High-permeability Minimally Invasive Sampleable Microneedle Based On Cladding Structure Reinforcement

With the continuous development of biomedical technology,Point of Care(POC)system comes to world.The system can analyse right after sampling and the results can be immediately obtained,which reduces patients’ turnaround time in hospital visits and enables patients to conduct regular monitoring at their homes,and promotes the progress of public health.As a new sampling/injection tool,microneedle has the potential to be widely used in a variety of POC systems because it is minimally invasive,painless,and does not even require specialized medical training.At the same time,with the development of medical technology and patients’ increasing pursuit of their own beauty,medical cosmetology has developed rapidly in recent years.Among them,microneedle products are widely used in clinical medical cosmetology as medical devices,and the scope of the indications for microneedle therapy is also very wide.Microneedle therapy is more and more welcomed by patients due to its advantages such as great efficacy and low pain during the treatment process,having an excellent development prospect.With the development of MEMS processing technology,the microneedle technology has also made great progress.Among them,minimally invasive and painless sampling/injection of microneedles are the important directions of current development.This application requires the miniaturization of the needle tube which inserts into human tissue.At the same time,not only must it have a sufficient length to effectively insert into the dermal tissue,but it must also have enough strength to overcome the skin’s viscoelasticity,which is technically difficult.Our team successfully developed an in-plane formed metal-based ultrahigh-aspect-ratio hollow microneedle before.The needle tube is slender,with minimally invasive sampling/injection functions.However,the two-layer stack structure is easy to delaminate during the insertion of the hard skin,which limits its popularization and application.Aiming at the above problems,this paper proposes a new design of a high-permeability minimally invasive sampling/injection microneedle based on cladding structure reinforcement.By constructing a cross-seal cladding structure at the junction of two stack microneedle tubes,overcoming the low strength in the joints,this paper solves the problem that the microneedle tip is easy to delaminate and crack in the hard skin.The rationality of the cladding structure was demonstrated through theoretical analysis of material mechanics and finite element simulation.Combined with the characteristics of the MEMS process,the specific cladding structure was proposed and the structural parameters was optimised.Then,following the design above,based on three-dimensional non-silicon micromachining technology,this paper puts forward a reasonable integrated manufacturing process,develops the corresponding process units,completes the process integration and a set of cladding hollow microneedle integrated manufacturing processes.On this basis,after repeated experiments,the cladding microneedle samples were fabricated after tape-out and the samples were subjected to strength testing and functional verification.The test results show that compared with traditional two-layer stack metal microneedle,the bonding strength of the cladding microneedle is increased by at least 260%,and the axial force bearing limit is increased by at least36.5%.The cladding microneedle can successfully penetrate into dehydrated pig skin with a satisfying safety factor,showing very wide applicability.In addition,in order to further improve the comprehensive performance of slender hollow microneedles and overcome the limitations of the MEMS in-plane process on the shape of the needle tube,this article further incorporates new process elements such as polymer wet etching,micromolding and chemical plating,and proposes the key process combination and full process design for realising the circular cladding and circular crosssection microneedles.Some of the key process modules were exploratory researched and developed,and the sample preparation of the near-circular cross-section microneedles was initially completed,which opens up new ideas for the integrated manufacturing of in-plane circular cross-section microneedles.