Fiber-sensor alignment based on surface microstructures.

Conventional methods have relied on specialized imaging equipment and advanced fabrication process to solve the problem of accurately aligning a microsensor to an optical fiber which is critical for its detection efficiency. To dramatically lower the barrier to high-precision alignment, we present a technique much easier to implement and much lower in cost. By fabricating replicable alignment and proximity structures on the surface of the sensor chip, we can achieve accurate alignment and position the fiber tip very close to the sensor without damaging it. We introduce an easy setup to examine the alignment result and demonstrate accurate alignment of dummy sensors as small as 5µm×5µm. We use our alignment method to realize efficient input coupling for a superconducting transition-edge sensor as an example of fruitful adoption in many possible applications.

Aligning Superconducting Transition-Edge Sensors by Reflected Wave Intensity Measurement.

It is critical to accurately align a quantum photon detector such as a superconducting transition-edge sensor (TES) to an optical fiber in order to optimize its detection efficiency. Conventionally, such alignment requires advanced infrared imaging equipment or sophisticated microfabrication. We introduce a novel technique based on the simple idea of reflected wave intensity measurement which allows to determine the boundary of the sensor and align it accurately with the fiber. By routing a light wave through an optical fiber for normal incidence on the surface of the sensor chip, and separating the reflected wave coupled back into the fiber from the input signal with a circulator, we can observe the variation in the reflected wave intensity when the beam spot of the fiber crosses the boundary between the sensor and substrate that have different reflectivity, and adjust the position of the fiber such that its output falls on the sensor. We evaluate quantitatively the precision of our alignment method, as well as the conditions that must be met to avoid photon loss caused by light beam divergence. After demonstrating the working principle of our scheme and verifying the alignment result experimentally, we employ it for efficient input signal coupling to a TES device, which is used for photon-number-resolving measurement to showcase the successful application of our alignment method in practice. Relying on only ordinary and widely used optical elements that are easy to operate and low in cost, our solution is much less demanding than conventional methods. Dramatically easier to implement and not restricted by the detection mechanism of the sensor, it is accessible to a much broader community.

ACY-1215 accelerates vemurafenib induced cell death of BRAF-mutant melanoma cells via induction of ER stress and inhibition of ERK activation.

BRAFV600E mutation is found in ~50% of melanoma patients and BRAFV600E kinase activity inhibitor, vemurafenib, has achieved a remarkable clinical response rate. However, most patients treated with vemurafenib eventually develop resistance. Overcoming primary and secondary resistance to selective BRAF inhibitors remains one of the most critically compelling challenges for these patients. HDAC6 has been shown to confer resistance to chemotherapy in several types of cancer. Few studies focused on the role of HDAC6 in vemurafenib resistance. Here we showed that overexpression of HDAC6 confers resistance to vemurafenib in BRAF-mutant A375 cells. ACY-1215, a selective HDAC6 inhibitor, inhibits the proliferation and induces the apoptosis of A375 cells. Moreover, ACY-1215 sensitizes A375 cells to vemurafenib induced cell proliferation inhibition and apoptosis induction, which occur partly through induction of endoplasmic reticulum (ER) stress and inactivation of extracellular signal-regulated kinase (ERK). Taken together, our results suggest that the inhibition of HDAC6 may be a promising strategy for the treatment of melanoma and overcoming resistance to vemurafenib.