A new tool called “µSCALE” will allow researchers to quickly test millions of mutated proteins in a matter of days. Stanford Engineers have created this tool to accelerate the protein evolution process. To that end, µSCALE allows researchers to efficiently test millions of mutated proteins in just a few days.

Capillaries in µSCALE slide can house yeast, bacteria and other microbes. Image courtesy of Stanford University.

The “SCALE” in µSCALE stands for Single Cell Analysis and Laser Extraction. As the name suggests, a focused laser is used to extract a sample within a single capillary on the slide. The µ stands for the micro-capillary glass slide, which can hold millions of protein samples created by yeast, bacteria or other microbes.

This tool has the potential to speed up the search for new medicines, industrial enzymes, and biosensors.

How µSCALE Uses Lasers and Micro-Capillaries to Isolate a Single Sample

The stages of the µSCALE process. Image courtesy of Stanford University.

The first step in the µSCALE process is to prepare your sample. To prepare the samples researchers must conduct mutagenisis. This process creates random variations of a gene, which are then taken and inserted into groups of yeast or bacteria. The microbes then express the mutated gene and create millions of random protein variants.

Next, researchers mix millions of tiny and opaque glass beads into the microbe samples. This mixture is then spread onto the micro-capillary slide. The slide features a million capillary tubes arranged like straws so that they are open on the top as well as the bottom.

Extremely small amounts of fluid enter the capillary tubes while carrying the individual cells. However, the surface tension within the capillary prevents the cell and liquid from escaping. At this point, the samples are ready for the µSCALE.

The slide is now inserted into the µSCALE device. A software controlled microscope is used to look into each capillary and take pictures. When a biochemical reaction occurs inside the capillary, the microscope takes pictures of the reaction.

These images are then studied to find what the researchers call “capillaries of interest.” A laser is directed at each capillary, one at a time, to remove the contents without disrupting the surrounding capillaries.

The next step is to analyze the contents of the capillary cell by spreading them onto a collector plate. The DNA of the isolated cell will then be sequenced, which allows for the gene variant connected to the protein of interest to be identified.

What Benefits does µSCALE bring to the Biotech Industry?

DNA mutations can generate new and more effective proteins for human consumption, medical advances and fermentations. In fact, one of the driving forces behind µSCALE is the need for scientists and engineers to better understand how to create protein variants designed for a specific use.

µSCALE works by allowing researchers to test millions of variants of a certain mutated protein and choose the best one for a certain task. Ultimately, this allows the researcher to determine the DNA sequence that produces that variant quickly and efficiently.

This will help engineers and researchers to find cures for certain diseases and more efficient fermentation processes in the future. Are you working on an engineering project that could benefit from this technology? Comment below.