Patent Document

CROSS-REFERENCE TO RELATED APPLICATIONS 
     The present application claims priority from provisional U.S. patent application Ser. No. 60/475,288, filed Jun. 3, 2003, which is incorporated herein by reference in its entirety. 
    
    
     FIELD OF THE DISCLOSURE 
     The present disclosure relates to an apparatus and method for optically inspecting a sample of body fluid and, more particularly, to a readhead for use with the apparatus. Even more particularly, the present disclosure relates to a readhead including components for conducting both fluorescence and reflectance spectroscopy. 
     BACKGROUND OF THE DISCLOSURE 
     It is useful for various medical diagnostic purposes to utilize a reflectance spectroscope to analyze samples of body fluid, for example, to determine the color of a person&#39;s urine or blood. As is known, spectroscopy uses the linear relationship between absorbance and concentration of an absorbing species (Beer&#39;s law), to determine the contents of a sample. An unknown concentration of an analyte can be determined by measuring the amount of light that a sample absorbs and applying Beer&#39;s law. If the absorptivity coefficient of the analyte is not known, the unknown concentration can be determined using a working curve of absorbance versus concentration derived from standards. 
     For example, immunoassay is a technology for identifying and quantifying organic and inorganic compounds. Immunoassay uses antibodies that have been developed to bind with a target compound or class of compounds. The technology has been used widely because the antibodies can be highly specific to the target compound or group of compounds and because immunoassay kits are relatively quick and simple to use. Concentrations of analytes are identified through the use of a sensitive colorimetric reaction. The determination of the target analyte&#39;s presence is made by comparing the color developed by a sample of unknown concentration with the color formed by the standard containing the analyte at a known concentration. The concentration of the analyte is determined by the intensity of color in the sample. The concentration can be estimated roughly by the naked eye or can be determined more accurately with a reflectance spectroscope. 
     Reflectance spectroscopy is the study of light as a function of wavelength that has been reflected or scattered from a solid, liquid, or gas. A conventional reflectance spectroscope may determine the color of a liquid sample, such as urine or blood, disposed on a white, non-reactive pad by illuminating the pad and taking a number of reflectance readings from the pad, each having a magnitude relating to a different wavelength of visible light. The color of the sample on the pad may then be determined based upon the relative magnitudes of red, green, blue and infrared reflectance signals. Reagent pads can be provided with different reagents which cause a color change in response to the presence of a certain type of constituent in urine, such as leukocytes (white blood cells) or red blood cells. A reagent strip may have ten or more different types of reagent pads, for example. Immunoassay strips or cassettes may also be used with other types of liquid samples, such as blood. 
     U.S. Pat. No. 5,654,803, which is assigned to the assignee of the present disclosure, discloses an apparatus and method for determination of non-hemolyzed levels of occult blood in urine using reflectance spectroscopy. The apparatus is provided with a light source for successively illuminating a plurality of different portions of a reagent pad on which a urine sample is disposed, and a detector array for detecting light received from the reagent pad and generating a plurality of reflectance signals in response to light received from a corresponding one of the different portions of the reagent pad. The apparatus is also provided with means for determining whether the magnitude of one of the reflectance signals is substantially different than the magnitude of another of the reflectance signals. Where the body-fluid sample is urine, this capability allows the apparatus to detect the presence of non-hemolyzed levels of occult blood in the urine sample. 
     U.S. Pat. No. 5,877,863, which is also assigned to the assignee of the present disclosure, shows an optical inspection apparatus for inspecting a liquid sample, such as urine, using reflectance spectroscopy. The apparatus includes a readhead for illuminating a target area substantially uniformly via only a single light-emitting diode for each wavelength of interest and receiving light from the target area so that reagent tests may be performed. The readhead is provided with a housing, first and second light sources mounted in a fixed position relative to the housing, a light guide mounted to receive light from each of the light sources which conveys, when only one of the light sources is illuminated, substantially all of the light from the light source to illuminate a target area substantially uniformly, and a light detector coupled to receive light from the target area. Each of the first and second light sources is composed of only a single light-emitting diode for emitting substantially monochromatic light of a different wavelength. 
     Fluorescence spectroscopy is the study of light that has been absorbed at one wavelength and re-emitted at a different wavelength (e.g., fluorescent light is re-emitted by a sample of body fluid in response to a light having a specific wavelength, such as ultraviolet light, being directed at the sample). It is useful for various medical diagnostic purposes to use fluorescence detection to analyze samples of body fluid, for example, to determine a level of glucose in a patient&#39;s blood or urine, or to determine a pH level of the patient&#39;s blood or urine. U.S. Pat. No. 6,232,609 to Snyder et al., for example, shows an apparatus for glucose monitoring. The glucose monitor illuminates a sample with water with ultraviolet excitation light that induces the water and any glucose present in the sample to emit return light that includes Raman scattered light and glucose emission or fluorescence light. The return light is monitored and processed using a predictive regression model to determine the concentration of glucose in the sample. The predictive regression model accounts for nonlinearities between the glucose concentration and intensity of return light within different wavelength bands at a predetermined excitation light energy or the intensity of return light within a predetermined wavelength band at different excitation energy levels. A fiber-optic waveguide is used to guide the excitation light from a laser excitation source to the sample and the return light from the sample to a sensor. 
     What is still desired is a new and improved apparatus and method for performing tests on a sample of body fluid and, more particularly, to a readhead for use with the apparatus. Preferably the readhead will include components for conducting both fluorescence spectropy and reflectance spectroscopy. 
     SUMMARY OF THE DISCLOSURE 
     The disclosure is directed to exemplary embodiments of a new and improved readhead for a diagnostic instrument for illuminating a sample carrier (e.g., a strip or cassette having a liquid sample) and receiving light from the sample carrier, and that allows both fluorescence spectroscopy and reflectance spectroscopy to be conducted in a simple and convenient manner. 
     One exemplary embodiment of the readhead includes a housing adapted to be incorporated in the diagnostic instrument and including an illumination chamber for receiving a sample carrier, an array of light sources mounted within the housing in a fixed position relative to the illumination chamber, and including a first light-emitting diode for emitting substantially monochromatic light of a first wavelength and a second light-emitting diode for emitting substantially monochromatic light of a second wavelength substantially different from the first wavelength, a light guide mounted in the housing to receive light from each of the light-emitting diodes, for conveying, when only one of the light-emitting diodes is illuminated, substantially all of the light from the one light-emitting diode to the illumination chamber so that the illumination chamber is illuminated substantially uniformly, and a light detector coupled to receive light from the illumination chamber. These components of the readhead allow reflectance spectroscopy to be conducted on a fluid sample. 
     The readhead also includes a fluorescence excitation light source for directing excitation light of a predetermined wavelength to the illumination chamber, and a light filter positioned between the illumination chamber and the light detector and adapted to prevent passage therethrough of the excitation light from the fluorescence excitation light source but allow passage of emissive light from a sample carrier in the illumination chamber having a wavelength different from the predetermined wavelength of the excitation light. These components of the readhead allow fluorescence spectroscopy to be conducted on a fluid sample. 
     Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in this art from the following detailed description, wherein only exemplary embodiments of the present disclosure are shown and described, simply by way of illustration of the best mode contemplated for carrying out the present disclosure. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Reference is made to the attached drawings, wherein elements having the same reference character designations represent like elements throughout, and wherein: 
         FIG. 1  is a side sectional view of a portion of an exemplary embodiment of a readhead constructed in accordance with the present disclosure, for use as part of a medical diagnostic optical inspection apparatus and which is adapted to perform both fluorescence spectroscopy and reflectance spectroscopy on a body fluid sample; 
         FIG. 2  is a perspective view of an exemplary embodiment of an optical inspection apparatus, which may be used to perform various tests of a body fluid sample; 
         FIG. 3  is a perspective view of an exemplary embodiment of a reagent strip for use with the apparatus of  FIG. 2 ; 
         FIG. 4  is a top sectional view of an exemplary embodiment of a readhead for use as part of the optical inspection apparatus of  FIG. 2 , and which is adapted to allow the apparatus of  FIG. 2  to perform reflectance spectroscopy on a body fluid sample; 
         FIG. 5  is a side sectional view of the readhead of  FIG. 4 ; and 
         FIG. 6  is a cross-sectional side view of a light-emitting diode array of the readhead of  FIG. 4 . 
     
    
    
     DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS 
       FIG. 1  shows an exemplary embodiment of a new and improved readhead  200  constructed in accordance with the present disclosure for use as part of an apparatus for optically inspecting samples of body fluid for medical diagnostic purposes. The read head of  FIG. 1  is adapted to perform both fluorescence spectroscopy and reflectance spectroscopy on a body fluid sample. 
     The new and improved readhead  200  of  FIG. 1  can be incorporated into a optical inspection apparatus. Prior to discussing the new and improved readhead  200  of  FIG. 1 , the apparatus shown in  FIGS. 2 through 6  will first be discussed to provide background information on an exemplary embodiment of an optical inspection apparatus.  FIG. 2  illustrates a reflectance spectroscope  100 , for optically inspecting liquid samples such as body fluid samples. The particular apparatus  100  shown in  FIG. 2  is a CLINITEK® 50 Urine Chemistry Analyzer available from Bayer Corporation, Diagnostics Division, of Tarrytown, N.Y. The apparatus  100  is described in greater detail in U.S. Pat. Nos. 5,654,803; 5,877,863; and 5,945,341, which are assigned to the assignee of the present disclosure and incorporated herein by reference. 
     It should be understood, however, that a new and improved readhead according to the present disclosure can be incorporated in optical inspection machines other than a CLINTEK® 50 Urine Chemistry Analyzer. For example, it is anticipated that a new and improved readhead according to the present disclosure will be incorporated into a CLINITEK STATUS® Chemistry Analyzer available from Bayer Corporation. Aspects of the CLINITEK STATUS® Chemistry Analyzer are disclosed in co-owned and co-pending U.S. patent application Ser. No. 10/821,441, filed on Apr. 9, 2004 and U.S. patent application Ser. No. 10/556,097, which are incorporated herein by reference and which also claim priority to provisional patent application Ser. No. 60/475,288, filed Jun. 3, 2003. 
     The exemplary inspection apparatus  100  shown in  FIG. 2  has an integral keyboard  102  for user input, and a visual display  106  for displaying various messages to a user relating to the operation of the inspection apparatus  100 . The inspection apparatus  100  also has a housing  107  with an opening  108  formed therein into which a support tray  120  may be retracted. As shown in  FIG. 2 , the support tray  120  is adapted to receive a first type of liquid sample carrier or removable insert, which may be in the form of a reagent cassette  122 . 
     The reagent cassette  122  may be a disposable, single-use cassette for doing a pregnancy test, for example, in a conventional manner. The reagent cassette  122  has an opening or well  124  into which a body fluid sample, such as urine, is placed. The interior of the reagent cassette  122  has a reagent strip (not shown) which may react with the body fluid sample placed in the well  124 . Depending on the results of the test, the reagent strip may change color (e.g., a colored stripe may appear), which is determinable from viewing the reagent strip through a window  128  of the reagent cassette  122 . Although not shown, the support tray  120  may have a calibration chip of a certain color, such as white, disposed in its upper surface to facilitate calibration. A new and improved readhead according to the present disclosure can also be used with a lateral flow immunoassay using a fluorescent particle as a label. 
     When turned over, the support tray  120  is adapted to receive sample carrier comprising a reagent strip. Referring to  FIG. 3 , a reagent strip  40  may have a thin, non-reactive substrate  41  on which a number of reagent pads  50  are fixed. Each reagent pad  50  may be composed of a relatively absorbent material impregnated with a respective reagent, each reagent and reagent pad  50  being associated with a particular test to be performed. When urinalysis tests are performed, they may include, for example, a test for leukocytes in the urine, a test of the pH of the urine, a test for blood in the urine, etc. When each reagent pad  50  comes into contact with a urine sample, the pad changes color over a time period, depending on the reagent used and the characteristics of the urine sample. The reagent strip  40  may be, for example, a MULTISTIX® reagent strip commercially available from Bayer Corporation, Diagnostics Division, of Tarrytown, N.Y. 
     Referring back to  FIG. 2 , during an inspection procedure the support tray  120  is moved between an outwardly extended position as shown in  FIG. 2  and an optical inspection position in which the tray  120  is retracted inwardly into the housing  107  of the inspection apparatus  100  and into a readhead contained in the housing. 
       FIGS. 4 and 5  show an exemplary embodiment of a readhead  10  of the inspection apparatus  100 . In the exemplary embodiment shown, the readhead  10  has a housing formed from an upper housing portion  12 , a middle housing portion  14 , and a lower housing portion  16  which may be connected together in any conventional manner. The housing portions  12 ,  14 ,  16  may be injection-molded parts comprising black plastic to substantially absorb any errant light rays that are incident upon the housing. 
     Light sources in the form of light-emitting diodes (LEDs)  20  are supported on a ledge  22  formed in the lower housing portion  16 . Each of the LEDs  20  is designed to emit monochromatic radiation of a different wavelength, corresponding to red light, green light, blue light and infrared. The wavelength of the light emitted may vary from about 400 nanometers (for blue light) to about 1,000 nanometers (for infrared). Each of the LEDs  20  may be selectively turned on and off via a plurality of wires  24  connected between the LEDs  20  and an activation circuit (not shown). The readhead  10  may be provided with additional LEDs providing additional wavelengths. The CLINITEK STATUS® Urine Chemistry Analyzer includes six LEDs, while the CLINITEK® 50 Urine Chemistry Analyzer includes four LEDs. 
     The LEDs  20  are disposed directly adjacent and in very close proximity with an inlet end  26   a  of a light guide  26  into which light from the LEDs  20  is radiated. As shown in  FIG. 5 , the light guide  26  has a relatively long, substantially planar portion  26   b  and a portion  26   c  that curves downwardly towards an outlet end  26   d  of the light guide  26 . As shown in  FIG. 4 , which is a top cross-sectional view of a portion of the readhead  10 , the light guide  26  has a pair of curved sides  26   e ,  26   f  that diverge outwardly from the inlet end  26   a  to the outlet end  26   d  of the light guide  26 . 
     The light guide  26 , which may be an injection-molded part composed of clear plastic such as acrylic or polycarbonate, conducts substantially all light that enters its inlet end  26   a  to its outlet end  26   d  via total internal reflection. To prevent any internally reflected light from exiting the light guide  26  between its inlet  26   a  and outlet  26   d , the exterior of the light guide  26  could optionally be coated with a highly reflective coating, such as silver. 
     The light guide  26  is supported within the lower housing portion  16  by a pair of supports  28  disposed beneath the light guide  26  at a point near its inlet end  26   a  and a plurality of supports  30  disposed beneath the light guide  26  at a point near its outlet end  26   d . The supports  28 ,  30  may be integrally formed with the lower housing portion  16 . As shown in  FIG. 4 , the light guide  26  is positioned between a pair of angled guide walls  32 ,  34 . 
     As shown in  FIG. 5 , light is emitted from the outlet end  26   d  of the light guide  26  towards the reagent strip  40  disposed on a support  42  in an illumination chamber  44 , as indicated by an arrow  46 . The support  42  is nonmovable relative to the housing portions  12 ,  14 ,  16 . Light from the reagent strip  40  passes through a rectangular opening  54  formed in the lower housing portion  16 , in a direction indicated by an arrow  56 , towards a mirror element  58  fixed in the upper left corner of the upper housing portion  12 . The mirror element  58  is composed of a cylindrical mirror  60  and a pair of mounting tabs  62  connected to the mirror  60 . The mirror element  58 , which may be a plastic injection molded part having the curved portion  60  being coated with a highly reflective material, extends approximately the length of the aperture  54  shown in  FIG. 5  (the CLINITEK STATUS® Urine Chemistry Analyzer includes a flat mirror). The mirror  60  reflects light that is incident upon it from the reagent strip  40  through a square aperture  64  formed in the middle housing portion  14  and to a lens  66  supported by the middle housing portion  14 , as indicated by an arrow  68 . One side of the lens  66  has a planar surface and the other side of the lens  66  has a convexly curved (aspheric) surface. Light passing through the lens  66  is transmitted to a light detector array  70 , as indicated by an arrow  72 . 
     The detector array  70 , which is fixed to a side wall  74  of the upper housing portion  12 , may comprise a conventional detector array, such as a TSL 1402 commercially available from Texas Instruments, which is composed of 256 individual light detectors aligned in a single horizontal row, or a Sony ILX511, a 2048 detector array, which is used in the CLINITEK STATUS® Urine Chemistry Analyzer includes. 
     In operation, only one of the LEDs  20  is illuminated at a time, and the illumination provided by that single LED  20  is sufficient to uniformly illuminate the reagent strip  40  to an extent that allows the detector array  70  to detect enough light from the reagent strip  40  to have the reagent tests described above satisfactorily performed. Each individual light detector in the array  70  senses light from a particular point along the length of the reagent strip  40 . For example, to detect light from the lowermost reagent pad  50 , a number of the light detectors on the corresponding end of the detector array  70  would be activated. Light from all of the reagent pads  50  could be simultaneously detected by activating all of the detectors in the array  70 . 
     The cross-sectional shape of the mirror  60  is curved so that each light detector in the detector array  70  detects light from a wider portion of the reagent strip  40  than if a mirror having a straight cross-sectional shape were used. However, depending on the particular design of the readhead  10 , a straight mirror could be used instead of the cylindrically curved mirror  60 . In an alternative design, the mirror element  58  could be omitted, and the detectors  70  could be placed directly above the aperture  54 . 
     Referring to  FIG. 4 , the light guide  26  is diverging, having a relatively small width at its inlet end  26   a  and a relatively large width at its outlet end  26   d . The fact that the light guide  26  is diverging acts to 1) spread the light from a single one of the LEDs  20  along a relatively large length, corresponding to the length of the outlet end  26   d , and 2) cause the light rays emitted by one of the LEDs  20  to be randomized, thus providing more uniform illumination at the target area in which the reagent strip  40  is located, by causing some of the light rays to be internally reflected within the light guide  26  at different angles. With respect to feature 2), it should be understood that in a light guide having diverging side walls, a single light ray may be reflected from the walls at different angles (i.e. at successively shallower angles of incidence with respect to the side walls as the light ray passes from the inlet to the outlet), thus increasing the randomness of the light rays and the uniformity of the illumination. 
     In the exemplary embodiment shown, the LEDs  20  comprise lensless LEDs, such as surface-mount LEDs. Conventional LEDs are typically provided with a lens which covers the light-emitting component of the LED, however, a lensless LED acts more of a Lambertian source by exhibiting a much lower degree of directionality.  FIG. 6  illustrates the structure of the conventional lensless LEDs  20 . Referring to  FIG. 6 , each LED  20  is shown to generally comprise a substrate  80  having a cavity  82  formed therein, with the light-emitting structure  84  being disposed within the cavity  82  and with no lens covering the cavity  82  or the light-emitting structure  84 . 
     Referring back to  FIG. 1 , the present disclosure provides a new and improved readhead  200  for use as part of an apparatus (such as the apparatus  100  of  FIG. 2 ) for optically inspecting samples of body fluid for medical diagnostic purposes. The read head  200  of  FIG. 1  is similar to the readhead  10  of  FIGS. 4 and 5  such that similar elements have the same reference numeral preceded by a “2”. The read head  200  of  FIG. 1  however is adapted to perform fluorescence spectroscopy, in addition to reflectance spectroscopy, on a body fluid sample. 
     In  FIG. 1  only an end portion of the readhead  200  is shown. Although not shown in  FIG. 1 , the readhead  200  also includes LEDs, a lens and a detector array, similar to the readhead  10  of  FIGS. 4 and 5 . In addition to the LEDs, however, the readhead  200  of  FIG. 1  further includes an ultraviolet light source chamber  300  containing an ultraviolet light source  302  and having an opening  304  for directing light from the ultraviolet light source  302  into the illumination chamber  244  of the readhead  200 . As shown, the interior of the chamber  300  may be lined with metal foil  306  to protect the plastic walls of the chamber from ultraviolet light degradation. The readhead  200  also includes an ultraviolet filter  308  in the light path  256  to prevent an excitation wavelength of the light source  302  from being detected by the detector array, so that the detector array will only detect an emission wavelength produced by the pads  50  of the reagent strip  40 . 
     Many substances will fluoresce (re-emit energy at a higher wavelength) when exposed to ultraviolet light. During use of the readhead  200  of the present disclosure, ultraviolet excitation light from the light source  302  is directed against the pads  50  of the reagent strip  40 , as illustrated by arrow  310 . Emission light from the pads  50  of the reagent strip  40  then travels through the ultraviolet filter  308  in the light path  256 , is reflected off the mirror  260  and directed along the light path  268  to the detector array. Determining the wavelength and intensity of emissive light received by the detector array can be used to determine properties of the sample being excited with the light source  302 . For instance, the wavelength and intensity of emissive light can be used to determine the amount of glucose in a blood sample. U.S. Pat. No. 6,232,609 to Snyder et al., for example, shows an apparatus for glucose monitoring that uses ultraviolet excitation and monitors the wavelength and intensity of emissive light to monitor glucose levels. 
     According to one exemplary embodiment of the present disclosure, the detector array monitors the return light and generates electrical signals indicative of the intensity of return light associated with glucose concentration distinguishing characteristics of the emission light. A processor connected to the detector array processes the electrical signals, using a predictive model, to determine the concentration of glucose in the sample. Suitable examples of predictive models are shown in U.S. Pat. No. 6,232,609 to Snyder et al. 
     According to another exemplary embodiment of the disclosure, the light source  302  comprises a black fluorescent lamp having a line output at 364 nanometers, 405 nanometers, and 436 nanometers, and a broadband output from 330-385 nanometers. Alternatively, the light source may comprise an ultraviolet LED positioned in the ultraviolet light source chamber  300  or adjacent to the other LEDs  20  at the input end of the light guide  26 . The ultraviolet LED may have an output of 370 nanometers or 400 nanometers, for example. The light guide  26  for an ultraviolet LED is made of glass or quartz. In addition, a high intensity green LED can be used to trigger fluorescence, and can be used with suitable filters. It should be anticipated that future LEDs will cover a wider range of UV wavelengths and that more fluorescent dyes or markers will also be developed. 
     Numerous further modifications and alternative embodiments of the disclosure will be apparent to those skilled in the art in view of the foregoing description. This description is to be construed as illustrative only, and is for the purpose of teaching those skilled in the art the best mode of carrying out the disclosure. The details of the structure and method may be varied substantially without departing from the spirit of the disclosure, and the exclusive use of all modifications which come within the scope of the appended claims is reserved.

Technology Category: g