There is a lot of research work on sensor . What kind of sensor can win the favor of Nature? Su Lin, who is doing postdoctoral research at Cambridge University , may have his own opinions and experiences.
Picture | Su Lin (Source: Su Lin)
Recently, the living bioelectric sensor developed by him and his PhD team has finally been officially made public, and the related paper has been accepted by Nature.
(Source: Nature)
Synthetic biology and microbiology "combine" a sensor
According to reports, in vivo bioelectric sensors can achieve rapid bioelectric sensing detection for environmental pollutants. Previously, response signals in the field of biosensing required secondary conversion into electrical signals for program analysis and transmission, which resulted in usually long response times. In response to this limitation, this result has been optimized and broken through.
The monitoring of environmental pollution, especially the pollution monitoring of water resources, has always been a global environmental challenge faced by mankind. The release of pollutants is often dynamic and instantaneous, so real-time monitoring of possible pollutants is required.
The traditional method generally takes samples at regular intervals and then sends them back to the laboratory for testing using large instruments, which has obvious disadvantages in terms of timeliness.
At present, combining biosensing technology and synthetic biology, the academic community has developed biosensors that can be deployed in the field. However, most of the signals output by sensor monitoring are visual signals, such as color changes and luminescence.
Although some bioelectric sensors can use modified electroactive microorganisms to identify specific substances and directly output electrical signals. However, these sensors all rely on the transcriptional regulation of genes. The detection process requires the process of transcribing DNA into mRNA and then translating it into protein, so the response time is generally 30 minutes or longer.
In addition, the water body is rich in various chemical substances, and environmental conditions will change all the time, such as temperature, pH, water speed, oxygen content, etc. These often cause interference to sensor signals, resulting in reduced signal-to-noise ratio and prolonged response time.
This research combines synthetic biology, electrochemistry , material science , etc., so that the time for monitoring target pollutants is reduced to three minutes, and electrical sensing signals can be directly output.
(Source: Nature)
It mainly includes the following three breakthroughs:
First, the team constructed an artificial electron transfer pathway composed of oxidoreductases from four different organisms and spanning two different biological domains, achieving the identification of target substances, information transmission, and energy supply for the monitoring process.
Second, researchers use protein switches to control the electron transfer process. The response time is short, which is very suitable for continuous monitoring of instantaneous pollutant emissions in the environment.
Third, the research team used hydrogel materials and conductive nanoparticles to encapsulate the modified microorganisms, which not only prevents the microorganisms from escaping into the environment, but also improves the signal-to-noise ratio of the sensing signal.
It can be said that this living bioelectric sensor has application prospects in many fields, especially in environmental monitoring. Moreover, in the design of the sensing path of , the research team adopted a modular concept, so in theory, each module can be modified and designed according to specific needs.
In addition, this sensor can play a role in smart agriculture, assisting industrial waste processing and water safety, and even detecting ocean and deep sea resources.
Regarding this study, a review expert said: “In the past 20 years, In recent years, there have been a lot of precedents for using organisms as sensors (such as plants changing color in the presence of explosives, etc.), but they have the limitation that it takes a long time to generate visual or electrical signals through biological sensing. The author of this article combines synthetic biology with microbial electrochemistry to achieve sensing monitoring of the analyte. Overall, this achievement has had a profound impact on the field of analytical chemistry and will arouse widespread interest in the fields of synthetic biology and microbiology. "
Another reviewer said: "This work has greatly improved the previous bioelectric sensing system and verified the possibility of using whole cell-based biosensors for real-time monitoring. The most important thing is to avoid delays in the gene transcription process."
Recently, a related paper was titled "Real-time Bioelectronic Sensing of Environmental Pollutants" (Real-time "bioelectronic sensing of environmental contaminants" was published on Nature [1].
Figure | Related papers (Source: Nature)
Dr. Joshua T. Atkinson and Dr. Su Lin from the Department of Biological Sciences at Rice University are co-authors, Professor Jonathan J. Silberg from the Department of Bioengineering at Rice University, and Caroline M. Franklin from the Department of Biological Sciences at Rice University. Professor Ajo-Franklin serves as the co-corresponding author.
"We got a 4HT sensor"
According to reports, the earliest idea for this topic originated from the 2015 "Synthetic Biology: Engineering, Evolution & Design" conference [2].
This involves two figures: Dr. Moshe Baruch from Professor Caroline's research group, and Dr. Josh Atkinson from Professor Silberg's research group.
The last names of the two people started with B and A respectively. At that time, the speech posters of the two doctors were at the front and happened to be arranged together.
One of the research directions of Caroline's research group is the electrical signal output of microorganisms, while Silberg's research group mainly studies the function of ferredoxin and the construction of protein switches, which correspond to the signal output module and signal input module in this paper respectively.
So, Moshe and Josh hit it off after seeing each other's work, and said: "We need to get together and talk about this!"
After that, the two research groups established contact and decided to cooperate. Six months later, they received the first research grant.
Su Lin joined Caroline’s research team in the fall of 2016. At first, he took over another project.
In the summer of 2017, after Sulin’s first project was basically completed, Moshe’s postdoc position was coming to an end.
"At this time, my supervisors Caroline and Moshe asked me to participate in the topic of electrical sensing. I collaborated with Josh and others from Professor Silberg's research group. The project progress was not as smooth as expected, and Josh and I had to postpone our respective doctoral defenses." Su Lin said.
Because the sensing pathway they designed was too complex, for most of three years, the research team continued to build engineering bacteria, verify, fail, and rebuild again, and so on. The biggest challenge during
was that the sensor signal was detected several times, but after careful analysis after excitement, it was found that it was a false positive, or the design of the control group was not rigorous enough, so we had to overturn it and start again.
(Source: Nature)
In the second half of 2020, the experiment began to pick up. Josh upgraded the protein switch part, and the test results were significantly improved.
“Later, Dr. Xu Zhang joined us, which helped solve many technical difficulties and made the experiment progress more smoothly.At the end of November 2020, I sent an email to two professors and Josh. The title of the email was ‘We got a 4HT sensor’. 4HT is the abbreviation of our target pollutant (4-hydroxytamoxifen). Generally speaking, there are not many opportunities to use 'Cheers' at the end of emails, which shows the excitement at the time. "Su Lin said.
Picture | Email sent by Su Lin at the time (Source: Su Lin)
The follow-up progress of the project has become more and more smooth. In February 2021, they completed the last experiment of the core data. After that, everyone began to divide the work to write the manuscript.
Su Lin said: "The process of constantly failing and persevering is quite unforgettable, and Nature The publication cycle is too long and excruciating. "
But what's interesting is that as the project progresses, some personnel changes have occurred in a geographical sense. Su Lin continued: "In 2018, Josh received a scholarship from the US Department of Energy, which allowed him to fly from Houston to Berkeley to do experiments with us for more than half a year; in 2019, Professor Caroline received an offer from Rice University and Texas. funding, so our laboratory moved from Berkeley to Houston; in 2020, after Josh graduated, he went to and the University of Southern California as a postdoc in . He flew back during the summer vacation to continue helping with experiments, and slept on the sofa at my house for more than a month. "
During this period, Su Lin and Josh also became good partners and friends. He taught Su Lin the experiments of synthetic biology, and Su Lin taught him electrochemistry. At the same time, they were neighbors upstairs. At that time, Su Lin often went downstairs to drink with Josh with Chinese dishes, and Josh It provides Texas-style barbecue, desserts and two cute cats.
It can be seen that even though he has lived abroad for several years, Su Lin still retains authentic Chinese eating habits, and he also said: "Returning to work in China has always been one of my goals. "
picture | Su Lin (Source: Su Lin)
Su Lin was born in Yingtan, Jiangxi Province. He studied biotechnology at Nanjing Agricultural University as an undergraduate. He said: "During the summer vacation of my sophomore year, I participated in the National College Student Innovative Experimental Program (it seemed to be the first session of Nanjing Agricultural University) with my friends. The research was on the control of weeds by fungal spores, which can be regarded as my earliest scientific research experience. "After
I took the postgraduate entrance examination and went to Southeast University to study for a master's degree in biophysics. My supervisor was Professor Fu Degang. The research topic at that time was the promotion of nanomaterials on extracellular electron transfer in microorganisms.
"After graduating from the master's degree, I continued to study for a Ph.D. in Professor Fu's group, and my professional direction was biomedical engineering nano-biodevices. During his Ph.D., he received funding from the China Scholarship Council , and went to Caroline's research group at the Berkeley National Laboratory in the United States to study synthetic biology. The topic of the doctoral thesis was finally determined to be the use of synthetic biology to edit electron transport in microorganisms and its application in microbial electrical sensing. "He said.
After graduating from the Ph.D., Su Lin came to the research group of Professor Erwin Reisner of the Department of Chemistry at the University of Cambridge in the UK to study artificial photosynthesis. He mainly studied how to achieve the conversion of light energy and the reduction of carbon dioxide by constructing a biological complex of microorganisms and nanomaterials [2].
He said: "I am currently a postdoctoral researcher at the University of Cambridge, and I was lucky enough to obtain a British Three-year Early Career Fellowships offered by the Leverhulme Trust and Trinity College Cambridge Isaac Newton Trust. After this, I plan to apply for a teaching position and build my own research team. I expect to start paying attention to job postings and contact domestic employers around 2024."
Reference:
. Atkinson, J.T., Su, L., Zhang, X. et al. Real-time bioelectronic sensing of environmental contaminants. Nature 611, 548–553 (2022). https://doi.org/10.1038/s41586-022-05356-y
.RICE NEWS: Bacterial sensors send a jolt of electricity when triggered. https://news.rice.edu/news/2022/bacterial-sensors-send-jolt-electricity-when-triggered
. University of Cambridge, Lucy Cavendish College, Dr Lin Su. https://www.lucy.cam.ac.uk/fellows/dr-lin-su
