Optical biosensing using particle diffusometry on thermoplastic microfluidic chips bonded using direct and indirect chip bonding methods.

Integrated optical biosensors have become one of the most compelling technologies for the achievement of highly sensitive, multianalyte, portable and easy to use point-of-care (POC) devices with tremendous impact in healthcare and environmental protection, among other application fields. In this context, bimodal waveguide (BiMW) interferometers have emerged over the last years as a powerful biosensor technology providing the benefits of extreme sensitivity under a label-free scheme, reliability and robustness within a highly compact footprint that can be integrated and multiplexed in lab-on-a-chip (LOC) platforms. In this review, we provide an overview of the state-of-the-art about integrated optical BiMW biosensors from the theoretical fundamentals to their practical implementation. Furthermore, we explore recent advances such as novel designs, integration in specific LOC systems and its application in real biosensing scenarios. Final remarks and perspectives on the potential impact of these biosensor interferometric structures are also provided, as well as some limitations that must be addressed in next steps.

The importance of biosensors based on optical fiber (OF) technology is increasing due to their high sensitivity and compatibility with minimally invasive real-time diagnostics and enormous potentials for in vivo biopsies. This study investigates the technical aspects behind integrating Lab-on-Tip optrodes within microfluidic channels, which is propaedeutic for guidelines setting towards their correct connection with minimally invasive clinical tools such as needles, catheters and nanoendoscopes. Here, as proof of concept, we investigated the integration of a plasmonic Metasurface-assisted Lab-on-Tip optrode, realized onto a single mode OF tip (OFMT), into a T-shaped microfluidic chip for the detection of a clinically relevant target molecule as the breast cancer biomarker receptor tyrosine protein kinase (ErbB2). The biosensor response to different ErbB2 concentrations (1–1000 ng/mL) was analyzed under controlled flow conditions. Experiments demonstrated a strong dependence of the detection performance on the probe position within the microfluidic channel, with increased performance frustration as the distance of the tip from the center is reduced. These findings, confirmed by numerical modeling, revealed an inverse relationship between the flow velocity and the biosensor performance. This relationship was further corroborated by additional experiments demonstrating that higher flow rates reduce the target molecule capability to correctly recognize the bioreceptor immobilized on the sensor surface due to the shorter analyte-probe interaction time. In summary, the present study highlights the importance of a multi-aspect microfluidics design considering local flow conditions for optimal probe placement, providing valuable guidelines for improving detection capabilities of microfluidic assisted Lab-on-Tip biosensing platforms for biomedical applications. • A Lab-on-Tip plasmonic optrode was integrated in a microfluidic chip to detect ErbB2. • The probe position in the channel and the flow rate affect the detection performance. • The biosensor response to different ErbB2 concentrations (1–1000 ng/mL) was analyzed.

In this study, we developed an optofluidic chip consisting of a guided-mode resonance (GMR) sensor incorporated into a microfluidic chip to achieve simultaneous blood plasma separation and label-free albumin detection. A sedimentation chamber is integrated into the microfluidic chip to achieve plasma separation through differences in density. After a blood sample is loaded into the optofluidic chip in two stages with controlled flow rates, the blood cells are kept in the sedimentation chamber, enabling only the plasma to reach the GMR sensor for albumin detection. This GMR sensor, fabricated using plastic replica molding, achieved a bulk sensitivity of 175.66 nm/RIU. With surface-bound antibodies, the GMR sensor exhibited a limit of detection of 0.16 μg/mL for recombinant albumin in buffer solution. Overall, our findings demonstrate the potential of our integrated chip for use in clinical samples for biomarker detection in point-of-care applications.

A unique technique for the rapid fabrication of thermoplastic microfluidic chips is described. The method enables the realization of fully-sealed microchannels in around one hour while requiring only minimal infrastructure by taking advantage of a solvent swelling mechanism that allows raised features to be patterned on the surface of homogeneous thermoplastic materials. Patterning is achieved without photolithography by simply drawing the desired microchannel pattern onto the polymer surface using a suitable ink as a masking layer, either manually or under robotic control, followed by timed exposure to solvent vapor to yield a desired depth for the masked channel features. The channels are then permanently sealed through solvent bonding of the microchannel chip to a mating thermoplastic substrate. The process is demonstrated using cyclic olefin copolymer as a thermoplastic material, with fully operational microfluidic devices fabricated following a true desktop manufacturing model suitable for rapid prototyping.