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Diatomaceous earth, or diatomite, is produced through the accumulation of diatom (Bacillariophyceae) skeletons (i.e. cell walls called frustules) made of amorphous silica. The porous, highly symmetrical structure and microscopic size of diatom cell walls make them ideal constituents of sensing devices and analytical chips. Here, we propose chemical methods to purify diatom frustules extracted from diatomaceous earth. Using photo deposition techniques, we grow gold nanoparticles on the surface of diatom skeletons and within the pores of the skeletons, where the size and density of nanoparticles can be controlled by changing the parameters of the synthesis. Resulting devices have an internal porous structure that can harvest molecules from a solution, and an external shell of gold nanoparticles that amplifies the electromagnetic field generated by the measurement laser in Raman or other spectroscopies. The combination of these effects enables the analysis of biological specimens, chemical analytes and pollutants in extremely low abundance ranges. The devices were demonstrated in the analysis of Bovine Serum Albumin in water with a concentration of 100 aM, and mineral oil with a concentration of 50 ppm. Keywords: Diatomite, Diatoms, Photo-deposition, Gold nanoparticles, SERS, Bio-sensors

Electroless deposition on patterned silicon substrates enables the formation of metal nanomaterials with tight control over their size and shape. In the technique, metal ions are transported by diffusion from a solution to the active sites of an autocatalytic substrate where they are reduced as metals upon contact. Here, using diffusion limited aggregation models and numerical simulations, we derived relationships that correlate the cluster size distribution to the total mass of deposited particles. We found that the ratio ξ between the rates of growth of two different metals depends on the ratio γ between the rates of growth of clusters formed by those metals through the linearity law ξ = 14(γ − 1). We then validated the model using experiments. Different from other methods, the model derives k using as input the geometry of metal nanoparticle clusters, decoded by SEM or AFM images of samples, and a known reference.

This work presents a disposable passive microfluidic system, allowing chemotaxis studies, through the generation of a concentration gradient. The device can handle liquid flows without an external supply of pressure or electric gradients, but simply using gravity force. It is able to ensure flow rates of 10 &micro, L/h decreasing linearly with 2.5% in 24 h. The device is made of poly(methylmethacrylate) (PMMA), a biocompatible material, and it is fabricated by micro-milling and solvent assisted bonding. It is assembled into a mini incubator, designed properly for cell biology studies in passive microfluidic devices, which provides control of temperature and humidity levels, a contamination-free environment for cells with air and 5% of CO2. Furthermore, the mini incubator can be mounted on standard inverted optical microscopes. By using our microfluidic device integrated into the mini incubator, we are able to evaluate and follow in real-time the migration of any cell line to a chemotactic agent. The device is validated by showing cell migration at a rate of 0.36 &micro, m/min, comparable with the rates present in scientific literature.

Porous silicon is a nano material in which pores with different sizes, densities and depths are infiltrated in conventional silicon imparting it augmented properties including biodegradability, biocompatibility, photoluminescence. Here, we realized porous silicon substrates in which the pore size and the fractal dimension were varied over a significant range. We loaded the described substrates with a PtCl(O,O'-acac)(DMSO) antitumor drug and determined its release profile as a function of pore size over time up to 15days. We observed that the efficacy of delivery augments with the pore size moving from small (~8nm, efficiency of delivery ~0.2) to large (~55nm, efficiency of delivery ~0.7). Then, we verified the adhesion of MCF-7 breast cancer cells on the described substrates with and without the administration of the antitumor drug. This permitted to decouple and understand the coincidental effects of nano-topography and a controlled dosage of drugs on cell adhesion and growth. While large pore sizes guarantee elevated drug dosages, large fractal dimensions boost cell adhesion on a surface. For the particular case of tumor cells and the delivery of an anti-tumor drug, substrates with a small fractal dimension and large pore size hamper cell growth. The competition between nano-topography and a controlled dosage of drugs may either accelerate or block the adhesion of cells on a nanostructured surface, for applications in tissue engineering, regenerative medicine, personalized lab-on-a-chips, and the rational design of implantable drug delivery systems. Display Omitted We realized porous silicon substrates with a varying pore size and fractal dimension.We loaded the substrates with an antitumor drug and determined its release profile over time.We verified the adhesion of MCF-7 cancer cells on the porous substrates.We decoupled the effects of nano-topography and drug delivery on cell adhesion.Large pore sizes boost drug release, large fractal dimensions accelerate cell adhesion.

Secretome of primary cultures is an accessible source of biological markers compared to more complex and less decipherable mixtures such as serum or plasma. The protonation state (PS) of secretome reflects the metabolism of cells and can be used for cancer early detection. Here, we demonstrate a superhydrophobic organic electrochemical device that measures PS in a drop of secretome derived from liquid biopsies. Using data from the sensor and principal component analysis (PCA), we developed algorithms able to efficiently discriminate tumour patients from non-tumour patients. We then validated the results using mass spectrometry and biochemical analysis of samples. For the 36 patients across three independent cohorts, the method identified tumour patients with high sensitivity and identification as high as 100% (no false positives) with declared subjects at-risk, for sporadic cancer onset, by intermediate values of PS. This assay could impact on cancer risk management, individual’s diagnosis and/or help clarify risk in healthy populations., Diagnostics: Proton state of secreted proteins in blood helps identify cancer A blood test that measures whether molecules secreted by cells contain titratable proton atoms can accurately discriminate between patients who have cancer and those who don’t. Titratable species may in turn influence the protonation state of a solution, i.e. the number of protons added to and the net charge of that solution. A team led by Natalia Malara from University Magna Graecia in Catanzaro, Italy and Enzo Di Fabrizio from the King Abdullah University of Science and Technology in Thuwal, Saudi Arabia, Francesco Gentile from the University Federico II in Naples, Italy, and Nicola Coppedè from the Institute of Materials for Electronics and Magnetism in Parma, Italy, created an eletrochemical device that can detect faulty metabolism by quantifying the proportion of secreted proteins with and without extra protons—an indicator of abnormal cell division, proliferation and invasion. The researchers tested the device on blood samples from patients with solid tumors and healthy controls. The method identified cancer patients with a high degree of accuracy. If the findings are confirmed in larger trials, the test could help with the screening, diagnosis and management of cancer.

Diatom shells are a natural, theoretically unlimited material composed of silicon dioxide, with regular patterns of pores penetrating through their surface. For their characteristics, diatom shells show promise to be used as low cost, highly efficient drug carriers, sensor devices or other micro-devices. Here, we demonstrate diatom shells functionalized with gold nanoparticles for the harvesting and detection of biological analytes (bovine serum albumin—BSA) and chemical pollutants (mineral oil) in low abundance ranges, for applications in bioengineering, medicine, safety, and pollution monitoring. Electronic supplementary material The online version of this article (10.1186/s11671-018-2507-4) contains supplementary material, which is available to authorized users.

Neural cells are the smallest building blocks of the central and peripheral nervous systems. Information in neural networks and cell-substrate interactions have been heretofore studied separately. Understanding whether surface nano-topography can direct nerve cells assembly into computational efficient networks may provide new tools and criteria for tissue engineering and regenerative medicine. In this work, we used information theory approaches and functional multi calcium imaging (fMCI) techniques to examine how information flows in neural networks cultured on surfaces with controlled topography. We found that substrate roughness S a affects networks topology. In the low nano-meter range, S a = 0–30 nm, information increases with S a . Moreover, we found that energy density of a network of cells correlates to the topology of that network. This reinforces the view that information, energy and surface nano-topography are tightly inter-connected and should not be neglected when studying cell-cell interaction in neural tissue repair and regeneration.

In this paper, we describe an innovative modular microfluidic platform allowing filtering, concentration and analysis of peptides from a complex mixture. The platform is composed of a microfluidic filtering device and a superhydrophobic surface integrating surface enhanced Raman scattering (SERS) sensors. The microfluidic device was used to filter specific peptides (MW 1553.73 D) derived from the BRCA1 protein, a tumor-suppressor molecule which plays a pivotal role in the development of breast cancers, from albumin (66.5 KD), the most represented protein in human plasma. The filtering process consisted of driving the complex mixture through a porous membrane having a cut-off of 12–14 kD by hydrodynamic flow. The filtered samples coming out of the microfluidic device were subsequently deposited on a superhydrophobic surface formed by micro pillars on top of which nanograins were fabricated. The nanograins coupled to a Raman spectroscopy instrument acted as a SERS sensor and allowed analysis of the filtered sample on top of the surface once it evaporated. By using the presented platform, we demonstrate being able to sort small peptides from bigger proteins and to detect them by using a label-free technique at a resolution down to 0.1 ng μL−1. The combination of microfluidics and nanotechnology to develop the presented microfluidic platform may give rise to a new generation of biosensors capable of detecting low concentration samples from complex mixtures without the need for any sample pretreatment or labelling. The developed devices could have future applications in the field of early diagnosis of severe illnesses, e.g. early cancer detection.

Super-hydrophobic (SH) surfaces are bio-inspired, nanotechnology artifacts which feature a reduced friction coefficient whereby they can be used for a number of very practical applications including, on the medical side, the manipulation of biological solutions. These surfaces can be combined with bio-photonic devices to obtain an integrated lab-on-a-chip system where, on a first stage, the SH surface would vehicle or transport the analytes of interest into a small area and, on a second stage, the bio-sensors would permit, in that area, the detection of the solute with the resolution of a single molecule. This novel diagnostic modality offers realistic possibilities for the early detection of cancers. Nevertheless, as it stands, the device still suffers from the severe disadvantage that the exact final position of the solute, upon evaporation, is unpredictable, and thus the localization and recognition of few molecules would be impractical. Conventional SH surfaces typically comprise micro pillars combined to form a regular hexagonal motif. Here, the periodicity of those pillars was broken introducing artificial gradients of wettability over the surface. In doing so, some regions are rendered more hydrophilic than others and, on account of this, a solute would preferentially target these hydrophilic regions upon evaporation. In this work, such non regular geometries were realized and used to condense diluted Rhodamine solutions in a small area. Randomly distributed silver nano aggregates, conveniently positioned upon the micropillars, permitted the identification of few molecules using enhanced Fourier transform infrared spectroscopy (FTIR) spectroscopy.

The study and the comprehension of the mechanism of cell adhesion and cell interaction with a substrate is a key point when biology and medicine meet engineering. This is the case of several biomedical applications, from regenerative medicine and tissue engineering to lab on chip and many others, in which the realization of the appropriate artificial surface allows the control of cell adhesion and proliferation.In this context, we aimed to design and develop a fabrication method of mesoporous (MeP) silicon substrates, doped with gold nanoparticles, in which we combine the capability of porous surfaces to support cell adhesion with the SERS capabilities of gold nanoparticles, to understand the chemical mechanisms of cell/surface interaction.MeP Si surfaces were realized by anodization of a Si wafer, creating the device for cell adhesion and growth. Gold nanoparticles were deposited on porous silicon by an electroless technique. We thus obtained devices with superior SERS capabilities, whereby cell activity may be controlled using Raman spectroscopy. MCF-7 breast cancer cells were cultured on the described substrates and SERS maps revealing the different expression and distribution of adhesion molecules were obtained by Raman spectroscopic analyses. Display Omitted designing and developing of a fabrication method of mesoporous (MeP) silicon substrates decorated with gold nanoparticlesthese devices are able to support cell adhesion and proliferation and simultaneously they works as SERS substratesSERS Raman analysis of cells cultured on MeP Si substrates provide indication about cells behaviour on them.

Recent progresses in nanotechnology fabrication gives the opportunity to build highly functional nano-devices. 3D structures based on noble metals or covered by them can be realized down to the nano-scales, obtaining different devices with the functionalities of plasmonic nano-lenses or nano-probes. Here, nano-cones decorated with silver nano-grains were fabricated using advanced nano-fabrication techniques. In fabricating the cones, the angle of the apex was varied over a significant range and, in doing so, different geometries were realized. In depositing the silver nano-particles, the concentration of solution was varied, whereby different growth conditions were realized. The combined effect of tip geometry and growth conditions influences the size and distribution of the silver nano grains. The tips have the ability to guide or control the growth of the grains, in the sense that the nano-particles would preferentially distribute along the cone, and especially at the apex of the cone, with no o minor concentration effects on the substrate. The arrangement of metallic nano-particles into three-dimensional (3D) structures results in a Surface Enhanced Raman Spectroscopy (SERS) device with improved interface with analytes compared to bi-dimensional arrays of metallic nanoparticles. In the future, similar devices may find application in microfluidic devices, and in general in flow chambers, where the system can be inserted as to mimic a a nano-bait, for the recognition of specific biomarkers, or the manipulation and chemical investigation of single cells directly in native environments with good sensitivity, repeatability and selectivity.

Silver nanoparticles (NPs) aggregates with an overall size in the nano meter range were fabricated employing non conventional electroless techniques. The structure of the aggregates was analyzed through direct SEM and AFM imaging; space-frequency based variables, including fractal dimension, were extracted in order to yield a quantitative measurement of the topography of the systems at study. These observations were explained within the framework of diffusion limited aggregation (DLA). DLA theory founds upon the paradigm that, in the limit of very fast chemical reactions, diffusion is the sole driving force that regulates the dynamics of aggregation of NPs. The mathematical model confirmed the experimental findings whereby the fractal dimension of the clusters is size dependent, that is, larger systems are more discontinuous than smaller. The model would also predict that, under certain conditions, a characteristic length exists beyond which the fractal dimension is constant. DLA theory is consistent and predictive in nature, and may be of valuable help in designing devices that utilize rough metal surfaces and the derived effects thereof, including SERS substrates.

Superhydrophobic surfaces were fabricated comprising cylindrical micro-pillars arranged in a regular hexagonal lattice. These structures are hierarchical in that the pillars incorporate, on the top, nanoporous silicon films. In sight of the superhydrophobicity of the system, the devices retain the ability of manipulating and concentrating diluted biological solutions, while, on account of the nanoporous films, they would efficiently filter the biological content of such solutions. The major advance, here, is the simultaneous use of the properties above, and thus important applications are envisioned where extremely small quantities of bio-markers are efficiently extracted from serum and analyzed employing conventional and well assessed spectroscopy techniques. Ultra low concentrated small Rhodamine molecules were here efficiently analyzed using FTIR spectroscopy techniques, thus demonstrating that these devices are effective.

The detection of a few molecules in a highly diluted solution is of paramount interest in fields including biomedicine, safety and eco-pollution in relation to rare and dangerous chemicals. Nanosensors based on plasmonics are promising devices in this regard, in that they combine the features of high sensitivity, label-free detection and miniaturization. However, plasmonic-based nanosensors, in common with general sensors with sensitive areas on the scale of nanometres, cannot be used directly to detect molecules dissolved in femto- or attomolar solutions. In other words, they are diffusion-limited and their detection times become impractical at such concentrations. In this Article, we demonstrate, by combining super-hydrophobic artificial surfaces and nanoplasmonic structures, that few molecules can be localized and detected even at attomolar (10−18 mol l−1) concentration. Moreover, the detection can be combined with fluorescence and Raman spectroscopy, such that the chemical signature of the molecules can be clearly determined.

The ability to manipulate matter to create non-conventional structures is one of the key issues of material science. The understanding of assembling mechanism at the nanoscale allows us to engineer new nanomaterials, with physical properties intimately depending on their structure. This paper describes new strategies to obtain and characterise metal nanostructures via the combination of a top-down method, such as electron beam lithography, and a bottom-up technique, such as the chemical electroless deposition. We realised silver nanoparticle aggregates within well-defined patterned holes created by electron beam lithography on silicon substrates. The quality characteristics of the nanoaggregates were verified by using scanning electron microscopy and atomic force microscopy imaging. Moreover, we compared the experimental findings to molecular dynamics simulations of nanoparticles growth. We observed a very high dependence of the structure characteristics on the pattern nanowell aspect ratio. We found that high-quality metal nanostructures may be obtained in patterns with well aspect ratio close to one, corresponding to a maximum diameter of 50 nm, a limit above which the fabricated structures become less regular and discontinuous. When regular shapes and sizes are necessary, as in nanophotonics, these results suggest the pattern characteristics to obtain isolated, uniform and reproducible metal nanospheres.

Early detection of diseases has great importance in terms of success of the disease treatment. In fact, it has a profound positive influence on the response provided by the patient, leading to shorter and less invasive treatment regimes. We consider here the Raman detection of low (atto-molar) concentrates of molecules by applying nanofabrication techniques in the fabrication of plasmonic devices fulfilling the requirement of superhydrophobicity. Plasmonic resonances will have the effect of substantially increasing the local electric field around the fabricated nano-device which, in turn, will positively affect the Raman signal. Similarly, the superhydrophobicity will play the crucial role in localizing the few molecules of the analyte around the plasmonic device, therefore allowing their detection in a manner otherwise impossible in diffusion-based devices. We will theoretically explain the concept of superhydrophobicity by providing also a roadmap for defining the optimal superhydrophobic device, then we will introduce the fabrication process to realize such a device and, finally, we will provide the Raman counting of a series of analytes together with electromagnetic simulations illustrating the role of the electric field in the formation of the Raman signal.

Exosomes are very small vesicles that are shed from a variety of cell types. They are present in body fluids comprising blood, urine and ascites, and they hold the potential to serve as indicators in the diagnosis, prognosis and surveillance of a variety of health conditions. In consideration of this, there is broad interest worldwide in deriving and understanding their biochemical composition. Here, small drops of solutions containing exosomes, isolated from either healthy (CCD841-CoN) or tumor (HCT116) colon cells, were manipulated using super-hydrophobic surfaces (SHSs) decorated with nano-geometry based photonics structures. SHSs are surfaces with superior properties, including a reduced friction coefficient, on account of which they can be used to control diluted solutions of biological or medical interest. The combination of this technology with optical resonance phenomena, open up terrific opportunities in the detection, analysis or characterization of biological compounds. Therefore, exosomes were conveniently concentrated and conveyed onto the Surface Enhanced Raman Spectroscopy (SERS) active areas of the substrate, whereby they were analyzed and characterized with extreme precision. Results indicate a difference in the concentration of some biological compounds, and namely: exosomes derived from healthy cells exhibit higher intensities of the peaks corresponding to lipids vibrations, while exosomes extracted from tumor cell lines exhibit a richer RNA content.

Surface-enhanced Raman scattering (SERS) substrates were fabricated using electro-plating and e-beam lithography techniques. Nano-structures were obtained comprising regular arrays of gold nanoaggregates with a diameter of 80 nm and a mutual distance between the aggregates (gap) ranging from 10 to 30 nm. The nanopatterned SERS substrate enabled to have better control and reproducibility on the generation of plasmon polaritons (PPs). SERS measurements were performed for various proteins, namely bovine serum albumin (BSA), myoglobin, ferritin, lysozyme, RNase-B, α-casein, α-lactalbumin and trypsin. Principal component analysis (PCA) was used to organize and classify the proteins on the basis of their secondary structure. Cluster analysis proved that the error committed in the classification was of about 14%. In the paper, it was clearly shown that the combined use of SERS measurements and PCA analysis is effective in categorizing the proteins on the basis of secondary structure.