Integrated semiconductor optical sensors for cellular and neural imaging

Abstract

Abstract-Intrinsic Optical Signal (IOS) imaging is a widely accepted technique for imaging brain activity. We propose an integrated device consisting of interleaved arrays of gallium arsenide (GaAs) based semiconductor light sources and detectors operating at telecommunications wavelengths in the near-infrared. Such a device will allow for long-term, minimally invasive monitoring of neural activity in freely behaving subjects, and will enable the use of structured illumination patterns to improve system performance. In this work we describe the proposed system and show that nearinfrared IOS imaging at wavelengths compatible with semiconductor devices can produce physiologically significant images in mice, even through skull. I. INTRODUCTIONptical imaging of neural activity is a widely accepted technique for imaging brain function in the field of neuroscience research, and has been used to study the cerebral cortex for nearly two decades [1]. Maps of brain activity are obtained by monitoring intensity changes in back-scattered light, called Intrinsic Optical Signals (IOS) that correspond to fluctuations in blood oxygenation and volume associated with neural activity. Current imaging systems typically employ benchtop equipment including lamps and CCD cameras to study animals using visible light. Such systems require the use of anesthetized or immobilized subjects with craniotomies, which imposes limitations on the Thomas T. Lee is with the

Implantable semiconductor biosensor for continuous in vivo sensing of far-red fluorescent molecules

“…Therefore the photodetector must be sensitive to low photon fluxes (~10 8 photons/sec/cm 2 /str, based on 675nm nude mouse autofluorescence values), with several orders of linear detection dynamic range. An integrated GaAs PIN photodiode compares favorably to a silicon-based photodetector because intrinsic material properties reduce the dark current, and therefore noise values, by approximately a factor of 10x [16], suitable for low noise un-cooled operation. In addition, we implemented a large-area pixel design (detector area ~0.75 mm 2 ) in order to collect photons from an approximate 3 x 3 mm tissue cross-section area with a depth of 1-2mm [26], which is suited to monitor the growth of a tumor.…”

“…The sensor incorporates three basic components of a fluorescence system, including: a 675nm vertical-cavity surface-emitting laser (VCSEL) excitation source, a GaAs PIN photodiode, and a fluorescence emission filter. Monolithic integration is important because all components of the device are fabricated using a semiconductor process flow from a single wafer, patterned using photolithography techniques, which allows for arbitrary arrangement of sources and detectors at separation distances on the order of 100µm [16] at minimal cost. The sensor is sensitive to cyanine 5.5 (Cy5.5; GE Healthcare/Amersham)-based NIR fluorescent probes.…”

Flexible Opto-Fluidic Fluorescence Sensors Based on Heterogeneously Integrated Micro-VCSELs and Silicon Photodiodes

“…The fabricated sensors were placed in a close proximity to a dye-coated glass substrate or a microfluidic channel filled with a dye solution to collect fluorescent signals. More recently, similar optoelectronic sensors using shorter-wavelength (675 nm) AlGaInP-based VCSELs were also reported for continuous monitoring of fluorescence from cyanine 5.5 dye in a mouse model with a maximum sensitivity of 50 nM. − Although configured well for many applications, such monolithically grown wafer-based sensor platforms fabricated by conventional semiconductor packaging schemes have limitations in the spatial layout and areal coverage of constituting devices, which therefore restrict the recording of fluorescence signals only at one or a few locations at a time and are not suited for spatiotemporal imaging over large subject areas. Moreover, the main system components (i.e., VCSEL and PD) are built on the rigid and brittle surface of a semiconductor wafer, thereby intrinsically limiting their conformal, harmonious integration onto soft, curvilinear surfaces such as those in biological systems.…”

Primal Remonstrance Evolution of NIR Single Chip Optical Sensor for Mental Tomography and their Practicability

“…Vertical Cavity Surface Emitting Lasers (VCSELs) designed for single mode Operation over a middle ground between LEDs and multi-mode VCSELs [3] and are easily incorporated into an integrated emitter/photodiode system [2,8]. The figure of merit used to characterize intensity noise is known as Relative Intensity Noise (RIN).…”