Ana Belén González-Guerrero

Integrated Bimodal Waveguide Interferometric Biosensor for Label-Free Analysis

The performance of an interferometric device based on integrated Bimodal Waveguides (BiMW) for sensing is demonstrated. The sensors are fabricated using standard silicon technology and can achieve a detection limit of 2.5·10- 7 RIU for homogeneous sensing, rendering in a very high sensitive device. The applicability of the bimodal waveguide interferometer as label-free biosensor has been demonstrated by the real-time monitoring of the biomolecular interaction of BSA and antiBSA. Due to their simplicity, the interferometric devices could be further integrated in complete lab-on-a-chip platforms for point-of-care diagnostics showing them as a powerful instrument for biochemical analysis.

All-optical phase modulation for integrated interferometric biosensors

We present the theoretical and the experimental implementation of an all-optical phase modulation system in integrated Mach-Zehnder Interferometers to solve the drawbacks related to the periodic nature of the interferometric signal. Sensor phase is tuned by modulating the emission wavelength of low-cost commercial laser diodes by changing their output power. FFT deconvolution of the signal allows for direct phase readout, immune to sensitivity variations and to light intensity fluctuations. This simple phase modulation scheme increases the signal-to-noise ratio of the measurements in one order of magnitude, rendering in a sensor with a detection limit of 1.9·10⁻⁷ RIU. The viability of the all-optical modulation approach is demonstrated with an immunoassay detection as a biosensing proof of concept.

Scalable fabrication of immunosensors based on carbon nanotube polymer composites

In this work we present the fabrication and characterization of immunosensors based on polystyrene (PS)-multiwalled carbon nanotube (MWCNT) composites. The electrochemical properties of the sensors have been investigated and show that the surface area is increased upon addition of the MWCNT-PS layer. Furthermore, a plasma activation process is used to partially remove the PS and expose the MWCNTs. This results in a huge increase in the electrochemical area and opens up the possibility of binding biomolecules to the MWCNT wall. The MWCNTs have been functionalized covalently with a model antibody (rabbit IgG). The biosensors have been tested using amperometric techniques and show detection limits comparable to standard techniques such as ELISA.

A comparative study of in-flow and micro-patterning biofunctionalization protocols for nanophotonic silicon-based biosensors.

Reliable immobilization of bioreceptors over any sensor surface is the most crucial step for achieving high performance, selective and sensitive biosensor devices able to analyze human samples without the need of previous processing. With this aim, we have implemented an optimized scheme to covalently biofunctionalize the sensor area of a novel nanophotonic interferometric biosensor. The proposed method is based on the ex-situ silanization of the silicon nitride transducer surface by the use of a carboxyl water soluble silane, the carboxyethylsilanetriol sodium salt (CTES). The use of an organosilane stable in water entails advantages in comparison with usual trialkoxysilanes such as avoiding the generation of organic waste and leading to the assembly of compact monolayers due to the high dielectric constant of water. Additionally, cross-linking is prevented when the conditions (e.g. immersion time, concentration of silane) are optimized. This covalent strategy is followed by the bioreceptor linkage on the sensor area surface using two different approaches: an in-flow patterning and a microcontact printing using a biodeposition system. The performance of the different bioreceptor layers assembled is compared by the real-time and label-free immunosensing of the proteins BSA/mAb BSA, employed as a model molecular pair. Although the results demonstrated that both strategies provide the biosensor with a stable biological interface, the performance of the bioreceptor layer assembled by microcontact printing slightly improves the biosensing capabilities of the photonic biosensor.

Label-free bimodal waveguide immunosensor for rapid diagnosis of bacterial infections in cirrhotic patients

Spontaneous bacterial peritonitis is an acute bacterial infection of ascitic fluid; it has a high incidence in cirrhotic patients and it is associated with high mortality. In such a situation, early diagnosis and treatment is crucial for the survival of the patient. However, bacterial analysis in ascitic fluid is currently based on culture methods, which are time-consuming and laborious. We report here the application of a photonic interferometer biosensor based on a bimodal waveguide (BiMW) for the rapid and label-free detection of bacteria directly in ascitic fluid. The device consists of a straight waveguide in which two modes of the same polarization interfere while interacting with the external medium through their evanescent fields. A bimolecular event occurring on the sensor area of the device (e.g. capturing bacteria) will differently affect each light mode, inducing a variation in the phase of the light exiting at the output of the waveguide. In this work, we demonstrate the quantitative detection of Bacillus cereus in buffer medium and Escherichia coli in undiluted ascitic fluid from cirrhotic patients. In the case of Bacillus cereus detection, the device was able to specifically detect bacteria at relevant concentrations in 12.5min and in the case of Escherichia coli detection, the analysis time was 25min. Extrapolation of the data demonstrated that the detection limits of the biosensor could reach few bacteria per milliliter. Based on the results obtained, we consider that the BiMW biosensor is positioned as a promising new clinical tool for user-friendly, cost-effective and real-time microbiological analysis.

Trends in photonic lab-on-chip interferometric biosensors for point-of-care diagnostics

Portable point-of care (POC) devices for in vitro diagnostics will be a milestone for the achievement of universal healthcare and environmental protection. The main goal is to reach a rapid, user-friendly and highly sensitive portable tool which can provide immediate results in any place at any time while having a competitive cost. Integrated optical (IO) waveguide based-biosensors are the most suitable candidates to achieve this ambitious objective. They are able to operate in real samples (such as blood, urine, wastewater…) affording relevant sensitivities even under a label-free scheme. In addition, arrays of IO sensors for multiplexed analysis can be integrated in lab-on-chip (LOC) platforms, providing a truly cost-effective fabrication and miniaturization. Among the different IO biosensors, interferometric ones have demonstrated the highest sensitivity for label-free detection ever reported. Although the first interferometric biosensors were developed in the early nineties, they focused mainly on preliminary proof-of-concept studies; only recently the resilient potential of interferometric biosensors as highly advanced POC devices has firmly emerged. This review provides an overview of the state-of-the art in photonic interferometric biosensors, their main biofunctionalisation routes and their integration in LOC platforms, while maintaining a special focus on the real analytical applications achieved so far.

Interferometric waveguide biosensors based on Si-technology for point-of-care diagnostic

Silicon photonic biosensors based on evanescent wave detection have revealed themselves as the most promising candidates for achieving truly point-of-care devices as they can overcome the limitations of current analytical techniques. Advantages such as miniaturization, extreme sensitivity, robustness, reliability, potential for multiplexing and mass production at low cost can be offered. Among the existing integrated optical sensors, the interferometric ones are the most attractive due to their extreme sensitivity for label-free and real-time evaluations with detection limits close to 10-7- 10-8 in bulk refractive index. In this article we will review the recent progress in the most common interferometric waveguide biosensors (Mach-Zehnder interferometers, Young interferometers, Hartman interferometers, dual polarization interferometers and bimodal optical waveguides). In particular, we will focus on the description of their optical structures and their applicability for bioanalytical detection.

Towards a complete lab-on-chip system using integrated Mach-Zehnder interferometers

Most clinical tests are time-consuming, expensive and have to be performed by specialized technicians in laboratory environments. Indeed this kind of tests require sampling and labelling with fluorescent or radioactive tags. There is an urgent and compelling need of methods which can allow the identification of any disease at the earliest stage possible in a fast, direct, simple and cost-effective way. To fulfill these requirements, integrated optical biosensors and, in particular, those based on evanescent field sensing, are very attractive, especially because they allow for compactness, sensitive, real-time and label-free on-site measurements [1], [2]. They also offer the possibility to perform different measurements in parallel or to integrate several analytical steps, from sample preparation to detection, into a single miniaturized device (the so-called “Lab-Ona-Chip” platform).

A low-cost integrated biosensing platform based on SiN nanophotonics for biomarker detection in urine

We present a low-cost integrated nanophotonic lab-on-a-chip platform suitable for point-of-care (POC) biomarker analysis. The sensor chip included in the platform contains multiplexed Mach–Zehnder interferometers with an on-chip optical spectral analyser consisting of an arrayed-waveguide grating. The sensor chip is fabricated in silicon nitride material, which makes it compatible with consumer-electronics-grade sources and detectors, leading to the possibility of low-cost instrumentation. The nanophotonic sensor chip exhibits a detection limit of 6 × 10−6 RIU (Refractive Index Units), which is in the same order of magnitude as the reported values for state-of-the-art evanescent wave sensors. The sensor chip is biofunctionalised with specific bioreceptors and integrated into a polymer microfluidic cartridge. The POC instrumentation platform contains optical excitation and read-out sub-systems and dedicated on-board software for real-time analysis of patient samples. To demonstrate the versatility of the platform, we present results both on the detection of an antigen related to tuberculosis directly in urine samples using a laboratory prototype and on the detection of a protein biomarker (CRP) related to inflammation using the integrated instrument.