Nanophotonic Biosensor Technologies for Lab on Chip Applications--a Focus Article on Optical Biosensors from Three EC Lab on Chip Projects with a Comparison to the State of Art

摘要

This paper compares the performances of various nanophotonic biosensors developed in three recent European Lab-on-Chip collaborations: SABIO, INTOPSENS and POSITIVE. These are attractive for biosensing due to their small footprint, high Q-factors and compatibility with on-chip optics and microfluidics enabling integrated sensor arrays for compact lab-on-chip (LOC) applications. Many applications typically require the addressing of a number of issues including: improving limit of detection, managing the influence of temperature, parallelization of the measurement for higher throughput and on-chip referencing, efficient light-coupling strategies to simplify alignment, and packaging of the nanophotonics chip and integration with microfluidics. For ring resonator-based sensors, volumetric sensitivities of 246 nm/RIU and 2169 nm/RIU and limits of detection of 5 × 10~(-6) RIU and 8.3 × 10~(-6) RIU were reported from SABIO (at 1.3 μm) and INTOPSENS (at 1.5 μm), respectively. For SABIO, this was for an eight-channel Si_3N_4 slot-waveguide ring resonator sensor array whilst for INTOPSENS this was for an individual Si Vernier cascade sensor. In POSITIVE for porous alumina-based membrane sensors, a volumetric limit of detection (LOD) was reported at 5 × 10~(-6) RIU but more importantly, in contrast to the sensors from the other two projects, the standard deviation of the measured values was below 5 %, sensing response times were fast and small sample volumes could be used (<100 μl). For biosensing within SABIO, a surface limit of detection of 0.9 pg/mm~2 for anti-BSA on a gluteraldehyde-covered surface was recorded corresponding to a 125 ng/ml anti-BSA solution, whilst Si slot-waveguide ring resonators have reported 2 pg/mm~2 and 10 ng/ml for biotin on a streptavidin-coated surface. In contrast, in POSITIVE, for an assay of β-lactoglobulin-anti-β-lactoglobulin-anti-rabbit-IgG-streptavidin-conjugated CdSe quantum dots, a noise floor for individual measurements of 3.7 ng/ml (25 pM) was obtained, with an overall statistical, or formal assay LOD of 33.7 ng/ml (225 pM), for total assay times of under 1 h. With similar volumetric limits of detection, the sensors are still poorer than that of the state of art in nanophotonic sensors; however, the POSITIVE device compared favourably to it at least for total assay times, response times and minimum volumes of analyte necessary.