700 research outputs found
Giant Magnetoresistive Biosensors for Time-Domain Magnetorelaxometry: A Theoretical Investigation and Progress Toward an Immunoassay.
Magnetorelaxometry (MRX) is a promising new biosensing technique for point-of-care diagnostics. Historically, magnetic sensors have been primarily used to monitor the stray field of magnetic nanoparticles bound to analytes of interest for immunoassays and flow cytometers. In MRX, the magnetic nanoparticles (MNPs) are first magnetized and then the temporal response is monitored after removing the magnetic field. This new sensing modality is insensitive to the magnetic field homogeneity making it more amenable to low-power portable applications. In this work, we systematically investigated time-domain MRX by measuring the signal dependence on the applied field, magnetization time, and magnetic core size. The extracted characteristic times varied for different magnetic MNPs, exhibiting unique magnetic signatures. We also measured the signal contribution based on the MNP location and correlated the coverage with measured signal amplitude. Lastly, we demonstrated, for the first time, a GMR-based time-domain MRX bioassay. This approach validates the feasibility of immunoassays using GMR-based MRX and provides an alternative platform for point-of-care diagnostics
Dynamic complex opto-magnetic holography
Computer-generated holograms with their animated, three-dimensional
appearance have long appealed to our imagination as the path towards truly
immersive displays with bi-directional natural parallax. Impressive progress in
updateable 3-D imagery has been achieved with liquid crystal modulators and
high-resolution, but quasi-static holograms are being recorded in
photosensitive materials. However, the memory requirements and computational
loads of real-time, large-area holography will be hard to tackle for several
decades to come with the current paradigm based on a matrix calculations and
bit-plane writing. Here, we experimentally demonstrate a conceptually novel,
holistic approach to serial computation and repeatable writing of
computer-generated dynamic holograms without Fourier transform, using minimal
amounts of computer memory. We use the ultrafast opto-magnetic recording of
holographic patterns in a ferrimagnetic film with femtosecond laser pulses,
driven by on-the-fly hardware computation of a single holographic point. The
intensity-threshold nature of the magnetic medium allows
sub-diffraction-limited, point-by-point toggling of arbitrarily localized
magnetic spots on the sample, according to the proposed circular detour-phase
encoding, providing complex modulation and symmetrical suppression of upper
diffractive orders and conjugated terms in holographically reconstructed 3-D
images
Two-Photon Excitation, Fluorescence Microscopy, and Quantitative Measurement of Two-Photon Absorption Cross Sections
As optical microscopy techniques continue to improve, most notably the development of super-resolution optical microscopy which garnered the Nobel Prize in Chemistry in 2014, renewed emphasis has been placed on the development and use of fluorescence microscopy techniques. Of particular note is a renewed interest in multiphoton excitation due to a number of inherent properties of the technique including simplified optical filtering, increased sample penetration, and inherently confocal operation. With this renewed interest in multiphoton fluorescence microscopy, comes an increased demand for robust non-linear fluorescent markers, and characterization of the associated tool set.
These factors have led to an experimental setup to allow a systematized approach for identifying and characterizing properties of fluorescent probes in the hopes that the tool set will provide researchers with additional information to guide their efforts in developing novel fluorophores suitable for use in advanced optical microscopy techniques as well as identifying trends for their synthesis.
Hardware was setup around a software control system previously developed [1]. Three experimental tool sets were set up, characterized, and applied over the course of this work. These tools include scanning multiphoton fluorescence microscope with single molecule sensitivity, an interferometric autocorrelator for precise determination of the bandwidth and pulse width of the ultrafast Titanium Sapphire excitation source, and a simplified fluorescence microscope for the measurement of two-photon absorption cross sections.
Resulting values for two-photon absorption cross sections and two-photon absorption action cross sections for two standardized fluorophores, four commercially available fluorophores, and ten novel fluorophores are presented as well as absorption and emission spectra
Single-Molecule Detection of Unique Genome Signatures: Applications in Molecular Diagnostics and Homeland Security
Single-molecule detection (SMD) offers an attractive approach for identifying the presence of certain markers that can be used for in vitro molecular diagnostics in a near real-time format. The ability to eliminate sample processing steps afforded by the ultra-high sensitivity associated with SMD yields an increased sampling pipeline. When SMD and microfluidics are used in conjunction with nucleic acid-based assays such as the ligase detection reaction coupled with single-pair fluorescent resonance energy transfer (LDR-spFRET), complete molecular profiling and screening of certain cancers, pathogenic bacteria, and other biomarkers becomes possible at remarkable speeds and sensitivities with high specificity. The merging of these technologies and techniques into two different novel instrument formats has been investigated. (1) The use of a charge-coupled device (CCD) in time-delayed integration (TDI) mode as a means for increasing the throughput of any single molecule measurement by simultaneously tracking and detecting single-molecules in multiple microfluidic channels was demonstrated. The CCD/TDI approach allowed increasing the sample throughput by a factor of 8 compared to a single-assay SMD experiment. A sampling throughput of 276 molecules s-1 per channel and 2208 molecules s-1 for an eight channel microfluidic system was achieved. A cyclic olefin copolymer (COC) waveguide was designed and fabricated in a pre-cast poly(dimethylsiloxane) stencil to increase the SNR by controlling the excitation geometry. The waveguide showed an attenuation of 0.67 dB/cm and the launch angle was optimized to increase the depth of penetration of the evanescent wave. (2) A compact SMD (cSMD) instrument was designed and built for the reporting of molecular signatures associated with bacteria. The optical waveguides were poised within the fluidic chip at orientation of 90° with respect to each other for the interrogation of single-molecule events. Molecular beacons (MB) were designed to probe bacteria for the classification of Gram +. MBs were mixed with bacterial cells and pumped though the cSMD which allowed S. aureus to be classified with 2,000 cells in 1 min. Finally, the integration of the LDR-spFRET assay on the cSMD was explored with the future direction of designing a molecular screening approach for stroke diagnostics
The Design of a Novel Tip Enhanced Near-field Scanning Probe Microscope for Ultra-High Resolution Optical Imaging
Traditional light microscopy suffers from the diffraction limit, which limits the spatial resolution to λ/2. The current trend in optical microscopy is the development of techniques to bypass the diffraction limit. Resolutions below 40 nm will make it possible to probe biological systems by imaging the interactions between single molecules and cell membranes. These resolutions will allow for the development of improved drug delivery mechanisms by increasing our understanding of how chemical communication within a cell occurs. The materials sciences would also benefit from these high resolutions. Nanomaterials can be analyzed with Raman spectroscopy for molecular and atomic bond information, or with fluorescence response to determine bulk optical properties with tens of nanometer resolution. Near-field optical microscopy is one of the current techniques, which allows for imaging at resolutions beyond the diffraction limit. Using a combination of a shear force microscope (SFM) and an inverted optical microscope, spectroscopic resolutions below 20 nm have been demonstrated. One technique, in particular, has been named tip enhanced near-field optical microscopy (TENOM). The key to this technique is the use of solid metal probes, which are illuminated in the far field by the excitation wavelength of interest. These probes are custom-designed using finite difference time domain (FDTD) modeling techniques, then fabricated with the use of a focused ion beam (FIB) microscope. The measure of the quality of probe design is based directly on the field enhancement obtainable. The greater the field enhancement of the probe, the more the ratio of near-field to far-field background contribution will increase. The elimination of the far-field signal by a decrease of illumination power will provide the best signal-to-noise ratio in the near-field images. Furthermore, a design that facilitates the delocalization of the near-field imaging from the far-field will be beneficial. Developed is a novel microscope design that employs two-photon non-linear excitation to allow the imaging of the fluorescence from almost any visible fluorophore at resolutions below 30 nm without changing filters or excitation wavelength. The ability of the microscope to image samples at atmospheric pressure, room temperature, and in solution makes it a very promising tool for the biological and materials science communities. The microscope demonstrates the ability to image topographical, optical, and electronic state information for single-molecule identification. A single computer, simple custom control circuits, field programmable gate array (FPGA) data acquisition, and a simplified custom optical system controls the microscope are thoroughly outlined and documented. This versatility enables the end user to custom-design experiments from confocal far-field single molecule imaging to high resolution scanning probe microscopy imaging. Presented are the current capabilities of the microscope, most importantly, high-resolution near-field images of J-aggregates with PIC dye. Single molecules of Rhodamine 6G dye and quantum dots imaged in the far-field are presented to demonstrate the sensitivity of the microscope. A comparison is made with the use of a mode-locked 50 fs pulsed laser source verses a continuous wave laser source on single molecules and J-aggregates in the near-field and far-field. Integration of an intensified CCD camera with a high-resolution monochromator allows for spectral information about the sample. The system will be disseminated as an open system design
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Old Dog, New Trick: High Fidelity, Background-free State Detection of an Ytterbium Ion Qubit
The highly popular ytterbium-171 () ion is commonly employed in quantum information research as a qubit whose excellent coherence time and fast, simple state preparation has allowed cutting edge work in quantum computation and simulation. Despite these large benefits, the demonstrated measurement fidelity of this ion has lagged the state preparation and gate fidelity achieved to date.In this thesis we investigate and realize methods of increasing the measurement fidelity of in a scaleable way for large quantum systems. Using methods of coherent control, we implement a pulsed state detection scheme using a mode-locked laser to perform background-free spectroscopy of the ``bright'' state of the qubit. The small hyperfine splitting of the ion necessitates the use of multiple (two) pulses to manipulate time dynamics of the ion to excite a single transition. A Mach-Zehnder interferometer is constructed to control these pulse separations both coarsely ( 237 ps) and on a fine sub-femtosecond scale. These pulses cause destructive/constructive interference of the electron wave packet of a single ion levitated in vacuum and are engineered to state-selectively excite the qubit. This allows measurement of the qubit whose transition frequency is much smaller than the bandwidth of the interrogation laser.During this spectroscopy, mechanical forces from the mode-locked laser frequency comb can drive the ion into large coherent states of motion. This motion has been dubbed ``phonon lasing''. We investigate the phonon lasing affect and how the ion interacts with multiple comb teeth. The large number of teeth leads to a protection mechanism from runaway energy gain by near-by blue detuned teeth, allowing ions to be trapped and cooled by the mode-locked laser, regardless of its detuning. We further explore these discrete amplitude coherent states by injecting energy into the ion's motion and exciting higher-order oscillations.We, for the first time, implement an ``electron shelving'' of the hyperfine qubit, and incoherently transfer the bright state population in the extremely long-lived (5 yr) F state of Yb, functionally disconnected state. This is accomplished via narrow-band optical pumping on the S to the D quadrupole which has a leaky dipole channel into the F. Narrow-band optical pumping is again used to rescue the ion at the end of the experiment with the aid of a 760 nm E2 transition back into the cooling cycle. Measurement with this scheme is no longer limited by off-resonant effects from the main cycling transition. Limits of this novel technique, as well as further directions using the F state as a utility for quantum information are explored. Finally, we combine the pulsed background-free spectroscopy with shelving and demonstrate high-fidelity, background free detection of a single trapped qubit
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