The development of modern biomedicine and high-end implant devices has put forward strict requirements for micro-nano manufacturing. Many biological samples, implantable devices, and polymer functional substrates are extremely sensitive to heat and mechanical stress. Traditional mechanical cutting, electric spark, and long pulse laser processing are prone to thermal burns, microcracks, burrs, and material denaturation, which can easily reduce implant biocompatibility and even induce inflammation, thrombosis and other risks. The femtosecond laser with femtosecond ultrashort pulse as the core, relying on the unique cold ablation mechanism, breaks through the bottleneck of traditional technology, and becomes the core means of biotechnology research, minimally invasive instruments, and micro-nano processing of implantable medical devices.
Femtosecond laser pulse action time is extremely short, the energy is absorbed and stripped by the material in an instant, and the heat is too late to conduct and diffuse to the surrounding substrate, forming a cold working effect that is almost free of heat-affected zone. There is no recast layer, slag and thermal deformation in the processing area, and the edge of the incision is clean and smooth, which can stably realize the forming of micron and even sub-micron precision. At the same time, it belongs to non-contact processing, has no tool extrusion wear, and is suitable for nickel-titanium alloy, degradable polymer, ceramic, hydrogel, biological thin film, transparent optical material and other biocompatible materials. It can not only do material reduction etching and microporous cutting, but also realize three-dimensional additive molding by relying on two-photon polymerization, which is very suitable for the manufacturing requirements of multi-material, micro-scale and high safety in the biological field.
In the field of implantable medical device manufacturing, cardiovascular stents are the scene of femtosecond laser landing earlier and outstanding value. Whether it is a nickel-titanium alloy self-expanding stent or a polylactic acid absorbable degradable stent, the mesh width, connection structure, and expansion deformation characteristics of the stent are directly related to the vascular fit effect and long-term safety. The cutting edge after nanosecond laser processing often has molten burrs, and the subsequent polishing is difficult, and the residual tiny protrusions will increase the probability of thrombosis. Femtosecond cold cutting can form complex hollow grids at one time, with uniform contours and smooth sections, greatly reducing post-processing procedures and better retaining the mechanical properties and biocompatibility of the substrate itself. In addition to vascular stents, various types of interventional microcatheters, nerve microelectrodes, cochlear implant electrodes, minimally invasive biopsy needles, and microneedle transdermal drug delivery patches also rely on femtosecond micromachining. Microneedle array needle thickness, needle tip shape needs to be accurately controlled, not only to penetrate the stratum corneum, but also can not cause excessive trauma, femtosecond laser can be in polymer, silicon-based film batch preparation of microneedle structure with consistent morphology, for controlled drug delivery, tissue fluid sampling, to help the development of painless transdermal diagnosis and treatment technology.
The processing of ophthalmic medical devices and optical medical components has the ultimate requirements for precision and surface quality. In addition to clinical surgical applications, femtosecond lasers are also used for the preparation of microstructures for intraocular lenses, corneal contact sensing lenses, and fundus imaging microoptics. In transparent optical materials, femtosecond laser can realize internal modification, writing microchannels and microlens arrays without multilayer lithography and chemical etching. Some intelligent contact lenses built-in micro-liquid cavity, sensing micro-channel, relying on femtoseconds directly on the lens substrate molding, will not damage the optical transparency, for continuous monitoring of intraocular pressure, tear biochemical indicators of wearable ophthalmic diagnosis and treatment equipment to lay the foundation for manufacturing. The zirconia all-ceramic substrate in the dental field and the micro-nano texture of the implant surface can also be functionalized by femtosecond laser to construct an orderly microstructure without damaging the strength of the substrate, promote the attachment of osteoblasts, and improve the bone binding efficiency of the implant.
In the direction of biotechnology and biochip, femtosecond laser has opened up a new path for the research and development of organ chips, microfluidic chips and cell culture scaffolds. Microfluidic chips need interlaced microchannels, reaction chambers, and filter micropores. The channel width is often only a dozen to tens of microns. The traditional soft etching process mold has a long development cycle and is difficult to flexibly adjust the three-dimensional structure. Femtosecond laser can directly etch three-dimensional fluid networks on glass, PDMS, hydrogel and other materials, process bifurcation channels, interception microsieves, and single cell capture sites for cell sorting, drug screening, and rapid pathogen detection. Relying on the two-photon polymerization effect, femtosecond laser can also print bionic three-dimensional cell scaffolds layer by layer in photosensitive bio-resin, copy complex bionic topological structures such as vascular branches, alveoli and nerve bundles, and control the pore connectivity of the scaffolds. It can guide the directional adhesion, proliferation and differentiation of stem cells, play an important role in tissue engineering and in vitro organoid culture research, and make up for the uncontrollable shortcomings of traditional porous scaffolds.
Biosample preparation and processing of biosensor devices also benefit from femtosecond lasers. Biological mass spectrometry target plates, electrode microstructures of biosensors, and fiber optic biological probes all require high-precision microgrooves and micropore arrays. Femtosecond processing does not cause thermal deterioration of the substrate, can maintain the activity of the biological recognition coating, enzyme film, antibody modification layer, and ensure the stable collection of biochemical signals. In terms of biometric traceability, for permanent marking of implanted devices and disposable precision consumables, femtosecond laser relies on the change of internal refractive index of the material to realize internal marking. The marking is buried inside the material, does not damage the surface smoothness, does not react with body fluids, and the two-dimensional code and serial number are wear-resistant for a long time, meeting the requirements of whole life cycle tracing of medical devices and drug administration specifications.
Of course, femtosecond laser still has practical constraints in the field of biomedical micromachining. The acquisition cost of equipment is high, the processing efficiency of large-scale and mass production needs to be improved, the processing speed of two-photon polymerization limits the large-scale preparation of large-scale bionic tissue scaffolds, the process window debugging of different biomaterials is complex, and the parameters need to be optimized repeatedly in combination with biocompatibility testing. With the continuous iteration of high-power, high-frequency femtosecond light source, high-speed galvanometer, five-axis linkage platform and online visual closed-loop inspection system, equipment costs are gradually declining, process stability is increasing, and more and more medical device manufacturers and biological laboratories are starting to build femtosecond micromachining platforms.
Facing the development wave of precision medicine, organ engineering and in vitro diagnosis, femtosecond laser is not only a precision cutting tool, but also the underlying manufacturing technology supporting the research and development of the next generation of micro implant devices, bionic biological structures and biochemical chips. In the future, femtosecond laser will be deeply integrated with biomaterial modification, surface functionalization and automated biological culture systems, continuously expanding the cutting-edge directions such as neural interfaces, degradable implant devices and single-cell analysis chips, and promoting continuous breakthroughs in biotechnology research and high-end medical devices towards a smaller, safer and more bionic direction.
