Towards real-time PGS range monitoring in proton therapy of prostate cancer.

Proton therapy of prostate cancer (PCPT) was linked with increased levels of gastrointestinal toxicity in its early use compared to intensity-modulated radiation therapy (IMRT). The higher radiation dose to the rectum by proton beams is mainly due to anatomical variations. Here, we demonstrate an approach to monitor rectal radiation exposure in PCPT based on prompt gamma spectroscopy (PGS). Endorectal balloons (ERBs) are used to stabilize prostate movement during radiotherapy. These ERBs are usually filled with water. However, other water solutions containing elements with higher atomic numbers, such as silicon, may enable the use of PGS to monitor the radiation exposure of the rectum. Protons hitting silicon atoms emit prompt gamma rays with a specific energy of 1.78 MeV, which can be used to monitor whether the ERB is being hit. In a binary approach, we search the silicon energy peaks for every irradiated prostate region. We demonstrate this technique for both single-spot irradiation and real treatment plans. Real-time feedback based on the ERB being hit column-wise is feasible and would allow clinicians to decide whether to adapt or continue treatment. This technique may be extended to other cancer types and organs at risk, such as the oesophagus.

Large Field Enhancement of Nanocoral Structures on Porous Si Synthesized from Rice Husks.

Silicon (Si) is a highly abundant, environmentally benign, and durable material and is the most popular semiconductor material; and it is used for the field enhancement of dielectric materials. Porous Si (PSi) exhibits high functionality due to its specific structure. However, the field enhancement of PSi has not been clarified sufficiently. Herein, we present the field enhancement of PSi by the fluorescence intensity enhancement of a dye molecule. The raw material used for producing PSi was rice husk, a biomass material. A nanocoral structure, consisting of spheroidal structures on the surface of PSi, was observed when PSi was subjected to chemical processes and pulsed laser melting, and it demonstrated large field enhancement with an enhancement factor (EF) of up to 545. Confocal microscopy was used for EF mapping of samples before and after laser melting, and the maps were superimposed on nanoscale scanning electron microscope images to highlight the EF effect as a function of microstructure. Nanocoral Si with high EF values were also evaluated by analyzing the porosity from gas adsorption measurements. Nanocoral Si was responsible for the high EF, according to thermodynamic calculations and agreement between experimental and calculation results as determined by Mie scattering theory.

Light-Addressable Electrochemical Sensing with Electrodeposited n-Silicon/Gold Nanoparticle Schottky Junctions.

Light-addressable electrochemical sensors (LAESs) are a class of sensors that use light to activate an electrochemical reaction on the surface of a semiconducting photoelectrode. Here, we investigate semiconductor/metal (Schottky) junctions formed between n-type Si and Au nanoparticles as light-addressable electrochemical sensors. To demonstrate this concept, we prepared n-Si/Au nanoparticle Schottky junctions by electrodeposition and characterized them using scanning electron microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. We found that the sensors behaved almost identically to Au disk electrodes for the oxidation of an outer-sphere redox couple (ferrocene methanol) and two inner-sphere redox couples (potassium ferrocyanide and dopamine). In buffered dopamine solutions, we observed broad linear ranges and submicromolar detection limits. We then used local illumination to generate a virtual array of electrochemical sensors for dopamine as a strategy for circumventing sensor fouling, which is a persistent problem for electrochemical dopamine sensors. By locally illuminating a small portion of the photoelectrode, many measurements of fouling analytes can be made on a single sensor with a single electrical connection by moving the light beam to a fresh area of the sensor. Altogether, these results pave the way for Schottky junction light-addressable electrochemical sensors to be useful for a number of interesting future applications in chemical and biological sensing.

Photoactivation of silicon rhodamines via a light-induced protonation.

Photoactivatable fluorophores are important for single-particle tracking and super-resolution microscopy. Here we present a photoactivatable fluorophore that forms a bright silicon rhodamine derivative through a light-dependent protonation. In contrast to other photoactivatable fluorophores, no caging groups are required, nor are there any undesired side-products released. Using this photoactivatable fluorophore, we create probes for HaloTag and actin for live-cell single-molecule localization microscopy and single-particle tracking experiments. The unusual mechanism of photoactivation and the fluorophore's outstanding spectroscopic properties make it a powerful tool for live-cell super-resolution microscopy.

Rapid antibacterial effect of sunlight-exposed silicon nanowire arrays modified with Au/Ag alloy nanoparticles.

The continuing emergence of antibiotic-resistant bacteria due to the excessive use of antibiotics has produced a strong demand for novel strategies and new materials that do not lead to bacterial resistance. In the present work silicon nanowire arrays modified with gold-silver alloy nanoparticles (SN-Au/Ag) was investigated as a photo-induced antibacterial material. It was shown that SN-Au/Ag can kill bacteria with high efficiency under sunlight in times of the order of a few minutes, and this is achieved through synergism between photothermal and photocatalytic effects. It appears that the combined effect of heat and reactive oxygen species (ROS) causes bacteria killing through damage to the cell membrane and leakage of cytoplasm contents. Both gold and silver in the alloy nanoparticles are required for the observed bactericidal action. Moreover, the SN-Au/Ag material can be "recycled" without loss of bactericidal activity. It is concluded that the silicon nanowire arrays modified with gold-silver alloy nanoparticles developed in this work has promise as an antibacterial nanomaterial for the development of novel antibiotics.

Performance comparison of depth-encoding detectors based on dual-ended readout and different SiPMs for high-resolution PET applications.

Silicon photomultipliers (SiPMs) are widely used in positron emission tomography (PET), however, SiPMs from different vendors vary in their performance characteristics. In addition, the specifications provided by the manufacturers are measured under different operating conditions and using different test setups, making it difficult to choose the optimal device for a specific application using the published specifications. In this work, we evaluated four state-of-the-art 8 × 8 arrays of ~3 × 3 mm2 SiPMs from SensL, KETEK, and Hamamatsu for high-resolution dual-ended readout detectors using the same experimental setup and procedures. The results showed that all four SiPM arrays are excellent candidates for high-resolution PET applications, although some interesting differences in performance were noted.

Near-Infrared Silicon Photonic Crystals with High-Order Photonic Bandgaps for High-Sensitivity Chemical Analysis of Water-Ethanol Mixtures.

Aqueous solutions of alcohols are used in several applications, from pharmaceutics and biology, to chemical, biofuel, and food industries. Nonetheless, development of a simple, inexpensive, and portable sensing device for the quantification of water in water-ethanol mixtures remains a significant challenge. Photonic crystals (PhCs) operating at very high-order photonic bandgaps (PBGs) offer remarkable opportunities for the realization of chemical sensors with high sensitivity and low detection limit. However, high-order PhC structures have been mostly confined to mere theoretical speculations so far, their effective realization requiring microfabrication tools enabling the control of periodic refractive index modulations at the submicrometric scale with extremely high accuracy and precision. Here, we report both experimental and theoretical results on high-sensitivity chemical analysis using vertical, silicon/air 1D-PhCs with spatial period of 10 and 20 µm (namely, over 10 times the operation wavelength) featuring ultra-high-order PBGs in the near-infrared region (namely, up to 50th at 1.1 µm). Fabrication of high-order 1D-PhCs was carried out by electrochemical micromachining (ECM) of silicon, which allowed both surface roughness and deviation from vertical of etched structures to be controlled below 5 nm and 0.1%, respectively. Optical characterization of ECM-fabricated 1D-PhCs, which was performed by acquiring reflectivity spectra over the wavelength range 1-1.7 µm, highlighted the presence of ultra-high-order PBGs with minor optical losses (i.e., <1 dB in reflectivity) separated by deep reflectivity notches with high Q-factors (i.e., >6000), in good agreement with theoretical calculations. Remarkably, the use of high-order 1D-PhCs as refractometric transducers for the quantitative detection of traces of water in water-ethanol mixtures, allowed high sensitivity (namely, either 1000 nm/RIU or ∼0.4 nm/% of water), good detection limit (namely, 5 × 10-3 RIU or ∼10% water), and excellent resolution (namely, either 6 × 10-4 RIU or 1.6% of water) to be reliably achieved on a detection volume of about 168 fL.

DNA-Hybridization Detection on Si(100) Surfaces Using Light-Activated Electrochemistry: A Comparative Study between Bovine Serum Albumin and Hexaethylene Glycol as Antifouling Layers.

Light can be used to spatially resolve electrochemical measurements on a semiconductor electrode. This phenomenon has been explored to detect DNA hybridization with light-addressable potentiometric sensors and, more recently, with light-addressable amperometric sensors based on organic-monolayer-protected Si(100). Here, a contribution to the field is presented by comparing sensing performances when bovine serum albumin (BSA) and hexaethylene glycol (OEG6) are employed as antifouling layers that resist nonspecific adsorption to the DNA-modified interface on Si(100) devices. What is observed is that both sensors based on BSA or OEG6 initially allow electrochemical distinction among complementary, noncomplementary, and mismatched DNA targets. However, only surfaces based on OEG6 can sustain electroactivity over time. Our results suggest that this relates to accelerated SiO x formation occasioned by BSA proteins adsorbing on monolayer-protected Si(100) surfaces. Therefore, DNA biosensors were analytically explored on low-doped Si(100) electrodes modified on the molecular level with OEG6 as an antifouling layer. First, light-activated electrochemical responses were recorded over a range of complementary DNA target concentrations. A linear semilog relation was obtained from 1.0 × 10-11 to 1.0 × 10-6 mol L-1 with a correlation coefficient of 0.942. Then, measurements with three independent surfaces indicated a relative standard deviation of 4.5%. Finally, selectivity tests were successfully performed in complex samples consisting of a cocktail mixture of four different DNA sequences. Together, these results indicate that reliable and stable light-activated amperometric DNA sensors can be achieved on Si(100) by employing OEG6 as an antifouling layer.

Engineering an in vitro organotypic model for studying cardiac hypertrophy.

Neonatal cardiomyocytes cultured on flat surfaces are commonly used as a model to study cardiac failure of diverse origin. A major drawback of such a system is that the cardiomyocytes do not exhibit alignment, organization and calcium transients, similar to the native heart. Therefore, there is a need to develop in vitro platforms that recapitulate the cellular microenvironment of the murine heart as organotypic models to study cardiovascular diseases. In this study, we report an engineered platform that mimics cardiac cell organization and function of the heart. For this purpose, microscale ridges were fabricated on silicon using ultraviolet lithography and reactive ion etching techniques. Physical characterization of the microstructures was done using scanning electron microscopy and atomic force microscopy. Cardiomyocytes grown on these micro-ridges showed global parallel alignment and elliptical nuclear morphology as observed in the heart. Interestingly, calcium currents traversed the engineered cardiomyocytes in a coordinated and directional manner. Moreover, the cardiomyocytes on the engineered substrates were found to be responsive to hypertrophic stimuli, as observed by the expression of a fetal gene, atrial natriuretic peptide and increase in calcium transients upon agonist treatment. Taken together, our work demonstrates that micro-ridges can be used to obtain cardiomyocyte response in vitro, which closely resembles mammalian heart.

Photonic ring resonance is a versatile platform for performing multiplex immunoassays in real time.

Photonic ring resonance is a property of light where in certain circumstances specific wavelengths are trapped in a ring resonator. Sensors based on silicon photonic ring resonators function by detecting the interaction between light circulating inside the sensor and matter deposited on the sensor surface. Binding of biological material results in a localized change in refractive index on the sensor surface, which affects the circulating optical field extending beyond the sensor boundary. That is, the resonant wavelength will change when the refractive index of the medium around the ring resonator changes. Ring resonators can be fabricated onto small silicon chips, allowing development of a miniature multiplex array of ring based biosensors. This paper describes the properties of such a system when responding to the refractive index changed in a simple and precise way by changing the ionic strength of the surrounding media, and in a more useful way by the binding of macromolecules to the surface above the resonators. Specifically, a capture immunoassay is described that measures the change of resonant wavelength as a patient serum sample with anti-SS-A autoantibodies is flowed over a chip spotted with SS-A antigen and amplified with anti-IgG. The technology has been miniaturized and etched into a 4×6mm silicon chip that can measure 32 different reactions in quadruplicate simultaneously. The variability between 128 rings on a chip as measured by 2M salt assays averaged 0.6% CV. The output of the assays is the average shift per cluster of 4 rings, and the assays averaged 0.5% CV between clusters. The variability between chips averaged 1.8%. Running the same array on multiple instruments showed that after some improvements to the wavelength referencing system, the upper boundary of variation was 3% between 13 different instruments. The immunoassay displayed about 2% higher variability than the salt assays. There are several outstanding features of this system. The amount of antigen used on the chip for each test is around 200 picograms, only a few microliters of sample is necessary, and the assays take <10min.

Porous Silicon's Photoactivity in Water: Insights into Environmental Fate.

Interest in porous silicon (pSi) (and, more broadly, silicon nanoparticles (NPs)) has increased along with their concomitant use in various commercial and consumer products, yet little is known about their behavior in the natural environment. In this study, we have investigated the photosensitization, optical, and surface properties of pSi as a function of time in aqueous systems. Samples were prepared via an anodic electrochemical etching procedure, resulting in pSi particles with diameters of ca. 500 nm, composed of a porous network of Si nanocrystallites of 2-4 nm. Initially, pSi particles generated significant amounts of (1)O2, yet they rapidly lost much of this ability due to the formation of an oxide layer on the surface, as determined by X-ray photoelectron spectroscopy, which likely prevented further photosensitization events. Addition of natural organic matter (NOM) did not significantly impact pSi's photosensitization abilities. The pSi lacked any intrinsic bactericidal properties on Escherichia coli and did not produce enough (1)O2 to considerably affect populations of a model virus, PR772, highlighting its relatively benign nature toward microbial communities. Results from this study suggest that the photoactivity of pSi is unlikely to persist in aqueous systems and that it may instead behave more similarly to silica particles from an environmental perspective.

Selective Area Modification of Silicon Surface Wettability by Pulsed UV Laser Irradiation in Liquid Environment.

The wettability of silicon (Si) is one of the important parameters in the technology of surface functionalization of this material and fabrication of biosensing devices. We report on a protocol of using KrF and ArF lasers irradiating Si (001) samples immersed in a liquid environment with low number of pulses and operating at moderately low pulse fluences to induce Si wettability modification. Wafers immersed for up to 4 hr in a 0.01% H2O2/H2O solution did not show measurable change in their initial contact angle (CA) ~75°. However, the 500-pulse KrF and ArF lasers irradiation of such wafers in a microchamber filled with 0.01% H2O2/H2O solution at 250 and 65 mJ/cm(2), respectively, has decreased the CA to near 15°, indicating the formation of a superhydrophilic surface. The formation of OH-terminated Si (001), with no measurable change of the wafer's surface morphology, has been confirmed by X-ray photoelectron spectroscopy and atomic force microscopy measurements. The selective area irradiated samples were then immersed in a biotin-conjugated fluorescein-stained nanospheres solution for 2 hr, resulting in a successful immobilization of the nanospheres in the non-irradiated area. This illustrates the potential of the method for selective area biofunctionalization and fabrication of advanced Si-based biosensing architectures. We also describe a similar protocol of irradiation of wafers immersed in methanol (CH3OH) using ArF laser operating at pulse fluence of 65 mJ/cm(2) and in situ formation of a strongly hydrophobic surface of Si (001) with the CA of 103°. The XPS results indicate ArF laser induced formation of Si-(OCH3)x compounds responsible for the observed hydrophobicity. However, no such compounds were found by XPS on the Si surface irradiated by KrF laser in methanol, demonstrating the inability of the KrF laser to photodissociate methanol and create -OCH3 radicals.

Simultaneous isolation and detection of circulating tumor cells with a microfluidic silicon-nanowire-array integrated with magnetic upconversion nanoprobes.

The development of sensitive and convenient methods for detection, enrichment, and analysis of circulating tumor cells (CTCs), which serve as an importance diagnostic indicator for metastatic progression of cancer, has received tremendous attention in recent years. In this work, a new approach characteristic of simultaneous CTC capture and detection is developed by integrating a microfluidic silicon nanowire (SiNW) array with multifunctional magnetic upconversion nanoparticles (MUNPs). The MUNPs were conjugated with anti-EpCAM antibody, thus capable to specifically recognize tumor cells in the blood samples and pull them down under an external magnetic field. The capture efficiency of CTCs was further improved by the integration with a microfluidic SiNW array. Due to the autofluorescence free nature in upconversion luminescence (UCL) imaging, our approach allows for highly sensitive detection of small numbers of tumor cells, which afterward could be collected for further analysis and re-culturing. We have further demonstrated that this approach can be applied to detect CTCs in clinical blood samples from lung cancer patients, and obtained consistent results by analyzing the UCL signals and the clinical outcomes of lung cancer metastasis. Therefore our approach represents a promising platform in CTC capture and detection with potential clinical utilization in cancer diagnosis and prognosis.

Programming cell fate on bio-functionalized silicon.

Controlling the growth of cells on the surface of silicon without an additive layer or topographical modification is unexplored. This research article delineates the discovery of unique properties of a bio-functionalized silicon substrate, programmed to repel or control cells, generated by ultrafast femtosecond pulse interaction with silicon. Remarkably, bio-functionalization in any shape or size without change in topology or morphology is observed indicating only sub-surface phase transformations. Material characterization reveals the presence of a unique mixture of phases of SiO2 and Si. Consequently, these variations in phase alter the physicochemical characteristics on the surface of silicon resulting in its bio-functionalization. The culture of mouse embryonic fibroblasts shows unique adhesion characteristics on these bio-functionalized silicon surfaces that include cell controlling, cell trapping, and cell shaping. Furthermore, the directionality of fibroblasts is restrained parallel to bio-functionalized zones as evidenced by changes in cytoskeleton. The controlling of proliferation, migration and adhesion of cells is attributed to unique phase bio-functionalization. This method presents considerable promise in a myriad of applications such as tissue engineering, MEMS, and lab-on-a-chip devices.

Comparative study of membranes induced by PMMA or silicone in rats, and influence of external radiotherapy.

The induced membrane technique has been used for long bone defect reconstruction after traumatism. One of the major drawbacks of this method is the difficult removal of the polymethyl methacrylate spacer after membrane formation. We therefore replaced the stiff PMMA spacer with a semi-flexible medical grade silicone spacer. This study aimed to compare subcutaneously formed membranes, induced by PMMA and silicone, in the irradiated or not irradiated areas within 28 rats that received the spacers. Histological analysis was performed to evaluate the composition of the membrane and to quantify the amount of vessels. Histomorphometric measurements were used to evaluate membranes' thickness, while fibrosis and inflammation were scored. The expression of VEGF and BMP-2 in lysates of the crushed membranes was determined by Western blotting. ALP expression was analyzed in HBMSC cultures in contact with the same lysates. Non-irradiated membranes induced by the two spacer types were non-inflammatory, fibrous and organized in layers. Irradiation did not change the macroscopic properties of membranes that were induced by silicone, while PMMA induced membranes were sensitive to the radiotherapy, resulting in thicker, strongly inflammatory membranes. Irradiated membranes showed an overall reduced osteogenic potential. Medical grade silicone is safe for the use in radiotherapy and might therefore be of great advantage for patients in need of cancer treatment.

Highly fluorescent, photostable, and ultrasmall silicon drug nanocarriers for long-term tumor cell tracking and in-vivo cancer therapy.

Silicon nanoparticle (SiNP) nanocarriers feature strong fluorescence, ultrasmall size, robust photostability, and tunable drug-loading capacity. Using SiNP nanocarriers, the first example of long-term cancer cell tracking is successfully demonstrated. Furthermore, in vivo experiments show that tumor-bearing mice treated with SiNP nanocarriers survive over 20 d without observable tumor growth, demonstrating the high-efficacy chemotherapy of the Si nanocarriers.

Further studies on the role of dopants in LiF:Mg,Cu,Si thermoluminescent material.

The 3-D thermoluminescence spectra and glow curves of LiF:Mg,Cu,Si, LiF:Mg,Cu, LiF:Mg,Si and LiF:Cu,Si with low concentrations of Mg and Cu were measured and were compared with those with high concentrations to investigate further the role of dopants in LiF:Mg,Cu,Si material. The shape of glow curves of the four samples is similar; however, LiF:Cu,Si sample had no Mg dopant. It is concluded that the TL emission to be from self-trapped excitons in LiF, and this emission could be enhanced and altered by Mg, Cu and Si dopants in LiF:Mg,Cu,Si; all three dopants are necessary to obtain the bright TL emission and may be involved in the luminescence process; Mg seems to be the most essential dopant and Cu is involved in the trapping although the role of Mg dominates; both Cu and Si play a role in the main emission process and Cu also plays a role in reducing the emission around 610 nm.

Polarization-dependent elliptical crater morphologies formed on a silicon surface by single-shot femtosecond laser ablation.

Formation of the elliptical-shaped craters on a silicon surface is investigated comprehensively using a single shot of a femtosecond laser. It is observed that the ablation craters are elongated along the major axis of the polarization direction, while their orientation is parallel to the polarization direction. The ablation area grows and the morphology of the craters evolves from an ellipse to nearly a circle with increasing fluence. The underlying physical mechanism is revealed through numerical simulations that are based on the finite-difference time-domain technique. It is suggested that the initially formed craters or surface defects lead to the redistribution of the electric field on the silicon surface, which plays a crucial role in the creation of the elliptical-shaped craters. In addition, the field intensity becomes enhanced along the incident laser polarization direction, which determines the elliptical crater orientations.

Silicon nanowire photocathodes for light-driven electroenzymatic synthesis.

The photoelectroenzymatic synthesis of chemical compounds employing platinum nanoparticle-decorated silicon nanowires (Pt-SiNWs) is presented. The Pt-SiNWs proved to be an efficient material for photoelectrochemical cofactor regeneration because the silicon nanowires absorbs a wide range of the solar spectrum while the platinum nanoparticle serve as an excellent catalyst for electron and proton transfer. By integrating the platform with redox enzymatic reaction, visible-light-driven electroenzymatic synthesis of L-glutamate was achieved. Compared to electrochemical and photochemical methods, this approach is free from side reactions caused by sacrificial electron donors and has the advantage of applying low potential to realize energy-efficient and sustainable synthesis of chemicals by a photoelectroenzymatic system.