Photonic Lab-on-a-chip Research Articles

Microfluidic In-Situ Spectrophotometric Approaches to Tackle Actinides Analysis in Multiple Oxidation States.

The study and development of present and future processes for the treatment/recycling of spent nuclear fuels require many steps, from design in the laboratory to setting up on an industrial scale. In all of these steps, analysis and instrumentation are key points. For scientific reasons (small-scale studies, control of phenomena, etc.) but also with regard to minimizing costs, risks, and waste, such developments are increasingly carried out on milli- or microfluidic devices. The logic is the same for the chemical analyses associated with their follow-up and interpretation. Due to this, over the last few years, opto-microfluidic analysis devices adapted to the monitoring of different processes (dissolution, liquid-liquid extraction, precipitation, etc.) have been increasingly designed and developed. In this work, we prove that photonic lab-on-a-chip (PhLoC) technology is fully suitable for all actinides concentration monitoring along the plutonium uranium refining extraction (plutonium, uranium, reduction, extraction, or Purex) process. Several PhLoC microfluidic platforms were specifically designed and used in different nuclear research and development (R&D) laboratories, to tackle actinides analysis in multiple oxidation states even in mixtures. The detection limits reached (tens of µmol·L-1) are fully compliant with on-line process monitoring, whereas a range of analyzable concentrations of three orders of magnitude can be covered with less than 150µL of analyte. Finally, this work confirms the possibility and the potential of coupling Raman and ultraviolet-visible (UV-Vis) spectroscopies at the microfluidic scale, opening the perspective of measuring very complex mixtures.

Uranium(VI) On-Chip Microliter Concentration Measurements in a Highly Extended UV-Visible Absorbance Linearity Range.

The reduction of effluents deriving from analytical control is a serious concern in the nuclear industry, for both production and R&D units. In this work we report an alternative methodology for the standard UV-vis absorbance analyses for actinides concentration monitoring along the plutonium uranium refining extraction (PUREX) process. This methodology, based on photonic lab-on-a-chip (PhLoC) technology, enables drastic sampling reduction down to a few microliters and simultaneously allows to track concentrations over several orders of magnitude while maintaining a detection linearity range. A PhLoC microfluidic platform was specifically designed to allow online sample injection with zero dead volume connectivity and the on-chip spectrophotometric approach, based on a multiple optical path configuration, was tested for the determination of uranium(VI) concentrations from 0.1 to 200 g L-1, showing that linearity is maintained within high levels of confidence. These results provide the proof of concept for the transposition of current analytical methods for actinides, including plutonium, to microfluidic systems.

Innovative High-Throughput SAXS Methodologies Based on Photonic Lab-on-a-Chip Sensors: Application to Macromolecular Studies.

The relevance of coupling droplet-based Photonic Lab-on-a-Chip (PhLoC) platforms and Small-Angle X-Ray Scattering (SAXS) technique is here highlighted for the performance of high throughput investigations, related to the study of protein macromolecular interactions. With this configuration, minute amounts of sample are required to obtain reliable statistical data. The PhLoC platforms presented in this work are designed to allow and control an effective mixing of precise amounts of proteins, crystallization reagents and buffer in nanoliter volumes, and the subsequent generation of nanodroplets by means of a two-phase flow. Spectrophotometric sensing permits a fine control on droplet generation frequency and stability as well as on concentration conditions, and finally the droplet flow is synchronized to perform synchrotron radiation SAXS measurements in individual droplets (each one acting as an isolated microreactor) to probe protein interactions. With this configuration, droplet physic-chemical conditions can be reproducibly and finely tuned, and monitored without cross-contamination, allowing for the screening of a substantial number of saturation conditions with a small amount of biological material. The setup was tested and validated using lysozyme as a model of study. By means of SAXS experiments, the proteins gyration radius and structure envelope were calculated as a function of protein concentration. The obtained values were found to be in good agreement with previously reported data, but with a dramatic reduction of sample volume requirements compared to studies reported in the literature.

Photonic Lab-on-a-Chip for Rapid Cytokine Detection

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...

Plug and measure - a chip-to-world interface for photonic lab-on-a-chip applications.

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.

Biofunctionalized all-polymer photonic lab on a chip with integrated solid-state light emitter

A photonic lab on a chip (PhLOC), comprising a solid-state light emitter (SSLE) aligned with a biofunctionalized optofluidic multiple internal reflection (MIR) system, is presented. The SSLE is obtained by filling a microfluidic structure with a phenyltrimethoxysilane (PhTMOS) aqueous sol solution containing a fluorophore organic dye. After curing, the resulting xerogel solid structure retains the emitting properties of the fluorophore, which is evenly distributed in the xerogel matrix. Photostability studies demonstrate that after a total dose (at λ=365 nm) greater than 24 J cm−2, the xerogel emission decay is only 4.1%. To re-direct the emitted light, the SSLE includes two sets of air mirrors that surround the xerogel. Emission mapping of the SSLE demonstrates that alignment variations of 150 µm (between the SSLE and the external pumping light source) provide fluctuations in emitted light smaller than 5%. After this verification, the SSLE is monolithically implemented with a MIR, forming the PhLOC. Its performance is assessed by measuring quinolone yellow, obtaining a limit of detection (LOD) of (0.60±0.01) µM. Finally, the MIR is selectively biofunctionalized with horseradish peroxidase (HRP) for the detection of hydrogen peroxide (H2O2) target analyte, obtaining a LOD of (0.7±0.1) µM for H2O2, confirming, for the first time, that solid-state xerogel-based emitters can be massively implemented in biofunctionalized PhLOCs.

PDMS based photonic lab-on-a-chip for the selective optical detection of heavy metal ions

The selective absorbance detection of mercury(II) (Hg(2+)) and lead(II) (Pb(2+)) ions using ferrocene-based colorimetric ligands and miniaturized multiple internal reflection (MIR) systems implemented in a low-cost photonic lab on a chip (PhLoC) is reported. The detection principle is based on the formation of selective stable complexes between the heavy metal ion and the corresponding ligand. This interaction modulates the ligand spectrum by giving rise to new absorbance bands or wavelength shifting of the existing ones. A comparative study for the detection of Hg(2+) was carried out with two MIR-based PhLoC systems showing optical path lengths (OPLs) of 0.64 cm and 1.42 cm as well as a standard cuvette (1.00 cm OPL). Acetonitrile solutions containing the corresponding ligand and increasing concentrations of the heavy metal ion were pumped inside the systems and the absorbance in the visible region of the spectra was recorded. The optical behaviour of all the tested systems followed the expected Beer-Lambert law. Thus, the best results were achieved with the one with the longest OPL, which showed a linear behaviour in a concentration range of 1 μM-90 μM Hg(2+), a sensitivity of 5.6 × 10(-3) A.U. μM(-1) and a LOD of 2.59 μM (0.49 ppm), this being 1.7 times lower than that recorded with a standard cuvette, and using a sample/reagent volume around 190 times smaller. This microsystem was also applied for the detection of Pb(2+) and a linear behaviour in a concentration range of 3-100 μM was obtained, and a sensitivity of 9.59 × 10(-4) A.U. μM(-1) and a LOD of 4.19 μM (0.868 ppm) were achieved. Such a simple analytical tool could be implemented in portable instruments for automatic in-field measurements and, considering the minute sample and reagent volume required, would enable the deployment of high throughput environmental analysis of these pollutants and other related hazardous species.

Development and integration of xerogel polymeric absorbance micro-filters into lab-on-chip systems

This work reports on the implementation of different absorption micro-filters based on a dye-doped hybrid organic-inorganic xerogel polymeric material synthesized by the sol-gel process. Microstructures containing eight different filter widths were fabricated in polydimethylsiloxane (PDMS), bonded to glass substrates and filled with the corresponding dye doped polymeric material by a soft lithography approach. The filtering capacity as a function of dye concentration and filter width was studied and revealed a linear dependence with both parameters, as expected according to the Beer-Lambert law. Zero passband transmittance values and relatively sharp stopband regions were achieved with all the filters, also showing rejection levels between -6 dB and -55 dB. Finally, such filters were monolithically integrated into a disposable fluorescence-based photonic lab-on-a-chip (PhLoC) approach. Calibration curves carried out with a model fluorophore target analyte showed an over two-fold increase in sensitivity and a thirty-fold decrease of the limit of detection (LOD) compared with the values recorded using the same PhLoC system but without the polymeric filter structure. The results presented herein clearly indicate the feasibility of these xerogel-based absorbance filtering structures for being applied as low-cost optical components that can be easily incorporated into disposable fluorescence-based photonic lab on a chip systems.

Cell analysis using a multiple internal reflection photonic lab-on-a-chip

Here we present a protocol for analyzing cell cultures using a photonic lab-on-a-chip (PhLoC). By using a broadband light source and a spectrometer, the spectrum of a given cell culture with an arbitrary population is acquired. The PhLoC can work in three different regimes: light scattering (using label-free cells), light scattering plus absorption (using stained cells) and, by subtraction of the two former regimes, absorption (without the scattering band). The acquisition time of the PhLoC is ∼30 ms. Hence, it can be used for rapid cell counting, dead/live ratio estimation or multiparametric measurements through the use of different dyes. The PhLoC, including microlenses, micromirrors and microfluidics, is simply fabricated in a single-mask process (by soft lithographic methods) using low-cost materials. Because of its low cost it can easily be implemented for point-of-care applications. From raw substrates to final results, this protocol can be completed in 29 h.