San Diego State University Research Foundation

William G Tong

This patent document discloses techniques, systems, and devices for detecting a target substance using optical nonlinear wave mixing for enhanced detection sensitivity and accuracy. In one aspect, a method for measuring &#x3b1;-synuclein in a body fluid of a patient with high detection sensitivity and accuracy and providing early stage Parkinson's disease detection is provided. The method may comprise: supplying to a capillary analyte cell a fluidic sample that includes a body fluid of a patient containing &#x3b1;-synuclein, wherein the capillary analyte cell is located in a nonlinear optical four-wave mixing device; directing laser light from the nonlinear optical four-wave mixing device into the capillary analyte cell to cause nonlinear optical four-wave mixing in the fluidic sample to generate a four-wave mixing signal that contains information on the &#x3b1;-synuclein in the fluidic sample; and processing the four-wave mixing signal to extract information on the &#x3b1;-synuclein in the fluidic sample.

Applications of optical detection of low-level chemical and biological substances by nonlinear laser wave mixing in medicine and food safety

Devices and techniques for using four wave mixing in optical sensing of various materials, including isotopes, chemical and biological substances.

Ultrasensitive detection of isotopes, chemical substances and biological substances using laser wave mixing detectors

Techniques and systems for using nonlinear four wave mixing to optically measure microarrays with sample cells of biological or chemical materials. Examples of suitable microarrays include but are not limited to DNA microchips and capillary electrophoresis microarrays.

Sensitive sensing based on optical nonlinear wave mixing

Devices and techniques for performing highly-sensitive spectroscopic measurements in a sample vapor by using a four-wave-mixing optical system and an atomizer chamber. One embodiment of a spectrometer comprises a gas-phase atomizer having an atomizer chamber operable to vaporize a sample solution to produce a sample vapor, first and second alignment templates having apertures to align a probe beam, first and second pump beams to form a four-wave mixing configuration, a laser tunable to generate a laser beam at a desired wavelength corresponding to an absorption line in the sample vapor, and a set of optical elements disposed relative to the laser and the atomizer to split the laser beam into the probe beam, the first pump beam, and the second pump beam. The probe beam, the first and second pump beams are directed to overlap with one another in the sample vapor to produce a signal beam through a four-wave mixing process.

Sensitive laser spectroscopic detection based on three-dimensional

A method and apparatus using either two or three input laser beams in a nonlinear degenerate four-wave mixing arrangement for ultrasensative analytical measurements of an analyte. In accordance with a first embodiment of the present invention, a two input beam F-D4WM arrangement is used to generate two phase conjugate signal beams. The input beams are narrowly focused to intersect within a very small volume of an analyte. The analyte may be in any physical state (e.g., liquid, solid, or gas). The intensity of the signal beam is used to detect trace concentrations of particular substances. The beam spot of each of the input beams can be focused to less than 34 .mu.m, thus allowing the present invention to directly focus the input beams within a capillary tube of a HPCE or a column of a HPLC system. In accordance with the second embodiment of the present invention, the input laser beams of a F-D4WM method are directed to points on a lens by immobilized fiber optic cables. In accordance with a third embodiment of the present invention, a three input beam B-D4WM method is used in which the three input laser beams are directed by an immobilized fiber optic cable.

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La Jolla, CA, United States of America

William G Tong