University of Minnesota Twin Cities

Researchers have constructed a robot that uses machine learning to fully automate a complicated microinjection process used in genetic research. University of Minnesota Twin Cities researchers have constructed a robot that uses machine learning to fully automate a complicated microinjection process used in genetic research. In their experiments, the researchers were able to use this automated robot to manipulate the genetics of multicellular organisms, including fruit fly and zebrafish embryos. The technology will save labs time and money while enabling them to more easily conduct new, large-scale genetic experiments that were not possible previously using manual techniques The research is featured on the cover of the April 2024 issue of GENETICS, a peer-reviewed, open access, scientific journal. The work was co-led by two University of Minnesota mechanical engineering graduate students Andrew Alegria and Amey Joshi. The team is also working to commercialize this technology to make it widely available through the University of Minnesota start-up company, Objective Biotechnology. Microinjection is a method for introducing cells, genetic material, or other agents directly into embryos, cells, or tissues using a very fine pipette. The researchers have trained the robot to detect embryos that are one-hundredth the size of a grain of rice. After detection, the machine can calculate a path and automate the process of the injections. "This new process is more robust and reproducible than manual injections," said Suhasa Kodandaramaiah, a University of Minnesota mechanical engineering associate professor and senior author of the study. "With this model, individual laboratories will be able to think of new experiments that you couldn't do without this type of technology." Typically, this type of research requires highly skilled technicians to perform the microinjection, which many laboratories do not have. This new technology could expand the ability to perform large experiments in labs, while reducing time and costs. "This is very exciting for the world of genetics. Writing and reading DNA have drastically improved in recent years, but having this technology will increase our ability to perform large-scale genetic experiments in a wide range of organisms," said Daryl Gohl, a co-author of the study, the group leader of the University of Minnesota Genomics Center's Innovation Lab and research assistant professor in the Department of Genetics, Cell Biology, and Development. Not only can this technology be used in genetic experiments, but it can also help to preserve endangered species through cryopreservation, a preservation technique conducted at ultra-low temperatures. "You can use this robot to inject nanoparticles into cells and tissues that helps in cryopreservation and in the process of rewarming afterwards," Kodandaramaiah explained. Other team members highlighted other applications for the technology that could have even more impact. "We hope that this technology could eventually be used for in vitro fertilization, where you could detect those eggs on the microscale level," said Andrew Alegria, co-lead author on the paper and University of Minnesota mechanical engineering graduate research assistant in the Biosensing and Biorobotics Lab.

Researchers show that non-invasive brain stimulation can change a specific brain mechanism that is directly related to human behavior. For the first time, researchers at the University of Minnesota Twin Cities showed that non-invasive brain stimulation can change a specific brain mechanism that is directly related to human behavior. This is a major step forward for discovering new therapies to treat brain disorders such as schizophrenia, depression, Alzheimer's disease, and Parkinson's disease. The study was recently published in Nature Communications, a peer-reviewed, open access, scientific journal. Researchers used what is called "transcranial alternating current stimulation" to modulate brain activity. This technique is also known as neuromodulation. By applying a small electrical current to the brain, the timing of when brain cells are active is shifted. This modulation of neural timing is related to neuroplasticity, which is a change in the connections between brain cells that is needed for human behavior, learning, and cognition. "Previous research showed that brain activity was time-locked to stimulation. What we found in this new study is that this relationship slowly changed and the brain adapted over time as we added in external stimulation," said Alexander Opitz, University of Minnesota biomedical engineering associate professor. "This showed brain activity shifting in a way we didn't expect." This result is called "neural phase precession." This is when the brain activity gradually changes over time in relation to a repeating pattern, like an external event or in this case non-invasive stimulation. In this research, all three investigated methods (computational models, humans, and animals) showed that the external stimulation could shift brain activity over time. "The timing of this repeating pattern has a direct impact on brain processes, for example, how we navigate space, learn, and remember," Opitz said. The discovery of this new technique shows how the brain adapts to external stimulation. This technique can increase or decrease brain activity, but is most powerful when it targets specific brain functions that affect behaviors. This way, long-term memory as well as learning can be improved. The long-term goal is to use this technique in the treatment of psychiatric and neurological disorders. Opitz hopes that this discovery will help bring improved knowledge and technology to clinical applications, which could lead to more personalized therapies for schizophrenia, depression, Alzheimer's disease, and Parkinson's disease. In addition to Opitz, the research team included co-first authors Miles Wischnewski and Harry Tran. Other team members from the University of Minnesota Biomedical Engineering Department include Zhihe Zhao, Zachary Haigh, Nipun Perera, Ivan Alekseichuk, Sina Shirinpour and Jonna Rotteveel. This study was in collaboration with Dr. Jan Zimmermann, associate professor in the University of Minnesota Medical School. This work was supported primarily by the National Institute of Health (NIH) along with the Behavior and Brain Research Foundation and the University of Minnesota's Minnesota's Discovery, Research, and InnoVation Economy (MnDRIVE) Initiative. Computational resources were provided by the Minnesota Supercomputing Institute (MSI).

Researchers may have discovered a mechanical explanation for instability observed in the lungs in cases of acute respiratory distress syndrome (ARDS), particularly in the aftermath of respiratory illnesses such as COVID-19 or pneumonia. Researchers at the University of Minnesota Twin Cities may have discovered a mechanical explanation for instability observed in the lungs in cases of acute respiratory distress syndrome (ARDS), particularly in the aftermath of respiratory illnesses such as COVID-19 or pneumonia. The research was recently published in the Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences. Currently, there is no known cure for ARDS, a life-threatening lung injury that allows fluid to leak into the lungs. The researchers in this study say that as many as two thirds of all patients that passed away from COVID-19 had ARDS. There is not a clear reason on why specific people with a severe respiratory illness may develop ARDS, while others may not, but researchers in this study were looking to find that answer. They identified the concentration of a lysolipid -- a byproduct of the immune response to viruses and bacteria -- that can have a major impact in adults suffering from ARDS. Increased concentration of this chemical eliminates the surfactant, a complex composed of fats and proteins generated in the lungs. The result is uneven lung inflation and, ultimately, respiratory distress in adults. "This study looked into the correlation of the concentration of the lysolipid in the lungs. Once that fluid reached a certain level, it started to cause severe impacts," said University of Minnesota Department of Chemical Engineering and Materials Science Professor Joseph Zasadzinski and lead professor on the research. "Your average everyday person usually won't need to think about this, but if a virus or infection is bothering your lung surfactant system and you end up in the hospital, then it could become top of mind very quickly," Zasadzinski added There are a natural amount of these lysolipids that exist in the human body, and as long as those stay below a specific concentration, the average person can breathe normally. When someone has a bad infection, those lysolipids increase, which can lead to respiratory distress. Once a patient is headed in that direction, there are not many ways of reversing those symptoms. "This research shows frequency dependence, or how quickly you open and close the lungs. This could help doctors try to tailor the treatment process for each specific patient," said Clara Ciutara, a 2023 Ph.D. chemical engineering and materials science graduate and first author of the study. Previous research of neonatal respiratory distress syndrome (NRDS) in premature infants found that it could be treated by introducing replacement lung surfactant, but that was not the case in adults. It is the amount of lysolipid that determines the outcome of the surfactant in the lungs, not the breakdown of the existing lung surfactant. The next step in the research will be to translate these ideas into a clinical environment and test to see if they can manipulate specific molecules to make them less active or stick to a specific place. This could help drop the concentration of the lysolipids to a threshold that may be able to reverse symptoms of ARDS and put people on the road to recovery. In addition to Zasadzinski and Ciutara, the research team included University of Minnesota Department of Chemical Engineering and Materials Science NIH postdoctoral fellow Steven V. Iasella, undergraduate student Boxun Huang, and former postdoctoral associate Sourav Barman. This work is supported by a grant from National Institutes of Health (NIH) Heart, Lung, and Blood Institute. All microscopy images were obtained at the University Imaging Center at the University of Minnesota.