Abstract:
A new architecture for implementing a time-resolved Raman spectrometer is 2-3 orders of magnitude faster than current systems. The system additionally is compact, environmentally rugged, low cost and can detect multiple components of a sample simultaneously. In one embodiment, the invention employs a rotating optical switch to time multiplex an input signal through multiple bandpass filters and into a single optical detector which is electrically activated only when the filtered input light pulse is about to impact it. 
     The combination of time-multiplexing the input signal through multiple optical filters and time-sequencing the optical detector enables the device to detect and analyze 2-3 orders of magnitude faster than current designs, processing spectra within milliseconds instead of seconds. The system can process multiple material samples (25+) simultaneously, instead of sequentially, and its mechanical ruggedness and simplicity enables using the system in harsh physical environments when traditional spectrometers can not be used reliably.

Description:
FIELD OF THE INVENTION 
       [0001]    This invention relates to a time-resolved Raman spectrometer that is two to three orders of magnitude faster than current Raman spectrometers and which is environmentally rugged, low cost and can detect multiple components of a sample simultaneously. 
       BACKGROUND OF THE INVENTION 
       [0002]    Raman spectroscopy is a proven technology in bio-medical, chemical, industrial and other sensing applications. However, significant problems exist for implementing this technique, such as detector sensitivity, processing speed, simultaneous multi-component analysis of a single sample, environmental ruggedness, and cost. In order to obtain Raman spectra from a sample, a high intensity optical source is needed (typically a laser) to pump the inelastic Raman scattering process within the material, be it a gas, a liquid, or a solid. As a result, the material scatters radiation, in all directions, at different frequencies. The component with frequency equal to that of the pump laser corresponds to Rayleigh scattering, and the component with frequency shifted lower than that of the pump laser is called Stokes radiation, a portion of which corresponds to Raman scattering. The main feature of Raman scattering is that it occurs regardless of the wavelength of the pumping optical source, while keeping the frequency shift between Stokes and pump radiation fixed. The Stokes radiation shift and intensity are dependent upon the material. Typically, Stokes Raman shifts are in the order of a few to tens of tera-Hertz (THz), and their intensity is 4 to 5 orders of magnitude lower than the Rayleigh scattered light. In order to discriminate and measure accurately the Raman scattered radiation from the Rayleigh radiation, a blocking filter for the Rayleigh frequency needs to be used in all Raman measurement systems. Fortunately, the typical Raman Stokes shift is large enough to allow for current state-of-the-art filters to block the Rayleigh radiation while marginally affecting the Raman Stokes radiation. 
         [0003]    Time-resolved Raman spectroscopy techniques have been used for years. Detection and analysis of the signal in these systems is typically difficult and expensive. Commercial Raman spectrometers are: 
         [0004]    1) too slow for many practical applications, with signal processing time of a few seconds or more. Real-time process monitoring is impossible, as are many medical and in-vivo applications; 
         [0005]    2) typically limited to measuring no more than two or three components within a given sample, at a time, due to high spectral overlap between different analytes; 
         [0006]    3) physically sensitive to the environment such as movement, vibration, and temperature changes, in their performance; and 
         [0007]    4) not optically sensitive for many applications such as detecting weak markers in biological samples or weak returns and noisy signals from long-range sensing applications. 
         [0008]    Techniques for processing multiple components, in the order of 20 to 100, with a 1 to 10 second typical collection for each, require an excessive amount of time to complete a full sample analysis. Weak signals from noisy environments result in the loss of important spectral information in many cases. Field applications in harsh environments are also off limits for currently available Raman systems. 
         [0009]    The most popular types of spectrometers in use today are Fourier-Transform type devices. Fourier Transform Infra-red (FTIR) and Fourier Transform Raman (FTR) spectrometers employ a motor to create a linear displacement of sensitive optical elements in the detection process. This technique has serious operational and environmental limitations, since alignment must be maintained as optical parts are being moved, and also time-calibration is necessarily complex since non-uniform linear motion is involved. 
         [0010]    Accordingly, there is a need for simpler, environmentally insensitive Raman spectrometers capable of determining multiple components in a sample within a very short time. 
       SUMMARY 
       [0011]    The present invention provides an environmentally rugged system that performs high-speed Raman spectroscopy with dramatically improved processing speed, enabling the monitoring of multiple components of a sample in a very short time. One embodiment of the system includes the unique ability to process and analyze an individual material sample with a time resolution of 1 ms to 100 ms. This is two to three orders of magnitude faster than currently available commercial devices, which operate at more than 1 second per sample. 
         [0012]    By using an ultra-sensitive photo-detector to enhance the system&#39;s sensitivity at high speed, the system provides the same sensitivity as current state-of-the-art devices Raman spectrometers but at a much higher speed. The system provides a simple time-calibration of the signal from the sample, therefore improving the accuracy of data collection at a reduced cost. 
         [0013]    The system can quantitatively determine a mixture composed of multiple components (for example 20 to 25 or more components), simultaneously. 
         [0014]    An embodiment of the system is field-deployable, suitable to be used in moving vehicles and aircraft, and hostile physical environments, with no degraded performance. Thus the system can operate in any given orientation relative to the ground, with no need for readjustments due to gravity. 
         [0015]    In its simplest form, the system represents a factor of ten (10) manufacturing cost reduction, relative to similar instruments, due to the reduced number of parts used and simplicity of construction. In particular, the system eliminates the use of gratings, prisms, and other dispersive elements that are lossy, expensive, and extremely sensitive to alignment. As part of the cost reduction, the system uses a single photo-sensitive element, replacing the need for expensive photo-detector arrays and CCD cameras, and simplifying data collection schemes. 
         [0016]    An embodiment of the system provides a wide detection bandwidth, being able to detect signals with bandwidths from 900 nm to 2.1 μm. 
         [0017]    An embodiment of the system uses a linear regression algorithm to process the data obtained from the sample, thereby reducing the number of data points to be processed by an order of magnitude. The algorithm is a discretized version of Principal Component Analysis techniques (dPCA). 
         [0018]    In one embodiment, the system can be directly adapted to perform resonance Raman spectroscopy by introduction of a UV emitting diode in the system, therefore increasing the sensitivity of the system by 2 to 3 orders of magnitude. 
         [0019]    The system makes possible a method to perform time-resolved Raman analysis of blood vessel angiography and also makes possible a method for fast detection of calcified plaque in a blood vessel, for real-time diagnosis. Also the Raman spectroscopy system of this invention provides real-time, non-invasive temperature measurements of samples in-vivo or for other applications. 
         [0020]    In particular, this invention allows one to determine multi-component concentrations in a given sample, whether a solid, a powder, a liquid, or a gas, using Raman spectroscopy and linear regression techniques. 
         [0021]    This invention will be more completely understood in conjunction with the following detailed description taken together with the drawings. 
     
     
       DESCRIPTION OF THE DRAWINGS 
         [0022]      FIG. 1   a  shows a fiber delivery collection system with an optical circulator in accordance with this invention. 
           [0023]      FIG. 2  shows a photonic crystal fiber delivery system in accordance with this invention. 
           [0024]      FIG. 3  shows a free space delivery and collection system in accordance with this invention. 
           [0025]      FIG. 4  shows a free space signal collection system utilizing the principles of this invention. 
           [0026]      FIG. 5   a  shows an embodiment of this invention using multiple illumination sources and multiple pump lasers. 
           [0027]      FIG. 5   b  shows an embodiment of this invention using multiple illumination sources and an emission lamp with filters. 
           [0028]      FIG. 6  shows a technique for implementing coarse and fine spectral coverage. 
           [0029]      FIG. 7  shows Raman spectra of compounds identified in the human carotid artery. 
           [0030]      FIG. 8  shows the concentration signal to noise ratio as a function of measurement time for different concentrations of the compounds shown in  FIG. 7 . 
       
    
    
     DETAILED DESCRIPTION 
       [0031]    The following detailed description is meant to be illustrative only and not limiting. Other embodiments of this invention will be obvious to those skilled in the art in view of this description. 
         [0032]    In accordance with this invention a Raman spectrometry device architecture is provided that combines a high speed time-division optical sampling engine with a unique data processing algorithm, discrete Principal Component Analysis (dPCA), in order to produce time-resolved, accurate Raman measurements with low signal levels. A variety of specific embodiments can be provided to implement the invention. The invention significantly decreases the sample processing time while increasing the number of material samples which can be processed at one time. This invention also improves the environmental ruggedness of the device while significantly decreasing the implementation cost. 
       Stokes Radiation Time-Multiplexing 
       [0033]    Referring to  FIG. 1   a , one embodiment of this invention employs a rotary switch such as disclosed in copending patent application Ser. No. 11/185,137 filed Jul. 20, 2005 based on provisional application No. 60/589,454 filed Jul. 20, 2004, both assigned to Neptec Optical Solutions, Inc., the assignee of this application. These two applications are hereby incorporated by reference in their entirety. This rotary switch essentially acts as a time-division multiplexing device. 
         [0034]    In the structure of  FIG. 1   a  (which corresponds to the best mode of the invention), light from a pump laser  1  (or other source such as a SLED (a “super-luminescent light emitting diode”) or a gas emission lamp using halogen gases or mercury or equivalent) illuminates a material sample  4  to be interrogated. Light back-scattered from the sample (called information light or “Stokes radiation”) contains specific information about the chemical and physical make up of the material being interrogated. Hereafter, in this written description, the term “Stokes radiation” will be used to mean the same as “information light”, which is light scattered from the sample as a result of light from source  1  impinging on sample  4 . 
         [0035]    In the embodiment of  FIG. 1   a , the optical delivery to the sample of the light from the illumination source and the optical collection from the sample of the Stokes radiation are performed through the same fiber  5  (sometimes called a “waveguide”). The light from source  1  to be incident on sample  4  is first passed through narrow bandpass filter  2  to remove spurious radiation outside the desired bandwidth and is then transmitted to the sample through optical fiber  5 . Stokes radiation scattered from sample  4  is also carried by waveguide  5  and is directed through an optical circulator  3  to a notch filter  6  to remove spurious information and into the z-axis of the device body. Notch filter  6  blocks the transmission of the residual back-scattered illumination light into the time-division multiplexing device  7 . Notch filter  6  can be a multilayer interference filter, a colored glass filter or an absorption cell (typically from an alkali metal vapor such as Rb or Cs). Taken together, the delivery/collection fiber  5 , optical circulator  3  and notch filter  6  comprise and will be referred to as the system “probe”. 
         [0036]    Optical circulator  3  is a well-known optical device with three channels wherein each channel allows the passage of light in a specific direction. In the system of  FIG. 1   a , circulator  3  lets light pass from the light source  1  to the sample  4  and on the third channel of the circulator  3  lets light scattered from the sample travel back from the sample  4  into the spectrometer and only in that direction. Optical circulators suitable for use with this invention are commercially available from a number of fiber optic device companies such as Optics for Research, located at Caldwell, N.J. 
         [0037]    The light from optical circulator  3  is passed through a notch filter  6  which blocks and thus removes light at the main frequency of the light source  1 . Filter  6  will pass light at frequencies other than the frequency of light from source  1 . The light that passes through filter  6  impacts a motor-driven, rotating prism  13  which can be of a type shown, for example, in copending patent application Ser. No. 11/185,137 filed Jul. 20, 2005 (published as U.S. Publication No. 2006/0072873 A1) incorporated by reference above. The mirrored surface of prism  13  reflects the incoming light through filters  8 - 1  to  8 - 12  into one of several waveguides  18 - 1  to  18 - 12  arranged circularly in a plane perpendicular to the z-axis of rotation and centered about the z-axis of rotation. While twelve (12) waveguides  18 - 1  through  18 - 12  are shown arranged in a circle in a plane around the rotating prism  13 , of course, a smaller or larger number of waveguides can be so arranged if desired. For example, in some embodiments 20 to 100 waveguides will be so arranged around the circumference of the rotating prism  13  within a plane to enable the system to determine at least 20 to 100 characteristics of the sample being analyzed. 
         [0038]    The rotation of the prism  13  sweeps the Stokes radiation beam across the inputs of the several waveguides  18 - 1  to  18 - 12  creating a “time multiplexing” of the single Stokes radiation beam. Thereby, each waveguide receives a time slice of the original optical information signal (i.e. the Stokes radiation). Each waveguide  18 - i  (where i is an integer varying from 1 to 12 in  FIG. 1   a  or from 1 to N when N filters and waveguides are placed around the circle in the plane perpendicular to the z-axis of rotation) is associated with a specific optical filter  8 - i  which is selected to transmit only a portion or selected portions of the broad wavelength range contained within the Stokes radiation. Each optical filter  8 - i  can be, for example, a molecular filter or an interference filter. The filtered Stokes radiation passing into waveguides  18 - 1  to  18 - 12  is then directed through multiplexer  9  to a single optical detector  10  and into electronic analytical equipment, such as a computer,  12  for processing. 
         [0039]    Electronic pulse generator  11  causes the photo-sensitive element  10  (which might be an avalanche photodetector, a photodiode, a photomultiplier or a micro channel plate, for example, or any other type of photo-sensitive element), to be turned on and activated whenever a signal from waveguide  18 - i  strikes the photo-sensitive element  10 . The pulse generator  11  essentially synchronizes the operation of photo-sensitive element  10  with the arrival of a signal scattered from prism  13  through a corresponding waveguide  18 - i.    
         [0040]    The filters  8  in front of waveguides  18  are each selected to allow certain light representative of certain types of components which might be present in the sample  4  to be transmitted from the probe to the optical fibers  18 - 1  through  18 - 12  to the multiplexer  9 . The multiplicity of filters  8 - 1  to  8 - 12  spectrally decompose the Stokes radiation and separate it into a timed sequence of pulses. These pulses are re-directed to a single photo-sensitive element  10  via a multiplexing element  9 . 
         [0041]    Multiplexer  9  (which might be a single mode fiber, a multi-mode fiber, or a photonic crystal fiber (PCF) depending on the desired numerical aperture, bandwidth and transmission loss of the device) will pass the signal being transmitted on the corresponding fiber  18 - i  when information light scattered from the rotating prism  13  impacts the corresponding waveguide  18 - i.    
         [0042]    The speed of rotation of prism  13  determines the frequency with which signal processing unit  12  (which might, for example, include a digital signal processor, certain recognition algorithms and a computer for carrying out the processing) receives the signals from each of the waveguides  18 - 1  through  18 - 12  on  FIG. 1   a . By increasing the speed of rotation of the prism  13 , the number of samples S 1 , S 2 , . . . S N , for example, capable of being processed by the signal processing unit  12  in a given time can be increased provided the speed of processing within processing unit is capable of analyzing the samples as they are delivered to the processing unit  12 . The speed of the processing unit  12  can be adjusted by including several processing units in parallel if necessary. 
         [0043]      FIGS. 1   b  and  1   c  show, respectively, the frequency spectrum of three signals S 1 , S 2  and S 3  and the times at which these three signals are made available through waveguides  18 - 1 ,  18 - 2  and  18 - 3  in sequence ( FIG. 1   c ). As shown in  FIG. 1   c , each signal S i  reaches an adjacent waveguide  18 - i  about 3 milliseconds after the preceding signal has reached its waveguide. Thus, if signal S 1  reached waveguide  18 - 1  at time 0, signal S 2  would reach waveguide  18 - 2  at a time 3 milliseconds thereafter and signal S 3  would reach waveguide  18 - 3  at a time 6 milliseconds after the first signal S 1  reach waveguide  18 - 1 . Three millisecond time between each of the signals with eight different signals being processed corresponds to 41 ⅔ revolutions per second. The actual revolutions per second will depend upon the number of samples to be generated which corresponds to the number of waveguides  8  which are employed on the circle in the plane perpendicular to the z-axis of the system shown in  FIG. 1   a.    
       Detector Time-Multiplexing 
       [0044]    The detector (made up of photo-sensitive element  10 , electronic pulse generator and synchronizing circuit  11  and the signal processing unit  12 ) is electrically turned off and optically isolated until it is required to be active to sense the weak information input signal. The position of the prism  13  with the Stokes radiation relative to a specific waveguide  18 - i  with filter  8 - i  is time correlated by electronic synchronizing circuit  11  with the electrical reactivation of the photo-sensitive element  10  in the detector; therefore, element  10  electrically turns on exactly when the Stokes radiation pulse reaches it. This innovation permits accurate signal timing and enables the photo-sensitive element  10  of the detector components  10 ,  11  and  12  to be at maximum optical sensitivity when light impacts element  10 . The combination of the above procedures results in a broad band data collection, within the duration of one rotation cycle of the prism  13 . 
         [0045]    One implementation employs pump laser  1  illuminating a sample  3  (which might consist of a solid, a liquid, or a gaseous material embedded in a pipeline, container, or in free space) and multi-mode optical fibers  18 - 1  to  18 - 12  as waveguides for directing the different light paths. Back-scattered light is connected to an optical collimator  3  (input collimator) which is mounted on top of the device body  15 , along the axis of rotation  16  (also called the z-axis) of the time-division multiplexer  7 . A 7,000-rpm motor (not shown) with a 7 mm×7 mm prism  13  is surrounded by the array of twelve (12) optical collimators  8 - 1  to  8 - 12  robotically aligned and mounted on a ceramic cylindrical shaped body (optical bench). These collimators  8 - 1  to  8 - 12  are positioned on a plane perpendicular to both the input collimator  3  and the axis of rotation  16  of the motor shaft. 
         [0046]    Along the optical path of each collimator, a wavelength specific filter  8 - 1  to  8 - 12  is placed, creating twelve (12) optical “channels”. Each channel filters a different region of the input spectrum allowing the detector  10  to sense only the selected wavelengths. The collection of the ceramic body, collimators, filters  8 - 1  to  8 - 12  rotating mirrored prism  13 , and motor and ancillary structures comprises the rotary optical switch device  15  ( FIG. 1   a ). 
         [0047]    The multiple collimators direct the filtered light channels into a detector  10  via multi-mode optical fibers  18 - 1  to  18 - 12  whose output signals are multiplexed to impact the surface of a single, ultra-sensitive photodetector device  10  (e.g. an avalanche photo-detector, or APD). The detector  10  is electrically pulsed on and off via a pulse generator  10  and electrically synchronized to the position of the motor shaft, enabling the coordination of the rotating prism  13  with the electrical activation of the photodetector  10 . By turning on and off the detector  10 , Raman spectroscopy is possible with lower level signals than heretofore used because keeping detector  10  off when no signal light (i.e. Stokes radiation) is incident on the detector  10  keeps the noise level down. This makes it possible for detector  10  to pick up weaker Stokes radiation than in prior art systems. 
         [0048]    Different types of detectors  10  can be used. A highly sensitive APD can be used (typically Si, GaAs or InGaAs material type, depending on the wavelength region to be measured), operated marginally (3-4%) above the internal breakdown-voltage of the device (˜40 V) to minimize noise and maximize sensitivity to light (Geiger-mode operation). 
         [0049]    Other embodiments can use photomultiplier tubes, to operate in the UV-visible spectral range. By sending only selected, pre-filtered light into the detector  10  and by only powering the detector  10  when the light pulse is about to impact detector  10 , an overall reduction in both electrical and optical noise of significant magnitude is achieved allowing for a collection of spectral information which is 2-3 orders of magnitude faster than conventional techniques. The rotary optical switch  15  combined with the optics  10  and electronics  11 ,  12  described above provides a vastly improved Raman spectrometer instrument. 
         [0050]    The signal from the photosensitive element  10  is amplified, filtered, and processed electronically by signal processing unit  12 . Signal processing can be performed by analog or digital electronics, or a combination of both. A digital signal processor (DSP) can be implemented as a very compact and fast device to perform such operations. The combination of multiplexing element  9 , photo-sensitive element  10 , pulse generator  11 , and signal processing unit  12  will be called the “back end” of the Raman spectrometer system described herein. 
         [0051]    An additional embodiment uses a pump laser through a multi-mode fiber that also acts as a collection mechanism where the return spectra is separated from the transmitted spectra via the use of a circulator or equivalent. 
         [0052]      FIG. 2  shows a photonic crystal fiber delivery system using a fiber bundle collection. In  FIG. 2 , many of the components are the same as or similar to those in  FIG. 1   a  but for simplicity will be shown schematically rather than in the detail shown in  FIG. 1   a . (A similar approach is taken with respect to the remaining  FIGS. 3 ,  4 ,  5   a ,  5   b  and  6 .) The system of  FIG. 2  uses a different probe than the system in  FIG. 1   a . The probe of the system in  FIG. 2  delivers the light from the illumination source  1  to the sample  4  by one optical fiber and collects the Stokes radiation scattered from the sample  4  by different optical fibers. The delivery of the light to sample  4  is done by a photonic crystal fiber to reduce the modal area of illumination on the sample  4 . The Stokes radiation is delivered by a set of optical fibers around the delivery fiber to maximize the efficiency of collection of the Stokes radiation. Multiplexer  3  collects the signal from the fiber bundle and directs it to the notch filter  6 , the time division multiplexer  7 , the filers  8 , a second multiplexer  9  and the photosensitive element  10 . The remainder of the back end is similar to what is shown in  FIG. 1   a  and includes the electronic pulse generator  11  and the signal processing unit  12 . Another difference between the system of  FIG. 1   a  and the system of  FIG. 2  is the use of multiplexer  3  in the optical channel between the scattered light from the sample  4  and the notch filter  6  located in the path followed by the Stokes radiation to prism  13  in the time-division multiplexing device  7 . The numbers set forth in the remainder of the structure in  FIG. 2  are identical with the numbers set forth in  FIG. 1   a  to the extent these components are the same. Therefore, these components operate as described in connection with  FIG. 1   a.    
         [0053]      FIG. 3  shows a system which uses a probe which includes a free space delivery component. The system shown in  FIG. 3  includes many of the components shown in  FIGS. 1   a  and  2 . Unless otherwise specified, identical components are numbered identically as in  FIGS. 1   a  and  2 . New components are numbered differently. The system shown in  FIG. 3  can be used in near field collection (microscopy) or far field collection (remote sensing) regimes. 
         [0054]    In  FIG. 3 , an illumination source  1 , which could be a laser or bright lamp, for example, provides light (such as CW pump radiation) which passes through narrow bandpass filter  2  to free space delivery optics  30  which could be a lens, a parabolic mirror or similar structure. From optics  30 , the focused light impacts on sample  4  at a selected position. The scattered light (i.e., the Stokes radiation) passes through notch filter  5   a  (which could be, for example, an interference grating, colored glass, an absorption cell or a fiber grating). Notch filter  5   a , if desired, can be embedded in fiber or located in free space. 
         [0055]    The signal from notch filter  5   a  is then transmitted in free space to collection optics  6  (which might include appropriate combinations of selected ones of lenses, mirrors, prisms and apertures, for example). Optics  6  couples the scattered Stokes radiation into an optical fiber  16  that directs the light to the time-division multiplexing device  7  (as described above). At least part of optical fiber  16  is located on the axis of rotation of the time division multiplexing device  7 . Notched filter  5   a  can, if desired, be replaced by an identical notched filter  5   b  located after optics  6  rather than before optics  6 . 
         [0056]    Prism  13  reflects the light transmitted along optical fiber  16  to an appropriate one of filters  8 - 1  through  8 - 8 . Filters  8 - 1  through  8 - 8  can be any one of a number of different types of filters such as molecular filters, or interference filters, for example as described above in conjunction with  FIG. 1   a  and  FIG. 2 . The signals from filters  8 - 1  through  8 - 8  are sent on optical fibers  18 - 1  through  18 - 8  to a multiplexer  9  where each of the signals then is transmitted to light detector  10 . Electronic synchronization circuit  11  activates light detector  10  before each of the signals from the corresponding filters  8 - 1  through  8 - 8  reach detector  10  and thus synchronizes the turning on of detector  10  with the application of the signal scattered by prism  13  to the appropriate one of filter  8 - 1  through  8 - 8 . 
         [0057]    The system otherwise operates just as the system shown in  FIGS. 1   a  and  2 . 
         [0058]      FIG. 4  shows another embodiment of this invention with a modified back end. An illumination source  1  (which can be a laser or bright lamp, for example), a narrow bandpass filter  2 , a multiplexer (which is of a well-known construction)  3 , a sample  4  and a delivery fiber  5  (which, for example, can be a photonic crystal fiber (PCF)) operate in much the same way as shown in  FIGS. 1   a ,  2  and  3 . In  FIG. 4 , these components are depicted in the box with the numbers  1  to  5 . The information signal scattered from the sample  4  is transmitted to the notched filter  6  (which again can be an interference grading, colored glass or an absorption cell, for example) and then to time-division multiplexing device  7 . The time-division multiplexing device  7  can be, for example, the rotating disk with a prism  13  on it as shown in  FIGS. 1   a ,  2  and  3 . From this disk, however, the signal is sent in a manner described above in conjunction with  FIGS. 1   a ,  2  and  3  to various molecular or interference filters  8 - 1 ,  8 - 2  and  8 - 3  as shown. Of course, other numbers of filters can be used if desired. Each filter  8 - 1 ,  8 - 2  and  8 - 3  is arranged in a structure known as a free space multiplexer box  9  which can be fabricated of any acceptable material such as ceramic, metal, or plastic. For example, Box  9  contains reflecting elements  10 - 1 ,  10 - 2 , and  10 - 3  (for example, mirrors) for reflecting the corresponding signals from filters  8 - 1 ,  8 - 2  and  8 - 3 , respectively, to a focusing lens  11 . The signal from lens  11  then is sent to a photo-sensitive element  12  which operates as described in the previous description of system shown in  FIGS. 1   a ,  2  and  3 . The detector  12  sends its signal to the signal processing unit  14 . Electronic pulse-generator and synchronization circuit  13  operates to turn on the detector  12  in response to the signals from multiplexing device  7  hitting the respective ones of mirrors  10 - 1  through  10 - 3  and thereby in time sequence as shown in  FIG. 1   c  striking detector  12 . The system in this respect operates as described above. 
         [0059]      FIG. 5   a  illustrates a system for Raman spectroscopy which employs multiple lasers. Thus, multiple lasers  1 - 1 ,  1 - 2  and  1 - 3  provide signals of different wavelengths λ 1 , λ 2 , λ 3 , respectively. These signals are transmitted to a time-division multiplexer which has thereon an optical system which allows these signals to be transmitted in sequence to a sample  4 . The Stokes radiation scattered from sample  4  is sent to optical circulator  3  and from there is sent to a block filter  5  which blocks the signals with wavelengths λ 1 , λ 2 , and λ 3  but which passes the stokes radiation associated with these wavelengths. Optical filter  5 , although a blocking filter for the wavelengths λ 1 , λ 2 , and λ 3 , is a single bandpass or band-block filter for the Stokes radiation. This combined filter is made possible by the large spectral range between the illumination radiation and the Stokes radiation in most Raman signals. 
         [0060]    Photo-sensitive element  6  then receives in sequence Stokes radiation signals associated with wavelengths λ 1 , λ 2 , λ 3  and is readily turned on in synchrony with the operation of time-division multiplexer  2  to transmit the signals to a processing unit  12  which operates as described above in conjunction with  FIGS. 1   a ,  2  and  3 . 
         [0061]      FIG. 5   b  shows a similar structure as in  FIG. 5   a  except here a single broadband light source  1  (for example, a metal-halogen light source, or a Mercury gas lamp, or a Xenon arc lamp, or a Neon arc lamp) provides light which is then transmitted through filters  3 - 1 ,  3 - 2  and  3 - 3  which are part of time-division multiplexer  2 . As time-division multiplexer  2  rotates, specific pulses of light are passed along the path from multiplexer  2  to sample  5  in a reverse direction from the direction of the light transmitted in the systems shown in  FIGS. 1   a ,  2 ,  3 ,  4  and  5   a . The Stokes radiation scattered from sample  5  is passed through optical circulator  4  and then through a filter  6  which passes λ 1 , λ 2  and λ 3  to the photo-sensitive element  7 . Photo-sensitive element  7  is again activated by the electronic pulse generator  11  (not shown in  FIG. 5   b ) which synchronizes the turning on of detector  7  with the incidence of the light from filters  3 - 1  through  3 - 3  on sample  5 . Processor  12  (also not shown in  FIG. 5   b ) then processes the output signal from detector  7  to determine the presence of selected components in the sample. 
         [0062]      FIG. 6   a  illustrates a structure which provides coarse and fine spectral coverage. Collected and filtered light from the sample  4  is passed through a time-division multiplexer  21  which operates as discussed above in conjunction with  FIGS. 1   a ,  2  and  3 . Collimators  31 - 1  to  31 -M (where M is an integer representing the number of correlators in multiplexer  21 ) send this light to auxiliary channels. Then a drum with a coarse set of filters  41 - 1  to  41 -P and a fine set of filters  42 - 1  to  42 -Q, where P and Q are each a selected integer representing the maximum number of coarse and fine filters, respectively, is inserted into the multiplexer  21  such that the light reflected from the prism  31  in time-division multiplexer  21  is then sent through in time sequence each filter in the coarse set of filters  41 - 1  to  41 -P to provide a broadband sensitivity to light. By further inserting the drum into multiplexer  21 , a narrow set of filters  42 - 1  to  42 -Q which provide a narrow band sensitivity to light, is placed between the rotating prism  13  and the transmission channels to the light detector. The bandwidth associated with the coarse set of filters  41  is shown in  FIG. 6   b  within the bracketed range “A” whereas the bandwidth associated with the fine set of filters  42  is shown bracketed with the range “B” in  FIG. 6   b . This particular structure allows the system to make a fast determination that there is a signal of interest within the broadband “A” and then determine using the fine set of filters whether or not that signal of interest actually contains information with respect to a component of interest. 
         [0063]    The drum shown in  FIG. 6  has two sets of filters, but more than two sets of filters can be employed in this embodiment if desired. The use of a plurality of filter sets allows the system to cover a wider spectral range in the Stokes radiation domain or possibly to increase the spectral resolution for a given feature as discussed above. 
         [0064]    The particular set of filters to receive the light from the multiplexer  21  is moved into position by moving the drum on which the filters are mounted laterally along its cylindrical axis by means of mechanical components of well known design but not shown here for clarity. The coarse set of filters or the fine set of filters are actually moved laterally along the z-axis of the time division multiplexer  21  until the particular ring of filters (either coarse or fine) is spaced precisely between the collimators  31 - 1  through  31 -M and the rotating prism  13  associated with the time division multiplexer  21 . As a result, as the time division multiplexer rotates, the beam from the prism  13  is filtered through either the coarse set or the fine set of filters and the particular collimator associated with each of the filters in the coarse set or the fine set will then pass the signal through the corresponding waveguide to the signal processing structure as described above, such as to processor  12  in  FIG. 1   a . Of course, the width W of each band of filters (i.e. the width of the coarse set  41 - 1  to  41 -P and the width of the fine set  42 - 1  to  42 -Q must be such that when taken together, the distance of the collimators  31 - 1  through  31 -M from the plane of the time division multiplexer  21  on which the collimators  31  are mounted is sufficient to allow the fine set of filters  42 - 1  to  42 -Q to actually be located between the collimators  31  and the rotating prism  13  such that the signal from the rotating prism  13  will in fact impact appropriately on each filter in the fine set of filters. 
         [0065]    The system shown in  FIG. 6  is highly convenient in applications where a layered response is necessary in order to activate an alarm, as in the case where the presence of a noxious substance is ultimately verified by a refined spectral analysis. 
       Description of the Data Processing Algorithm 
       [0066]    The algorithm used for processing the electrical signal from the photosensitive unit is a discrete principal component analysis procedure (dPCA) which will be outlined in the following. The amount of Raman power, P R (ν i ), produced by frequency mode, ν i , from a given scattering material, upon the incidence of pump radiation with power, P p , is given by the following expression 
         [0000]    
       
         
           
             
               
                 
                   
                     
                       P 
                       R 
                     
                      
                     
                       ( 
                       
                         v 
                         i 
                       
                       ) 
                     
                   
                   = 
                   
                     
                       
                         P 
                         P 
                       
                       · 
                       
                         ɛχ 
                         i 
                       
                     
                      
                     ρ 
                      
                     
                         
                     
                      
                     
                       
                         l 
                          
                         
                           ( 
                           
                             
                               ∂ 
                               σ 
                             
                             
                               ∂ 
                               Ω 
                             
                           
                           ) 
                         
                       
                       
                         λ 
                         R 
                       
                     
                      
                     ΔΩ 
                   
                 
               
               
                 
                   ( 
                   1 
                   ) 
                 
               
             
           
         
       
     
         [0067]    where, ε, is the optical collection efficiency of the system, χ i  is the relative concentration of the scattering substance (a number between 0 and 1), and ρ, is the density of the scattering substance (g/cm 3 ), l, is the transversal dimension of the illumination area of the sample, (∂σ/∂Ω) λR , is the Raman scattering cross section of the material (in cm 2 /(gSr)), and ΔΩ is the total solid angle of collection. 
         [0068]    For the quantitative determination of a mixture with m different substances, assume that n different Stokes Raman spectral bands have been selected for the channels of the time-division multiplexing device. The number n has to equal or be greater than m, its exact value being application specific. Normally, n will range between just a few (3 or 4), and several tens of channels (50 to 100). The judicious selection of a limited number of spectral bands is essential for the discretization of the analysis technique to make it simple. Typical PCA algorithms make use of the whole spectrum across a broad collection band, with 100-1000 values per spectrum. Due to the lower dimensionality of the data sets (by a factor of 10-100), the number of operations to complete the algorithm is 3 to 6 orders of magnitude lower than for conventional algorithms. If σ ij  denotes the normalized contribution of the Raman spectrum from substance j onto filter i, and χ i  is the relative concentration of substance j in the mixture, then the collected light intensity by the switch at channel k, A k , is: 
         [0000]    
       
         
           
             
               
                 
                   
                     A 
                     k 
                   
                   = 
                   
                     
                       ∑ 
                       l 
                     
                      
                     
                       
                         σ 
                         kl 
                       
                        
                       
                         χ 
                         l 
                       
                     
                   
                 
               
               
                 
                   ( 
                   2 
                   ) 
                 
               
             
           
         
       
     
         [0069]    The validity of Eq. (2) in the case of a Raman spectrum is supported by the linear dependence on the concentration, Ω I , expressed in Eq. (1). The same statement is not true in the case of Infra-red absorption, and complicates the analysis in the case of high analyte concentrations. In general, Eq. (2) is a system of n inhomogeneous linear equations with m unknowns. The basic proposition of chemometrics is that it is always possible to find enough independent bands, n, in the Raman spectra of the substances of interest, so that Eq. (2) can be solved for χ. Following the spirit of Chemical Factor Analysis, 1  we can write Eq. (2) in matrix notation as  1  Edmund R. Malinowski; Factor Analysis in Chemistry, 3rd Edition, Wiley-Interscience, New York (2002). ISBN 0-471-13479-1. 
         [0000]        A=σ·χ   (3) 
         [0070]    where, σ, is an n×m rectangular matrix. A new matrix, Z, is defined: 
         [0000]        Z=σ   t ·σ  (4) 
         [0071]    Z is a square, symmetric matrix, and therefore it can be diagonalized and inverted by a unitary matrix, Q, as in: 
         [0000]        Z=Q   t   ·Λ·Q   (5) 
         [0072]    where, Λ, is a diagonal matrix containing the eigen values of Z. Finally, from Eq. (3), (4) and (5), a solution can be found for χ as 
         [0000]      χ= Q·Λ   −1   ·Q   t ·σ t   ·A   (6) 
         [0073]    The matrix of eigen values, Λ, is relevant because it dissects the parameter space, χ, in terms of linear combinations of its components such that their net effect in the measurement, A, can be quantified. This is accomplished by evaluating the relative magnitude of the eigen values (Λ i ). The parameter(s) that has the highest value indicates the relevant variable(s) in the problem, whereas the others give an indication of the dispersion of the data around the qualifying parameter(s). 
         [0074]    Equation (6) is basically the equation that is used in the signal processing unit  12  to calculate the concentration of each analyte (i.e. the concentration of each different component in the sample) from the information represented by A. Each entry in vector A corresponds to a photodetector measurement from a particular waveguide connecting to the photodetector  10  ( FIG. 1   a ) when a signal from a particular filter  8 - i  is impacting on detector  10 . Thus, this particular signal as produced by detector  10  will be processed by processing unit  12  using constants which have been placed in a table in memory for access by computer  12 , together with all other signals from each filter  8 - i , after each cycle of the time-division multiplexing device is completed. The user would identify the particular sample being analyzed and the computer then would automatically go to a table corresponding to the possible components of that sample to determine the constants Q·Λ −1  Q t  and σ t  to be used in the calculation of the concentration of each analyte which constitutes the sample. Q and σ a depend on the particular filters selected. An example set forth below will explain what the units are for each of these symbols and give therefor a calculation as would be done by signal processing unit  12  based upon a typical sample to be analyzed by the system. Example 1. 
         [0075]    The construction of the matrix, σ, starts by selecting n bandpass filters, f i , with bandwidth Δλ i . The elements of the matrix are thus given by the following expression: 
         [0000]    
       
         
           
             
               
                 
                   
                     
                       σ 
                       ij 
                     
                     = 
                     
                       κ 
                        
                       
                         
                           ∫ 
                           
                             
                               λ 
                               i 
                             
                             - 
                             
                               Δ 
                                
                               
                                   
                               
                                
                               
                                 
                                   λ 
                                   i 
                                 
                                 / 
                                 2 
                               
                             
                           
                           
                             
                               λ 
                               i 
                             
                             + 
                             
                               Δ 
                                
                               
                                   
                               
                                
                               
                                 
                                   λ 
                                   i 
                                 
                                 / 
                                 
                                   2 
                                   i 
                                 
                               
                             
                           
                         
                          
                         
                           
                             
                               
                                 f 
                                 i 
                               
                                
                               
                                 ( 
                                 λ 
                                 ) 
                               
                             
                             · 
                             
                               
                                 g 
                                 j 
                               
                                
                               
                                 ( 
                                 λ 
                                 ) 
                               
                             
                           
                            
                           
                               
                           
                            
                           
                              
                             λ 
                           
                         
                       
                     
                   
                   ; 
                 
               
               
                 
                   ( 
                   7 
                   ) 
                 
               
             
           
         
       
     
         [0000]    where f i  is the pass-band function for filter i, and g j  is the wavelength-dependent Raman efficiency for substance j, including all its active Raman bands. The factor, κ, is a constant that relates the unit-less numbers, χ j , to the photodetector measurements, A i , in Watts, through Eq. (3). Two fundamental issues are: the number of filters to be used, and which filters to use, f i  in terms of their center wavelength, λ i , and their bandwidths, Δλ i . For a given number of filters, n, the error in measurement can be proven to be inversely proportional to √{square root over (ξ)} 2 , with ξ=Det(Z). Therefore, the essential step of the dPCA technique comprises the selection of a filter set {f 1 , f 2 , . . . , fn} such that ξ is maximized, for a given n, resulting in a value ξ n . It can also be proven that ξ n  grows monotonically with n. The final decision of the number of filters to be used, n, is made as a compromise between the tolerance level for the measurement error, and the architectural considerations for device construction.  2  Real-Time Broad-Band Measurement of Cholesterol, Collagen, and Elastin Using a Novel Rotary Switch Spectrometer; Ricardo Claps, Roy Guynn, Wiktor Serafin, Jeff Virojanapa, Aaron Urbas, and Robert A. Lodder  Proc. SPIE  6078, 60782G (2006). 
       EXAMPLE 
       [0076]    As an illustration of the procedure mentioned above, a description of a specific example will be sketched in this paragraph. Let us consider the problem of cardiovascular angiography. The substances of interest in this case are Cholesterol, Collagen and Elastin (Ch, C, and E),  FIG. 7  shows the characteristic Raman spectra for these compounds. Table I shows the details of the spectra, to be used in the calculations. 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE I 
               
             
             
               
                   
               
               
                 Stokes Raman spectra of Collagen, Elastin and Cholesterol 
               
             
          
           
               
                   
                   
                 Frequency Band 
                 Cross Section 
               
               
                   
                 Substance 
                 (cm −1 ) 
                 (×10 −9  cm 2 /gSr) 
               
               
                   
                   
               
             
          
           
               
                   
                 Collagen 
                 1668 
                 1.39 
               
               
                   
                 Elastin 
                 1664 
                 1.7 
               
               
                   
                 Cholesterol 
                 1440 
                 4.44 
               
               
                   
                   
               
               
                   
                 Information from Ref. [a, b]. Pump wavelength is λ p  = 1064 nm Due to the uncertainty or variability in Molecular Weight of large bio-polymers, the cross-section is more adequately expressed in mass (g). 
               
               
                   
                 [a] J. M. Dudik, C. R. Johnson, S. A. Asher; “Wavelength dependence of the preresonance Raman cross sections of CH 3 CN, SO 4   2− , CIO 4   − , and NO 3   − ”, J. Chem. Phys. 82 (4) 1732 (1985). 
               
               
                   
                 [b] R. Manoharan, J. J. Baraga, M. S. Feld, R. P. Rava; “Quantitative histochemical analysis of human artery using Raman spectroscopy”, J. Photochem. Photobiol. B: Biol. 16 211 (1992). 
               
             
          
         
       
     
         [0077]    The construction of the matrix, σ, begins by selecting 3 filters, whose specifications are listed in Table II below. 
         [0000]    
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                   
                 TABLE II 
               
               
                   
                   
               
               
                   
                 nm 
                 f 1   
                 f 2   
                 f 3   
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 Center λ 
                 1258 
                 1294 
                 1229 
               
               
                   
                 Δλ 
                 1.2 
                 0.2 
                 2.0 
               
               
                   
                   
               
             
          
         
       
     
         [0078]    Using Eq. (7), matrix σ becomes 
         [0000]    
       
         
           
             σ 
             = 
             
               ( 
               
                 
                   
                     0.330 
                   
                   
                     0.210 
                   
                   
                     0.226 
                   
                 
                 
                   
                     0.228 
                   
                   
                     0.303 
                   
                   
                     0.219 
                   
                 
                 
                   
                     0.003 
                   
                   
                     0.055 
                   
                   
                     0.121 
                   
                 
               
               ) 
             
           
         
       
     
         [0079]    And from Eq. (4) we have: 
         [0000]    
       
         
           
             Z 
             = 
             
               ( 
               
                 
                   
                     0.160 
                   
                   
                     0.137 
                   
                   
                     0.124 
                   
                 
                 
                   
                     0.137 
                   
                   
                     0.137 
                   
                   
                     0.119 
                   
                 
                 
                   
                     0.124 
                   
                   
                     0.119 
                   
                   
                     0.114 
                   
                 
               
               ) 
             
           
         
       
     
         [0080]    The decomposition of z takes place by matrices Λ and Q (Eq. (5)), given by: 
         [0000]    
       
         
           
             Λ 
             = 
             
               ( 
               
                 
                   
                     0.393 
                   
                   
                     0 
                   
                   
                     0 
                   
                 
                 
                   
                     0 
                   
                   
                     0.013 
                   
                   
                     0 
                   
                 
                 
                   
                     0 
                   
                   
                     0 
                   
                   
                     0.005 
                   
                 
               
               ) 
             
           
         
       
       
         
           
             Q 
             = 
             
               
                 ( 
                 
                   
                     
                       
                         - 
                         0.707 
                       
                     
                     
                       
                         - 
                         0.690 
                       
                     
                     
                       
                         - 
                         0.156 
                       
                     
                   
                   
                     
                       0.608 
                     
                     
                       0.480 
                     
                     
                       0.633 
                     
                   
                   
                     
                       0.362 
                     
                     
                       
                         - 
                         0.542 
                       
                     
                     
                       0.758 
                     
                   
                 
                 ) 
               
               . 
             
           
         
       
     
         [0081]    Once the matrices shown above have been constructed, the implementation of the algorithm in the Raman device is quite simple: The set of power readings obtained in one cycle of the time-division multiplexer with the photodetector comprises the measurement vector A. This vector is introduced in Eq. (6), with σ, Λ and Q as shown above, to obtain the concentration vector, χ. 
         [0082]    The result of using the previously chosen set of filters for the specific task of measuring Cholesterol, Collagen and Elastin is shown in  FIG. 8 .  FIG. 8  displays different curves for the Signal-to-Noise ratio (SNR) of the concentration measurement, as a function of the measurement time of the Raman device. Clearly, for larger concentrations the SNR is higher, allowing for a faster measurement of the sample. As the concentrations are reduced, the SNR approaches the limiting value of 1, so longer measurement periods are needed in order to obtain a precise measurement. 
         [0083]    The above description is illustrative only. Those skilled in the art will recognize other embodiments of the invention which can be implemented in view of this disclosure. As technology advances, other embodiments of this invention will be capable of being implemented. The claims are intended to cover all these possible embodiments.