Exploring Diamond Nanoneedle Arrays: Fabrication and Emerging Applications in Biomedical Engineering

Diamond nanomaterials have attracted significant interest in recent years due to their unique physical and chemical properties. Their exceptional mechanical strength, chemical stability, biocompatibility, and high thermal conductivity make them ideal candidates for a wide range of biomedical applications. Various formats, including nanodiamonds, diamond nanofilms, and diamond nanoneedle arrays (DNNAs), have been fabricated and used, exhibiting remarkable stability and low cytotoxicity. In particular, high-aspect-ratio and high-density DNNAs demonstrate promising potential for live cell manipulation and analysis because of their unique combination of mechanical robustness, chemical stability, and well-forged bio–nanointerfaces. On the other hand, the chemical stability of diamond material makes fabrication and functionalization challenging, which could be improved for their wider adoption. Recent research efforts have focused on the development and optimization of diamond nanoneedle fabrication techniques, aiming to achieve precise control over the geometry and array layout, as well as enhancing their functionalization for targeted drug delivery, cellular manipulation, and biosensing applications. One notable breakthrough in this area is the successful synthesis of well-ordered DNNAs through innovative fabrication processes, such as combining top-down and bottom-up approaches. These efforts have led to significant improvements in the uniformity, reproducibility, and scalability of the resulting nanoneedle structures. Leveraging their unique structure, diamond nanoneedle arrays have become a novel and versatile platform for a variety of biomedical applications. Through chemical modifications and biological functionalization of their surfaces, DNNAs offer a distinct biointerface capable of penetrating cell interiors and profiling intracellular molecules without compromising cell integrity. Furthermore, the nanoscale distribution of these nanoneedles enables DNNAs to gather heterogeneous information from biological samples with spatial resolution. Consequently, DNNAs have been effectively utilized in diverse areas, ranging from targeted drug delivery to highly sensitive and selective biosensing. In this talk, we introduce our continuous efforts on utilizing bias-assisted plasma etching for the fabrication of high-aspect-ratio DNNA, which was subsequently functionalized and integrated as a generally applicable platform technology for various biomedical applications. The summary starts by elucidating the working principles of DNNA fabrication with bias-assisted plasma etching, followed by showcasing numerous biomedical applications. Specifically, we demonstrate the outstanding performance of DNNAs in live cell manipulation, especially for highly efficient intracellular delivery across multiple cell types, high-throughput intracellular molecular tracking in living cells, and spatiotemporal transcriptomic mapping in disease models. In the concluding section, we summarize unresolved challenges and discuss future potential applications facilitated by DNNAs. We emphasize the importance of continued research and innovation in this area to further unlock the transformative potential of DNNAs in biomedical engineering and beyond.

Diamond nanoneedle arrays for high-throughput intracellular delivery

It is of great importance to introduce foreign materials and molecules into living cells in both cell biology research and gene and cell therapy. The major barrier of intracellular delivery is to cross the cell membrane. To overcome this, a wide variety of biological, chemical and physical approaches have been developed. Here, I present our work of utilizing diamond nanoneedle arrays to facilitate efficient and high-throughput intracellular delivery of fluorescence probes, drugs, nanoparticles and genes. Particularly, this technology has been demonstrated to be able to achieve extremely high transfection efficiency in neurons (~ 45% versus ~ 1-5% of commercial transfection approach). Beyond applications, the biological effects of this technology have also been studied. It is expected that this technique will be very useful in basic cell biology research and also a range of clinical applications.