In this paper, a fully functional low light 128 X 128 contact image sensor for cell detection in biosensing applications is presented. The imager, fabricated in 0.18 mum CMOS technology, provides low-noise operation by employing both a modified version of the active reset (AR) technique and a modified version of the active column sensor (ACS) readout method. High-sensitivity, low noise performance of the presented sensor is well-suited for fluorescence imaging. For this purpose, an emission filter was fabricated and integrated with the sensor. The filter was fabricated using PDMS and Sudan II Blue dye mix, spin-coated and deposited in a class 1000 clean room. The designed filter is suitable for excitation at wavelengths below 340 nm and emission at 450 nm and above. The fabricated imager architecture and operation are described, noise analysis is presented and measurements from a test chip are shown. Experimental results using live neurons from the pond snail, Lymnaea stagnalis, and fluorescence polystyrene micro-beads prove the functionality of the fabricated system and indicate its biocompatiblity.

Early diagnosis of disease onset requires sensor systems that detect multiple disease-related processes within the body. However, major obstacles must be surmounted for in vivo sensor use, including size, biocompatibility, sensitivity, and selectivity. As an initial study, here we fabricated a multidimensional gold nanorod (GNR)-based bio-barcode sensing array for sensitive and selective detection of biological events. The sensor comprises an array of gold nanocavities and GNRs that are bound to the array as well as to fluorescein via bio-barcode peptides. Exposure of the sensor to peptide-specific enzymes as inputs led to bio-barcode cleavage, which produced distinct optical-based output, that is, changes in fluorescence lifetime and surface plasmon resonance. The sensor showed sensitivity and selectivity to each biomarker input alone, as well as simultaneous distinguishable responses to their combination. By performing AND, OR, and XOR operations at the sensing system level, the biological events can be simply detected. This GNR-based bio-barcode sensor, incorporating plasmonic and fluorescent-enhancing nanotechnologies, is versatile and adaptable and thus has the potential to enable detection of a wide range of biomarkers to provide complex and advanced detection capabilities that have not been previously possible.

Nanoplasmonic biosensors incorporating noble metal nanocavity arrays are widely used for the detection of various biomarkers. Gold nanorods (GNRs) have unique properties that can enhance spectroscopic detection capabilities of such nanocavity-based biosensors. However, the contribution of the physical properties of multiple GNRs to resonance enhancement of gold nanocavity arrays requires further characterization and elucidation. In this work, we study how GNR aspect ratio (AR) and surface area (SA) modify the plasmonic resonance spectrum of a gold triangular nanocavity array by both simulations and experiments. The finite integration technique (FIT) simulated the extinction spectrum of the gold nanocavity array with 300 nm periodicity onto which the GNRs of different ARs and SAs are placed. Simulations showed that matching of the GNRs longitudinal peak, which is affected by AR, to the nanocavity array’s spectrum minima can optimize signal suppression and shifting. Moreover, increasing SA of the matched GNRs increased the spectral variations of the array. Experiments confirmed that GNRs conjugated to a gold triangular nanocavity array of 300 nm periodicity caused spectrum suppression and redshift. Our findings demonstrate that tailoring of the GNR AR and SA parameters to nanoplasmonic arrays has the potential to greatly improve spectral variations for enhanced plasmonic biosensing.

This paper presents a 128x128 low noise CMOS image sensor with emission filter for fluorescence detection. The imager, fabricated in 0.18µm CMOS technology, provides lownoise operation by employing both the active reset (AR) technique and the active column sensor (ACS) readout method. The emission filter was fabricated using PDMS and Sudan II Blue dye mixed, spin-coated and deposited in the class 1000 clean room. The designed filter is suitable for excitation at wavelengths below 340 nm and emission at 450nm and above. Filter properties, such as thickness, transmission and efficiency of utilization with the fabricated imager are discussed. Preliminary measurements of the system using microbeads are also presented.

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