1,721,010 research outputs found
Sensitive label-free and fluorescence cancer biomarker detection using one dimensional photonic crystal biochips
Biological and biochemical processes play a very important role in living organisms and their understanding is particularly important in medicine, biology and biotechnology. Optical biosensors hold great promise for solving challenging molecular recognition issues, such as the detection of biomolecules at very low concentration. In this framework, a direct measurement of the binding of analytes to a target molecule in biological samples is an essential step in diagnosis and in understanding how biomolecules interact under physiological conditions.
In this thesis, I contributed to the development of an optical platform that combines label-free and fluorescence detection modes. Such a platform makes use of one-dimensional photonic crystals (1DPC) sustaining Bloch surface waves (BSW) to detect relevant cancer biomarkers in body fluids.
BSWs are surface electromagnetic waves that propagate along the truncation interface between a 1DPC and an external medium (the analyte) and can be strongly confined with a significantly enhanced field at the surface. By exploiting such features, 1DPC sustaining BSW (BSW biochips) are used as optical transducers that convert refractive index changes and fluorescence emission at their surface into a measurable optical signal.
After discussing the results of the platform development, I report on the use I made of BSW biochips to detect clinically relevant concentrations of Angiopoietin 2 and ERBB2 in different biological matrices. The aim of such a research endeavour is clear: to reveal cancer by means of integrated optofluidic structures before cancer reveals itself. In the case of breast cancer, for example, it is a fact that ERBB2 is a pivotal biomarker and targetable oncogenic driver associated
with several different aggressive subtypes. To quantitate Angiopoietin 2 and soluble ERBB2, I developed and implemented specific sandwich detection assays in which the BSW biochips’ sensitive surface is tailored with monoclonal antibodies for highly specific biological recognition.
In a second step, a second antibody quantitatively detects the bound analytes. The strategy of the present approach takes advantage of the combination of both label-free and fluorescence techniques, making bio-recognition more robust and sensitive. In the fluorescence operation mode, the platform can attain the limit of detection 0.3 ng/mL (1.5 pM) for ERBB2 in cell lysates, which is the most complex biological matrix studied in the present work. Such a resolution meets the international guidelines and recommendations (15 ng/mL) for diagnostic ERBB2 assays that in the future may help to assign more precisely therapies counteracting cancer cell proliferation and metastatic spread
Multilayer coatings for Bloch surface wave optical biosensors
Sensors using surface plasmon resonance (SPR) are established as themethod of choice in label-free optical biosensing.
Their sensitivity for small refractive index changes at the surface originates from the enhanced evanescent
field at the surface of a thin metal layer. However, the small number of well-suited metals (Ag, Au) with
fixed optical constants limits a further refinement of the SPR performance in terms of dispersion and resonance
width. An alternative can be found in Bloch SurfaceWaves (BSW) sustained at specially designed dielectricmultilayer
stacks with low absorption losses. Due to the low losses an enormous narrowing of the resonance is obtained,
promising the reduction of the detection limit for such a label-free sensor. In order to deposit these
multilayers on plastic sensor chips, plasma ion assisted vacuum evaporation (PIAD) was applied as deposition
method. SiO2, TiO2, and Ta2O5 single layer properties were balanced in terms of absorption losses, stability in
aqueous environment and film stress. Dielectricmultilayer stacks could be designed in away, that resonance performance
is optimal and the total stack thickness as low as possible. Optimized Bloch stacks were successfully
coated on a large number of polymer chips. The application could be demonstrated by the detection of cancer biomarkers
using an analytical instrument that was developed with the BSWchips as core element
Limit of detection comparison for surface wave biosensors
Bloch surface waves (BSW) propagating at the surface of truncated, one-dimensional crystals are valid candidates to improve sensors based on surface plasmon polaritons, usually referred to as surface plasmon resonance (SPR). The low losses introduced by the dielectric BSW stacks enable to achieve resonance widths much below the ones of SPR, thus proposing improved sensing results. A simplified, bi-linear model of the resonance intensity distribution is applied to estimate the effect of the resonance properties onto the measurement noise. This yields a limit of detection (LoD) that is used to optimize a BSW supporting thin film stack and to quantitatively compare SPR and BSW sensors. The results indicate that an order of magnitude reduction of the LoD is within reach when sufficient sampling of narrow BSW resonances is achieved. © 2014 SPIE
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Direct comparison of the performance of Bloch surface wave and surface plasmon polariton sensors
We report on the direct experimental comparison of the sensitivity and figure of merit of biosensors based either on surface plasmon polaritons on metal layers or on Bloch surface waves on one dimensional photonic crystals. The comparison was carried out by making use of a commercial surface plasmon resonance platform that was slightly adapted for these experiments. Although the experimental conditions are not optimized for Bloch surface waves, our experiments demonstrate that both types of biosensors show a similar figure of merit for biochips deposited on low cost molded plastic substrates. For glass substrates with better optical quality, the increased homogeneity of the photonic crystals results in the Bloch surface wave sensors outperforming the surface plasmon polariton sensors by a factor 1.7 in terms of figure of merit. Considerations on the illumination bandwidth indicate options to further increase such a factor. © 2012 Elsevier B.V
Improving the sensitivity of optical biosensors by means of Bloch surface waves
One factor limiting the performance of Surface Plasmon Resonance (SPR) biosensors is the width of the resonance that basically originates from metal absorption. In contrast, comparable sensing schemes based upon the concept of Bloch surface waves (BSW) have been proposed. As such sensors are prepared from dielectric materials only, losses as well as the resonance width decrease significantly in comparison to SPR. By preparing BSW stacks that feature a similar reso-nance position as Gold based SPR sensors, both approaches are compared directly using one detection system only. We obtain an increased performance of BSW although utilizing an optical system optimized for SPR analysis. © 2012 by Walter de Gruyter Berlin Boston
Design rules for combined label-free and fluorescence Bloch surface wave biosensors
We report on the fabrication and physical characterization of optical biosensors implementing simultaneous label-free and fluorescence detection and taking advantage of the excitation of Bloch surface waves at a photonic crystal’s truncation interface. Two types of purposely-designed one dimensional photonic crystals on molded organic substrates with micro-optics were fabricated. These feature either high or low finesse of the Bloch surface wave resonances and were tested on the same optical readout system. The experimental results show that designing biochips with a large resonance quality factor does not necessarily lead in the real case to an improvement of the biosensor performance. Conditions for optimal biochips’ design and operation of the complete bio-sensing platform are established
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