Optical waveguides are proving to be an optimal platform for on-the-spot biosensors. Optical signal transduction provides high discrimination, where even a single fluorescent molecule can be detected. The use of evanescent wave illumination, where the light field extends a fraction of the wavelength above a sensor surface, provides a clean signal for surface reactions with minimal background. By only illuminating a volume extending above the surface by a few hundred nanometers, evanescent wave sensors often don’t require wash steps or other sample processing complexities. The cost of optical technology has been reduced considerably over the past decade with the explosion of digital imaging. All of these factors combine to make for a very practical biosensor design. We will present the architecture and design features of the MBio Diagnostics LightDeck® evanescent planar waveguide sensor, and two of the applications where these practical features enable commercial devices: testing for antibiotic residues in milk, and tests to manage sepsis.
Antibiotic residue testing in milk products is widely performed and requires prompt results on-site at a dairy processor. The cost constraints are quite severe. We detail the approach using waveguide sensors, and present data on residue testing. In a second application, sepsis presents a complex disease state that requires a number of results in real time. With multiple biomarkers, and often algorithmic approaches to analysis, a multiplex platform is essential to delivering the necessary data on-the-spot. We detail host response biomarker panels with applications in risk stratification and therapy optimization.
Fluorescence microscopy has long been a standard tool in laboratory medicine. Implementation of fluorescence microscopy for near-patient diagnostics, however, has been limited due to cost and complexity associated with traditional fluorescence microscopy techniques. There is a particular need for robust, low-cost imaging in high disease burden areas in the developing world, where access to central laboratory facilities and trained staff is limited. Here we
describe a point-of-care assay that combines a disposable plastic cartridge with an extremely low cost fluorescence
imaging instrument. Based on a novel, multi-mode planar waveguide configuration, the system capitalizes on advances
in volume-manufactured consumer electronic components to deliver an imaging system with minimal moving parts and
low power requirements. A two-color cell imager is presented, with magnification optimized for enumeration of
immunostained human T cells. To demonstrate the system, peripheral blood mononuclear cells were stained with
fluorescently labeled anti-human-CD4 and anti-human-CD3 antibodies. Registered images were used to generate
fractional CD4+ and CD3+ staining and enumeration results that show excellent correlation with flow cytometry. The
cell imager is under development as a very low cost CD4+ T cell counter for HIV disease management in limited resource settings.
Cost-effective disease diagnosis in resource-limited settings remains a critical global health challenge. Qualitative rapid
tests based on lateral flow technology provide valuable screening information, but require relatively expensive
confirmatory tests and generally lack quantitation. We report on a fluorescence technology that combines low cost
instrumented readout with passive pumping in a disposable cartridge. The detection system utilizes a novel waveguide
illumination approach in conjunction with commercial CMOS imagers. Total instrument cost in production are
projected to be around $100 This cost structure and instrument ease of use will enable use in point-of-care settings,
outside of centralized laboratories. The system has been used for detection and analysis of proteins, antibodies, nucleic
acids, and cells. Here we will report first on our development of a multiplexed, array-based serology assay for HIV and
common AIDS co-infections. Data will be presented for HIV/HCV antibody testing in human serum samples. In
addition, we will present data on the use of the system for sensitive detection of bacterial RNA. Current detection limit
for the model multiplexed RNA sandwich assay is 1 femtomolar target RNA. Finally, a high magnification version of
the system is used to image immunostained human T cells.
Optical fiber sensors must compete in performance with traditional electronic sensors, such as quartz crystal pressure and temperature monitors. The precision of commercial electronic sensors can reach the parts-per-billion (ppb) level. To test the precision of a laser based spectrometer system, repeated measurements of an absorption line of a molecular gas cell were made. The Allan deviation is computed, and it is shown that the laser interrogation system, built completely out of commercially available components, can achieve precision at the 10-ppb level.
A miniature, elliptical ring rf ion trap has been sued in recent experiments toward realizing a quantum computer in a trapped ion system. With the combination of small spatial dimensions and high rf drive potentials, around 500 V amplitude, we have achieved secular oscillation frequencies in the range of 5-20 MHz. The equilibrium positions of pairs of ions that are crystallized in this trap lie along the long axis of the ellipse. By adding a static potential to the trap, the micromotion of two crystallized ions may be reduced relative to the case of pure rf confinement. The presence of micromotion reduces the strength of internal transitions in the ion, an effect that is characterized by a Debye-Waller factor, in analogy with the reduction of Bragg scattering at finite temperature in a crystal lattice. We have demonstrated the dependence of the rates of internal transitions on the amplitude of micromotion, and we propose a scheme to use this effect to differentially address the ions.
Conference Committee Involvement (4)
Frontiers in Biological Detection: From Nanosensors to Systems
21 January 2012 | San Francisco, California, United States
Frontiers in Biological Detection: From Nanosensors to Systems
22 January 2011 | San Francisco, California, United States
Frontiers in Pathogen Detection: From Nanosensors to Systems
23 January 2010 | San Francisco, California, United States
Frontiers in Pathogen Detection: From Nanosensors to Systems
24 January 2009 | San Jose, California, United States
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