Processing accuracy is 14nm, Chinese scientists use spider silk to 3D print nano “fish”

Shanghai Institute of Microsystems, Chinese Academy of Sciences and Shanghai
transportation
The 3D nanorobot jointly developed by the university is expected to play a huge potential in the fields of intelligent bionic sensing and drug delivery.
3D printing materials are an important material basis for the development of 3D printing technology. To a certain extent, the development of materials determines whether 3D printing can be more widely used. Mankind uses materials (including natural and synthetic materials) through modern technology to find new technological opportunities. Many new opportunities and discoveries are essentially rooted in manufacturing innovation. 3D manufacturing has been intensively researched in the past two decades.

With the coordinated progress of material development, many applications have greatly benefited from the high-resolution manufacturing of micro/nano-scale 3D structures and devices, such as microfluidics, refractive/diffractive optics, photonics, and mechanical metamaterials. However, when features become smaller, especially when they reach deep nanometer scales (ie, <100 nm), the challenges of 3D manufacturing technology become more prominent, and resolution, structural stability, and shape accuracy are key factors.For cell scaffolds and therapeutic micro/nano robots, etc.
biology
medicine
In terms of application, it is necessary to systematically evaluate the biocompatibility, physicochemical stability, and ease of functionalization of 3D manufacturing structures.

Recently, the Tao Hu team of the Shanghai Institute of Microsystems, Chinese Academy of Sciences, in cooperation with Xia Xiaoxia and Qian Zhigang of Shanghai Jiaotong University, used genetically recombined spider silk protein to 3D print a nanorobot with a processing accuracy of 14 nanometers. Relevant research results were published in the internationally renowned academic journal “Nature · Communication”.
Specifically, the research team innovated and developed genetically recombined spider silk protein photoresist. By optimizing the recombined spider silk gene fragment and molecular weight, combined with large-scale electron-based
simulation
Simulation, real-time control of acceleration voltage to regulate the penetration depth, stay position and energy absorption peak of electrons in silk protein photoresist, realizing the direct writing of true three-dimensional nano-functional devices with molecular level precision. The processing precision of this technology can reach 14nm, which is close to the single molecule size of natural silk protein (~10nm), which is an order of magnitude higher than the previous technology.

This technology is expected to be used in fields such as intelligent bionic perception and drug delivery nanorobots. Tao Hu said, “14 nanometers is equivalent to the size of a single molecule of spider silk protein, and it has reached the limit of precision.”

Paper address:
https://www.nature.com/articles/s41467-021-25470-1

Among them, the spider silk protein required for 3D printing is a strong and reproducible gene sequence extracted from natural spider silk by researchers, and then placed in E. coli for cultivation. In addition, researchers use electron beams for three-dimensional lithography to further improve processing accuracy. Compared with the traditional electron beam lithography, high voltage (tens of kV) and thin glue (tens of nanometers) are used to ensure the collimation and resolution of lithography. This research focuses on low voltage (several kV) and thick glue (several microns). Get started.

Because it has to swim in blood and other environments, the nanorobot is designed to be in the shape of a fish, which can swim in the human blood sugar environment. When the environment reaches the set pH and other conditions, it can automatically degrade and release the drug.

Through genetic engineering recombination of spider silk protein, arbitrary high-resolution and high-strength three-dimensional structures can be created on the nanoscale. By using high-energy electrons at different depths of the 3D protein matrix to quantify the ability to define structural transformations, polymorphic spider silk proteins can be brought close to the molecular level. In addition, the genetic or mesoscopic modification of spider silk protein provides opportunities to embed and stabilize physicochemical and biological functions in the prepared three-dimensional nanostructures. The method used in the research can quickly and flexibly manufacture heterogeneous functional and layered 3D nano-components and nano-devices, providing opportunities for bionics, therapeutic devices and nano-robots.

Regarding this research, netizens can’t help but sigh: Science fiction is gradually becoming a reality.

Technical interpretation

Experimental setup and manufacturing capabilities

Electron beam lithography (EBL) is known for providing deep nanometer-scale processing resolution. Currently, a major limitation of EBL technologies is that they are not capable of performing arbitrary 3D nanofabrication. Among them, resolution, structural integrity and functionality are the most important factors.

The key to achieving 3D EBL at the deep nanometer scale is to develop a cross-link that can not only be cross-linked at different controllable depths by electron beams, but also has excellent mechanical strength and maintains good structural integrity at the nanometer size. Suitable material.

In this work, the researchers modified the commercial EBL tool-Hitachi S-4800 scanning electron microscope, so that the acceleration voltage can be adaptively adjusted according to different structural geometries during exposure (usually 0.5