Abstract:
Apparatus for assaying an analyte in blood in a patient&#39;s blood vessel comprising: a light provider comprising at least one light source that illuminates a tissue region in which a blood vessel is located with light that stimulates photoacoustic waves in the region; at least one acoustic transducer that generates signals responsive to the photoacoustic waves; a controller that receives the signals and processes them to determine which are responsive to photoacoustic waves that originate in the blood vessel and uses the determined signals to assay the analyte; wherein, the light provider and at least one transducer define a field of view that overlaps the blood vessel, said field of view having a central region and a lateral extent greater than about 4 mm.

Description:
RELATED APPLICATIONS  
       [0001]     The present application claims the benefit under 35 USC 119(e) of U.S. provisional application No. 60/536,510 filed on Jan. 15, 2004, the disclosure of which is incorporated herein by reference. 
     
    
     FIELD OF THE INVENTION  
       [0002]     The invention relates to wearable apparatus that can be coupled to a body and continuously assay a substance in the body for an extended period of time and in particular wearable apparatus for continuously monitoring glucose levels in a body.  
       BACKGROUND OF THE INVENTION  
       [0003]     Methods and apparatus for determining blood glucose levels for use in the home, for example by a diabetic who must monitor blood glucose levels frequently, are available. These methods and associated devices are generally invasive and usually involve taking blood samples by finger pricking. Often a diabetic must determine blood glucose levels many times daily and finger pricking is perceived as inconvenient and unpleasant. To avoid finger pricking, diabetics tend to monitor their glucose levels less frequently than is advisable.  
         [0004]     Non-invasive in-vivo methods and apparatus for monitoring blood glucose are known. PCT Publication WO 98/38904, the disclosure of which is incorporated herein by reference, describes a “non-invasive, in-vivo glucometer” that uses a photoacoustic effect to measure a person&#39;s blood glucose. PCT Publication WO 02/15776, the disclosure of which is incorporated herein by reference, describes locating a blood vessel in the body and determining glucose concentration in a bolus of blood in the blood vessel. The glucose concentration in the blood bolus is determined by illuminating the bolus with light that is absorbed and/or scattered by glucose to generate photoacoustic waves in the bolus. Intensity of the photoacoustic waves, which is a function of glucose concentration, is sensed and used to assay glucose in the bolus.  
         [0005]     Wearable devices for assaying glucose are known, are generally based on near-infrared (NIR) spectroscopic methods and usually comprise a light source and optical detector that are attached to a patient&#39;s finger, wrist or other part of the body. Wearable NIR devices for assaying glucose are described in U.S. Pat. No. 6,241,663 to Wu, et al. and U.S. Pat. No. 5,551,422, to Simonsen et al., the disclosures of which are incorporated herein by reference.  
         [0006]     An apparatus for determining glucose levels is hereinafter referred to as a “glucometer”.  
       SUMMARY OF THE INVENTION  
       [0007]     An aspect of some embodiments of the present invention relates to providing a wearable glucometer that may be mounted to a patient&#39;s skin in alignment with a blood vessel in the patient&#39;s body and thereafter operates to repeatedly assay glucose in blood in the blood vessel without requiring substantial user intervention.  
         [0008]     It is generally advantageous to determine glucose levels for a patient from blood glucose levels. Prior art wearable glucometers do not in general distinguish between glucose levels in blood and glucose levels in interstitial fluid and cannot therefore assure that glucose assays they provide are blood glucose levels. Unlike prior art wearable glucometers, a glucometer in accordance with an embodiment of the invention provides measurements of glucose levels that are substantially independent of glucose levels in interstitial fluid.  
         [0009]     An aspect of some embodiments of the present invention relates to providing a glucometer, which once aligned with a blood vessel will continue to operate properly, providing glucose assays for blood in the blood vessel, in the event that it becomes misaligned by displacements typically encountered during assay operation.  
         [0010]     A glucometer in accordance with an embodiment of the present invention comprises an array of acoustic transducers, a light provider, and a controller. The controller controls the light source and the array of transducers to assay glucose in blood in the patient&#39;s blood vessel using a photoacoustic effect. To perform the assay, the controller controls the light provider to illuminate a tissue volume defined by a field of view of the glucometer located below the skin to which the glucometer is attached with light that is absorbed and/or scattered by glucose and stimulates photoacoustic waves in the tissue volume. The field of view of the glucometer is defined as a size and location of a volume of tissue below a region of skin to which the glucometer is attached for which the glucometer stimulates photoacoustic waves that are detectable by its transducer array and practically useable to assay glucose in blood in a blood vessel located in the tissue volume. When properly aligned with the blood vessel, a region of the blood vessel is located substantially at the center of the glucometer&#39;s field of view. The transducer array generates signals responsive to acoustic energy that is incident on the array from the photoacoustic waves stimulated in the tissue volume.  
         [0011]     The controller receives and processes the signals provided by the transducer array to determine which of the signals corresponds to photoacoustic waves originating in the blood vessel and uses those signals in accordance with methods known in the art to assay glucose in blood in the blood vessel. Examples of photoacoustic assay methods useable in the practice of the invention are described in PCT publication WO 02/15776, and in U.S. Provisional Application 60/458,973 filed on Apr. 1, 2003, the disclosures of which are incorporated herein by reference.  
         [0012]     In time, during extended assay operation, a glucometer initially properly aligned with a blood vessel so that a region of the blood vessel is located at the center of the glucometer&#39;s field of view, may become misaligned because, for example, of drift in the glucometer position on the skin or because of motion of the skin relative to the blood vessel.  
         [0013]     In accordance with an aspect of an embodiment of the invention, the transducer array and light provider are configured so that the field of view of the glucometer is sufficiently large in at least one dimension so that for misalignments typically encountered during assay operation, the blood vessel remains substantially within the glucometer field of view. As a result, assay operation can continue satisfactorily uninterrupted.  
         [0014]     In some embodiments of the invention, to align the glucometer with a blood vessel the controller controls the array of transducers to acoustically image a tissue region in the patient&#39;s body beneath the skin. In some embodiments of the invention, to align the glucometer, the controller controls the light provider to illuminate the field of view of the glucometer with light that stimulates photoacoustic waves in the glucometer field of view. The controller processes signals generated by the transducer array responsive to the photoacoustic waves to generate a “photoacoustic image” of features below the skin.  
         [0015]     The acoustic and/or photoacoustic image provided by the controller is used to align the glucometer with the blood vessel. Optionally, the controller generates a signal responsive to the acoustic and/or photoacoustic image to aid a user of the glucometer to align the glucometer with the blood vessel. Optionally, the glucometer comprises a display screen and the controller displays the acoustic and/or photoacoustic image, or icons responsive to the images, to facilitate aligning the glucometer with the blood vessel.  
         [0016]     In some embodiments of the invention, the glucometer is coupled to an insulin pump which is mounted to the patient. The glucometer controls the insulin pump to administer insulin to the patient responsive to glucose measurements acquired by the glucometer.  
         [0017]     There is therefore provided, in accordance with an embodiment of the invention, apparatus for assaying an analyte in blood in a patient&#39;s blood vessel comprising: a light provider comprising at least one light source that illuminates a tissue region in which a blood vessel is located with light that stimulates photoacoustic waves in the region; at least one acoustic transducer that generates signals responsive to the photoacoustic waves; a controller that receives the signals and processes them to determine which are responsive to photoacoustic waves that originate in the blood vessel and uses the determined signals to assay the analyte; wherein, the light provider and at least one transducer define a field of view that overlaps the blood vessel, said field of view having a central region and a lateral extent greater than about 4 mm.  
         [0018]     Optionally, the field of view has a lateral extent greater than or equal to about 6 mm. Optionally, the field of view has a lateral extent greater than or equal to about 10 mm.  
         [0019]     In some embodiments of the invention, the light provider comprises optics for each of the at least one light source that receives light from the light source and configures the received light into a fan shaped light beam that is used to illuminate the tissue region.  
         [0020]     Optionally, the at least one light source comprises a plurality of light sources. Optionally, the fan beams of the plurality of light sources are substantially parallel. Optionally, the plurality of light sources are collinear. Optionally, the plurality of light sources are configured in an array of rows and columns.  
         [0021]     In some embodiments of the invention, the light provider comprises a mirror that receives light from the light source and reflects the received light to the tissue region and wherein the mirror is rotatable about an axis and for different rotation angles of the mirror about the axis the fan beam illuminates a different portion of the tissue region. Optionally the apparatus comprises a controller that controls the angle of the mirror to scan the tissue region with light from the light source.  
         [0022]     In some embodiments of the invention, the light provider comprises a light pipe having an input surface region to which at least one light source is coupled and an output surface region through which light that enters the light pipe from the at least one light source exits the light pipe. Optionally, the light pipe has a shape of a planar plate having two large parallel face surfaces and narrow edge surfaces, Optionally, the input surface region to which the at least one light source is coupled is a narrow edge surface of the light pipe. Optionally, the output surface region from which light exits the light pipe is a narrow edge surface opposite the input surface region.  
         [0023]     In some embodiments of the invention, the at least one transducer comprises a plurality of transducers. Optionally, the transducers are configured in an array of rows and columns of transducers. Additionally or alternatively, the apparatus comprises a mounting plate, which is attached to the skin to acoustically couple the apparatus to the skin. Optionally, the transducers are mounted to the mounting plate. Optionally, the mounting plate comprises a layer of piezoelectric material. Optionally, each of at least two of the plurality of transducers comprises a different region of the layer of piezoelectric material sandwiched between a first and a second electrode. Optionally, the first electrodes of each of the at least two transducers are substantially electrically isolated from each other. Optionally, the second electrode of each of the at least two transducers comprises a different region of a same conductor.  
         [0024]     In some embodiments of the invention, a transducer of the at least one transducer is acoustically coupled to the skin via an acoustic waveguide. Optionally, the acoustic waveguide is an optic fiber.  
         [0025]     In some embodiments of the invention, a light source of the at least one light source is optically coupled to the skin via an optic fiber that transmits light from the light source to the skin. Optionally, a transducer of the at least one transducer light is acoustically coupled to the skin by the optic fiber.  
         [0026]     In some embodiments of the invention, the controller controls the at least one transducer to acoustically image the blood vessel.  
         [0027]     In some embodiments of the invention, the controller processes signals generated by the at least one transducer responsive to acoustic energy from the photoacoustic waves to image the blood vessel. Optionally, at least some of the light provided by the light provider is light at a wavelength at which light is strongly absorbed and or scattered by blood.  
         [0028]     In some embodiments of the invention, the controller uses the image to determine if the blood vessel is substantially aligned with the central region of the field of view. Optionally, the apparatus comprises an indicator light and the controller controls the indicator light to generate an optical signal indicative of a degree to which the blood vessel is aligned with the central region. Additionally or alternatively, the apparatus comprises a speaker and the controller controls the speaker to generate an audio signal indicative of a degree to which the blood vessel is aligned with the central region.  
         [0029]     In some embodiments of the invention, the apparatus comprises a display screen and the controller displays a fiducial mark representing the central region of the field of view and the image of the blood vessel on the screen and wherein a distance on the screen between the blood vessel and the fiducial mark represents a distance between the blood vessel and the central region.  
         [0030]     In some embodiments of the invention, the light provider and at least one transducer are comprised in a wearable housing. Optionally, when worn by the patient the housing provides optical and acoustic coupling of the light provider and at least one transducer respectively to the patient&#39;s skin.  
         [0031]     In some embodiments of the invention, the analyte is glucose.  
         [0032]     There is further provided in accordance with an embodiment of the invention apparatus for controlling blood glucose level in a patient comprising: assay apparatus according to an embodiment of the invention; an insulin delivery system controllable to administer insulin to a patient; wherein the controller controls the insulin delivery system responsive to glucose assays provided by the assay apparatus. 
     
    
     BRIEF DESCRIPTION OF FIGURES  
       [0033]     Non-limiting examples of embodiments of the present invention are described below with reference to figures attached hereto, which are listed following this paragraph. In the figures, identical structures, elements or parts that appear in more than one figure are generally labeled with a same numeral in all the figures in which they appear. Dimensions of components and features shown in the figures are chosen for convenience and clarity of presentation and are not necessarily shown to scale.  
         [0034]      FIGS. 1A and 1B  schematically show a perspective view and cross-section view respectively of a glucometer, in accordance with an embodiment of the present invention;  
         [0035]      FIGS. 2A and 2B  schematically show a perspective view and cross-section view respectively of a glucometer comprising a linear array of light sources, in accordance with an embodiment of the present invention;  
         [0036]      FIG. 2C  schematically shows a perspective view of a glucometer comprising a two dimensional array of light sources, in accordance with an embodiment of the present invention;  
         [0037]      FIG. 2D  schematically shows a perspective view of another glucometer, in accordance with an embodiment of the present invention;  
         [0038]      FIGS. 3A and 3B  schematically show a perspective view and cross-section view respectively of a glucometer having a light beam that can be steered to scan tissue below a region of skin to which the glucometer is mounted, in accordance with an embodiment of the present invention;  
         [0039]      FIG. 3C  schematically shows another glucometer having a steerable light beam, which is similar to the glucometer shown in  FIGS. 3A and 3B , in accordance with an embodiment of the present invention; and  
         [0040]      FIG. 4  schematically shows a glucometer comprising an array of light pipes for directing light to illuminate tissue below a region of skin to which the glucometer is mounted, in accordance with an embodiment of the present invention. 
     
    
     DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS  
       [0041]      FIGS. 1A and 1B  schematically show a perspective view and cross-section view respectively of a glucometer  20  in accordance with an embodiment of the present invention. The cross section view shown in  FIG. 1B  is taken in a plane indicated by a line “AA” in  FIG. 1A . Glucometer  20  is shown attached to a region of skin  22  of a patient after it has been aligned with a blood vessel  24  located under the patient&#39;s skin in order to assay glucose in blood in the blood vessel.  
         [0042]     Glucometer  20  comprises a plurality of acoustic transducers  30  mounted to a mounting plate  32 , which are optionally configured in an array  34  of rows  36  and columns  38 , and a light provider  40  comprising a light source  42  and optics represented by a lens  44 . By way of example, the number of transducers  30  in array  34  is eight and the number of rows  36  and columns  38  in the array are two and four respectively. A controller  46  controls light provider  40  and transducer array  34 . The components of glucometer  20  are comprised in a housing  47  indicated by dashed lines.  
         [0043]     Optionally, a power source  45  for powering controller  46  and light source  42  is mounted inside housing  47 . In some embodiments of the invention, power for controller  46  and light source  42  is provided by an external power source to which glucometer  20  is connected. Optionally, the external power source is mounted to the patient&#39;s body. Housing  47  optionally has a visual display screen  48  and control buttons  49  for interfacing with controller  46 . Glucometer  20  is optionally attached to skin  22  by a layer  26  of a suitable adhesive that bonds mounting plate  32  to skin  22 .  
         [0044]     In some embodiments of the invention, mounting plate  32  is formed from a flexible piezoelectric material, such as PVDF and acoustic transducers  30  are integrally formed elements of the mounting plate. Each integrally formed acoustic transducer  30  comprises a region of mounting plate  32  sandwiched between a first electrode on a top surface of the mounting plate and a second electrode on a bottom surface of the mounting plate. Voltage generated between the first and second electrode of a transducer  30  responsive to acoustic energy incident on the transducer is used to sense the acoustic energy. Whereas first electrodes of transducers are substantially electrically isolated from each other, each second electrode may be a region of a same single large electrode optionally on the bottom surface of the mounting plate.  
         [0045]     In some embodiments of the invention, mounting plate  32  comprises a flexible membrane, which is adhered to the skin by a suitable adhesive, and each transducer  30  comprises a reflective coating on a different region of the membrane, which may be a different region of a single continuous reflective coating on the membrane. A suitable light source is used to scan and selectively illuminate the reflective coatings. Light from the light source reflected by a given reflective coating is received by an optical sensor or sensor system. Acoustic energy incident on the membrane distorts and/or displaces regions of the membrane and thereby distorts and/or displaces reflective coatings on the membrane. Intensity and/or phase of light from the light source reflected by a reflective coating of a given transducer and/or a location on the sensor or sensor system at which the reflected light is received is responsive to the distortion and/or displacement and is used to generate a signal responsive to the incident acoustic energy. Methods of sensing acoustic energy responsive to intensity, phase or location of incidence on an optical detector of light reflected from a flexible membrane on which the acoustic energy is incident are known in the art and any of these methods may be used in the practice of the present invention.  
         [0046]     For convenience of presentation, in  FIGS. 1A and 1B  and figures that follow transducers  30  are shown as separate elements mounted on mounting plate  32 .  
         [0047]     Light from light source  42  is optionally shaped by optics  44  into a relatively thin fan shaped beam of light schematically indicated by dashed lines  50  and directed so that it is incident on mounting plate  32  between rows  36  of transducers  30 . Fan beam  50  has a central axis  52  and a fan angle θ. To enable light in fan beam  50  to pass through mounting plate  32  and illuminate tissue below skin  22 , mounting plate  32  is optionally formed from a material that is transparent to light in fan beam  50 . Additionally or alternatively, mounting plate  32  is formed with a slot  54  through which light beam  50  passes. Optionally, adhesive layer  26  is formed from a material that is transparent to light in fan beam  50 . Additionally or alternatively, adhesive layer  26  does not cover slot  54  so as not to interfere with passage of light through the slot.  
         [0048]     Intensity of light in fan beam  50  and a number and configuration of transducers  30  in array  34  are such that photoacoustic waves stimulated by the light beam in tissue to a depth below skin  22  indicated by dashed “depth” lines  55  are generally detectable by the transducer array. A region  56  of the tissue in which photoacoustic waves that are detectable by transducer array  34  are stimulated is substantially bounded by the envelope of fan beam  50  and dashed depth lines  55 . Region  56  is coincident with the field of view of glucometer  20  and will be referred to as “field of view  56 ”.  
         [0049]     Since glucometer  20  is assumed to be aligned with blood vessel  24 , the blood vessel passes substantially through axis  52  in a direction substantially perpendicular to the plane of fan beam  50 . In accordance with an embodiment of the invention, lens  44  forms fan beam  50  having a fan angle θ large enough so that at an expected depth of blood vessel  24  below skin  22  a cross section of field of view  56  in the plane of the fan beam  50  is substantially larger than a typical cross section of the blood vessel.  
         [0050]     Optionally, fan beam  50  is configured so that at a depth of blood vessel  24  below skin  22 , fan beam  50  extends on either side of the blood vessel by a distance, hereinafter an “alignment margin”, equal to about 3 mm. For example, for a diameter of blood vessel  24  equal to about 1 mm and having an expected location about 2 mm below the surface of skin  22 , fan beam  50  is optionally configured so that at about 2 mm below the skin, width of the fan beam in the plane of the fan beam is equal to or greater than about 7 mm and the fan beam has a fan angle θ equal to about 120°.  
         [0051]     In some embodiments of the invention, a glucometer similar to glucometer  20  is configured to have an alignment margin different from about 3 mm. For example, for a glucometer similar to glucometer  20  that is to be used to monitor glucose levels in an athlete during exercise, displacements by which the glucometer might become misaligned may be expected to be greater than usual and the glucometer configured to have an alignment margin greater than about 3 mm. Optionally the alignment margin is equal to about 5 mm. For a bed-ridden patient a glucometer may have an alignment margin less than about 3 mm. Optionally, the alignment margin is equal to about 2 mm.  
         [0052]     To align glucometer  20  with blood vessel  24  as shown in  FIGS. 1A and 1B , glucometer  20  is placed on a region of skin  22  below which blood vessel  24  is expected to be located. A suitable gel or oil is optionally used to acoustically couple the glucometer to the skin. A control signal is input to glucometer  20  via interface buttons  49  instructing controller  46  to operate in an alignment mode and the glucometer is oriented so that the plane of fan beam  50  is substantially perpendicular to the length of the blood vessel. Optionally, controller  46  indicates orientation of the plane of fan beam  50  by generating a suitable icon on display screen  48 .  
         [0053]     The patient and/or a person aiding the patient, then moves glucometer  20  back and forth substantially in a direction perpendicular to the length of blood vessel  24 . Optionally, during motion of glucometer  20 , controller  46  controls transducer array  34  to image features below skin  22  and in particular blood vessel  24  with ultrasound using methods known in the art. In some embodiments of the invention, Doppler shifted ultrasound imaging methods known in the art are used to image blood vessel  24 . Optionally, during motion of glucometer  20 , controller  46  controls light provider  40  to illuminate tissue below skin  22  with light that stimulates photoacoustic waves in the tissue. Optionally, controller  467  controls light provider  40  to illuminate tissue below skin  22  with light at at least one wavelength that is strongly absorbed by blood. Signals generated by transducer array  34  responsive to the photoacoustic waves are used to provide a “photoacoustic” image of features below skin  22  and in particular blood vessel  24 .  
         [0054]     Optionally, controller  46  generates a signal responsive to the ultrasound and/or photoacoustic image to aid a user of glucometer  20  to align the glucometer with the blood vessel. For example, controller  46  may control a LED and/or a small speaker (not shown) responsive to the image to provide an optical and/or audio signal indicating when glucometer  20  is aligned with blood vessel  24 .  
         [0055]     Optionally, controller  46  displays the ultrasound and/or photoacoustic image on screen  48  to facilitate aligning the glucometer with the blood vessel. For example, in some embodiments of the invention controller  46  displays the ultrasound or photoacoustic image on screen  48  together with a suitable fiducial mark representing the center of the field of view of glucometer  20 . The patient, and/or the patient&#39;s aid, aligns glucometer  20  with blood vessel  24  responsive to a location in the image of blood vessel  24  relative to the fiducial mark.  
         [0056]     Once the glucometer is substantially aligned with blood vessel  24 , the position of the aligned glucometer on the patient&#39;s skin is optionally marked using any suitable marking device, such as a pen for marking skin with non-toxic ink. The patient then removes glucometer  20  from skin  22  and applies a layer of adhesive  26  to mounting plate  32  or removes a protective coating on a layer of adhesive  26  already in place on the mounting plate. The patient and/or the patient&#39;s aid then repositions glucometer  20  on skin  22  responsive to the alignment marks with the adhesive in contact with the skin and presses the glucometer to the skin to assure proper contact of the skin to the adhesive. Methods of aligning a glucometer with a blood vessel are described in U.S. Provisional Application 60/476,623, filed on Jun. 9, 2003, the disclosure of which is incorporated herein by reference.  
         [0057]     Once properly aligned, a control signal is input to the glucometer via interface buttons  49  instructing controller  46  to operate in an assay mode to assay glucose in blood vessel  24 . In the assay mode controller  46  controls light provider  40  to illuminate region  56  with fan beam  50  at at least one wavelength that is scattered and/or absorbed by glucose. Signals generated responsive to photoacoustic waves generated in blood in blood vessel  24  by the light are used to determine concentration of glucose in the blood. Any suitable method known in the art for processing the signals to determine the glucose concentration in the blood may be used. As noted above, exemplary methods for assaying glucose in blood in blood vessel  24  responsive to a photoacoustic effect are described in PCT publication WO 02/15776 and in U.S. Provisional Application 60/458,973 cited above.  
         [0058]     As a result of the relatively large fan angle θ of fan beam  50  and its orientation substantially perpendicular to blood vessel  24 , even if glucometer  20  becomes substantially misaligned with the blood vessel, the blood vessel will in general remain inside field of view  56  of the glucometer. (Displacements of glucometer  20  in a direction along the length of blood vessel  24  do not in general result in the blood vessel being displaced relative to the center of the field of view of the glucometer. On the other hand, displacements in a direction perpendicular to the length of blood vessel  24 , do in general result in the blood vessel displacing relative to the center of field of view  56 . However, because of the relatively large opening angle θ of fan beam  50 , for typical misaligning displacements of glucometer  20  perpendicular to the length of blood vessel  24 , in general the blood vessel remains within field of view  56  of the glucometer.) As a result, degrees of misalignment typically encountered during operation of glucometer  20  will not in general substantially compromise satisfactory operation of the glucometer. It is expected that, for normal activity not including extreme physical exercise, glucometer  20  may become misaligned relative to blood vessel  24  during assay operation over a period of time equal to about a working day by distances of magnitude less than or equal to about 2 mm.  FIGS. 2A and 2B  schematically show a perspective view and a cross section view of another glucometer  60 , in accordance with an embodiment of the present invention.  
         [0059]     Glucometer  60  is similar to glucometer  20  except that glucometer  60  comprises a light provider  62  having a plurality of light sources  64  each optionally optically coupled to optics represented by a lens  66 . By way of example, in  FIGS. 2A and 2B  the number of light sources  64  and associated optics  66  is equal to three. Light from each light source  64  is optionally formed by optics  66  associated with the light source into a fan beam of light  68 . Light from each fan beam  68  passes through slot  54  to illuminate tissue beneath skin  22 . The plurality of fan beams  68  provides glucometer  60  with a relatively large field of view  70  which is determined substantially by the envelopes of fan beams  68  and depth lines  72 . Because a plurality of light sources  64  is used to provide field of view  70 , light sources  64  may provide light at lower intensity than is provided by single light source  42  comprised in glucometer  20  ( FIGS. 1A and 1B ).  
         [0060]     In some embodiments of the present invention, controller  46  controls light provider  62  so that less than all the light sources  64  are on simultaneously. By turning on less than all light sources  64  at a same given time, light from light provider  62  illuminates a known region of field of view  70 , which is smaller than the field of view. At the given time therefore, photoacoustic waves stimulated by the light have origins in a spatial region smaller than that occupied by the field of view  70  and spatial resolution with which the origins can be located may be improved.  
         [0061]      FIG. 2C  schematically shows a glucometer  100  that is a variation of glucometer  60 . Whereas glucometer  60  comprises a linear array of light sources  64 , glucometer  100  comprises a two-dimensional array  102  of rows  101  and columns  103  of light sources  64 . As in the case of glucometer  60 , light from each light source  64  is optionally shaped by associated optics  66  into a fan beam  68  of light. The planes of fan beams  68  are optionally substantially parallel to each other. Fan beams  68  are shown for only a few light sources  64  for clarity of presentation and to prevent clutter. Optionally, mounting plate  32  is transparent to light in fan beams  68  and light in a fan beam  68  passes through the mounting plate to illuminate tissue below a region of a patient&#39;s skin  22  to which glucometer  100  is attached. Optionally, light from each light source  64  is transmitted through a suitably shaped slot  104  formed in mounting plate  32 . In some embodiments of the invention, different rows  101  provide light at different wavelengths of a plurality of wavelengths used to assay glucose in blood vessel  24 .  
         [0062]     Glucometers  20  ( FIGS. 1A and 1B ) and  60  ( FIGS. 2A and 2B ) described above have fields of view that are relatively “thin” in directions perpendicular to their respective fan beams and relatively large in a direction parallel to the planes of their fan beams. As a result of the shape of their fields of view, it is generally advantageous to align glucometers  20  and  60  with a blood vessel so that the planes of their fan beams are substantially perpendicular to the length of the blood vessel. For “perpendicular alignment”, displacement of glucometer  20  or  60  along the length of blood vessel  24  does not substantially misalign the glucometers nor as a result substantially affect their operation. Displacement of glucometer  20  or  60  perpendicular to blood vessel  24  will generally not remove the blood vessel from their respective fields of view, and as a result will also not in general injure operation of the glucometers. Such perpendicular alignment is relatively easy to achieve for blood vessels in the arm or wrist whose lengths are often substantially parallel to the lengths of the appendages in which they are located.  
         [0063]     Glucometer  100  shown in  FIG. 2C  has a field of view that is thicker in a direction perpendicular to the planes of its fan beams  68  than that of glucometers  20  and  60 . As result of its thicker field of view, glucometer  100  may often be easier to align with a patient&#39;s blood vessel than are glucometers  20  and  60 . It is expected that aligning glucometer  100  should be easier than aligning glucometers  20  and  60  with a blood vessel for situations in which a direction of a length of the blood vessel is not known or the patient&#39;s blood vessel is relatively twisted.  
         [0064]     In glucometers  20 ,  60  and  100 , a relatively large, in at least one direction, field of view is generated using, in addition to an appropriate array of transducers, optics to form at least one fan beam of light from light received from a suitable light source. In some embodiments of the invention, a relatively large field of view is provided using an array of acoustic transducers and a light pipe that receives light from at least one light source and transmits the light from an output aperture of the light pipe as a beam of light having a large cross section in at least one direction. For example, the light pipe may receive light from a plurality of light sources and transmit the received light from a relatively long output aperture to provide a beam of light having a large cross section.  
         [0065]      FIG. 2D  schematically shows an exemplary glucometer  200  comprising a light provider  202  comprising a light pipe  204  coupled to a plurality of light sources  206 , in accordance with an embodiment of the present invention. Glucometer  200  optionally comprises an array of transducers  30  similar to that shown in  FIGS. 1A, 1B  and  2 C. (Transducers  30  behind light pipe  204  are not shown.)  
         [0066]     Light pipe  202  is optionally rectangular having relatively large face surfaces  208  and a relatively narrow edge surface  210  along which light sources  206  are coupled using methods known in the art. Optionally, substantially all surface regions of light pipe  204 , except for a narrow edge surface, an “output aperture” of the light pipe, opposite edge surface  210 , are covered with a reflective coating that reflects light provided by light sources  206 . Light provided by light sources  206  exits light pipe  204  from the output aperture edge opposite edge  210  as a relatively thin but wide beam of light  212  that has a cross section in the plane of light pipe substantially larger than the cross section of blood vessel  24 . Optionally, light pipe  204  is formed having scattering centers using methods known in the art to homogenize light that the light pipe receives from light sources  206  so that light exiting the light pipe has fairly uniform intensity along the output aperture.  
         [0067]     It is noted that whereas light pipe  204  is rectangular, light pipes having shapes different from light pipe  204  and configurations of light sources different from that shown in  FIG. 2D  may be used in the practice of the present invention. For example, the light pipe may be a relatively long tube-like light pipe having a square, triangular or hemispherical cross section. The light pipe has a relatively long narrow surface running substantially the length of the tube that functions as an output aperture. Light is inserted into the light pipe from a light source optically coupled to a surface region at at least one end of the tube. In addition, more than one light pipe may be used to provide an appropriate light beam form illuminating a field of view of a glucometer, in accordance with an embodiment of the present invention.  
         [0068]      FIGS. 3A and 3B  schematically show yet another glucometer  80 , in accordance with an embodiment of the present invention. Glucometer  80  is similar to glucometers  20 ,  60  and  100  but comprises a light provider  82  having a light source  84  and associated optics  86  and a mirror  90 . Optics  86  optionally forms light from light source  84  into a fan shaped beam  88  and directs the light to mirror  90 , which is rotatable about an axis  92 . Mirror  90  reflects light that it receives as a fan beam  94  through slot  54  to illuminate tissue below skin  22 . Orientation of mirror  90  about axis  92  is controlled by controller  46  to direct fan beam  94  at different angles into tissue below skin  22  so that the light beam scans a relatively large region of the tissue and thereby provides glucometer  80  with a relatively large field of view.  
         [0069]     In some embodiments of the invention, controller  46  correlates position of mirror  90  and thereby the position of fan beam  94  with acoustic signals generated by transducers  30  responsive to photoacoustic waves sensed by the transducers. By correlating the position of fan beam  94  with the acoustic signals, a portion of the field of the view of glucometer  80  in which the sensed photoacoustic waves originate is localized and spatial resolution for locating origins of the photoacoustic waves may be improved.  
         [0070]     In the glucometers described above (glucometers  20 ,  60 ,  80  and  100 ), optics are optionally used to form light from a light source into a fan shaped light beam having a relatively large cross section in the plane of the fan beam. In accordance with some embodiments of the invention, scattering of light in body tissue is relied upon to provide a glucometer with a light beam having a relatively large cross section. Light from a light source in the glucometer is directed into body tissue at a localized spot on a skin region to which the glucometer is attached. Upon entry into the body tissue the tissue scatters the light and spreads it into a substantially cone shaped beam having a relatively large cross section in a plane through an axis of the cone.  
         [0071]      FIG. 3C  schematically shows a cross section view of a glucometer  180  similar to glucometer  80  comprising a light provider  182  having an optic fiber  186  to direct light from light source  84  to mirror  90 , in accordance with an embodiment of the invention. Glucometer  180 , optionally, does not comprise optics to shape light from light source  84  into a fan shaped light beam. Light from optic fiber  186  is reflected by mirror  90  onto skin  22 . Upon entering tissue below skin the tissue scatters the light into a cone shaped beam  194  having a relatively large cross section in a plane that includes an axis  196  of cone beam  194 , which plane in the cross section view of  FIG. 3C  is the plane of the paper.  
         [0072]      FIG. 4  schematically shows a glucometer  120  comprising a light provider having an array  124  of optic fibers  126  through which light is transmitted to illuminate tissue and blood vessel  24  below a region of a patient&#39;s skin  22  to which the glucometer is attached.  
         [0073]     A first end  130  of each optic fiber  126  is optionally coupled to an acoustic transducer  132  and a suitable light source  134 . Acoustic transducer  132  is formed from a piezoelectric material transparent to light provided by light source  134  and light radiated by the light source propagates through the piezoelectric sensor to enter optic fiber  126 . Optionally, sources  134  and acoustic transducers  132  are formed in a suitable substrate  136  using micro-manufacturing techniques known in the art.  
         [0074]     A second end  138  of each fiber  126  is mounted to a mounting plate  140  so that when the mounting plate is attached (optionally using a suitable adhesive  26 ) to a region of skin  22 , the second ends of the fibers are in optical and acoustic contact with the skin. Optionally, each second end  138  is formed with a lens (not shown) and/or coupled to optics (not shown) formed in mounting plate  140  that shapes light from light source  134  that exits the second end into a beam of light (not shown) having a desired shape. Optionally, the lens and/or optics shapes the light into a cone beam. In some embodiments of the invention the lens and/or optics shapes the light into a fan beam. Each optical fiber  126  functions not only to transmit light from its associated light source  134  to illuminate tissue below skin  22 . It also functions to propagate acoustic energy that reaches its end  138  from photoacoustic waves stimulated in the tissue by the light to its associated acoustic transducer  132 .  
         [0075]     A controller  46  controls light sources  134  and receives signals generated by transducers  132  responsive to acoustic energy that the transducers receive via optic fibers  126 . Optionally controller  46  is configured to control transducers  132  to transmit ultrasound into tissue below skin  22  via optic fibers  126  for situations in which it is advantageous to acoustically image features in the tissue.  
         [0076]     Components of glucometer  120  are contained in a housing  150  shown in dashed lines. Optionally, a power source  45  for powering light sources  134  and controller  45  is mounted inside the housing. In some embodiments of the invention glucometer  120  receives power from an external power source optionally mounted to the patient&#39;s body. Housing  150  optionally comprises a visual display screen and control buttons (not shown) for transmitting commands and or data to controller  46 .  
         [0077]     Whereas in glucometer  120  each fiber  126  functions to transmit light and acoustic energy and is mounted to both an acoustic transducer  132  and to a light source  134 , in some embodiments of the invention, optic fibers in a glucometer similar to glucometer  120  are not coupled to both an acoustic transducer and a light source. Instead, each acoustic transducer  132  is mounted to an acoustic waveguide, which may be an optic fiber, which is not coupled to a light source  134  and each light source  134  is mounted to an optic fiber  126 , which is not mounted to an acoustic transducer  132 .  
         [0078]     In some embodiments of the invention, a glucometer similar to a glucometer described herein is used not only to monitor a patient&#39;s blood glucose but also to control the patient&#39;s blood glucose. The glucometer is connected to a suitable insulin delivery system, such as for example, an insulin pump coupled to a needle or a drug delivery patch that is controllable to administer insulin to a patient. The glucometer and delivery system are mounted to the patient&#39;s body. The glucometer controller controls the delivery system to administer insulin to the patient and control thereby the patient&#39;s blood glucose level responsive to blood glucose measurements provided by the glucometer.  
         [0079]     It is noted that whereas the glucometers discussed above are described as being used to assay glucose, the glucometers may be used to assay an analyte in blood in a blood vessel other than glucose. To assay an analyte in a blood vessel other than glucose, a glucometer in accordance with an embodiment of the invention is operated similarly to the way in which it is operated to assay glucose but with the glucometer&#39;s light provider providing light that is absorbed and/or scattered by the other analyte.  
         [0080]     In the description and claims of the present application, each of the verbs, “comprise” “include” and “have”, and conjugates thereof, are used to indicate that the object or objects of the verb are not necessarily a complete listing of members, components, elements or parts of the subject or subjects of the verb.  
         [0081]     The present invention has been described using detailed descriptions of embodiments thereof that are provided by way of example and are not intended to limit the scope of the invention. The described embodiments comprise different features, not all of which are required in all embodiments of the invention. Some embodiments of the present invention utilize only some of the features or possible combinations of the features. Variations of embodiments of the present invention that are described and embodiments of the present invention comprising different combinations of features noted in the described embodiments will occur to persons of the art. The scope of the invention is limited only by the following claims.