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In multiplexed analysis, lab on a chip (LoC) devices are advantageous due to the low sample and reagent volumes required. Although optical detection is preferred for providing high sensitivity in a contactless configuration, multiplexed optical LoCs are limited by the technological complexity for integrating multiple light sources and detectors in a single device. To address this issue, we present a microfluidic-controlled optical router that enables measurement in four individual optical channels using a single light source and detector, and without movable parts. The optofluidic device is entirely fabricated in polydimethylsiloxane (PDMS) by soft-lithography, compatible with standard microfabrication technologies, enabling monolithic integration in LoCs. In the device, in-coupled light from an optical fiber is collimated by a polymeric micro-lens and guided through a set of four sequentially connected micro-chambers. When a micro-chamber is filled with water, light is transmitted to the next one. If it is empty of liquid, however, total internal reflection (TIR) occurs at the PDMS-air interface, re-directing the light to the output optical fiber. The router presents high performance, with low cross-talk (, The research leading to these results has received funding from the European Research Council under the European Community's ERC grant agreement no 209243 and the Horizon 2020 (H2020) project ND4ID (grant agreement no 675412). Dr. X. M.-B. was supported by the “Ramón y Cajal” program from the Spanish Government. We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).

A photonic lab-on-a-chip (PhLoC) was developed for rapid determination of interleukin-2 (IL-2) levels secreted by lymphocytes using measurement of optical absorbance. Optical and microfluidic components, including lenses, mirrors, and flow channels, were monolithically created using poly(dimethylsiloxane) (PDMS). Sample and reagent solutions were processed in the form of liquid columns separated by air. A flow channel structure with an air bypass was used to release air between solution columns and to exchange solutions in the measuring chamber, avoiding the intrusion of air into the measuring chamber and the denaturation of the capture antibodies. The concentration of IL-2 was measured by enzyme-linked immunosorbent assay (ELISA) in the PhLoC. The total time required for the ELISA was less than 30 min. Clear concentration dependence was confirmed for IL-2 concentrations ranging from 50 to 1000 pg/mL. Thus, the concentration of IL-2 secreted by lymphocytes following activation by concanavalin A (Con A) co...

The integration of micro-optical elements with microfluidics leads to the highly promising photonic lab-on-a-chip analytical systems (PhLoCs). In this work, we re-examine the main principles which are underneath the on-chip spectrophotometric detection, approaching the PhLoC concept to a nonexpert audience.

We propose a PDMS-based photonic system for the accurate measurement of protein concentration with minute amounts of the sample. As opposed to the state of the art approach, in the multiple path photonic lab on a chip (MPHIL), analyte concentration or molar absorptivity is obtained with a single injection step, by performing simultaneous parallel optical measurements varying the optical path length. Also, as opposed to the standard calibration protocol, the MPHIL approach does not require a series of measurements at different concentrations. MPHIL has three main advantages: firstly the possibility of dynamically selecting the path length, always working in the absorbance vs. concentration linear range for each target analyte. Secondly, a dramatic reduction of the total volume of the sample required to obtain statistically reliable results. Thirdly, since only one injection is required, the measurement time is minimized, reducing both contamination and signal drifts. These characteristics are clearly advantageous when compared to commercial micro-spectrophotometers. The MPHIL concept was validated by testing three commercial proteins, lysozyme (HEWL), glucose isomerase (d-xylose-ketol-isomerase, GI) and Aspergillus sp. lipase L (BLL), as well as two proteins expressed and purified for this study, B. cereus formamidase (FASE) and dihydropyrimidinase from S. meliloti CECT41 (DHP). The use of MPHIL is also proposed for any spectrophotometric measurement in the UV-VIS range, as well as for its integration as a concentration measurement platform in more advanced photonic lab on a chip systems.

Phenolic compounds are one of the main contaminants of soil and water due to their toxicity and persistence in the natural environment. Their presence is commonly determined with bulky and expensive instrumentation (e.g. chromatography systems), requiring sample collection and transport to the laboratory. Sample transport delays data acquisition, postponing potential actions to prevent environmental catastrophes. This article presents a portable, miniaturized, robust and low-cost microbial trench-based optofluidic system for reagentless determination of phenols in water. The optofluidic system is composed of a poly(methyl methacrylate) structure, incorporating polymeric optical elements and miniaturized discrete auxiliary components for optical transduction. An electronic circuit, adapted from a lock-in amplifier, is used for system control and interfering ambient light subtraction. In the trench, genetically modified bacteria are stably entrapped in an alginate hydrogel for quantitative determination of model phenol catechol. Alginate is also acting as a diffusion barrier for compounds present in the sample. Additionally, the superior refractive index of the gel (compared to water) confines the light in the lower level of the chip. Hence, the optical readout of the device is only altered by changes in the trench. Catechol molecules (colorless) in the sample diffuse through the alginate matrix and reach bacteria, which degrade them to a colored compound. The absorbance increase at 450 nm reports the presence of catechol simply, quickly (~10 min) and quantitatively without addition of chemical reagents. This miniaturized, portable and robust optofluidic system opens the possibility for quick and reliable determination of environmental contamination in situ, thus mitigating the effects of accidental spills.

Elementary PDMS-based building blocks of fluidic, optical and optofluidic components for Lab on a chip (LOC) platforms has here been developed. All individual modules are compatible and can be anchored and released with the help of puzzle-type connectors This approach is a powerful toolbox to create modular optofluidic systems (MOPS), which can be modified/upgraded to user needs and in-situ reconfigurable. In addition, the PDMS can locally be functionalized, defining a modular biosensor. Measurements in absorbance and fluorescence have been pursued as demonstrator.

A label-free compact method for performing photonic characterization of "healthy" versus "diseased" arteries has been developed. It permits the detection of atherosclerotic lesion in living mouse arteries. Using this prototype, we observed that the spectral response (photonic fingerprint, PIN) obtained from aortas of wild-type mice differs from the response of ApoE-KO mice fed with high-fat diet (an atheroprone mouse model). Benchmark of the results against gold standard was performed by staining the aortas with Oil-Red-O to visualize atherosclerotic plaques.

The LiPhos project (EU FP7 Grant Agreement No.: 317916, www.liphos.eu) aims to develop three different biophotonic diagnosis tools (BDTs), based on living photonics, namely: single layer living photonics (SLLP), single cell analysis (SCA); and multi-layer living photonics (MLLP). By Measuring of what we term the Photonic Fingerprint (or PIN), of the cells in such BDTs, should make it is possible to differentiate between healthy and non-healthy cell or tissue states. Moreover, the effect of specific drugs and pro-inflammatory agents could be assessed. This concept is currently being applied to the diagnosis of cardiovascular diseases (CVD).

A polymer-based Micro-optoelectromechanical system (MOEMS) design as a Variable Optical Attenuator (VOA) is presented. It consists on a SU-8 quad-beam structure containing a suspended waveguide aligned to input/output fiber optics. Actuation is achieved by defining photonic-heat transition regions at the anchoring of the mechanical beams. Such actuation points are manufactured by means of a dye-doped SU-8 with a strong absorption at specific wavelengths. When irradiated, the actuation points increase in size, entailing a displacement of the seismic mass, This causes a misalignment (i.e. an increase of the coupling losses) between the waveguides and the input/output fiber optics. Experimental results have validated this approach, by showing the effect of the pumping power on the optical losses, with an excellent repeatability and a response time of 1 ms.

Magnetically-actuable, polymer-based variable optical attenuators (VOA) are presented in this paper. The design comprises a cantilever which also plays the role of a waveguide and the input/output alignment elements for simple alignment, yet still rendering an efficient coupling. Magnetic properties have been conferred to these micro-opto-electromechanical systems (MOEMS) by implementing two different strategies: in the first case, a magnetic sensitive stimuli material (M-SSM) is obtained by a combination of polydimethylsiloxane (PDMS) and ferrofluid (FF) in ratios between 14.9 wt % and 29.9 wt %. An M-SSM strip under the waveguide-cantilever, defined with soft lithography (SLT), provides the required actuation capability. In the second case, specific volumes of FF are dispensed at the end of the cantilever tip (outside the waveguide) by means of inkjet printing (IJP), obtaining the required magnetic response while holding the optical transparency of the waveguide-cantilever. In the absence of a magnetic field, the waveguide-cantilever is aligned with the output fiber optics and thus the intrinsic optical losses can be obtained. Numerical simulations, validated experimentally, have shown that, for any cantilever length, the VOAs defined by IJP present lower intrinsic optical losses than their SLT counterparts. Under an applied magnetic field (B-app), both VOA configurations experience a misalignment between the waveguide-cantilever and the output fiber optics. Thus, the proposed VOAs modulate the output power as a function of the cantilever displacement, which is proportional to B-app. The experimental results for the three different waveguide-cantilever lengths and six different FF concentrations (three per technology) show maximum deflections of 220 mu m at 29.9 wt % of FF for VOA(SLT) and 250 mu m at 22.3 wt % FF for VOA(IJP), at 0.57 kG for both. These deflections provide maximum actuation losses of 16.1 dB and 18.9 dB for the VOA(SLT) and VOA(IJP), respectively.

The integration of detection mechanisms with microfluidics may be one of the most promising routes towards widespread application of Lab-on-a-Chip (LoC) devices. Photonic detection methods like in the so-called Photonic Lab-on-a-Chip (PhLoC) have advantages such as being non-invasive, easy to sterilize and highly sensitive even with short integration times and thus allow in situ monitoring and quantification of biological and chemical processes. The readout of such detection methods usually requires special training of potential users, as in most cases they are confronted with the need of establishing fiber-optics connections to and from the PhLoC and/or rely on the use of complex laboratory equipment. Here, we present a low-cost and robust chip-to-world interface (CWI), fabricated by CO2-laser machining, facilitating the non-expert use of PhLoCs. Fiber-optics with standard SMA-connectors (non-pigtailed) and PhLoCs can be plugged into the CWI without the need for further adjustments. This standardization bestows great versatility on the interface, providing a direct link between PhLoCs and a wide range of light sources and photo-detectors. The ease-of-use of the proposed simple plug mechanism represents a step forward in terms of user-friendliness and may lead PhLoC devices to practical applications., The research leading to these results has been partly funded by the European Union's Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 317916. X. Muñoz-Berbel acknowledges the Spanish Ministry of Economy and Competitiveness for the Ramon y Cajal grant. P. Giménez-Gómez is grateful to MINECO, Spain for the financial support through a research studentship of the FPI Program.

Cardiovascular diseases are the first cause of death globally. Their early diagnosis requires ultrasensitive tools enabling the detection of minor structural and functional alterations in small arteries. Such analyses have been traditionally performed with video imaging-based myographs, which helped to investigate the pathophysiology of the microvessels. Since new vascular questions have emerged, substantial modifications are necessary to improve the performance of imaging and tracking software, reducing the cost and minimizing the microvessel cleaning and manipulation. To address these limitations, we present a photonic microsystem fabricated in polydimethylsiloxane and integrating micro-optical elements and a lightguide-cantilever for sub-micrometric analysis of small arteries (between 125 and 400μm of basal diameter). This technology enables simultaneous measurement of arterial distension, stiffness, vasomotion, and heartbeat and without the need for advanced imaging system. The microsystem has a limit of detection of 2μm, five times lower than video imaging-based myographs, is two times more sensitive than them (0.5 μm/mmHg), reduces variability to half and doubles the linear range reported in these myographs. More importantly, it allows the analysis of intact arteries preserving the integrity and function of surrounding tissues. Assays can be conducted in three configurations according to the surrounding tissue: (i) isolated arteries (in vitro) where the surrounding tissue is partially removed, (ii) non-isolated arteries (in vivo) with surrounding tissue partially removed, and (iii) intact arteries in vivo preserving surrounding tissue as well as function and integrity. This technology represents a step forward in the prediction of cardiovascular risk. info:eu-repo/semantics/acceptedVersion