Dozens of pharmaceutical companies and research institutions have already ordered our fused quartz three-dimensional microreaction chips, and have achieved transformative pharmaceutical capabilities and chemical production capabilities within the chips. Professor Cheng Ya from East China Normal University believes that this microreaction chip and reactor will be widely used in the fields of biomedicine, as well as high added value fine chemicals.

Recently, he and his team created a fused quartz microreaction chip. Regarding the relevant paper, the review experts said that the use of this microchannel chip with three-dimensional internal components will make a significant contribution to the field of microfluidics and chemical synthesis.

In the efficient synthesis of drugs, ultraviolet photochemistry will play a key role.

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Specifically: Cheng Ya's research group used lasers to manufacture the fused quartz microreaction chips, and designed a unique three-dimensional mixing unit, proving that it has excellent photochemical reaction effects.

At the same time, he and his team conducted simulation and experimental diagnosis for the three-dimensional microchannels, and found that the three-dimensional internal components they created can improve the absorption efficiency of deep ultraviolet photons while achieving efficient mixing.Traditional deep ultraviolet (UV) photochemical synthesis equipment, such as those based on quartz reactors or quartz glass tubes, has inherent flaws and bottlenecks in aspects such as thermal management, safe scaling, and photon utilization efficiency. The results of this study have largely addressed the aforementioned issues.

Combining the advantages of low cost and high efficiency of deep ultraviolet light-emitting diode (LED) light sources, it is expected to further promote the industrial application of deep ultraviolet photochemical continuous flow synthesis.

Cheng Ya said, "At present, we have only taken a small step, choosing the application scenario of continuous flow photochemical synthesis of vitamin D3 to demonstrate the potential of this new chip."

In fact, high-performance three-dimensional microreaction chips and related manufacturing processes can also be used for high-throughput drug screening, high-throughput nanomaterial synthesis, organ-on-chip construction, in vitro point-of-care testing in the biomedical field, efficient photochemical synthesis in the micro-chemical engineering field, and advanced packaging in the integrated circuit and optoelectronic fields.

For current photochemical synthesis in the visible light band, expensive catalysts are generally required for assistance. Deep ultraviolet microreactors are very promising in avoiding the use of such catalysts, and can directly utilize high-energy ultraviolet photons to break chemical bonds, thereby facilitating the required chemical reactions.Interestingly, recently scholars from Italy and the United States jointly published an article in the "Perspectives" column of the journal Nature Chemistry, and they also put forward similar views.

This article points out that ultraviolet (UV) photochemistry plays a key role in the development of new efficient synthetic methods.

It also emphasizes that a deep understanding of the processes and mechanisms of UV-driven chemical synthesis is crucial for the transition from UV to visible light photochemical synthesis.

Once created a high-performance three-dimensional micro-reaction chip based on quartz glass substrates.

The origin of this study can be traced back more than twenty years ago when Cheng Yagang obtained a doctoral degree from the Shanghai Institute of Optics and Fine Mechanics, Chinese Academy of Sciences.He said: "My doctoral supervisor is the renowned laser scientist Academician Xu Zhizhan, so during my doctoral stage, I entered the field of femtosecond laser interaction with matter, which was very new at that time. And at that time, there were very few people engaged in femtosecond laser technology and physical research worldwide."

In 2001, Dr. Koji Sugioka of the team at the Institute for Molecular Science in Japan, drawing on the idea of American scientists to create three-dimensional microstructures in transparent glass, hoped to implement three-dimensional micro-reaction channel structures in glass for use in miniaturized chemical and biological analysis.

However, at that time, Sugioka was mainly engaged in traditional laser micro-nano manufacturing, and the laser he used was mainly a nanosecond laser in the ultraviolet band.

Therefore, Sugioka invited Cheng Ya to join the research team led by him at the Institute for Molecular Science in Japan, to carry out collaborative research and development using Cheng Ya's research results in femtosecond laser physics.

In 2003, they initially achieved the controllable preparation of three-dimensional glass micro-channels, and Cheng Ya published a paper as the first author [1].However, for femtosecond laser internal micro-machining, the main technical bottleneck lies in the inability to achieve large-sized microreaction chips, hence it cannot be promoted to large-scale industrial applications.

There are mainly two factors:

First, due to the limitation of the optical diffraction limit, it is impossible to achieve high-precision focusing in materials with a relatively large thickness;

Second, due to the defects of the laser direct writing technology, the preparation efficiency is usually too low, which leads to the cost cannot be reduced.In 2006, Cheng Ya returned to his homeland to take up a position and began to address the aforementioned two issues. In 2009, he came up with a method called "Spatiotemporal Focused Laser Shaping."

"I consider this to be an especially ingenious approach, and combined with the new high-speed direct writing scheme for internal carving that my team and I independently proposed, in 2012 we demonstrated the world's first high-performance three-dimensional microreaction chip based on quartz glass substrate," he stated. Since then, the research group has started to delve deeply into this field and initiated this study.

"Astronomical Scale"

According to the introduction, the purpose of this study is to provide high-performance microreaction chips and microreactors for continuous flow photochemical reactions, especially for continuous flow photochemical reactions in the ultraviolet light band.For drugs and drug intermediates such as Vitamin D3 and progesterone, they hold significant market value and are considered high-value pharmaceuticals.

In terms of the efficient, clean, low-carbon, and safe production of these drugs, continuous flow photochemical reactions under ultraviolet light offer an irreplaceable advantage, and they also have broad application prospects in fields such as fine chemicals, energy storage, and biomedicine.

However, the energy of ultraviolet photons is high, which can severely damage the material's properties. The ultraviolet rays in sunlight can cause skin cancer in humans, which is based on the same principle.

Therefore, many glass materials that appear transparent under visible light will become opaque under ultraviolet light due to the absorption of ultraviolet rays.

For current commercial microchannel photochemical reactors, the materials commonly used are borosilicate glass, which has an extremely low transmission rate for deep ultraviolet light below 300nm.It is precisely for this reason that the light source working bands of photochemical microreactors in the current market are all confined to the visible light band.

This leads to the fact that even on a global market scale, it is difficult to find high-performance, low-cost ultraviolet photochemical microreaction chips.

Ultraviolet fused quartz, which has high transparency in the 200-3500nm band, is the most ideal substrate for deep ultraviolet photochemical reactors to date.

However, due to the limitations of traditional processing technology capabilities, there is currently no quartz-based microchannel reaction chip that has been widely accepted by the market.

In this study, they took vitamin D3 as the research object, and fully investigated the market size of vitamin D3, the current main synthetic methods, and the prominent issues in industrial production.Further, they investigated the current status and development trends of light sources for deep ultraviolet photochemistry.

After these investigations, the research team basically confirmed this fact: when combining a fused quartz three-dimensional microchannel reactor with a deep ultraviolet light-emitting diode light source, there are certain advantages in the deep ultraviolet photochemical synthesis of vitamin D3.

Subsequently, the research team selected methods such as pressurization and heating, and adopted a one-step ultraviolet photochemical synthesis method, successfully producing vitamin D3. They also constructed a controllable temperature, pressurizable deep ultraviolet photochemical micro-reactor system based on the three-dimensional microchannel reactor.

With multiple measures in parallel, they ensured the stability and continuous production of deep ultraviolet photochemical reactions, and the prepared synthetic products also have a higher yield, better efficacy, and higher raw material conversion rate.

(From: Light: Advanced Manufacturing)During this period, the first author of this paper, PhD student Zhang Aodong, demonstrated a focus on work and a passion for scientific research, said Cheng Ya.

The chip in question is actually a cross-scale material manufacturing achievement, spanning from micron-level processing precision to a chip size in the order of 10 centimeters, with each dimension spanning about five orders of magnitude.

Therefore, from the perspective of the entire three-dimensional space, the number of focal spot units contained in this chip is roughly 10 to the 15th power, which is a scale akin to an astronomical number.

"And the final number of defects in the chip is almost zero, which is a huge achievement in manufacturing technology and process, and also a reflection of Zhang Aodong's outstanding ability," said Cheng Ya.

Professor Xu Jian, who served as the co-corresponding author of this paper, was Cheng Ya's first student at the Institute of Optics and Mechanics of the Chinese Academy of Sciences at that time."Xu Jian's characteristic is to be serious in doing things and to consider problems comprehensively," said Cheng Ya.

He continued, "Professor Hu Ming is another corresponding author, who is an expert in the field of chemical materials. This study involves a lot of research on chemical reactions, including the reaction mechanism, reaction conditions, and product analysis, etc., Professor Hu Ming has played a key role in it."

Finally, the related paper was published in Light: Advanced Manufacturing[2] with the title "Efficient synthesis of vitamin D3 in a 3D ultraviolet photochemical microreactor fabricated using an ultrafast laser."

Zhang Aodong is the first author, Cheng Ya, Xu Jian, and Hu Ming are the corresponding authors.

In response to the needs of the actual industry, the follow-up work of this study has already started, and some important progress has been made.

Note: The original text contains a few errors and inconsistencies, such as the lack of punctuation and the use of "共同通讯作者" which is not a standard term in English. I have made some adjustments to the translation for clarity and correctness.At the same time, they hope to continue to enhance the production capacity of individual reaction equipment, which requires further improving reaction efficiency, increasing the degree of equipment integration, and reducing the volume of the reactor.

In addition, the research team is also carrying out the integrated integration of temperature control and online detection modules, and will explore new deep ultraviolet photochemical reaction systems with partners.

Cheng Ya added: "The application of AI technology to continuous flow photochemical reactions is also very much worth looking forward to. This helps to open up a brand new paradigm for fully automatic photochemical synthesis, and our transparent chips can also play a huge advantage."

In the thin transparent chips, a large amount of reaction information can be easily obtained through optical methods, and it is real-time and fully visible.

At the same time, the development of AI technology requires the support of data, which can be obtained by shooting the reaction process or analyzing real-time spectra.In response to this, they have also begun related explorations. For instance, they have integrated an online spectroscopic detection module on a microreaction chip, which can provide feedback signals online through high spatial and temporal resolution spectroscopy.

This enables the optimization of reaction conditions, thereby laying the foundation for the realization of fully automatic AI-assisted chemical synthesis. "Currently, we are working with scientists in the field of AI to advance this, and we welcome everyone to pay attention to our new progress," said Cheng Ya.