A Single Drop of Blood Can Reveal Stress Hormones

A Rutgers-led team of researchers has developed a microchip that can measure stress hormones in real time from a drop of blood.

Cortisol and other stress hormones regulate many aspects of our physical and mental health, including sleep quality. High levels of cortisol can result in poor sleep, which increases stress that can contribute to panic attacks, heart attacks and other ailments.

Currently, measuring cortisol takes costly and cumbersome laboratory setups, so the Rutgers-led team looked for a way to monitor its natural fluctuations in daily life and provide patients with feedback that allows them to receive the right treatment at the right time.

The researchers used the same technologies used to fabricate computer chips to build sensors thinner than a human hair that can detect biomolecules at low levels. They validated the miniaturized device’s performance on 65 blood samples from patients with rheumatoid arthritis.

The use of nanosensors allowed us to detect cortisol molecules directly without the need for any other molecules or particles to act as labels,” said lead author Reza Mahmoodi, a postdoctoral scholar in the Department of Electrical and Computer Engineering at Rutgers University-New Brunswick.

With technologies like the team’s new microchip, patients can monitor their hormone levels and better manage chronic inflammation, stress and other conditions at a lower cost, said senior author Mehdi Javanmard, an associate professor in RutgersDepartment of Electrical and Computer Engineering.

Our new sensor produces an accurate and reliable response that allows a continuous readout of cortisol levels for real-time analysis,” he added. “It has great potential to be adapted to non-invasive cortisol measurement in other fluids such as saliva and urine. The fact that molecular labels are not required eliminates the need for large bulky instruments like optical microscopes and plate readers, making the readout instrumentation something you can measure ultimately in a small pocket-sized box or even fit onto a wristband one day.”

The study included Rutgers co-author Pengfei Xie, a Ph.D. student, and researchers from the University of Minnesota and University of Pennsylvania. The research was funded by the DARPA ElectRX program.

The study appears in the journal Science Advances.

Source: https://www.rutgers.edu/

DNA Nanorobots Target Breast Cancer Cells

According to the Mayo Clinic, about 20% of breast cancers make abnormally high levels of a protein called human epidermal growth factor receptor 2 (HER2). When displayed on the surface of cancer cells, this signaling protein helps them proliferate uncontrollably and is linked with a poor prognosis. Now, researchers have developed a DNA nanorobot that recognizes HER2 on breast cancer cells, targeting them for destruction.

Current therapies for HER2-positive breast cancer include monoclonal antibodies, such as trastuzumab, that bind to HER2 on cells and direct it to the lysosome — an organelle that degrades biomolecules. Lowering the levels of HER2 slows cancer cell proliferation and triggers cell death. Although monoclonal antibodies can lead to the death of cancer cells, they have severe side effects and are difficult and expensive to produce. In a previous study, Yunfeng Lin and colleagues identified a short sequence of DNA, called an aptamer, that recognizes and binds HER2, targeting it for lysosomal degradation in much the same way that monoclonal antibodies do. But the aptamer wasn’t very stable in serum. So the researchers wanted to see if adding a DNA nanostructure, called a tetrahedral framework nucleic acid (tFNA), could increase the aptamer‘s biostability and anti-cancer activity.


To find out, the team designed DNA nanorobots consisting of the tFNA with an attached HER2 aptamer. When injected into mice, the nanorobots persisted in the bloodstream more than twice as long as the free aptamer. Next, the researchers added nanorobots to three breast cancer cell lines in petri dishes, showing that they killed only the HER2-positive cell line. The addition of the tFNA allowed more of the aptamer to bind to HER2 than without tFNA, leading to reduced HER2 levels on cell surfaces. Although the nanorobot is much easier and less expensive to make than monoclonal antibodies, it likely needs further improvement before it could be used to treat breast cancer in the clinic, the researchers say.

The findings are published  in the ACS journal Nano Letters.

Source: https://www.eurekalert.org/

How To Measure The NanoWorld

A worldwide study involving 20 laboratories has established and standardized a method to measure exact distances within individual biomolecules, down to the scale of one millionth of the width of a human hair. The new method represents a major improvement of a technology called single-molecule FRET (Förster Resonance Energy Transfer), in which the movement and interaction of fluorescently labelled molecules can be monitored in real time even in living cells. So far, the technology has mainly been used to report changes in relative distances – for instance, whether the molecules moved closer together or farther apart. Prof. Dr. Thorsten Hugel of the Institute of Physical Chemistry (University of Freiburg) in Germany is one of the lead scientists of the study, which was recently published in Nature MethodsFRET works similarly to proximity sensors in cars: the closer the object is, the louder or more frequent the beeps become. Instead of relying on acoustics, FRET is based on proximity-dependent changes in the fluorescent light emitted from two dyes and is detected by sensitive microscopes. The technology has revolutionised the analysis of the movement and interactions of biomolecules in living cells.

Hugel and colleagues envisioned that once a FRET standard had been established, unknown distances could be determined with high confidence. By working together, the 20 laboratories involved in the study refined the method in such a way that scientists using different microscopes and analysis software obtained the same distances, even in the sub-nanometer range.

The absolute distance information that can be acquired with this method now enables us to accurately assign conformations in dynamic biomolecules, or even to determine their structures”, says Thorsten Hugel, who headed the study together with Dr. Tim Craggs (University of Sheffield/Great-Britain), Prof. Dr. Claus Seidel (University of Düsseldorf) and Prof. Dr. Jens Michaelis (University of Ulm). Such dynamic structural information will yield a better understanding of the molecular machines and processes that are the basis of life.

Source: https://www.pr.uni-freiburg.de/