Precision cancer medicine has changed the treatment landscape of non-small cell lung cancer (NSCLC) as illustrated by the introduction of tyrosine kinase inhibitors (TKIs) towards mutated epidermal growth factor receptor (EGFR). However, as responses to EGFR-TKIs are heterogenous among NSCLC patients, there is a need for ways to early monitor changes in treatment response in a non-invasive way e.g., in patient's blood samples. Recently, extracellular vesicles (EVs) have been identified as a source of tumor biomarkers which could improve on non-invasive liquid biopsy-based diagnosis of cancer. However, the heterogeneity in EVs is high. Putative biomarker candidates may be hidden in the differential expression of membrane proteins in a subset of EVs hard to identify using bulk techniques. Using a fluorescence-based approach, we demonstrate that a single-EV tech-nique can detect alterations in EV surface protein profiles. We analyzed EVs isolated from an EGFR-mutant NSCLC cell line, which is refractory to EGFR-TKIs erlotinib and responsive to osimertinib, before and after treatment with these drugs and after cisplatin chemotherapy. We studied expression level of five proteins; two tetraspanins (CD9, CD81), and three markers of interest in lung cancer (EGFR, programmed death-ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2)). The data reveal alterations induced by the osimertinib treatment compared to the other two treatments. These include the growth of the PD-L1/HER2-positive EV population, with the largest increase in vesicles exclusively expressing one of the two proteins. The expression level per EV decreased for these markers. On the other hand, both the TKIs had a similar effect on the EGFR-positive EV population.

A microfabricated biosensor based on the streaming current method is presented in this work. The microfabricated sensor consists of a silicon microchannel, which is enclosed with a glass capping to form a closed microchannel. The depth of the microchannel is approximately 10 µm in width and length varying from 50 to 100 µm. The silicon is etched using deep reactive ion etching (DRIE) to form a microchannel. For the capping of the channel, a glass wafer of type Borofloat is used and anodically bonded to the silicon wafer to form a closed microchannel. The microchannel is then functionalized to be specific to certain biomarkers which can be a potential biomarker for cancer, for example. The method used for detection is called the streaming current method. In this method, fluid is flown through the microchannel with high pressure close to six bars. The surface of the silicon is oxidized, which has a zeta potential of approximately 2.7. Depending on the type of fluid the charge concentration varies. By having a pressure in the channel, the charges get distributed as an anode and cathode at the inlet and outlet electrodes of the microfluidic channels. At a fixed potential, a streaming current is observed, which is proportional to the charge accumulated. The difference between the streaming current with and without the biomarker is correlated to the concentration. Hence, a biosensor based on the streaming current method can be realized, which could be used for potential cancer biomarker detection.

A concept of transparent “quantum dot glass”(TQDG) is proposed for a combination of a quantum dot(QD)-based glass luminescent solar concentrator (LSC) and itsedge-attached solar cells, as a type of transparent photovoltaics(TPVs) for building-integrated photovoltaics (BIPVs). Differentfrom conventional LSCs, which typically serve as pure opticaldevices, TQDGs have to fulfill requirements as both powergeneratingcomponents and building construction materials. In thiswork, we demonstrate large-area (400 cm2) TQDGs based onsilicon QDs in a triplex glass configuration. An overall powerconversion efficiency (PCE) of 1.57% was obtained with back-reflection for a transparent TQDG (average visible transmittance of84% with a color rendering index of 88 and a low haze ≤3%), contributing to a light utilization efficiency (LUE) of 1.3%, which isamong the top reported TPVs based on the LSC technology with similar size. Most importantly, these TQDGs are shown to havebetter thermal and sound insulation properties compared to normal float glass, as well as improved mechanical performance andsafety, which significantly pushes the TPV technology toward practical building integration. TQDGs simultaneously exhibit favorablephotovoltaic, aesthetic, and building envelope characteristics and can serve as a multifunctional material for the realization of nearlyzero-energy building concepts.

Large-sized 2D semiconductor materials have gained significant attention for their fascinat-ing properties in various applications. In this work, we demonstrate the fabrication of nanoperforated ultrathin β-Ga2 O3 membranes of a nanoscale thickness. The technological route includes the fabrication of GaN membranes using the Surface Charge Lithography (SCL) approach and subsequent thermal treatment in air at 900◦ C in order to obtain β-Ga2 O3 membranes. The as-grown GaN membranes were discovered to be completely transformed into β-Ga2 O3, with the morphology evolving from a smooth topography to a nanoperforated surface consisting of nanograin structures. The oxidation mechanism of the membrane was investigated under different annealing conditions followed by XPS, AFM, Raman and TEM analyses. 

An electrical immuno-sandwich assay utilizing an electrokinetic-based streaming current method for signal transduction is proposed. The method records the changes in streaming current, first when a target molecule binds to the capture probes immobilized on the inner surface of a silica micro-capillary, and then when the detection probes interact with the bound target molecules on the surface. The difference in signals in these two steps constitute the response of the assay, which offers better target selectivity and a linear concentration dependent response for a target concentration within the range 0.2-100 nM. The proof of concept is demonstrated by detecting different concentrations of Immunoglobulin G (IgG) in both phosphate buffered saline (PBS) and spiked in E. coli cell lysate. A superior target specificity for the sandwich assay compared to the corresponding direct assay is demonstrated along with a limit of detection of 90 pM in PBS. The prospect of improving the detection sensitivity was theoretically analysed, which indicated that the charge contrast between the target and the detection probe plays a crucial role in determining the signal. This aspect was then experimentally validated by modulating the zeta potential of the detection probe by conjugating negatively charged DNA oligonucleotides. The length of the conjugated DNA was varied from 5 to 30 nucleotides, altering the zeta potential of the detection probe from -9.3 +/- 0.8 mV to -20.1 +/- 0.9 mV. The measurements showed a clear and consistent enhancement of detection signal as a function of DNA lengths. The results presented here conclusively demonstrate the role of electric charge in detection sensitivity as well as the prospect for further improvement. The study therefore is a step forward in developing highly selective and sensitive electrokinetic assays for possible application in clinical investigations.

We present an approach to improve the detection sensitivity of a streaming current-based biosensor for membrane protein profiling of small extracellular vesicles (sEVs). The experimental approach, supported by theoretical investigation, exploits electrostatic charge contrast between the sensor surface and target analytes to enhance the detection sensitivity. We first demonstrate the feasibility of the approach using different chemical functionalization schemes to modulate the zeta potential of the sensor surface in a range -16.0 to -32.8 mV. Thereafter, we examine the sensitivity of the sensor surface across this range of zeta potential to determine the optimal functionalization scheme. The limit of detection (LOD) varied by 2 orders of magnitude across this range, reaching a value of 4.9 x 10(6) particles/mL for the best performing surface for CD9. We then used the optimized surface to profile CD9, EGFR, and PD-L1 surface proteins of sEVs derived from non-small cell lung cancer (NSCLC) cell-line H1975, before and after treatment with EGFR tyrosine kinase inhibitors, as well as sEVs derived from pleural effusion fluid of NSCLC adenocarcinoma patients. Our results show the feasibility to monitor CD9, EGFR, and PD-L1 expression on the sEV surface, illustrating a good prospect of the method for clinical application.

As a cost-effective batch synthesis method, Si quantum dots (QDs) with nearinfrared photoluminescence, high quantum yield (>50% in polymer nanocomposite), and nearunity internal quantum efficiency were fabricated from an inexpensive commercial precursor (triethoxysilane, TES), using optimized annealing and etching processes. The optical properties of such QDs are similar to those prepared from state-of-the-art precursors (hydrogen silsesquioxane, HSQ) yet featuring an order of magnitude lower cost. To understand the effect of synthesis parameters on QD optical properties, we conducted a thorough comparison study between common solid precursors: TES, HSQ, and silicon monoxide (SiO), including chemical, structural, and optical characterizations. We found that the structural nonuniformity and abundance of oxide inherent to SiO limited the resultant QD performance, while for TES-derived QDs this drawback can be avoided. The presented low-cost synthetic approach would significantly favor applications requiring high loading of good-quality Si QDs, such as light conversion for photovoltaics.

Being a key player in intercellular communications, nanoscale extracellular vesicles (EVs) offer unique opportunities for both diagnostics and therapeutics. However, their cellular origin and functional identity remain elusive due to the high heterogeneity in their molecular and physical features. Here, for the first time, multiple EV parameters involving membrane protein composition, size and mechanical properties on single small EVs (sEVs) are simultaneously studied by combined fluorescence and atomic force microscopy. Furthermore, their correlation and heterogeneity in different cellular sources are investigated. The study, performed on sEVs derived from human embryonic kidney 293, cord blood mesenchymal stromal and human acute monocytic leukemia cell lines, identifies both common and cell line-specific sEV subpopulations bearing distinct distributions of the common tetraspanins (CD9, CD63, and CD81) and biophysical properties. Although the tetraspanin abundances of individual sEVs are independent of their sizes, the expression levels of CD9 and CD63 are strongly correlated. A sEV population co-expressing all the three tetraspanins in relatively high abundance, however, having average diameters of <100 nm and relatively low Young moduli, is also found in all cell lines. Such a multiparametric approach is expected to provide new insights regarding EV biology and functions, potentially deciphering unsolved questions in this field.