Flexible Single-Photon Image Sensors, CMOS Circuits for Biological Sensing and Processing

Photon-counting imaging technology has applications in many fields such as fluorescence lifetime imaging microscopy (FLIM), time-resolved Raman spectroscopy, 3D imaging, and even space communications. The requirement to detect single photons with picosecond temporal resolution makes single-photon avalanche photodiode (SPAD) a popular choice. Advanced biomedical imaging applications such as pill cameras, retinal prosthesis, and implantable biocompatible monitoring sensors require a compact image system, which can be implanted into a living body. To meet these requirements, novel single-photon image sensor solution needs to be developed, in which new substrate post-processing and backside illumination or even dual-side illumination are core technologies, with inherent CMOS compatibility as a prerequisite. This chapter proposed and demonstrated the world’s first flexible CMOS single-photon avalanche diode image sensor, providing a suitable solution for implantable biomedical imaging or monitoring applications, and wherever a curved imaging plane is essential

High-Throughput and Label-Free Single Nanoparticle Sizing Based on Time-Resolved On-Chip Microscopy

Sizing individual nanoparticles and dispersions of nanoparticles provides invaluable information in applications such as nanomaterial synthesis, air and water quality monitoring, virology, and medical diagnostics. Several conventional nanoparticle sizing approaches exist; however, there remains a lack of high-throughput approaches that are suitable for low-resource and field settings, <i>i.e.</i>, methods that are cost-effective, portable, and can measure widely varying particle sizes and concentrations. Here we fill this gap using an unconventional approach that combines holographic on-chip microscopy with vapor-condensed nanolens self-assembly inside a cost-effective hand-held device. By using this approach and capturing time-resolved <i>in situ</i> images of the particles, we optimize the nanolens formation process, resulting in significant signal enhancement for the label-free detection and sizing of individual deeply subwavelength particles (smaller than λ/10) over a 30 mm² sample field-of-view, with an accuracy of ±11 nm. These time-resolved measurements are significantly more reliable than a single measurement at a given time, which was previously used only for nanoparticle detection without sizing. We experimentally demonstrate the sizing of individual nanoparticles as well as viruses, monodisperse samples, and complex polydisperse mixtures, where the sample concentrations can span ∼5 orders-of-magnitude and particle sizes can range from 40 nm to millimeter-scale. We believe that this high-throughput and label-free nanoparticle sizing platform, together with its cost-effective and hand-held interface, will make highly advanced nanoscopic measurements readily accessible to researchers in developing countries and even to citizen-scientists, and might especially be valuable for environmental and biomedical applications as well as for higher education and training programs

Computational On-Chip Imaging of Nanoparticles and Biomolecules using Ultraviolet Light

Significant progress in characterization of nanoparticles and biomolecules was enabled by the development of advanced imaging equipment with extreme spatial-resolution and sensitivity. To perform some of these analyses outside of well-resourced laboratories, it is necessary to create robust and cost-effective alternatives to existing high-end laboratory-bound imaging and sensing equipment. Towards this aim, we have designed a holographic on-chip microscope operating at an ultraviolet illumination wavelength (UV) of 266 nm. The increased forward scattering from nanoscale objects at this short wavelength has enabled us to detect individual sub-30 nm nanoparticles over a large field-of- view of > 16 mm(2) using an on-chip imaging platform, where the sample is placed at <= 0.5 mm away from the active area of an opto-electronic sensor-array, without any lenses in between. The strong absorption of this UV wavelength by biomolecules including nucleic acids and proteins has further enabled high-contrast imaging of nanoscopic aggregates of biomolecules, e.g., of enzyme Cu/Zn-superoxide dismutase, abnormal aggregation of which is linked to amyotrophic lateral sclerosis (ALS)-a fatal neurodegenerative disease. This UV-based wide-field computational imaging platform could be valuable for numerous applications in biomedical sciences and environmental monitoring, including disease diagnostics, viral load measurements as well as air-and water-quality assessment.Army Research Office (ARO) [W911NF-13-1-0419, W911NF-13-1-0197]; ARO Life Sciences Division; National Science Foundation (NSF) CBET Division Biophotonics Program; NSF Emerging Frontiers in Research and Innovation (EFRI) Award; NSF EAGER Award; NSF INSPIRE Award; NSF Partnerships for Innovation; Building Innovation Capacity (PFI: BIC) Program; Office of Naval Research (ONR); National Institutes of Health (NIH); Howard Hughes Medical Institute (HHMI); Vodafone Americas Foundation; Vodafone Americas Foundation, the Mary Kay Foundation; Steven & Alexandra Cohen Foundation; KAUST; RGK Foundation [20143057]; National Science Foundation [0963183]; American Recovery and Reinvestment Act of 2009 (ARRA)This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]