University of Washington

The Washington Technology Center

Sinclair S Yee

Ralph C Jorgenson

Timothy M Chinowsky

Kyle Johnston

Clement E Furlong

Peter C Kauffman

Michael S Grow

Alexei N Naimushin

Scott D Soelberg

Jared Tritz

Martin A Afromowitz

Robert Bruce Darling

Chuck C Jung

Hsian-Pei Yee

Scott Karlson

Stevan B Saban

Hong Jin

Lawrence K Lam

Peter O Lauritzen

Shuai Shen

This specification discloses various improvements in the field of SPR sensing systems. One improvement relates to a portable SPR sensing system, e.g., a system contained within a suitcase that can be hand-carried to a monitoring site. Another improvement relates to a portable, cartridge-based SPR sensing system. In this system, selected portions of the system's electrical and fluidics systems are allocated between a base unit and a removable/disposable cartridge. Other improvements relate to methods or protocols for operating an SPR sensing system. Such methods provide for the elimination of false positives and increased sensitivity, e.g., by using secondary antibodies with specificity for different target epitopes and by sensor element redundancy. In addition, protocols are provided for the detection of small molecules. Such protocols may employ a competition type assay where the presence of the analyte inhibits the binding of antibodies to surface immobilized analyte, or a displacement assay, where antibodies bound to the analyte on the sensor surface are displaced by free analyte.

Portable and cartridge-based surface plasmon resonance sensing systems

SPR sensors and multisensors having capillary geometry. Sensors have a capillary substrate in which at least a portion of the inside surface of the capillary is provided with an SPR-sensing area. Samples for analysis are introduced into the capillary cavity. SPR is measured by radially illuminated the capillary SPR-sensing area with light having a TM-polarized component. Light reflected from the SPR-sensing area exiting radially from the capillary is detected at selected angles to obtain reflectivity as a function of incidence angle to determine RI of the sample in the vicinity of the SPR-sensing area. The capillary geometry is readily adaptable to simultaneous measurement of several optical properties of a given sample in addition to SPR by radial and/or axial illumination of the sample. Multisensors with capillary geometry which simultaneously measure SPR and bulk RI are provided. Multisensors which combine SPR measurements with fluorescence or chemiluminescence, Raman scattering, or absorption measurements are also provided.

Capillary surface plasmon resonance sensors and multisensors

The present invention provides SPR sensors in which the sensing element is a planar lightpipe. The sensors of this invention include configurations which employ multiwavelength light incident on the SPR sensing area at a single angle or at a range of angles. Sensors of this invention also include configurations that employ monochromatic light at a range of angles. Many of the configurations of the SPR lightpipe sensors of this invention involve imaging of input light through the lightpipe. In one embodiment, the invention provides a first order SPR sensor system in which the sensing element is a planar lightpipe. Light coupled into the lightpipe reflects off an SPR sensing area positioned on an external surface planar surface of the lightpipe. Multiwavelength light that is coupled into the lightpipe input face at a range of angles propagates through the lightpipe by total internal reflection (TIR), making multiple reflections, and exits in a series of angular bands each containing spectral information (including SPR features)for a small range of incidence angles. A detector or detectors are positioned to measure the reflection spectrum, including any surface plasmon resonance feature, of one or preferably more than one of the angular bands exiting the lightpipe. SPR sensor configurations include those that have multiple sensing channels and those which can be multiplexed. This invention provides SPR sensors with planar lightpipe sensing elements and method of detecting analytes in samples using these sensors. The invention also provides planar lightpipe that have a plurality of SPR sensing layers on a planar surface.

Surface plasmon resonance light pipe sensor

This disclosure describes new methods and devices for sensing redox-active analytes in solution. The invention combines a surface plasmon resonance (SPR) sensor and a chemical electrode sensor. A conducting layer which supports SPR is attached to a voltage source. The voltage source is also connected to a reference electrode, which is in the aqueous solution with the SPR sensor. As the voltage is varied, the analytes undergo oxidation and reduction at the surface of the conducting film. The current is measured, just as it would be in a standard chemical electrode, with current peaks appearing at different potentials indicating different ions in the solution. Unlike a standard chemical electrode, the surface of the conducting film is also used to excite a surface plasmon wave (SPW). The SPW provides new information which is not available from any standard chemical electrode, such as the effective index of refraction at the surface of the conducting film as the analytes are being oxidized and/or reduced. This additional source of information can be used to minimize the effects of overlapping stripping peaks and interspecies compound formation as well as determine the thickness of surface layers during measurements. Additionally, the simultaneous determination of reaction properties and optical properties of reaction products can provide additional information about the aqueous support solution such as the quantity and types of natural oxidants in solution, such as oxygen or hydroxides. The formation of oxides and hydroxides will lead to measurably different optical properties.

Surface plasmon resonance chemical electrode

There is disclosed fiber optic sensor which detects a sample in contact with the sensor by surface plasmon resonance (SPR) measurements, as well as methods and apparatus relating thereto. The fiber optic SPR sensor of this invention employs a limited range of incident angles and uses incident light having multiple wavelengths. In preferred embodiments, both an in-line transmission-based fiber optic SPR sensor and a terminated reflection-based fiber optic SPR sensor are disclosed. The fiber optic SPR sensor includes a surface plasmon supporting metal layer in contact with an exposed portion of the optical fiber core, and may optionally contain one or more additional layers deposited on the surface plasmon supporting metal layer. In further embodiments, methods are disclosed for detecting a sample by contacting the sample with the fiber optic SPR sensor of this invention, as well as sensing apparatus which contain the fiber optic SPR sensor in combination with a source of electromagnetic radiation of multiple wavelengths and a detection device.

Fiber optic sensor and methods and apparatus relating thereto

The present invention relates in general to SPR sensors in which the sensing element is a planar lightpipe. More specifically, a planar lightpipe sensor configuration for measurement of SPR at a single angle operation is provided. The lightpipe of this sensor is beveled to facilitate coupling of substantially collimated white light, preferably TM polarized white light, at a selected single angle that excites SPR at the sensing area. Angle of incidence on the SPR sensing area is determined by bevel angle used. This embodiment is a zero order sensor in the sense that it allows measurement for a given analyte at only a single angle of incidence. In this embodiment, however, the lightpipe can have a plurality of SPR sensing area across its width to provide for multichannel sensing. Refractive index sensitivity of this configuration is estimated as 4.times.10.sup.-5 RI units.

Optical lightpipe sensor based on surface plasmon resonance

The present invention provides SPR sensors in which the sensing element is a planar lightpipe. The sensors of this invention include configurations that employ multi-wavelength light (including broad band and white light) incident on the SPR sensing area at a single angle or at a range of angles. Sensors and probes of this invention also include configurations that employ monochromatic light at a range of angles. Many of the configurations of the SPR lightpipes of this invention involve imaging of input light through the folded lightpipe. In one general embodiment, the invention provides a SPR sensor system in which the sensing element is a folded planar lightpipe.

Surface plasmon resonance light pipe sensing probe and related interface

A power diode having substantially no reverse-recovery time and relatively high conductance. The power diode is a majority carrier semiconductor having a structure that is similar to that of a metal oxide semiconductor field effect transistor (MOSFET), in that it includes a source, a drain, a gate, and a body. In one embodiment, to increase conductance of the power diode, a linked-cell configuration that reverses the geometry of a conventional cell-type MOSFET is employed, thereby increasing the width of a conductance channel over that of a conventional MOSFET, and compensating for a relatively low level of inversion in the channel region. Negative and positive feedback circuits are used to further improve the conductance of the power diode by dynamically setting a bias voltage applied between the gate and the source to a level just below a threshold voltage. In the positive feedback circuit, the magnitude of the bias voltage is greater than the threshold voltage if the power diode is forward biased, but substantially reduced if the power diode is reverse biased, thereby minimizing its turn-on delay without risking reverse conductance. Although separate components are used for biasing the device in the disclosed embodiments, it is contemplated that these components be integrated on a common substrate with the source, drain, and gate in a commercially practiced preferred embodiment. Another embodiment employs a charge carrier region diffused into the body and at least in part underlying the gate. This region provides a variable threshold voltage along the channel and reduces the effective length of the channel to increase its conductance. A threshold voltage ranges between a higher value, V.sub.TMAX, adjacent the source, to a lower value, V.sub.T, elsewhere in the device.

Majority carrier power diode

A liquid junction electrode 10 formed from a silicon body 14 and having a glass membrane 22 attached thereto. A reference electrode is constructed by forming the glass membrane 22 from porous glass having a preferable pore size in the range of 40 angstroms to 75 angstroms. The porous glass membrane 22 has a coating 24 of glass containing mobile ions that is electrostatically bonded to the silicon body 14. Alternatively, a glass plug 92 is formed from a paste of ground glass and organic binder that is heated to cause formation of pores and bonding of the glass plug 92 to a silicon body 94. An ion-sensitive electrode is constructed by forming the membrane 52 from an ion-sensitive glass or by filling the pores of the porous glass membrane 22 with an ion-sensitive material.

Ion electrode and method of making it

An improved ion-sensitive electrode is described, particularly in terms of the structure of a pH electrode and first and second processes for making the same. The pH electrode includes a substrate, preferably of forsterite, which is configured as a wafer having a substantially planar wafer surface. A continuous conducting layer, formed by either thin-film vapor deposition or thick-film screening processes, is formed on the substantially planar wafer surface in a desired configuration. A first region of the continuous conducting layer, and contiguous portions of the substantially planar wafer surface, are covered by a continuous membrane layer preferably composed of a pH-sensitive glass such as Corning Code 0150 glass. Typically, the membrane layer is formed by a thick-film process which involves the reduction of the glass to a fine powder, the mixing of the powder with an organic vehicle including an organic solvent and an organic binder to form a glass paste, and the application of the glass paste to the wafer through a wire mesh screen having an open region therethrough corresponding in configuration to that of the desired membrane layer. The paste when applied to the wafer is fused into a continuous membrane layer by the application of heat, at a first temperature to drive off the organic solvent and at a second temperature or temperatures to drive off the organic binder and to fuse the glass. An insulated output lead is connected directly to a second region of the conducting layer. Alternatively, an active device chip, such as that including a field effect transistor, is bonded to the wafer and interconnected with the second region of the conducting layer and with the output lead or leads. The exposed conducting elements of the electrode, including the second region of the conducting layer, the active device chip, and all exposed portions of the leads, are covered by a fluid-tight seal. Other ion-sensitive electrodes and variations of the aforementioned processes are described.

Growing community of inventors

Seattle, WA, United States of America

Sinclair S Yee