A 25 micron-thin microscope for imaging upconverting nanoparticles with NIR-I and NIR-II illumination.

Rationale: Intraoperative visualization in small surgical cavities and hard-to-access areas are essential requirements for modern, minimally invasive surgeries and demand significant miniaturization. However, current optical imagers require multiple hard-to-miniaturize components including lenses, filters and optical fibers. These components restrict both the form-factor and maneuverability of these imagers, and imagers largely remain stand-alone devices with centimeter-scale dimensions. Methods: We have engineered INSITE (Immunotargeted Nanoparticle Single-Chip Imaging Technology), which integrates the unique optical properties of lanthanide-based alloyed upconverting nanoparticles (aUCNPs) with the time-resolved imaging of a 25-micron thin CMOS-based (complementary metal oxide semiconductor) imager. We have synthesized core/shell aUCNPs of different compositions and imaged their visible emission with INSITE under either NIR-I and NIR-II photoexcitation. We characterized aUCNP imaging with INSITE across both varying aUCNP composition and 980 nm and 1550 nm excitation wavelengths. To demonstrate clinical experimental validity, we also conducted an intratumoral injection into LNCaP prostate tumors in a male nude mouse that was subsequently excised and imaged with INSITE. Results: Under the low illumination fluences compatible with live animal imaging, we measure aUCNP radiative lifetimes of 600 μs - 1.3 ms, which provides strong signal for time-resolved INSITE imaging. Core/shell NaEr0.6Yb0.4F4 aUCNPs show the highest INSITE signal when illuminated at either 980 nm or 1550 nm, with signal from NIR-I excitation about an order of magnitude brighter than from NIR-II excitation. The 55 μm spatial resolution achievable with this approach is demonstrated through imaging of aUCNPs in PDMS (polydimethylsiloxane) micro-wells, showing resolution of micrometer-scale targets with single-pixel precision. INSITE imaging of intratumoral NaEr0.8Yb0.2F4 aUCNPs shows a signal-to-background ratio of 9, limited only by photodiode dark current and electronic noise. Conclusion: This work demonstrates INSITE imaging of aUCNPs in tumors, achieving an imaging platform that is thinned to just a 25 μm-thin, planar form-factor, with both NIR-I and NIR-II excitation. Based on a highly paralleled array structure INSITE is scalable, enabling direct coupling with a wide array of surgical and robotic tools for seamless integration with tissue actuation, resection or ablation

High-speed imaging in fluids

High-speed imaging is in popular demand for a broad range of experiments in fluids. It allows for a detailed visualization of the event under study by acquiring a series of image frames captured at high temporal and spatial resolution. This review covers high-speed imaging basics, by defining criteria for high-speed imaging experiments in fluids and to give rule-of-thumbs for a series of cases. It also considers stroboscopic imaging, triggering and illumination, and scaling issues. It provides guidelines for testing and calibration. Ultra high-speed imaging at frame rates exceeding 1 million frames per second is reviewed, and the combination of conventional experiments in fluids techniques with high-speed imaging techniques are discussed. The review is concluded with a high-speed imaging chart, which summarizes criteria for temporal scale and spatial scale and which facilitates the selection of a high-speed imaging system for the applicatio

Lensfree computational microscopy tools for cell and tissue imaging at the point-of-care and in low-resource settings.

The recent revolution in digital technologies and information processing methods present important opportunities to transform the way optical imaging is performed, particularly toward improving the throughput of microscopes while at the same time reducing their relative cost and complexity. Lensfree computational microscopy is rapidly emerging toward this end, and by discarding lenses and other bulky optical components of conventional imaging systems, and relying on digital computation instead, it can achieve both reflection and transmission mode microscopy over a large field-of-view within compact, cost-effective and mechanically robust architectures. Such high throughput and miniaturized imaging devices can provide a complementary toolset for telemedicine applications and point-of-care diagnostics by facilitating complex and critical tasks such as cytometry and microscopic analysis of e.g., blood smears, Pap tests and tissue samples. In this article, the basics of these lensfree microscopy modalities will be reviewed, and their clinically relevant applications will be discussed

Study of macroscopic and microscopic properties of liposomes produced using microfluidic methods

For the last decades, lipid vesicles or liposomes, vesicles formed by a bilayer of amphiphilic lipids, have been used as a toy model for studying the cell membrane and for applications in cosmetics and drug delivery. Traditional methods for producing liposomes face some problems such as the heterogeneity in size and composition of the liposomes produced. A few years ago, a novel method that produces liposomes with homogeneous size and composition was developed. This novel method is based on the use of water in oil in water ultra-thin double emulsions, with lipids dissolved in the oil phase, as templates for the liposome production. These ultra-thin double emulsions are produced using glass capillary microfluidic devices. This new method for producing liposomes seems very promising, but since the liposomes are formed by the oil phase evaporation of the double emulsions, the doubt that some residual oil in the bilayer may alter the properties of the liposomes appears. In this work different phenomena and properties of liposomes that have been studied for the ones produced using conventional methods are studied for liposomes produced using microfluidic methods. The microfluidic apprOutgoin

Flexible neural probes: a review of the current advantages, drawbacks, and future demands

Brain diseases affect millions of people and have a huge social and economic impact. The use of neural probes for studies in animals has been the main approach to increasing knowledge about neural network functioning. Ultimately, neuroscientists are trying to develop new and more effective therapeutic approaches to treating neurological disorders. The implementation of neural probes with multifunctionalities (electrical, optical, and fluidic interactions) has been increasing in the last few years, leading to the creation of devices with high temporal and spatial resolution. Increasing the applicability of, and elements integrated into, neural probes has also led to the necessity to create flexible interfaces, reducing neural tissue damage during probe implantation and increasing the quality of neural acquisition data. In this paper, we review the fabrication, characterization, and validation of several types of flexible neural probes, exploring the main advantages and drawbacks of these devices. Finally, future developments and applications are covered. Overall, this review aims to present the currently available flexible devices and future appropriate avenues for development as possible guidance for future engineered devices.This work was supported by the CMEMS-UMinho Strategic Project (Nos. UIDB/04436/2020 and UIDP/04436/2020) and the MPhotonBiopsy (No. PTDC/FIS-OTI/1259/2020; https:// doi.org/10.54499/PTDC/FIS-OTI/1259/2020). João R. FREITAS thanks Fundação para a Ciência e a Tecnologia (FCT) for the Ph.D. grant (No. 2020.07708.BD). Sara PIMENTA thanks FCT for the grant (No. 2022.00101.CEECIND/CP1718/CT0008; https:// doi.org/10.54499/2022.00101.CEECIND/CP1718/CT0008)

Diagnostic and Therapeutic MEMS (Micro-Electro-Mechanical Systems) Devices for the Identification and Treatment of Human Disease

abstract: Early detection and treatment of disease is paramount for improving human health and wellness. Micro-scale devices promote new opportunities for the rapid, cost-effective, and accurate identification of altered biological states indicative of disease early-onset; these devices function at a scale more sensitive to numerous biological processes. The application of Micro-Electro-Mechanical Systems (MEMS) in biomedical settings has recently emerged and flourished over course of the last two decades, requiring a deep understanding of material biocompatibility, biosensing sensitively/selectively, biological constraints for artificial tissue/organ replacement, and the regulations in place to ensure device safety. Capitalizing on the inherent physical differences between cancerous and healthy cells, our ultra-thin silicone membrane enables earlier identification of bladder cancer—with a 70% recurrence rate. Building on this breakthrough, we have devised an array to multiplex this sample-analysis in real-time as well as expanding beyond bladder cancer. The introduction of new materials—with novel properties—to augment current and create innovative medical implants requires the careful analysis of material impact on cellular toxicity, mutagenicity, reactivity, and stability. Finally, the achievement of replacing defective biological systems with implanted artificial equivalents that must function within the same biological constraints, have consistent reliability, and ultimately show the promise of improving human health as demonstrated by our hydrogel check valve. The ongoing proliferation, expanding prevalence, and persistent improvement in MEMS devices through greater sensitivity, specificity, and integration with biological processes will undoubtedly bolster medical science with novel MEMS-based diagnostics and therapeutics.Dissertation/ThesisDoctoral Dissertation Electrical Engineering 201

The Boston University Photonics Center annual report 2016-2017

This repository item contains an annual report that summarizes activities of the Boston University Photonics Center in the 2016-2017 academic year. The report provides quantitative and descriptive information regarding photonics programs in education, interdisciplinary research, business innovation, and technology development. The Boston University Photonics Center (BUPC) is an interdisciplinary hub for education, research, scholarship, innovation, and technology development associated with practical uses of light.This has undoubtedly been the Photonics Center’s best year since I became Director 10 years ago. In the following pages, you will see highlights of the Center’s activities in the past year, including more than 100 notable scholarly publications in the leading journals in our field, and the attraction of more than 22 million dollars in new research grants/contracts. Last year I had the honor to lead an international search for the first recipient of the Moustakas Endowed Professorship in Optics and Photonics, in collaboration with ECE Department Chair Clem Karl. This professorship honors the Center’s most impactful scholar and one of the Center’s founding visionaries, Professor Theodore Moustakas. We are delighted to haveawarded this professorship to Professor Ji-Xin Cheng, who joined our faculty this year.The past year also marked the launch of Boston University’s Neurophotonics Center, which will be allied closely with the Photonics Center. Leading that Center will be a distinguished new faculty member, Professor David Boas. David and I are together leading a new Neurophotonics NSF Research Traineeship Program that will provide $3M to promote graduate traineeships in this emerging new field. We had a busy summer hosting NSF Sites for Research Experiences for Undergraduates, Research Experiences for Teachers, and the BU Student Satellite Program. As a community, we emphasized the theme of “Optics of Cancer Imaging” at our annual symposium, hosted by Darren Roblyer. We entered a five-year second phase of NSF funding in our Industry/University Collaborative Research Center on Biophotonic Sensors and Systems, which has become the centerpiece of our translational biophotonics program. That I/UCRC continues to focus on advancing the health care and medical device industries