A detection platform that can taste 17 kinds of water pollutants in minutes. The "taste buds" of this platform come from bacteria.

Can water quality detection be as quick, convenient, and accurate as pregnancy detection?

Recently, a new technology developed by researchers at Northwestern University in the United States was published in Nature Biotechnology. This technology uses a handheld platform to detect 17 different pollutants in water, including toxic metals, pharmaceuticals, cosmetics, and cleaning products, in just a few minutes. 17 different pollutants When the detected pollutants exceed the standards published by the United States Environmental Protection Agency (EPA), it emits a green light. It emits a green light when pollutants exceed EPA standards.

Qi Hao, a professor at the School of Chemical Engineering, Tianjin University, introduced that this seemingly convenient and simple new technology relies on the tremendous improvement in human ability to transform nature. This new technology is based on cell-free synthetic biology technology. Through engineered design, it manipulates more than 100 biomolecules to work together to achieve the goal of wastewater monitoring.

Breaking cell membranes, designing cells more conveniently

" This pollutant detection ' test strip ' is very interesting. It seems to be used in the same way as a ' pregnancy test ' stick, but it completely surpasses the biochemical system of traditional test strips, and its preparation method is much more complex than traditional test strips. ” Qi Hao explained that the research team used molecular machines from bacterial cells. They used bacteria as "taste buds" to detect small molecules in water. "taste buds" ” removed from cells and then redesigned and recombined them. These reprogrammed "taste buds" ” become storage-resistant after freeze-drying and can be made " test strip ” convenient to use.

" This technology mainly utilizes cell-free synthetic biology. Synthetic biology technology mainly uses cells as a chassis for engineering design. However, engineering design of cells is time-consuming and difficult. ” Qi Hao introduced that due to the complexity of living cell systems, the difficulty in standardizing gene elements, and the obstacles of cell membranes, the growth and adaptability processes of cells are usually inconsistent with engineering design goals, producing a large number of ineffective products, which greatly limits the modification of biological components.

" If we want to use artificial design to achieve more artificial purposes, we must break free from the constraints of cells. Cell-free synthetic biology uses cell resources, breaks cell membranes, and extracts molecular components including DNA 、 RNA and proteins from cells, and then reprogram them to perform new tasks. That is, gene transcription, protein translation, and metabolic processes are achieved in an in vitro open system. ” Qi Hao explained that a cell is like a computer. The motherboard, sound card, graphics card, and other components in the computer each have their own uses. After understanding the use of each component, we can disassemble the computer, decompose the various components, and use the functions of each component according to our own purposes to process and transform to produce more products.

" Cell-free synthetic biology is a more microscopic technology that enters the interior of cells and carries out engineering modifications at the molecular level to achieve our set goals. ” Qi Hao introduced that this transformation project is a huge system. For example, this pollutant monitoring technology uses high-sensitivity RNA polymerase, allosteric protein transcription factors, and synthetic DNA transcription templates are combined to regulate the activation of fluorescence RNA The synthesis of aptamers makes the presence of pollutants induce the transcription of these aptamers, thus leading to the generation of fluorescence signals.

Rapid development and wide range of research fields

" When people can freely use various molecular machines in cells, they have already made a big step forward compared to technologies that can only utilize entire cells. ” Qi Hao introduced that as early as the 20 century 50 era, researchers had already discovered the core mechanism of cell protein synthesis, and found that the cytoplasm obtained after breaking the cell membrane also has the ability of protein synthesis. Since then, researchers have begun to conduct research on protein synthesis, establishing preparation methods and basic experimental steps.

However, the transformative potential of cell-free gene expression is subject to various limitations, including low and variable protein synthesis yields, short reaction durations, and small reaction scales. However, in the past 20 years, synthetic biology researchers have gradually overcome the limitations of the potential of cell-free gene expression, and new breakthroughs have been made in laboratory research, leading to higher efficiency and a wider range of applications. In addition to using microorganisms, plant and mammalian cells are also used to cultivate cells, and many eukaryotic cell systems have also been developed. At the same time, the amount of protein synthesis is also increasing with the development of preparation technology.

" The research field of cell-free synthetic biology is very broad, and the cell-free protein expression system is one of its main research directions. ” Qi Hao introduced that this pollutant monitoring uses this system to extract small molecule-level " "taste buds" ” from E. coli and design them into an expression system targeting a specific protein. The green fluorescence that appears is also achieved by expressing a fluorescent protein.

" Thousands of different sequences can also be used DNA to form various different nanostructures, which also belongs to the field of cell-free synthetic biology technology; in metabolic engineering, various metabolic enzymes can be purified through cell-free synthetic biology technology and placed in a system. Through different biochemical reaction environments, these proteins cooperate to complete a complex metabolic process of chemical substances. ” Qi Hao introduced.

" In addition, an important area of research in cell-free synthetic biology is to go beyond nature and create things that do not exist in nature. ” Qi Hao explained that we know that proteins are synthesized from 20 types of natural amino acids, while cell-free synthetic biology can artificially synthesize new amino acids. For example, the technique of DNA origami, through artificial design DNA molecular sequences, can be DNA folded into letters, two-dimensional, three-dimensional, and any other structures. This origami technique cannot be achieved within cells, but with cell-free synthetic biology, substances that have never existed in nature can be created.

Broad Prospects, but Still a Distance from Real Application

" Although cell-free synthetic biology has developed rapidly in recent years and has broad application prospects, before this pollutant monitoring project released by Northwestern University in the United States, it was more often used as a research tool. ” Qi Hao introduced that laboratories and pharmaceutical companies use cell-free synthetic biology to synthesize protein expression tools, which is quick and easy. Because before this technology, to obtain a protein, separation and purification were needed, which took a long time. With this technology, researchers can obtain the protein they want to study in a short period of time, so it is often used as a technology for screening and developing biological drugs.

" Using similar technology, high-sensitivity virus detection has been achieved, which is more sensitive than nucleic acid detection and has higher accuracy. It has been used to produce detection reagents for Zika virus. In fact, protein drugs, vaccines, and detection antibodies are all protein-based drugs, and they can all be generated using the protein expression system of cell-free synthetic biology. ” Qi Hao said that these are currently considered cutting-edge technologies, but they are still in the process of transformation.

" In addition, cell-free synthetic technology is easier to implement in engineering design. By separating and purifying biological materials, biochemical reagents can be generated. Without the constraints of cells, these reagents are easier to match with existing automated equipment, and therefore easier to achieve large-scale production in the laboratory. ” Qi Hao gave an example, saying that synthesizing proteins using synthetic biology takes two or three days, while using cell-free technology, it can be completed in one or two hours, which allows for better control of protein yield and standardization.

" Using cell-free synthetic biology to synthesize amino acids can also better expand the functions of proteins. For example, for some enzymes, when we put artificially synthesized amino acids into the core of the enzyme, the activity of the enzyme can be increased by hundreds or thousands of times. ” Qi Hao continued, using DNA origami technology, similar biomolecular robots can be made. These nanometer-scale robots can perform controllable operations on other molecules. For example, DNA folded into a box, and anticancer drugs are placed in the box. When the box encounters cancer cells, it will release the anticancer drugs. These have expanded the range of human intervention in nature.

" To better utilize and control this technology, humans need to have a deeper understanding of the characteristics of each molecule in the cell. Although cell-free synthetic biology is widely studied in laboratories, it is still a long way from being truly applied in people's lives. ” Qi Hao predicts that in the future, cell-free synthetic biology may be first applied to the pharmaceutical research and development field, and detection products may undergo faster technological transformation.

(Source: Science and Technology Daily)