Dan Nicolau

• PhD Chemical Engineering, Politehnica University of Bucharest
• Chair at McGill University

Gas embolism is a rare but life-threatening process characterized by the presence of gas bubbles in the venous or arterial systems. These bubbles, if sufficiently large or numerous, can block the delivery of oxygen to critical organs, in particular the brain, and subsequently they can trigger a cascade of adverse biochemical reactions with severe m...

Gas (or air) embolism is a medical condition caused when gas bubbles are present in venous or arterial blood vessels, leading to limited or blocked blood and oxygen supply to...

A challenge of any biosensing technology is the detection of very low concentrations of analytes. The fluorescence interference contrast (FLIC) technique improves the fluorescence-based sensitivity by selectively amplifying, or suppressing, the emission of a fluorophore-labeled biomolecule immobilized on a transparent layer placed on top of a mirro...

Abstract: Polydimethylsiloxane (PDMS), a silicone elastomer, is increasingly being used in health and biomedical fields due to its excellent optical and mechanical properties. Its biocompatibility and resistance to biodegradation led to various applications (e.g., lung on a chip replicating blood flow, medical interventions, and diagnostics). The m...

Gas embolism is a medical condition leading to the blockage of blood flow in the microvasculature by gas bubbles. While reported as rare, gas embolism often has devastating, fatal physiological consequences. Despite this acute importance, the genesis and evolution of air bubbles in blood vessels under different physiological conditions, such as blo...

Motor proteins, such as myosin and kinesin, are biological molecular motors involved in force generation and intracellular transport in living cells. They were proposed to drive molecular shuttles for the active transport of analytes, thus significantly accelerating the sensing process of biosensors. Integrating motor proteins into biosensors requi...

All known algorithms to solve Nondeterministic Polynomial (NP) Complete problems, relevant to many real-life applications, require the exploration of a space of potential solutions, which grows exponentially with the size of the problem. Since electronic computers can implement only limited parallelism, their use for solving NP-complete problems is...

Non-deterministic polynomial (NP-) complete problems, whose number of possible solutions grows exponentially with the number of variables, require by necessity massively parallel computation. Because sequential computers, such as solid state-based ones, can solve only small instances of these problems within a reasonable time frame, parallel comput...

Significance Understanding bacterial movement is crucial for health, agriculture, environment, and industry. Studying the motility of five bacterial species in microfluidic environments showed that bacterial motility behavior is the result of a “tug-of-war” between hydrodynamics and local nanomechanics. In less confining spaces, bacterial motility...

Garlic is a well-known example of natural self-defence system consisting of an inactive substrate (alliin) and enzyme (alliinase) which, when combined, produce highly antimicrobial allicin. Increase of alliinase stability and its activity are of paramount importance in various applications relying on its use for in-situ synthesis of allicin or its...

We present for the first time a lens-free, oblique illumination imaging platform for on-sensor dark- field microscopy and shadow-based 3D object measurements. It consists of an LED point source that illuminates a 5-megapixel, 1.4 µm pixel size, back-illuminated CMOS sensor at angles between 0° and 90°. Analytes (polystyrene beads, microorganisms, a...

Severe circumstances, such as the present pandemic, require us to focus on immediate and major concerns, but they also ask us to reflect on where we were, are, and want to be in the future. In doing so, severe circumstances are, essentially, asking us to design a future, one with new emphases, attitudes and activities, and which will mitigate, so...

[This corrects the article DOI: 10.1098/rsfs.2018.0034.].

Phase contrast imaging is widely employed in the physical, biological, and medical sciences. However, typical implementations involve complex imaging systems that amount to in-line interferometers. We adapt differential phase contrast (DPC) to a dual-phone illumination-imaging system to obtain phase contrast images on a portable mobile phone platfo...

Many bacteria dwell in micro-habitats, e.g., animal or plant tissues, waste matter, and soil. Consequently, bacterial space searching and partitioning is critical to their survival. However, the vast majority of studies regarding the motility of bacteria have been performed in open environments. To fill this gap in knowledge, we studied the behavio...

Significance Many filamentous fungi colonizing animal or plant tissue, waste matter, or soil must find optimal paths through the constraining geometries of their microenvironment. Imaging of live fungal growth in custom-built microfluidics structures revealed the intracellular mechanisms responsible for this remarkable efficiency. In meandering cha...

Bacterial movement in confined spaces is routinely encountered either in a natural environment or in artificial structures. Consequently, the ability to understand and predict the behavior of motile bacterial cells in confined geometries is essential to many applications, spanning from the more classical, such as the management complex microbial ne...

In this paper we present for the first time a system comprised of two mobile phones, one for illumination and the other for microscopy, as a portable, user-friendly, and cost-effective microscopy platform for a wide range of applications. Versatile and adaptive illumination is made with a Retina display of an Apple mobile phone device. The phone sc...

One contribution of 10 to a theme issue 'Computation by natural systems'. On-chip network-based computation, using biological agents, is a new hardware embedded approach which attempts to find solutions to combinatorial problems, in principle, in a shorter time than the fast, but sequential electronic computers. This analytical review starts by des...

Continuous improvements of the fluorescence-based sensitivity and specificity, required for high throughput screening, diagnostics, and molecular biology studies, are usually addressed by better readout systems, or better reporting elements. However, while Fluorescence Interference Contrast (FLIC), which modulates the fluorescence by materials-base...

The uniformity of the protein patterns, their shape, and the contrast between the fluorescence signal of the pattern and the background, critically modulate the quantitative accuracy of the microarray-derived data. While significant research focused of the identification of the factors that impact the protein microarray patterns, these studies usua...

The underlying intracellular mechanisms involved in the fungal growth received considerable attention, but the experimental and theoretical work did not take into account the modulation of these processes by constraining microenvironments similar to many natural fungal habitats. To fill this gap in the scientific knowledge, we used time-lapse live-...

Experimental studies have shown that fungi use a natural program for searching the space available in micro-confined networks, e.g., mazes. This natural program, which comprises two subroutines, i.e., collision-induced branching and directional memory, has been shown to be efficient compared with the suppressing one, or both subroutines. The presen...

This review describes recent advances associated with the development of surface imprinting methods for the synthesis of polymeric membranes and thin films, which possess the capability to selectively and specifically recognise biomacromolecules, such as proteins and single–and double-stranded DNA, employing “epitope” or “whole molecule” approaches...

The actin-myosin system, responsible for muscle contraction, is also the force-generating element in dynamic nanodevices operating with surface-immobilized motor proteins. These devices require materials that are amenable to micro- and nano-fabrication, but also preserve the bioactivity of molecular motors. The complexity of the protein-surface sys...

Micro-patterned surfaces with alternate, hydrophilic, and hydrophobic rectangular areas, effectively confine water droplets down to attolitre volumes. The contact angle, volume, and geometry of the confined droplets as a function of the geometry and physico-chemical properties of the confining surfaces have been determined by phenomenological simul...

Previous experiments have shown that fungi use an efficient natural algorithm for searching the space available for their growth in micro-confined networks, e.g., mazes. This natural 'master' algorithm, which comprises two 'slave' sub-algorithms, i.e., collision-induced branching and directional memory, has been shown to be more efficient than alte...

This study describes a versatile computational method to determine the hydrophobicity of small peptides at the atomic level. Free energies of transfer for individual atoms in peptide structures were derived, utilising two specifically defined parameters: (i) the water-excluding distance to define the dynamic interface between a peptide solute and i...

Significance Electronic computers are extremely powerful at performing a high number of operations at very high speeds, sequentially. However, they struggle with combinatorial tasks that can be solved faster if many operations are performed in parallel. Here, we present proof-of-concept of a parallel computer by solving the specific instance {2, 5,...

Micro-contact printing, μCP, is a well-established soft-lithography technique for printing biomolecules. μCP uses stamps made of Poly(dimethylsiloxane), PDMS, made by replicating a microstructured silicon master fabricated by semiconductor manufacturing processes. One of the problems of the μCP is the difficult control of the printing process, whic...

In vitro motility assays using cytoskeletal proteins have been used extensively for fundamental studies of protein molecular motors. Both the further development of nano-devices using these protein molecular motors, and fundamental studies focused on their function, would benefit from the ability to direct the motion using external forces. To achie...

Protein molecular motors, which convert chemical energy into kinetic energy, are prime candidates for use in nanodevice in which active transport is required. To be able to design these devices it is essential that the properties of the cytoskeletal filaments propelled by the molecular motors are well established. Here we used micro-contact printed...

Protein microarrays are used various research areas including drug discovery, diagnosis, and analysis of protein-ligand interactions. Their efficacy depends on a well-defined pattern of immobilized proteins that also have retained their bioactivity. Protein microarrays are classically fabricated using the robotic spotting drop method (€pin printing...

Protein molecular motors, which convert, directly and efficiently, chemical energy into motion, are excellent candidates for integration in hybrid dynamic nanodevices. To integrate and use the full potential of molecular motors in these devices, their design requires a quantitative and precise prediction of the fundamental mechanical and physicoche...

A precise representation of the spatial distribution of hydrophobicity, hydrophilicity and charges on the molecular surface of proteins is critical for the understanding of the interaction with small molecules and larger systems. The representation of hydrophobicity is rarely done at atom-level, as this property is generally assigned to residues. A...

First lab-on-chip devices based on active transport by biomolecular motors have been demonstrated for basic detection and sorting applications. However, to fully employ the advantages of such hybrid nanotechnology, versatile spatial and temporal control mechanisms are required. Using a thermo-responsive polymer, we demonstrated a temperature contro...

Many areas of biochemistry and molecular biology, both fundamental and applications-orientated, require an accurate construction, representation and understanding of the protein molecular surface and its interaction with other, usually small, molecules. There are however many situations when the protein molecular surface gets in physical contact wi...

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In recent years there has been increasing interest in the use of molecular motors and cytoskeletal filaments in nanotechnological applications, particularly in the production of biomedical microdevices. In order for this to be possible it is important to exert a high level of control over the movement of the filaments. Chemical patterning technique...

We investigated the difference in electrically guided acto-myosin motility on two surfaces. Rabbit skeletal muscle heavy meromyosin (HMM) was absorbed onto surfaces coated with Nitrocellulose (NC) and Poly(butyl methacrylate) (PBMA). A modified in vitro motility assay with sealed chambers for the insertion of electrodes allowed an electrical field...

Nearly all aptamers identified so far for any given target molecule have been specific for the same binding site (epitope). The most notable exception to the 1 aptamer per target molecule rule is the pair of DNA aptamers that bind to different epitopes of thrombin. This communication refutes the suggestion that these aptamers exist because differen...

This contribution reports on the quantification of the parameters of the motility assays for actomyosin system using a quartz crystal microbalance (QCM). In particular, we report on the difference in the observed resonance frequency and dissipation of a quartz crystal when actin filaments are stationary as opposed to when they are motile. The chang...

The paper presents a classification of the protein surface atom neighbourhoods from the hydrophobicity perspective. Hydrophobicity is the property which is considered around each surface atom. The actual hydrophobicity distribution on the atoms that form an atom's vicinity is replaced by an equivalent hydrophobicity density distribution, computed i...

Human acetylcholinesterase (AChE) is a widely studied target enzyme in drug discovery for Alzheimer’s disease (AD). In this paper we report evaluation of the optimum structure and chemistry of the supporting material for a new AChE-based fluorescence sensing surface. To achieve this objective, multilayered silicon wafers with spatially controlled g...

The paper presents an image-oriented functional description of protein surfaces in terms of amphiphilicity (hydrophobicity / hydrophilicity) distribution. The actual discrete surface atom amphiphilicity distribution is replaced by an approximately equivalent amphiphilicity density distribution, computed in a standardized octagonal pattern around ea...

Nano-structured silicon wafers with arrays of dots and lines of different width and pitch were manufactured by e-beam lithography. The resulting arrays were composed of 50×50 μm fields. These arrays consisted of either dots (gold) of different width (400-800 nm) and pitch (500-1000 nm) or lines (gold) of different width (100-1000 nm) and pitch (200...

The paper presents an image-oriented modality to functionally describe articially and biologically nanostruc- tured surfaces, which can be used for the characterization of the atom neighborhoods on the surface of proteins. The both properties,hydrophobicity and charge distribution on protein surface, are analyzed in this paper. The actual discrete...

An image-oriented modality of describing protein surfaces in terms of hydrophobicity and charge distributions seen as signals has been used to classify surface atom neighborhoods. Global similitude and interaction measures of pairs of surface atom neighborhoods are defined, as well as vector descriptions of hydrophobicity and charge density distrib...

The fabrication of electrode pairs with a small electrode gap separation using a focussed-ion-beam is reported. Using a previously developed technique, the gap between the electrodes was bridged using several benzenedimethanethiol molecules and a single gold nanoparticle. The electrical properties of this whole ensemble were measured and the result...

An image-oriented modality to functionally describe protein surfaces is presented, in terms of the hydrophobicity distribution on protein surface. Distributions of charges and mutual electrical potentials can also be considered in a similar way. The discrete hydrophobicities of the atoms that form a surface atom neighborhood are replaced by an appr...

The image-oriented modality of describing protein surfaces in terms of the hydrophobicity distribution has been used to classify surface atom neighborhoods. In addition to the similitude and interaction of the pairs of atom neighborhoods, a vector description has been defined. Surface atom neighborhoods have been classified in terms of both resembl...

Despite occupying physically and chemically heterogeneous natural environments, the growth dynamics of filamentous fungi is typically studied on the surface of homogeneous laboratory media. Fungal exploration and exploitation of complex natural environments requires optimal survival and growth strategies at the colony, hyphal, and intra hyphal leve...

Extensive evidence suggests that the self-assembly of amyloid-beta peptide (Aβ) is a nucleation-dependent process that involves the formation of several oligomeric intermediates. Despite neuronal toxicity being recently related to Aβ soluble oligomers, results from aggregation studies are often controversial, mainly because of the low reproducibili...

Optical antenna: The fluorescence of analyte molecules in proximity to noble-metal nanostructures is enhanced by plasmon-induced electric fields (see schematic). This phenomenon allows the progress of molecular binding events of biological molecules to be monitored in real-time.

The paper presents an image-oriented modality to functionally describe artificially and biologically nanostructured surfaces, which can be used for the characterization of the atom neighborhoods on the surface of proteins. The property which is mainly analyzed in this paper is the hydrophobicity distribution on protein surface, but the distribution...

Filamentous fungi include serious plant and animal pathogens that explore their environment efficiently in order to penetrate the host. This environment is physically and chemically heterogeneous and the fungi rely on specific physical and chemical signals to find the optimal point/s of attack. This study presents a methodology to introduce distinc...

A protein functional imaging in terms of their surface hydrophobicity distribution is presented. Atom level hydrophobicities, obtained from amino acid hydrophobicities, are used to compute approximately equivalent hydrophobicity density distributions around each surface atom, in a standardized octagonal framework. Surface atom neighborhoods are cla...

The performance of biomedical microdevices requires the accurate control of the biomolecule concentration on the surface, as well as the preservation of their bioactivity. This desideratum is even more critical for proteins, which present a significant propensity for surface-induced denaturation, and for microarrays, which require high multiplexing...

The paper presents an image-oriented description of artificial and biological nanostructured surfaces, with applicability to the functional characterization of atom neighborhoods at the surface of proteins. The property which is considered is the hydrophobicity around each surface atom. The actual hydrophobicity distribution on the atoms that form...

Although filamentous fungi live in physically and chemically complex natural environments that require optimal survival strategies, both at colony and individual cell level, their growth dynamics are usually studied on homogenous media. This study proposes a new research methodology based on the purposeful design, fabrication and operation of micro...

Traditionally bacteria are cultivated on the surface of agar, an environment that is experimentally convenient, but it does not resemble the diverse micro-geometries of their natural habitat, such as abiotic (e.g., soil) and biotic (e.g., plant and other organisms) surfaces. In this work, microstructured environments were manufactured from a biocom...

Bead-based technologies are an attractive alternative to classical microarrays due to the high surface area of the beads which enables the immobilization of large numbers of probe molecules leading to increased kinetics and improved signal/noise ratios. A simple, versatile and inexpensive method for the fabrication of magnetic bead arrays is presen...

As top-down nanolithography is inexorably approaching its ultimate limits, the techniques based on bottom-up self-assembly become increasingly attractive. Among these, the ion-beam-induced self-assembly of thin films occupies a special place, as they combine both the top-down, focused micro-fabrication with the bottom-up self-assembly nano-processe...

The fabrication of biomedical microdevices requires patterning techniques that can print structures ranging from hundreds of microns to sub-micron sizes, on large areas, with a low cost of ownership, and using essentially any material, but with relatively relaxed requirements for pattern precision. Addressing these specific needs and opportunities,...

The paper presents a methodology using atom or amino acid hydrophobicities to describe the surface properties of proteins in order to predict their interactions with other proteins and with artificial nanostructured surfaces. A standardized pattern is built around each surface atom of the protein for a radius depending on the molecule type and size...

Biomolecules, such as DNA and cytoskeleton proteins, self-assemble in long-range-ordered nano-aggregates. The process of formation of these long-range ordered nanostructures have large biological interest but, increasingly, they also offer good inspiration for bottom-up 'fabrication' processes leading to large nanostructured areas with the design e...

Microtubules are a crucial part of the fungal cytoskeleton and facilitate long-distance vesicle transport to the growing apex that constitutes one of the main driving forces of polarized growth. This study observed the spatial and temporal distribution of microtubules in growing Neurospora crassa hyphae in two and three dimensions. The fungal strai...

Motility assays are the tools of choice for the studies regarding the motility of protein molecular motors in vitro. Despite their wide usage, some simple, but fundamental issues still need to be specifically addressed in order to achieve the best and the most meaningful motility analyses. An analysis of the errors in the calculation of the average...

a b s t r a c t Nano-structured thin films with protruding PtBA nanodomain structures were obtained from the depo-sition, spin-coating, self-assembly and annealing of the diblock copolymer poly(styrene)-block-poly(tert-butyl acrylate) (PS-b-PtBA). The topography has been documented by atomic force microscopy. The sac-rificial removal of the PtBA bl...

Filamentous fungi are very successful in colonising various microconfined environments, but their behaviour is usually tested on flat surfaces. This contribution presents the design, the fabrication and the use of microstructures, made of a biocompatible polymer (poly(dimethylsiloxane), PDMS) for studying the dynamic micro-scale behaviour of the fi...

Protein adsorption at solid-liquid interfaces is critical to many applications, including biomaterials, protein microarrays and lab-on-a-chip devices. Despite this general interest, and a large amount of research in the last half a century, protein adsorption cannot be predicted with an engineering level, design-orientated accuracy. Here we describ...

Microorganisms live in environments that are geometrically, physically and chemically heterogeneous at the micro-scale. Consequently, they have to optimise their behaviour at the cellular level within limited time frames by responding to stimuli that are spatially distributed at the micro-scale. Microorganisms achieve this by using a range of diffe...

Photobleaching of photoresists has been at the core of high resolution relative to a particular exposure wavelength, but the accelerated advancements dictated by the sharp economic considerations of the roadmap, as well as the complexity of exposure-material-technology triad, made photobleaching a secondary subject of interest. However, the still-s...

a b s t r a c t Micro-structured arrays on silicon wafers with pyramids of different sizes (base of 2, 3.5 or 5 lm 2) and spacings (4–64 lm; 6–96 lm and 10–160 lm, respectively) were manufactured by optical lithography and coated with a 100 nm gold layer. Some of these micro-structured wafers were further modified through direct self-assembly proce...

All multi-cellular living organisms are very complex microfluidics systems, which are assembled 'inside-out', as the result of a complex 'tug-of-war' process comprising both feed-forward modules, in particular the program embedded in the species' DNA, and feed-back processes, in particular the response to external environmental conditions. Living o...

Advanced nanofabrication is capable of producing structures in the vicinity of the size of large biomolecules or their aggregates. Some of these protein aggregates emerge as having deleterious medical effects, e.g., degenerative diseases, or essential for biological processes, e.g., actin, cytoskeleton formation. Therefore it became possible, and i...