with uniform spacing to provide precise sites for subsequent fixation of probe molecules; In microfluidic chips, complex microchannel networks require multi-layer lithography and bonding processes to ensure precise flow and reaction of liquids within the chip.

Next is biological functionalization: endowing chips with detection capabilities. After the substrate microstructure is completed, probe molecules need to be immobilized on the chip surface through biological functionalization processes, which is the key to achieving specific detection of biochips. Firstly, the substrate surface needs to be modified - for example, coating silane coupling agent on the glass substrate surface, introducing amino or carboxyl active groups, and enhancing the binding stability of probe molecules; Subsequently, the probe molecules were accurately dropped onto the micro array sites using a spot sampling method, with a spot sampling accuracy controlled within ± 5 μ m to ensure uniform probe concentration at each site; Finally, the probe molecules are firmly fixed through baking, cross-linking and other processes to avoid detachment during the detection process. Taking protein chips as an example, antibody probes need to bind to the substrate surface through covalent bonds with a binding efficiency of over 90% to ensure high sensitivity capture of target antigens.

Finally, packaging and integration: ensuring the stable operation of the chip. Biochips need to be packaged to achieve sample injection, signal detection, and external device connection, while avoiding external contamination. The packaging process requires the integration of sample inlet, sample outlet, and detection window on the surface of the chip. Laser welding or low-temperature bonding technology is used to seal the cover plate and substrate, and the sealing strength needs to ensure that the chip does not leak under a pressure of 1-5 atm; For chips that require optical detection, the detection window should be made of high transmittance quartz or sapphire material to avoid optical signal loss; In addition, some biochips also need to integrate microsensors and signal processing circuits to achieve the integration of "detection signal conversion data output". For example, in gene sequencing chips, the integration of CMOS image sensors can capture real-time fluorescence signals during DNA synthesis, greatly improving sequencing efficiency.

With the development of precision medicine and personalized diagnosis and treatment, the processing technology of biochips is upgrading towards "higher throughput, higher sensitivity, and lower cost". From the nanoscale precision of substrate microfabrication to the high specificity of biological functionalization, and then to the intelligence of packaging integration, every technological innovation has promoted the widespread application of biochips in clinical diagnosis, drug development, and other fields.