Snapshot hyperspectral imaging of intracellular lasers

This work received financial support from a UK EPSRC Programme Grant (EP/P030017/1). PW was supported by the 1851 Research Fellowship from the Royal Commission. KD acknowledges support from the Australian Research Council (FL210100099). MCG acknowledges support from the Alexander von Humboldt Foundation (Humboldt professorship).Intracellular lasers are emerging as powerful biosensors for multiplexed tracking and precision sensing of cells and their microenvironment. This sensing capacity is enabled by quantifying their narrow-linewidth emission spectra, which is presently challenging to do at high speeds. In this work, we demonstrate rapid snapshot hyperspectral imaging of intracellular lasers. Using integral field mapping with a microlens array and a diffraction grating, we obtain images of the spatial and spectral intensity distribution from a single camera acquisition. We demonstrate widefield hyperspectral imaging over a 3×3 mm2 field of view and volumetric imaging over 250×250×800 µm3 volumes with a spatial resolution of 5 µm and a spectral resolution of less than 0.8 nm. We evaluate the performance and outline the challenges and strengths of snapshot methods in the context of characterising the emission from intracellular lasers. This method offers new opportunities for a diverse range of applications, including high-throughput and long-term biosensing with intracellular lasers.Preprin

Snapshot hyperspectral imaging of intracellular lasers

Intracellular lasers are emerging as powerful biosensors for multiplexed tracking and precision sensing of cells and their microenvironment. This sensing capacity is enabled by quantifying their narrow-linewidth emission spectra, which is presently challenging to do at high speeds. In this work, we demonstrate rapid snapshot hyperspectral imaging of intracellular lasers. Using integral field mapping with a microlens array and a diffraction grating, we obtain images of the spatial and spectral intensity distribution from a single camera acquisition. We demonstrate widefield hyperspectral imaging over a 3$\times$3 mm$^2$ field of view and volumetric imaging over 250$\times$250$\times$800 $\mu$m$^3$ volumes with a spatial resolution of 5 $\mu$m and a spectral resolution of less than 0.8 nm. We evaluate the performance and outline the challenges and strengths of snapshot methods in the context of characterising the emission from intracellular lasers. This method offers new opportunities for a diverse range of applications, including high-throughput and long-term biosensing with intracellular lasers.Comment: 15 pages, 6 figure

Micro-fabricated devices for manipulating terahertz radiation

This thesis reports on the design, fabrication and testing of microstructured devices for the manipulation of terahertz radiation. In particular, there is an emphasis on the fabrication and test of diffractive optics type components; including a surface micromachined, multilevel SU-8 based Fresnel lens and a micromilled aluminium Fresnel Zone Plate Reflector (FZPR). For both of these devices, the focal spot is characterized by measuring the electric field intensity and phase as a function of distance along the optical axis. This is carried out using a THz Vector Network Analyzer with associated free space optics. The results are compared directly with Finite Difference Time Domain simulations. A commercial FDTD solver, Lumerical, is used throughout the thesis. FDTD is first introduced for the design of antireflective subwavelength surfaces. These surface structures are bulk micromachined in silicon and their performance experimentally validated using THz Time-Domain Spectroscopy and Durham's THz VNA. A compact THz VNA based S11 measurement configuration is presented which uses the FZPR and a single parabolic mirror. This reflection configuration is used for the characterization of liquid samples (e.g. water and Isopropyl Alcohol mixtures) in microfluidic channels. Two types of channels are presented; one is formed using bulk micromachined silicon whereas the other type uses acetate films to create low cost, disposable devices. The results from the compact measurement configuration are compared with those obtained using a more conventional four parabolic mirror transmission arrangement (as found in THz Time-Domain Spectroscopy systems). Even in the compact configuration, the alignment of the components is found to be a significant factor in determining the measurement performance. Consequently, a six-axis micropositioner (Hexapod), is used to automatically sweep the reflector with the aim of producing a self-aligning system

Study on Buckling of Stiff Thin Films on Soft Substrates as Functional Materials

abstract: In engineering, buckling is mechanical instability of walls or columns under compression and usually is a problem that engineers try to prevent. In everyday life buckles (wrinkles) on different substrates are ubiquitous -- from human skin to a rotten apple they are a commonly observed phenomenon. It seems that buckles with macroscopic wavelengths are not technologically useful; over the past decade or so, however, thanks to the widespread availability of soft polymers and silicone materials micro-buckles with wavelengths in submicron to micron scale have received increasing attention because it is useful for generating well-ordered periodic microstructures spontaneously without conventional lithographic techniques. This thesis investigates the buckling behavior of thin stiff films on soft polymeric substrates and explores a variety of applications, ranging from optical gratings, optical masks, energy harvest to energy storage. A laser scanning technique is proposed to detect micro-strain induced by thermomechanical loads and a periodic buckling microstructure is employed as a diffraction grating with broad wavelength tunability, which is spontaneously generated from a metallic thin film on polymer substrates. A mechanical strategy is also presented for quantitatively buckling nanoribbons of piezoelectric material on polymer substrates involving the combined use of lithographically patterning surface adhesion sites and transfer printing technique. The precisely engineered buckling configurations provide a route to energy harvesters with extremely high levels of stretchability. This stiff-thin-film/polymer hybrid structure is further employed into electrochemical field to circumvent the electrochemically-driven stress issue in silicon-anode-based lithium ion batteries. It shows that the initial flat silicon-nanoribbon-anode on a polymer substrate tends to buckle to mitigate the lithiation-induced stress so as to avoid the pulverization of silicon anode. Spontaneously generated submicron buckles of film/polymer are also used as an optical mask to produce submicron periodic patterns with large filling ratio in contrast to generating only ~100 nm edge submicron patterns in conventional near-field soft contact photolithography. This thesis aims to deepen understanding of buckling behavior of thin films on compliant substrates and, in turn, to harness the fundamental properties of such instability for diverse applications.Dissertation/ThesisPh.D. Mechanical Engineering 201

Tuning localized plasmons in nanostructured substrates for surface-enhanced Raman scattering

Comprehensive reflectivity mapping of the angular dispersion of nanostructured arrays comprising of inverted pyramidal pits is demonstrated. By comparing equivalently structured dielectric and metallic arrays, diffraction and plasmonic features are readily distinguished. While the diffraction features match expected theory, localised plasmons are also observed with severely flattened energy dispersions. Using pit arrays with identical pitch, but graded pit dimensions, energy scaling of the localised plasmon is observed. These localised plasmons are found to match a simple model which confines surface plasmons onto the pit sidewalls thus allowing an intuitive picture of the plasmons to be developed. This model agrees well with a 2D finite-difference time-domain simulation which shows the same dependence on pit dimensions. We believe these tuneable plasmons are responsible for the surface-enhancement of the Raman scattering (SERS) of an attached layer of benzenethiol molecules. Such SERS substrates have a wide range of applications both in security, chemical identification, environmental monitoring and healthcare

Snapshot hyperspectral imaging of intracellular lasers

This work received financial support from a UK EPSRC Programme Grant (EP/P030017/1). PW was supported by the 1851 Research Fellowship from the Royal Commission. KD acknowledges support from the Australian Research Council (FL210100099). MCG acknowledges support from the Alexander von Humboldt Foundation (Humboldt professorship).Intracellular lasers are emerging as powerful biosensors for multiplexed tracking and precision sensing of cells and their microenvironment. This sensing capacity is enabled by quantifying their narrow-linewidth emission spectra, which is presently challenging to do at high speeds. In this work, we demonstrate rapid snapshot hyperspectral imaging of intracellular lasers. Using integral field mapping with a microlens array and a diffraction grating, we obtain images of the spatial and spectral intensity distribution from a single camera acquisition. We demonstrate widefield hyperspectral imaging over a 3 × 3 mm2 field of view and volumetric imaging over 250 × 250 × 800 µm3 (XYZ) volumes with a lateral (XY) resolution of 5 µm, axial (Z) resolution of 10 µm, and a spectral resolution of less than 0.8 nm. We evaluate the performance and outline the challenges and strengths of snapshot methods in the context of characterizing the emission from intracellular lasers. This method offers new opportunities for a diverse range of applications, including high-throughput and long-term biosensing with intracellular lasers.Publisher PDFPeer reviewe

Program Annual Technology Report: Physics of the Cosmos Program Office

From ancient times, humans have looked up at the night sky and wondered: Are we alone? How did the universe come to be? How does the universe work? PCOS focuses on that last question. Scientists investigating this broad theme use the universe as their laboratory, investigating its fundamental laws and properties. They test Einsteins General Theory of Relativity to see if our current understanding of space-time is borne out by observations. They examine the behavior of the most extreme environments supermassive black holes, active galactic nuclei, and others and the farthest reaches of the universe, to expand our understanding. With instruments sensitive across the spectrum, from radio, through infrared (IR), visible light, ultraviolet (UV), to X rays and gamma rays, as well as gravitational waves (GWs), they peer across billions of light-years, observing echoes of events that occurred instants after the Big Bang. Last year, the LISA Pathfinder (LPF) mission exceeded expectations in proving the maturity of technologies needed for the Laser Interferometer Space Antenna (LISA) mission, and the Laser Interferometer Gravitational-Wave Observatory (LIGO) recorded the first direct measurements of long-theorized GWs. Another surprising recent discovery is that the universe is expanding at an ever-accelerating rate, the first hint of so-called dark energy, estimated to account for 75% of mass-energy in the universe. Dark matter, so called because we can only observe its effects on regular matter, is thought to account for another20%, leaving only 5% for regular matter and energy. Scientists now also search for special polarization in the cosmic microwave background to support the notion that in the split-second after the Big Bang, the universe inflated faster than the speed of light! The most exciting aspect of this grand enterprise today is the extraordinary rate at which we can harness technologies to enable these key discoveries

Developing Integrated Optofluidic Platforms for Cellular Phenotyping.

This research demonstrates two optofluidic platforms to address three major problems of current fluorescence-based optical detection methods for cellular phenotyping: (1) limited number of fluorescent probes, (2) laborious and time-consuming assay preparation and manipulation steps, and (3) compromised sensing performance in a point-of-care setting. The first optofluidic platform is called the “microfluidic multispectral flow cytometry (MMFC) device”. The function of the MMFC device is to discriminate multiple cell types based on their fluorescent proteins or surface biomarkers at single cell level with a simplified optical setup. It represents a unique class of optofluidic system incorporating a MEMS-based tunable nanoimprinted grating microdevice, a single excitation laser, and a single PMT detector. The system enables us to achieve in-situ continuous spectral profile detection for bioparticles flowing in a microfluidic channel with high specificity and high speed. The second optofluidic platform is called the “microfluidic immunophenotyping assay (MIPA) device”. The function of the MIPA device is to achieve on-chip cell trapping, cell stimulation and in-situ secreted cytokine detection in one single chip with a shorten assay time and less sample requirements. Compared to previous studies using heterogeneous immunoassay techniques and requiring a longer assay time due to multiple surface immobilization processes and washing steps, our immunophenotyping assay with the MIPA device holds significant promise to open ways for rapid immune status determination in real clinical settings.PHDMechanical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/97933/1/nthuang_1.pd

Micro/Nano Manufacturing

Micro manufacturing involves dealing with the fabrication of structures in the size range of 0.1 to 1000 µm. The scope of nano manufacturing extends the size range of manufactured features to even smaller length scales—below 100 nm. A strict borderline between micro and nano manufacturing can hardly be drawn, such that both domains are treated as complementary and mutually beneficial within a closely interconnected scientific community. Both micro and nano manufacturing can be considered as important enablers for high-end products. This Special Issue of Applied Sciences is dedicated to recent advances in research and development within the field of micro and nano manufacturing. The included papers report recent findings and advances in manufacturing technologies for producing products with micro and nano scale features and structures as well as applications underpinned by the advances in these technologies