WO1994005984A1 - Method and apparatus for use of polarized light vectors in evaluating constituent compounds in a specimen - Google Patents
Method and apparatus for use of polarized light vectors in evaluating constituent compounds in a specimen Download PDFInfo
- Publication number
- WO1994005984A1 WO1994005984A1 PCT/US1993/008319 US9308319W WO9405984A1 WO 1994005984 A1 WO1994005984 A1 WO 1994005984A1 US 9308319 W US9308319 W US 9308319W WO 9405984 A1 WO9405984 A1 WO 9405984A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- radiation
- specimen
- primary
- polarized
- polarizing means
- Prior art date
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/21—Polarisation-affecting properties
Definitions
- Field of The Invention relates to the field o spectroscopic analysis of test specimens to determine t identity and concentration of the constituent elements o compounds of the test specimen.
- the invention relates mo specifically to an apparatus and method for utilizing spectra transmission signatures involving polarization analysis f known compounds to identify and quantify those compounds i unknown test specimens.
- spectrophotometric analysis relies on the principle that every compound has a unique "pattern" determined by the amount of light absorbed (or transmitted) by the compound at different wavelengths.
- analytical spectro- photometric methods target the specimen with light of known intensity, and measure the absorption of light by the specimen, at various wavelengths, or conversely, measure the intensity of light passing through the specimen, at various wavelengths, and then compare this "pattern" of absorption (or intensity) at different wavelengths with the known pattern of absorption per wavelength of various compounds.
- typical spectrophotometric analysis of a specimen is only of limited usefulness when the specimen is complex, (i.e.
- Polarimetric analysis uses polarized light rather than randomly polarized light to irradiate the specimen and relies on the principle that specimens containing an optically active compound, such as glucose, will rotate the plane of polarized light, thereby causing a measurable "shift" in the plane of polarization.
- an optically active compound such as glucose
- the degree and direction of the polarization shift that is caused by a compound is unique for each compound.
- certain compounds "depolarize" polarized light in a unique manner.
- the inadequacy of the limited information obtained by using polarized light to irradiate a specimen is especially evident when the specimen contains two or more compounds, because the compounds may cause similar polarization shifts in the specific polarization plane in which the light is polarized, thereby making it very difficult to determine the identity and concentration of the different compounds in the specimen.
- the presence of more than one compound in the specimen may also "mask" the polarization shift that is actually caused by the targeted compound sought to be identified, because the presence of other compounds in the specimen may cause an enhancement or decrease in the polarization shift at the specific polarization plane in which the light is polarized. This masking effect on the polarization shift may cause either the identity or the concentration of the targeted compound to be incorrectly determined.
- Measuring the polarization "shift" of light also requires that a polarizer be physically placed upstream from the specimen, to polarize the light in a specific plane of polarization prior to irradiating the specimen, and a separate polarizer/analyzer be physically placed downstream of the specimen through which light exiting the specimen is passed.
- This required use of two polarizers clearly causes the device to be more cumbersome and expensive than an invention that only requires the use of one polarizer.
- organic molecules are structured in spiraled form and have a definite helicity or handedness. It is this helicity which gives a molecule its ability to rotate the polarization of the incident light.
- dextrose d-glucose
- levulose fruit sugar
- Molecules or material which exhibit this kind of optical activity are said to possess optical rotary power.
- dextrorotary or levorotator respectively depending upon the action on the polarization o the incident light.
- the magnitude of the angle, through whic the polarization direction rotates is, in simple theory proportional to the inverse of the wavelength of the inciden light squared.
- Sometimes called a dispersion function, thi relationship has a weak dependence on wavelength but i strongly a function of the type of material or molecula structure being irradiated. This functional dependence on th physical properties of the medium manifests itself in th difference of the indices of refraction for right- and left handed polarized light.
- Two circularly polarized waves o opposite helicity form a set of basic fields for th description of any general state of polarization.
- th constituent molecules Since th constituent molecules all have a definite helicity which i the same, they cannot be brought into coincidence with thei mirror images - they are enantiomorhpous. Thus, the effect o the rotary power of an individual molecule is enhanced in fluid state. Substances which exhibit both optical rotar power and circular dichroism are referred to as chiral media.
- a glucose solution is an isotropic chiral substance. When plane-polarized light impinges normally on glucose th vibration ellipse of the transmitted light is different fro the vibration ellipse of the incident light.
- the difference is characterized by two quantities: (i) Optical rotation (OR) , which is the angle by which the transmission ellipse rotates with respect to the incidence ellipse; (ii) Circular dichrois (CD) , which is a measure of the difference in the eccentricities of the two ellipses.
- OR Optical rotation
- CD Circular dichrois
- Profiles of the OR and the CD of an isotropic chiral substance with respect to frequency are sufficiently unique that they can be used as a component in the signature of a substance to be identified. Because the OR and the CD of any substance have been shown to be Kramers-Kronig-consistent, complete knowledge of either of the two quantities as a function of the frequency is sufficient to determine the other; therefore, the more easily measured OR is often used to characterize isotropic chiral substances.
- a first issue that must be addressed is that of polarization of the light incident on the biological sample whose glucose content has to be monitored.
- the incident light is a planewave traveling in the +z direction (of a cartesian coordinate system) at a frequency f.
- the electric field phasor associated with this planewave may be adequately set up as
- E lnc (Z,t) [A, U, + A-. U,] ⁇ - i ** ⁇ *- / %>, (1)
- Eq. (1) represents an elliptically polarized planewave whose vibration ellipse does not change with time t.
- a » 0 or A y « 0 the planewave is said to be linearly polarized.
- a z ⁇ ⁇ iA- the planewave is circularly polarized.
- a partially polarized planewave can be thought of as combination of a totally unpolarized planewave and a elliptically polarized planewave.
- the second component of th partially polarized polarized wave suffers a definite rotatio on passage through a glucose cell, therefore can be used fo OR measurements.
- the present invention has a source that delivers a slightly polarised planewave, thus its rotation by the glucose cell is meaningful.
- a second issue that must be addressed is that of chromaticity.
- f c is the center-frequency of a source and it 3-db bandwidth is denoted by ⁇ f; then, we can define a qualit factor
- the QTH lamp used in the preferred embodimentof th present invention is a white-light lamp operating from 400 t 2000 nm with a peak at 900 n ; thus, its useful frequenc spectrum ranges from 1.5x10" Hz to 7.5x10" Hz with its pea intensity at 3.3x10" Hz.
- the QTH lamp i definitely a polychromatic source.
- the present invention also utilizes a polarization preserving analyzer whose response is flat over the 2.3x10" H to 4.3x10" Hz range, and it uses a compensated polychromati detector to measure the intensity of the beam transmitted b the analyzer.
- the present invention is polychromati (low-Q)
- the devices described in the prior art ar monochromatic (high-Q)
- Polychromaticity has a definite advantage ove monochromaticity for such things as blood glucos measurements.
- the OR spectrum of a chiral solute in a non chiral solvent depends on the concentration of the solute.
- the amount of glucose in a (diabetic) biological sample varie with time and from sample to sample. This means that the O spectrum of a diabetic sample shifts with time. polychromatic system therefore has a much better chance o monitoring a continuously varying non-normoglycemic sampl than a monochromatic one.
- Applicant's present invention teaches a novel non-invasiv method and apparatus for identifying compounds in a tes specimen, such as blood, by irradiating the test specimen wit randomly polarized light and then measuring the intensity o light passing through or reflected from the specimen a various degrees of polarization and at various wavelengths.
- applicant' invention relies on the heretofore unrecognized principle tha each element or compound has a recognizable and unique patter determined by the intensity of light that it transmits o reflects at various angles of polarization and at variou wavelengths.
- identity and concentration of compound can be accurately determined by determining th intensity of light passing through or reflected by th compound per degree (or smaller unit) of polarization pe wavelength.
- Applicant's invention permits its practitioner t more accurately determine the constituent compounds of specimen than is possible using conventiona spectrophotometric analysis or by irradiating the specime with polarized light.
- Fig. 1 is a perspective view of a preferred componen composition of the optical path of Applicant's invention.
- Fig. 2 is a graphic depiction of white light transmissio intensity along a continuum of angularly distinguishe polarization planes.
- Fig. 3 is a graphic depiction of the transmissio intensity of three discrete wave length bands along continuum of angularly distinguished polarization planes.
- Figs. 4a-b and 5a-b are graphic representations of th rotation of plane polarized light.
- Figs. 6a-b and 7a-b are graphic representations o circular dichroism of pure elliptically polarized light.
- Figs. 8a-b and 9a-b are graphic representations o circular dichroism of partially polarized light.
- Optica path (10) includes a light source (12).
- the light source (12 in the preferred embodiment of Applicant's invention is tungsten halogen lamp, but the light source (12) may be an suitably energized radiation source that creates appropriatel polarized radiation.
- the peak radiance of the light source i the preferred embodiment, when directed towards the detectio of glucose occurs at a value of approximately 900 nm.
- Th spectral range of relevance for the glucose measurements is 800 nm - 1000 nm, thus making this an ideal source.
- the emitted light of this source is partially polarized, but wit a dominant elliptical character due to its internal elliptically contoured reflecting mirror.
- randomly or partiallly polarized radiation limited to specific range(s) of wavelengths, can be utilized through use of a light source, such as a laser source, or by the use of a monochrometer. Such a modification would be advantageous in particular applications, when a narrow frequency band of light is desired (most likely because of the particular light transmission properties of the analyzed specimens) .
- the second element in the set-up is an optical filter housing (13) .
- laser line filters are employed - separately - with spectral transmissions at 850 n. ; 905 nm; and 1064 nm.
- the next item in the optical path (10) is a test specimen (14) .
- the test specimen (14) may be a vial of blood or other bodily fluids or tissues or, in non-invasive tests, may be a patient's ear lobe, finger, etc. (not shown in the drawings).
- the sample is placed directly after the optical filter housing (13) .
- the sample solution is placed in a cuvett which in turn is mounted in a cuvette holder. Within the spectral region of concern, the cuvettes should produce literally no reflection and possess greater than 98% transmission.
- a rectangular finger mount is utilized and should be highly reflective to background radiation and source generated noise.
- a circular aperture of diameter 6.50 mm through the full width of the mount is centered on the rectangular faces allowing for the entrance and exit of light.
- a cylindrical finger port perpendicular to and intersecting the aperture is positioned on one side of the mount.
- the design of the mount should be such that there will be a constant optical path length per individual for various measurements.
- the constituent compounds of the test specimen (14) will naturally polarize and rotate the polarization of the beam of light passing therethrough, thereby causing the intensity value of light exiting from the test specimen (14) in a first plane of polarization to differ from the intensity value of light exiting from the test specimen (14) in a second plane of polarization and will effect a circular dichroism for the partially polarized light as described in Figs. 6a-b, 7a-b, 8a-b, and 9a-b.
- the intensity value of light at a specific wavelength in each plane of polarization would be substantially identical and no circular dichroism would be seen.
- the next component of the optical path in Applicant's preferred embodiment is a convex BK-7 lens (16)
- Lens (16) merely serves to focus the light originating from the light source (12) and transmitted through the test specimen (14) onto an adjustable polarizer (18) .
- Polarizer (18) polarize the light as is transmitted through the test specimen (12) an emits the light along one or more specified polarizatio planes (20).
- the preferred embodiment of Applicant' invention includes a Glan Thompson polarizer as polarize (18) , because such a polarizer absorbs or reflects relatively small portion of the light passing through it an can be easily adjusted between zero and 180 degrees o rotation to coincide with any polarization plane of light a exits the test specimen (14) .
- An acceptable substitute for a mechanical polarizer (18) such as the Glan Thompson polarizer, would be a electromagnetic field capable of effecting polarization of th light as exits the specimen (14) .
- a second convex BK-7 lens (22) is placed after th polarizer (18) to focus the light exiting the polarizer (18) onto a detector panel (24) , such as an ORIEL silicon detecto (available from ORIEL Corp.; 250 Long Beach Blvd; Stratford, CT 06497) .
- the detector (24) is linked to an analyzer (not shown i the drawings) , such as a standard spectrophotometric analyze or other means, to measure and analyze the intensity of th polarized light at one or more wavelengths.
- a preferre analyzer for this purpose is a Merlin Optical Radiatio Measuring System (also available from ORIEL Corp) .
- an oscilloscope (not show in the drawings) such as a Tech 2438 oscilloscope, may b linked to the detector (24) in the preferred embodiment o Applicant's invention, to allow a visual observation of th relative magnitude of the intensity of light being detected b the detector (24) in each of the analyzed polarization planes
- the light source (12) is activated, the ligh travels the optical path and the intensity value of the ligh in a first plane of polarization is detected by the detecto (24) and is measured at one or more wavelengths by th analyzer.
- the polarizer (18) i rotated to change the plane of polarization of the ligh emitted from the polarizer (18) to a second polarization plan and the intensity value of the light in this secon polarization plane is measured at one or more wavelengths
- This process of rotating the polarizer (18) to distinguish an measure the intensity of light in each of several polarizatio planes, at one or more wavelengths, is continued unti sufficient intensity values have been measured and plotted s as to establish a pattern of such intensities and of th circular dichroism relative to the particular specimen (14 under analysis.
- Such a pattern can be compared (preferably b computer) against known "signature curves" of polarizatio transmittance of known substances at known concentrations t make possible the identification of substance(s) in the tes specimen (14) .
- certain elements o the preferred embodiment as illustrated in Figure 1, such as the BK-7 lenses (16 and 22) and the Tech 2438 oscilloscope, are not essential components of Applicant's invention, bu merely provide greater efficiency in focusing the light and i gathering and analyzing information.
- Previous measurements that have relied only upon linearly polarized monochromatic light, which yields a single rotational angle, have had difficulty indicating the presence of a particular substance or molecule in the host material o solution.
- the apparatus of the present invention approaches the problem with partially polarized polychromatic light - chromatic polarization.
- Each wavelength possesses a dominant polarization character; in general, elliptical.
- the envelop of the dominant polarization is inscribed with a series of spike-like peaks (See Figs. 8a-b and 9a-b) . If the intensity of this light is plotted as a function of the polarization angle, there would be a maximum primary peak, plus a series of secondary peaks displaced at various angles relative to the primary peak. These secondary peaks act as markers increasing the sensitivity of the apparatus of the present invention.
- FIG. 9a-b When the light is transmitted through a chiral medium, the primary peak shifts by an angular displacement (Figs. 9a-b) .
- each secondary peak possesses its own rotational dynamic, and relative to the primary peak the secondary peaks are now displaced at different angles than before the ligh entered the chiral medium.
- Figures 4a-b/5a-b, 6a-b/7a-b, an 8a-b/9a-b illustrate in a step-by-step fashion the effects o optical rotary power, circular dichroism, and partia polarization.
- the subscript naught on the angles in thes figures indicates they are fixed.
- the circular dichrois distorts the shape of the ellipse and thus changes th eccentricity.
- Figure 2 graphically illustrates the distribution of light intensity values (y-axis) of specimen-transmitted white light along a continuum of angularly distinguished polarization planes (x-axis) .
- Such plotting of the polarization plane-specific transmission intensity values at each of a plurality of polarization planes will yield a graphic pattern which is unique for that compound.
- a pattern will emerge, one which can be compared with known patterns for identification purposes.
- each birefringent compoun yields a "signature curve" of light intensity values a varying polarization planes which curve shifts in tot relative to the y-axis (non-relative, gross light intensity) depending on concentration or density of the sample.
- Thi shift of the "signature curve” can, in fact, be used to deriv the concentration of a constituent compound once standards fo measured compounds are known.
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU51011/93A AU5101193A (en) | 1992-09-03 | 1993-09-03 | Method and apparatus for use of polarized light vectors in evaluating constituent compounds in a specimen |
EP93920479A EP0721575A1 (en) | 1992-09-03 | 1993-09-03 | Method and apparatus for use of polarized light vectors in evaluating constituent compounds in a specimen |
US08/392,728 US5956144A (en) | 1992-09-03 | 1995-11-22 | Method and apparatus for use of polarized light vectors in identifying and evaluating constituent compounds in a specimen |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US94007592A | 1992-09-03 | 1992-09-03 | |
US07/940,075 | 1992-09-03 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US08/392,728 Continuation-In-Part US5956144A (en) | 1992-09-03 | 1995-11-22 | Method and apparatus for use of polarized light vectors in identifying and evaluating constituent compounds in a specimen |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1994005984A1 true WO1994005984A1 (en) | 1994-03-17 |
Family
ID=25474184
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1993/008319 WO1994005984A1 (en) | 1992-09-03 | 1993-09-03 | Method and apparatus for use of polarized light vectors in evaluating constituent compounds in a specimen |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP0721575A1 (en) |
AU (1) | AU5101193A (en) |
CA (1) | CA2143836A1 (en) |
WO (1) | WO1994005984A1 (en) |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5748308A (en) * | 1996-02-02 | 1998-05-05 | Abbott Laboratories | Programmable standard for use in an apparatus and process for the noninvasive measurement of optically absorbing compounds |
US5788632A (en) * | 1996-03-19 | 1998-08-04 | Abbott Laboratories | Apparatus and process for the non-invasive measurement of optically active compounds |
DE19815932A1 (en) * | 1998-04-09 | 1999-10-21 | Glukomeditech Ag | Process for the miniaturization of a polarimeter for the analysis of low concentration components in the liquid material to be measured on an optical basis and device for its implementation |
EP0966664A4 (en) * | 1996-09-09 | 1999-12-29 | ||
US6241663B1 (en) | 1998-05-18 | 2001-06-05 | Abbott Laboratories | Method for improving non-invasive determination of the concentration of analytes in a biological sample |
US6526298B1 (en) | 1998-05-18 | 2003-02-25 | Abbott Laboratories | Method for the non-invasive determination of analytes in a selected volume of tissue |
US6567678B1 (en) | 1997-12-02 | 2003-05-20 | Abbott Laboratories | Multiplex sensor and method of use |
US6594510B2 (en) | 1996-09-10 | 2003-07-15 | Xoetronics Llc | Photonic molecular probe |
US6662030B2 (en) | 1998-05-18 | 2003-12-09 | Abbott Laboratories | Non-invasive sensor having controllable temperature feature |
US6662031B1 (en) | 1998-05-18 | 2003-12-09 | Abbott Laboratoies | Method and device for the noninvasive determination of hemoglobin and hematocrit |
US7043287B1 (en) | 1998-05-18 | 2006-05-09 | Abbott Laboratories | Method for modulating light penetration depth in tissue and diagnostic applications using same |
CN102798463A (en) * | 2011-06-30 | 2012-11-28 | 深圳光启高等理工研究院 | Method and system for displaying light intensity of polarized light |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
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US4901728A (en) * | 1988-05-31 | 1990-02-20 | Eol, Inc. | Personal glucose monitor |
US5009230A (en) * | 1988-05-31 | 1991-04-23 | Eol, Inc. | Personal glucose monitor |
JPH0443659A (en) * | 1990-06-11 | 1992-02-13 | Hitachi Ltd | Semiconductor manufacturing apparatus |
US5209231A (en) * | 1990-11-02 | 1993-05-11 | University Of Connecticut | Optical glucose sensor apparatus and method |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2513937A1 (en) * | 1975-03-26 | 1976-10-07 | Schmidt & Haensch Franz | Determining several optically active components in a single sample - using a series of polarimetric determinations |
DE3117687A1 (en) * | 1981-05-05 | 1982-04-01 | Eckhard Dr.rer.nat. 2800 Bremen Küpper | Measuring method for determining optical or electromagnetic properties of measurement objects |
-
1993
- 1993-09-03 CA CA 2143836 patent/CA2143836A1/en not_active Abandoned
- 1993-09-03 AU AU51011/93A patent/AU5101193A/en not_active Abandoned
- 1993-09-03 EP EP93920479A patent/EP0721575A1/en not_active Withdrawn
- 1993-09-03 WO PCT/US1993/008319 patent/WO1994005984A1/en not_active Application Discontinuation
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4901728A (en) * | 1988-05-31 | 1990-02-20 | Eol, Inc. | Personal glucose monitor |
US5009230A (en) * | 1988-05-31 | 1991-04-23 | Eol, Inc. | Personal glucose monitor |
JPH0443659A (en) * | 1990-06-11 | 1992-02-13 | Hitachi Ltd | Semiconductor manufacturing apparatus |
US5209231A (en) * | 1990-11-02 | 1993-05-11 | University Of Connecticut | Optical glucose sensor apparatus and method |
Non-Patent Citations (1)
Title |
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See also references of EP0721575A4 * |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5748308A (en) * | 1996-02-02 | 1998-05-05 | Abbott Laboratories | Programmable standard for use in an apparatus and process for the noninvasive measurement of optically absorbing compounds |
US5788632A (en) * | 1996-03-19 | 1998-08-04 | Abbott Laboratories | Apparatus and process for the non-invasive measurement of optically active compounds |
EP0966664A1 (en) * | 1996-09-09 | 1999-12-29 | International Diagnostics Technologies Inc. | Photonic molecular probe |
EP0966664A4 (en) * | 1996-09-09 | 1999-12-29 | ||
US6594510B2 (en) | 1996-09-10 | 2003-07-15 | Xoetronics Llc | Photonic molecular probe |
US6567678B1 (en) | 1997-12-02 | 2003-05-20 | Abbott Laboratories | Multiplex sensor and method of use |
DE19815932C2 (en) * | 1998-04-09 | 2000-06-21 | Glukomeditech Ag | Method for miniaturizing a polarimeter for the analysis of low concentration components in the liquid material to be measured on an optical basis and device for carrying it out |
DE19815932A1 (en) * | 1998-04-09 | 1999-10-21 | Glukomeditech Ag | Process for the miniaturization of a polarimeter for the analysis of low concentration components in the liquid material to be measured on an optical basis and device for its implementation |
US6241663B1 (en) | 1998-05-18 | 2001-06-05 | Abbott Laboratories | Method for improving non-invasive determination of the concentration of analytes in a biological sample |
US6526298B1 (en) | 1998-05-18 | 2003-02-25 | Abbott Laboratories | Method for the non-invasive determination of analytes in a selected volume of tissue |
US6654620B2 (en) | 1998-05-18 | 2003-11-25 | Abbott Laboratories | Method for improving non-invasive determination of the concentration of analytes in a biological sample |
US6662030B2 (en) | 1998-05-18 | 2003-12-09 | Abbott Laboratories | Non-invasive sensor having controllable temperature feature |
US6662031B1 (en) | 1998-05-18 | 2003-12-09 | Abbott Laboratoies | Method and device for the noninvasive determination of hemoglobin and hematocrit |
US7043287B1 (en) | 1998-05-18 | 2006-05-09 | Abbott Laboratories | Method for modulating light penetration depth in tissue and diagnostic applications using same |
CN102798463A (en) * | 2011-06-30 | 2012-11-28 | 深圳光启高等理工研究院 | Method and system for displaying light intensity of polarized light |
Also Published As
Publication number | Publication date |
---|---|
EP0721575A4 (en) | 1996-02-15 |
AU5101193A (en) | 1994-03-29 |
EP0721575A1 (en) | 1996-07-17 |
CA2143836A1 (en) | 1994-03-17 |
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