Research Roundup: Lab-on-a-Chip, Alzheimer’s Advances, Breast Cancer and More

row of test tubes with dropper depositing pink liquid

There are plenty of great scientific research stories out this week. Here’s a look at just a few of them.

A 3D-Printed All-Liquid Lab-on-a-Chip

Researchers at the Department of Energy (DOE)’s Lawrence Berkeley National Laboratory developed a 3D-printed all-liquid lab-on-a-chip. It can be reconfigured with the click of a button for a wide range of applications, from creating materials for batteries to screening drug candidates. They published their research in the journal Nature Communications.

“What we demonstrated is remarkable,” stated Brett Helms, staff scientist in Berkeley Lab’s Materials Sciences Division and Molecular Foundry, who led the study. “Our 3D-printed device can be programmed to carry out multistep, complex chemical reactions on demand. What’s even more amazing is that this versatile platform can be reconfigured to efficiently and precisely combine molecules to form very specific products, such as organic battery materials.”

They began by designing a glass substrate with a special pattern. Two liquids, one containing nanoscale clay particles, the other containing polymer particles, were printed onto the substrate. They came together at the interface of the two liquids. Within milliseconds they formed a channel or tube about 1 millimeter in diameter. Catalysts can be inserted in different channels of the chip. Then, using a 3D printer, create bridges between channels so a chemical flowing through the channels encounters catalysts in a specific order, which creates a cascade of chemical reactions.

“The form and functions of these devices are only limited by the imagination of the researcher,” Helms stated.

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3D Optical Biopsies

Scientists with Royal Melbourne Institute of Technology (RMIT) in Melbourne, Australia demonstrated that existing optical fiber technology could be used to create microscopic 3D images of tissues inside the body. This has the potential to be used as 3D optical biopsies. They published their research in the journal Science Advances.

Currently optical biopsy technology, which uses microendoscopes to look inside the body for diagnosis or during surgery, typically create 2D images. The new technique uses light field imaging to create microscopic images in stereo vision.

“Stereo vision is the natural format for human vision, where we look at an object from two different viewpoints and process these in our brains to perceive depth,” stated Antony Orth, lead author of the study and Research Fellow in the RMIT node of the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP). “We’ve shown it’s possible to do something similar with the thousands of tiny optical fibers in a microendoscope. It turns out these optical fibers naturally capture images from multiple perspectives, giving us depth perception at the microscale. Our approach can process all these microscopic images and combine the viewpoints to deliver a depth-rendered visualization of the tissue being examined—an image in three dimensions.”

A Framework for Differentiating Alzheimer’s from Other Dementias

Alzheimer’s is a form of dementia. But there are other types of dementias that are not Alzheimer’s. Researchers with the University of Kentucky and other centers developed a framework for a newly characterized type of dementia called LATE. The research was published in the journal Brain.

Nina Silverberg, director of the Alzheimer’s Disease Centers Program at National Institute on Aging (NIA), part of the National Institutes of Health (NIH), who also co-chaired the consortium, stated, “Recent research and clinical trials in Alzheimer’s disease have taught us two things: First, not all of the people we thought had Alzheimer’s have it; second, it is very important to understand the other contributors to dementia.”

The goal of the consortium was to define diagnostic criteria and other guidelines for future research into the newly-named dementia, LATE. LATE (Limbic-predominant Age-related TDP-43 Encephalopathy) usually appears in the oldest group of Alzheimer’s or dementia patients. Although it appears symptomatically very much like Alzheimer’s, what’s going on in the brain is different. It appears to progress more slowly than Alzheimer’s, but when combined with Alzheimer’s, which is common, the deterioration is faster than either disease alone.

Peter Nelson, who co-chaired the consortium, and is with the Sanders-Brown Center on Aging at the U of K, stated, “LATE probably responds to different treatments than AD, which might help explain why so many past Alzheimer’s drugs have failed in clinical trials. Now that the scientific community is on the same page about LATE, further research into the ‘how’ and ‘why’ can help us develop disease-specific drugs that target the right patients.”

Yet Another Study Suggests Microglia Are Significant in Alzheimer’s Disease

Microglia are a type of specialized immune cell found in the brain. Its job is to respond to and clear toxic proteins in the brain, such as those seen in Alzheimer’s disease. The failure of microglia to do so has implications related to neuroinflammation, aging and cellular energy production. Researchers with the Flanders Institute for Biotechnology published research in the journal Cell Reports further outlining these connections.

“We know microglia get involved in Alzheimer’s disease by switching into an activated mode,” stated Carlo Sala Frigerio, who worked in Bart De Strooper’s laboratory in Leuven. De Strooper is the senior author on the paper and Frigerio is the lead author. Frigerio is now with the UK Dementia Research Institute in London. “We were interested to know if aging in the presence or absence of amyloid beta deposition would affect this activation.”

The researchers utilized a genetic mouse model where beta-amyloid progressively accumulates. They analyzed the gene expression of more than 10,000 individual microglia cells isolated from different brain regions of the mice.

“Our data indicate that major Alzheimer risk factors, such as age, sex and genetic risk affect the complex microglia response to amyloid plaques in the brain,” De Strooper stated. “In other words, different Alzheimer’s risk factors converge on the activation response of microglia.”

How Cancer Cells Survive Treatment

Researchers with the Mayo Clinic have identified at least one way that cancer cells survive various treatment modalities. They used cell lines and patient-derived cancer cells to find how the PD-L1 cell surface protein also helps cancer cells do this. They published their research in the journal Molecular Cell.

“PD-L1 has a function inside the tumor cell that helps to make the cell resistant to chemotherapy and radiation therapy,” stated Zhenkun Lou, co-leader of the Experimental Therapeutics Program at Mayo Clinic Cancer Center and one of the senior authors. “Our data suggest that cancer cells with high levels of PD-L1 may be more resistant to standard radiation and chemotherapy.”

PD-L1 promotes repair during chemotherapy or radiation treatment. It acts as an RNA-binding protein. They took the findings further, utilizing an antibody, H1A, that blocked the internal function of PD-L1, which made the cancer cells more sensitive to treatment. They tested H1A successfully in breast cancer cells.

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