Apparatus and methods relating to high speed raman spectroscopy

Abstract

Systems and methods for rapid Raman spectroscopy. The speed is improved by providing light from a sample to a light-dispersive element, such as a holographic grating, in a pattern that inversely complements distortion caused by the grating. For example, if the grating imparts a curve to the spectral lines emanating from the grating, then the light is inserted into the grating in a curve in the opposite direction. Also calibration light guides able to transmit a known, or standard, light to the detection or spectroscopy system. The calibration light guide can be useful both with traditional light transmission guides and with the light transmission guides of the present invention.

What is claimed is:  
     
         1 . A light transmission bundle suitable for use for Raman spectroscopy, the light transmission bundle comprising a proximal end and a distal end and comprising at least 5 light guides, wherein the light guides are arranged in a substantially filled-in geometrical shape at the proximal end of the light transmission bundle and a substantially linear curve at the distal end.  
     
     
         2 . The light transmission bundle of  claim 1  wherein the substantially linear curve is a parabolic curve.  
     
     
         3 . The light transmission bundle of  claim 2  wherein the parabolic curve is substantially identical to a curve of a substantially linear line of light after it has been passed through a holographic grating.  
     
     
         4 . The light transmission bundle of  claim 3  wherein the holographic grating is a volume phase technology (VPT) holographic grating.  
     
     
         5 . The light transmission bundle of  claim 1  wherein the filled-in geometrical shape is a circle.  
     
     
         6 . The light transmission bundle of  claim 1  wherein at least one of the light guides at the distal end of the light transmission bundle is a calibration light guide.  
     
     
         7 . The light transmission bundle of  claim 6  the calibration light guide is disposed at the center of the substantially linear curve.  
     
     
         8 . The light transmission bundle of  claim 6  or  7  wherein a proximal end of the calibration light guide is optically connected to a calibration light source.  
     
     
         9 . A Raman spectrometer system comprising a detection light guide able to detect light emanating from a sample, a distal end of the detection light guide optically connected to a plane grating that is in turn optically connected to a pixelated light detector operably connected to a controller containing computer-implemented programming that detects light impinging on detection pixels in the pixelated light detector, wherein a light transmissive portion of the distal end of the detection light guide is arranged in a substantially inverse shape that is complementary to a distortion to the light caused by passing the light through the plane grating, to provide light in a substantially straight line at the pixelated light detector.  
     
     
         10 . The Raman spectrometer system of  claim 9  wherein the detection light guide comprises a light transmission bundle comprising at least 5 light guides, wherein the light guides are arranged in a filled-in geometrical shape at a proximal end of the light transmission bundle and a substantially linear curve at the distal end, and the plane grating comprises a holographic grating.  
     
     
         11 . The Raman spectrometer system of  claim 10  wherein the system further comprises a monochromatic illumination light source that provides illumination light to the sample.  
     
     
         12 . The Raman spectrometer system of  claim 11  wherein the system further comprises an illumination light guide and a probe located at the distal end of the illumination light guide, wherein the illumination light guide transmits the monochromatic illumination light from the light source to the probe, which in turn transmits the illumination light to the sample.  
     
     
         13 . The Raman spectrometer system of  claim 11  wherein the monochromatic illumination light source comprises an infrared laser.  
     
     
         14 . The Raman spectrometer system of  claim 12  wherein the illumination light guide comprises a single optical fiber having a diameter less than about 200 μm.  
     
     
         15 . The Raman spectrometer system of  claim 11  wherein the illumination light source provides light having a power of at least about 250 mW.  
     
     
         16 . The Raman spectrometer system of claim,  12  wherein the monochromatic illumination light source provides light having a wavelength of about 785 nm, and a power of about 300 mW.  
     
     
         17 . The Raman spectrometer system of  claim 12  wherein the proximal end of the detection light guide is optically connected to the probe.  
     
     
         18 . The Raman spectrometer system of  claim 17  wherein the probe comprises a compound parabolic concentrator optically connected at the proximal end of the detection light guide, wherein the compound parabolic concentrator collects light emanating from the sample and concentrates it and transmits it into the distal end of detection light guide.  
     
     
         19 . The Raman spectrometer system of  claim 17  wherein the proximal end of the detection light bundle has a diameter greater than about 1 mm and the detection probe does not comprise a compound parabolic concentrator.  
     
     
         20 . The Raman spectrometer system of  claim 17  wherein the probe is sized to provide an illumination spot on the sample that is substantially larger than a detection spot detected by the probe.  
     
     
         21 . The Raman spectrometer system of  claim 9  or  10  wherein the substantially inverse shape is a parabolic curve.  
     
     
         22 . The Raman spectrometer system of  claim 9  or  10  wherein the plane grating is a volume phase technology (VPT) holographic grating.  
     
     
         23 . The Raman spectrometer system of  claim 9  or  10  wherein the light transmissive portion of the proximal end of the detection light guide comprises a filled-in geometrical shape.  
     
     
         24 . The Raman spectrometer system of  claim 23  wherein the filled-in geometrical shape is a circle.  
     
     
         25 . The Raman spectrometer system of  claim 9  wherein the detection light guide further comprises a calibration light guide optically connected to a calibration light source.  
     
     
         26 . The Raman spectrometer system of  claim 25  the calibration light guide is disposed at the center of the detection light guide.  
     
     
         27 . The Raman spectrometer system of  claim 9  wherein detector comprises an array of detection pixels and the detection light guide comprises a bundle comprising enough light guides to substantially fill a column or row of the array.  
     
     
         28 . The Raman spectrometer system of  claim 27  wherein bundle comprises more than about 50 light guides.  
     
     
         29 . The Raman spectrometer system of  claim 28  wherein the light guides are selected from the group consisting of an optical fiber, a liquid light guide and a hollow reflective light guide.  
     
     
         30 . The Raman spectrometer system of  claim 9  wherein the system is portable.  
     
     
         31 . A light transmission means suitable for use for Raman spectroscopy, the light transmission means comprising a means for receiving light in a substantially filled-in geometrical shape at a proximal end of the light transmission means and means for emitting the light in a substantially linear curve at a distal end of the light transmission means.  
     
     
         32 . The light transmission means of  claim 31  wherein the substantially linear curve is substantially identical to a curve of a substantially linear line of light after it has been passed through a holographic grating.  
     
     
         33 . The light transmission means of  claim 31  wherein the light transmission means further comprises a means for transmitting calibration light.  
     
     
         34 . A Raman spectrometer system comprising a means for transmitting detection light emanating from a sample, a distal end of the detection means optically connected to a plane grating means that is in turn optically connected to a means for detecting that is operably connected to a controller means containing computer-implemented programming that detects light impinging on means for detecting, wherein the means for transmitting detection light provides light in a substantially inverse shape that is complementary to a distortion to the light caused by passing the light through the plane grating, to provide light in a substantially straight line at the means for detecting.  
     
     
         35 . The Raman spectrometer system of  claim 34  wherein the system further comprises a means for providing monochromatic illumination light to the sample.  
     
     
         36 . The Raman spectrometer system of  claim 35  wherein the system further comprises a probe means for emitting illumination light to the sample and for receiving light emanating from the sample, the probe means optically connected to a distal end of a means for transmitting illumination light and to a proximal end of the means for transmitting detection light.  
     
     
         37 . The Raman spectrometer system of  claim 36  wherein the probe means provides an illumination spot on the sample that is substantially larger than a detection spot detected by the probe means.  
     
     
         38 . The Raman spectrometer system of  claim 31  wherein the system further comprises a means for transmitting calibration light.  
     
     
         39 . The Raman spectrometer system of  claim 31  wherein the system is portable.  
     
     
         40 . A method of making a light transmission bundle comprising 
 a) providing at least 5 light guides;    b) arranging the light guides in a filled-in geometrical shape at a proximal end of the light transmission bundle; and    c) arranging the light guides in a substantially linear curve at the distal end of the light transmission bundle.    
     
     
         41 . The method of  claim 40  wherein the light guides are arranged in a substantially parabolic curve at the distal end of the light transmission bundle.  
     
     
         42 . The method of  claim 41  wherein the parabolic curve is substantially identical to a curve of a substantially linear line of light after it has been passed through a holographic grating.  
     
     
         43 . The method of  claim 40  wherein the filled-in geometrical shape is a circle.  
     
     
         44 . The method of  claim 40  wherein the method further comprises adding a calibration light guide to the light transmission bundle.  
     
     
         45 . A method of taking a Raman measurement comprising: 
 a) illuminating a sample under conditions and for a time sufficient to induce measurable Raman scattered light to emanate from the sample;    b) collecting the emanating light;    c) providing the emanating light with a substantially inverse shape that is complementary to a distortion to the light caused by passing the light through a light-dispersive element;    d) passing the light having the substantially inverse shape through the plane grating to provide substantially straight spectral lines; and,    e) performing Raman spectroscopic analysis on the substantially straight spectral lines.    
     
     
         46 . The method of  claim 45  wherein the providing the substantially inverse shape further comprises transmitting the emanating light through a detection light guide wherein the light transmissive portion of the distal end of the detection light guide is arranged in a substantially inverse shape that is complementary to a distortion to the light caused by passing the light through the light transmissive element, and wherein the light transmissive element comprises a plane grating.  
     
     
         47 . The method of  claim 45  wherein the method further comprises illuminating the sample and collecting the emanating light through a probe optically connected to an illumination light source and to the detection light guide.  
     
     
         48 . The method of  claim 45  wherein the method further comprises providing an illumination spot on the sample that is substantially larger than the detection spot detected by the probe.  
     
     
         49 . The method of  claim 45  wherein the method further comprises providing calibration light.  
     
     
         50 . The method of  claim 45  wherein the method is performed using a portable Raman system.  
     
     
         51 . The method of  claim 45  wherein the Raman measurement is obtained in vivo.  
     
     
         52 . The method of  claim 45  or  51  wherein the Raman measurement is obtained in less than about 1 second.