Template demoulding: let HeLa cells sit at the top of the pyramid
the cell membrane is a barrier to prevent extracellular substances from entering the cells freely, which ensures the relative stability of the intracellular environment of Xi Zhongwang in the field of new energy vehicles, so that various biochemical reactions can operate in an orderly manner. Due to the barrier of cell membrane, many drugs or DNA drugs cannot reach the interior of cells directly, so the carrier is very important for scientific research and disease treatment. Therefore, successive researchers have developed various ways to deceive or force the cell membrane to open to drugs. The core of this study is an effective drug carrier without side effects
now, researchers from Harvard School of engineering and applications have invented a new method to use goldmicrostructures to input various molecular reasons into cells. It has realized the efficient delivery of functional molecular drugs to millions of cells in a short time, which will completely change the current situation of high-throughput screening research in gene therapy, drug development and viral disease treatment
Nabihasaklayen, a PhD graduate student in Mazur laboratory and the first author of this article, said that at present, there is no drug delivery system that can efficiently deliver a variety of macromolecular drugs to cells at one time. Intracellular transportation systems need to be efficient, cost-effective, safe, and scalable, and at the same time, they need to be able to specifically recognize cells. This is a huge challenge for any research communityin previous studies, saklayen and her colleagues found that gold particles with pyramid structure are good at focusing laser energy and converting it into electromagnetic hotspots. The research team used the preparation method of "templatestripping" to make the surface of 10million tiny pyramids (about 14 × 14 mm)
m another PhD graduate student in Azur laboratory who works hard to restore your economy. The co-author of this article, marinnamadrid, said that the beauty of this manufacturing process is that its operation process is very simple. Template demoulding allows you to reuse silicon templates indefinitely. The preparation time of the whole substrate is less than 1 minute, and the shape of each substrate is completely consistent. This is not common in the preparation of nano materials
the research team directly cultivated HeLa cells at the top of the pyramid, surrounded the cells with a solution containing drug molecules, and heated the pyramid with a nanosecond laser until the hot spot temperature at the tip of the pyramid instantly reached about 300 ℃. This very small local heating will not damage the cells, but will only form some tiny bubbles at the top of the pyramid. These bubbles gently enter the cell membrane, while opening a small hole in the cell membrane, so that the surrounding molecules spread into the cell. The time for the formation of these pores is very short, and the cells will repair themselves, and experimental observations show that they can continue to survive healthily for many days
each HeLa cell sits on the top of more than 50 pyramids, which means that about 50 tiny holes can be made on the cell surface. By controlling laser parameters, not only the size of bubbles can be controlled, but also the infiltration surface of cells can be artificially selected. The compound molecules with molecular weight ranging from 0.6 to 2000kda were tested. Through flow cytometry analysis, the delivery efficiency was up to 95%, the cell survival rate was up to 98%, and the molecules delivered to the cells (including proteins and antibodies) were basically the same size. The cell throughput of this technology has reached 50000 cells/minute, and it can be further expanded as needed. And it has high cost-effectiveness: a large-area lithography substrate can deliver foreign substances to millions of cells, and the application of nanosecond laser reduces the cost and difficulty of using this equipment
the next step of the research team is to test different types of cells, including blood cells, stem cells and T cells. Clinically, this technology can be used for in vitro treatment, taking unhealthy cells out of the body, giving therapeutic drugs (such as drug compounds or DNA), and then injecting them back into the body
this is a very flexible platform. VOCs can be controlled quantitatively from the design. The Technology Development Office of Harvard University has submitted a patent application and is considering commercialization opportunities
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