On Unlimited Sampling

Shannon's sampling theorem provides a link between the continuous and the discrete realms stating that bandlimited signals are uniquely determined by its values on a discrete set. This theorem is realized in practice using so called analog--to--digital converters (ADCs). Unlike Shannon's sampling theorem, the ADCs are limited in dynamic range. Whenever a signal exceeds some preset threshold, the ADC saturates, resulting in aliasing due to clipping. The goal of this paper is to analyze an alternative approach that does not suffer from these problems. Our work is based on recent developments in ADC design, which allow for ADCs that reset rather than to saturate, thus producing modulo samples. An open problem that remains is: Given such modulo samples of a bandlimited function as well as the dynamic range of the ADC, how can the original signal be recovered and what are the sufficient conditions that guarantee perfect recovery? In this paper, we prove such sufficiency conditions and complement them with a stable recovery algorithm. Our results are not limited to certain amplitude ranges, in fact even the same circuit architecture allows for the recovery of arbitrary large amplitudes as long as some estimate of the signal norm is available when recovering. Numerical experiments that corroborate our theory indeed show that it is possible to perfectly recover function that takes values that are orders of magnitude higher than the ADC's threshold.Comment: 11 pages, 4 figures, copy of initial version to appear in Proceedings of 12th International Conference on Sampling Theory and Applications (SampTA

Implantable Fluorescence Imager for Deep Neuronal Imaging

This thesis describes the design, fabrication, and characterization of the Implantable Fluorescence Imager (IFI): a camera chip with a needle-like form factor designed for imaging neuronal activity in the deep brain. It is fabricated with a complementary metal oxide semiconductor (CMOS) process, allowing for hundreds or thousands of single- photon-sensitive photodetectors to be densely packed onto a device width comparable to a single-channel fiber optic cannula (~100 μm). The IFI uses a combination of spectral and temporal filters as a fluorescence emission filter, and per-pixel Talbot gratings for 3D light-field imaging. The IFI has the potential to overcome the imaging depth limit of multi-photon microscopes imposed by the scattering and absorption of photons in brain tissue, and the resolution limit of noninvasive imaging techniques, such as functional magnetic resonance imaging and photoacoustic imaging. It competes with graded index lens-based miniaturized microscopes in imaging depth, but offers several comparative advantages. First, its cross sectional area is at least an order of magnitude smaller for an equal field of view. Second, the distribution of pixels along its entire length allows the study of multi- layer or multi-region dynamics. Finally, the scalability advantage of silicon integrated circuit technology in system miniaturization and data bandwidth may allow thousands of such imaging shanks to be simultaneously deployed for large-scale volumetric recording

Integrated Electronics for Wireless Imaging Microsystems with CMUT Arrays

Integration of transducer arrays with interface electronics in the form of single-chip CMUT-on-CMOS has emerged into the field of medical ultrasound imaging and is transforming this field. It has already been used in several commercial products such as handheld full-body imagers and it is being implemented by commercial and academic groups for Intravascular Ultrasound and Intracardiac Echocardiography. However, large attenuation of ultrasonic waves transmitted through the skull has prevented ultrasound imaging of the brain. This research is a prime step toward implantable wireless microsystems that use ultrasound to image the brain by bypassing the skull. These microsystems offer autonomous scanning (beam steering and focusing) of the brain and transferring data out of the brain for further processing and image reconstruction. The objective of the presented research is to develop building blocks of an integrated electronics architecture for CMUT based wireless ultrasound imaging systems while providing a fundamental study on interfacing CMUT arrays with their associated integrated electronics in terms of electrical power transfer and acoustic reflection which would potentially lead to more efficient and high-performance systems. A fully wireless architecture for ultrasound imaging is demonstrated for the first time. An on-chip programmable transmit (TX) beamformer enables phased array focusing and steering of ultrasound waves in the transmit mode while its on-chip bandpass noise shaping digitizer followed by an ultra-wideband (UWB) uplink transmitter minimizes the effect of path loss on the transmitted image data out of the brain. A single-chip application-specific integrated circuit (ASIC) is de- signed to realize the wireless architecture and interface with array elements, each of which includes a transceiver (TRX) front-end with a high-voltage (HV) pulser, a high-voltage T/R switch, and a low-noise amplifier (LNA). Novel design techniques are implemented in the system to enhance the performance of its building blocks. Apart from imaging capability, the implantable wireless microsystems can include a pressure sensing readout to measure intracranial pressure. To do so, a power-efficient readout for pressure sensing is presented. It uses pseudo-pseudo differential readout topology to cut down the static power consumption of the sensor for further power savings in wireless microsystems. In addition, the effect of matching and electrical termination on CMUT array elements is explored leading to new interface structures to improve bandwidth and sensitivity of CMUT arrays in different operation regions. Comprehensive analysis, modeling, and simulation methodologies are presented for further investigation.Ph.D

An Optofluidic Lens Biochip and an x-ray Readable Blood Pressure Microsensor: Versatile Tools for in vitro and in vivo Diagnostics.

Three different microfabricated devices were presented for use in vivo and in vitro diagnostic biomedical applications: an optofluidic-lens biochip, a hand held digital imaging system and an x-ray readable blood pressure sensor for monitoring restenosis. An optofluidic biochip–termed the ‘Microfluidic-based Oil-Immersion Lens’ (mOIL) biochip were designed, fabricated and test for high-resolution imaging of various biological samples. The biochip consists of an array of high refractive index (n = 1.77) sapphire ball lenses sitting on top of an oil-filled microfluidic network of microchambers. The combination of the high optical quality lenses with the immersion oil results in a numerical aperture (NA) of 1.2 which is comparable to the high NA of oil immersion microscope objectives. The biochip can be used as an add-on-module to a stereoscope to improve the resolution from 10 microns down to 0.7 microns. It also has a scalable field of view (FOV) as the total FOV increases linearly with the number of lenses in the biochip (each lens has ~200 microns FOV). By combining the mOIL biochip with a CMOS sensor, a LED light source in 3D printed housing, a compact (40 grams, 4cmx4cmx4cm) high resolution (~0.4 microns) hand held imaging system was developed. The applicability of this system was demonstrated by counting red and white blood cells and imaging fluorescently labelled cells. In blood smear samples, blood cells, sickle cells, and malaria-infected cells were easily identified. To monitor restenosis, an x-ray readable implantable blood pressure sensor was developed. The sensor is based on the use of an x-ray absorbing liquid contained in a microchamber. The microchamber has a flexible membrane that is exposed to blood pressure. When the membrane deflects, the liquid moves into the microfluidic-gauge. The length of the microfluidic-gauge can be measured and consequently the applied pressure exerted on the diaphragm can be calculated. The prototype sensor has dimensions of 1x0.6x10mm and adequate resolution (19mmHg) to detect restenosis in coronary artery stents from a standard chest x-ray. Further improvements of our prototype will open up the possibility of measuring pressure drop in a coronary artery stent in a non-invasively manner.PhDMacromolecular Science and EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111384/1/toning_1.pd

Towards Single-Chip Nano-Systems

Important scientific discoveries are being propelled by the advent of nano-scale sensors that capture weak signals from their environment and pass them to complex instrumentation interface circuits for signal detection and processing. The highlight of this research is to investigate fabrication technologies to integrate such precision equipment with nano-sensors on a single complementary metal oxide semiconductor (CMOS) chip. In this context, several demonstration vehicles are proposed. First, an integration technology suitable for a fully integrated flexible microelectrode array has been proposed. A microelectrode array containing a single temperature sensor has been characterized and the versatility under dry/wet, and relaxed/strained conditions has been verified. On-chip instrumentation amplifier has been utilized to improve the temperature sensitivity of the device. While the flexibility of the array has been confirmed by laminating it on a fixed single cell, future experiments are necessary to confirm application of this device for live cell and tissue measurements. The proposed array can potentially attach itself to the pulsating surface of a single living cell or a network of cells to detect their vital signs

Implantable photonic neural probes for light-sheet fluorescence brain imaging

Significance: Light-sheet fluorescence microscopy (LSFM) is a powerful technique for highspeed volumetric functional imaging. However, in typical light-sheet microscopes, the illumination and collection optics impose significant constraints upon the imaging of non-transparent brain tissues. We demonstrate that these constraints can be surmounted using a new class of implantable photonic neural probes.Aim: Mass manufacturable, silicon-based light-sheet photonic neural probes can generate planar patterned illumination at arbitrary depths in brain tissues without any additional micro-optic components.Approach: We develop implantable photonic neural probes that generate light sheets in tissue. The probes were fabricated in a photonics foundry on 200-mm-diameter silicon wafers. The light sheets were characterized in fluorescein and in free space. The probe-enabled imaging approach was tested in fixed, in vitro, and in vivo mouse brain tissues. Imaging tests were also performed using fluorescent beads suspended in agarose.Results: The probes had 5 to 10 addressable sheets and average sheet thicknesses Conclusions: The neural probes can lead to new variants of LSFM for deep brain imaging and experiments in freely moving animals

Patterned photostimulation via visible-wavelength photonic probes for deep brain optogenetics

Optogenetic methods developed over the past decade enable unprecedented optical activation and silencing of specific neuronal cell types. However, light scattering in neural tissue precludes illuminating areas deep within the brain via free-space optics; this has impeded employing optogenetics universally. Here, we report an approach surmounting this significant limitation. We realize implantable, ultranarrow, silicon-based photonic probes enabling the delivery of complex illumination patterns deep within brain tissue. Our approach combines methods from integrated nanophotonics and microelectromechanical systems, to yield photonic probes that are robust, scalable, and readily producible en masse. Their minute cross sections minimize tissue displacement upon probe implantation. We functionally validate one probe design in vivo with mice expressing channelrhodopsin-2. Highly local optogenetic neural activation is demonstrated by recording the induced response—both by extracellular electrical recordings in the hippocampus and by two-photon functional imaging in the cortex of mice coexpressing GCaMP6