Abstract:
A blood glucose monitor for non-invasive, in-vivo characterization of a blood glucose level in a living body, the monitor comprising: a microwave resonator having a resonant response to input microwaves and designed such that said response will experience a perturbation by a living body in proximity or contact with the resonator; and detection means for detecting changes in said resonant response from which said level can be characterized.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a national phase application of International Application No. PCT/GB2011/052107, filed Oct. 28, 2011, claiming priority to UK Application No. 1018413.3, filed Nov. 1, 2010, both of which are incorporated by reference herein in their entirety. 
     FIELD 
     The invention relates to in-vivo monitoring of a blood glucose level using microwaves. 
     BACKGROUND 
     The monitoring of a blood glucose level in a living body, typically a human, is a well known diagnostic test. A person may need to monitor their blood glucose level carefully if they suffer from diabetes. 
     There are many known kinds of blood glucose level monitoring device. A commonplace class of blood glucose level monitoring device is the “blood strip meter”. A blood strip meter makes measurements on a very small amount of blood captured on a disposable, strip-like carrier that is docked with the device to perform the analysis. The blood is obtained by wiping the strip over a pin-prick wound. 
     SUMMARY 
     The invention is defined by the appended claims, to which reference should now be made. Some features of some embodiments of the invention will now be described. 
     In certain embodiments, the resonator is designed to feature first and second resonances, with the first resonance experiencing a perturbation by a living body in proximity or contact with the resonator, and the second resonance experiencing no such perturbation. Actually, in a practical embodiment, the second resonance may in fact exhibit such a perturbation, but to a small degree that is negligible relative to the perturbation experienced by the first resonance. The first and second resonance may be, for example, peaks or notches, depending on implementation. The detecting means may be arranged to measure the height of one or both of the resonances; the height could be the height to the crest of a peak or to the bottom of the trough of a notch. 
     The ring or rings mentioned in the claims are preferably circular but not necessarily so. Where there are several rings, they may differ in shape to one another. The ring or rings may be mounted on a pillar or support made of electrically insulating material. 
     The detection means typically comprises means for measuring the power versus frequency for microwaves passing through the resonator. 
     Typically, the frequency of the microwaves that are passed through the resonator is swept or stepped and the power of microwaves that have travelled through the resonator is measured at various frequencies. 
     Where the resonator comprises two rings, each ring will give rise to a respective peak in the resonant response of the resonator. Measurements made on one peak may be used to provide a reference point for measurements done on the other peak so that systematic errors such as those due to changes in temperature or humidity can be avoided. 
     At least some embodiments of the invention provide one or more of the following advantages:
         The monitoring is conducted non-invasively. This means that there is no risk of the scarring that can occur with devices such as blood strip meters.   The monitoring may be conducted continuously. The non-invasive nature of the invention greatly facilitates continuous monitoring. That is to say, a monitor according to the invention may be attached to a subject (e.g. by a belt or adhesive) to assess a blood glucose level periodically over an extended interval (e.g. every 10 minutes over a 72 hour period).   Relative insensitivity to placement. That is to say, certain monitors embodying the invention need not be mounted to a specific body part and/or the same location on a given body part.   Relative insensitivity to the pressure with which the monitor is applied to a subject. That is to say, certain monitors embodying the invention produce blood glucose measurements that are unbiased by the degree to which the monitor is pressed against the subject&#39;s body.       

    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       By way of example only, certain embodiments of the invention will now be described by reference to the accompanying drawings, in which: 
         FIG. 1  is a schematic block diagram of a non-invasive blood glucose monitor; 
         FIG. 2  is a cross section through the sensor shown in  FIG. 1 ; 
         FIG. 3  is a spectrum obtained from the sensor of  FIG. 1 ; 
         FIG. 4  is another spectrum obtained from the sensor of  FIG. 1 ; and 
         FIG. 5  is a further representation of the spectrum of  FIG. 3 . 
     
    
    
     DETAILED DESCRIPTION 
       FIG. 1  shows a non-invasive blood glucose monitor (NIGBM)  10  according an embodiment of the invention. The NIGBM  10  includes a sensor  12 , a vector network analyser (VNA)  16 , coaxial leads  18  and  20 , a USB lead  22  and a laptop computer  24 . 
     The sensor  12  is for application to a living body  14  on which blood glucose monitoring is to be performed. The vector network analyser  16  is connected to the sensor  12  via the coaxial leads  18  and  20 . The VNA  16  sends microwaves into the sensor  12  through lead  18  and receives through lead  20  microwaves that have passed through the sensor  12 . The VNA  16  sweeps the frequency of the microwaves that it inputs to the sensor  12  and records in digital form the power versus frequency spectrum of the microwaves that are received from the sensor. The laptop computer  24  retrieves the spectrum from the VNA  16  via the USB lead  22  and makes measurements on it to assess the blood glucose level of the living body  14  (hereinafter referred to as the “subject”). These measurements will be described later with reference to  FIG. 5 . 
     The sensor  12  is a largely a cylinder and  FIG. 2  shows the sensor in cross-section through the plane containing the cylinder&#39;s axis. The cylinder&#39;s axis is substantially perpendicular to the subject when the sensor is applied to the subject. The sensor  12  comprises a brass housing  26  that provides the curved walls and one face of the cylinder. The other face of the cylinder is provided by a window  28  of insulating material that is transparent to microwaves (e.g. a material such as PTFE). Thus, the housing  26  defines a space  30  that has, as far as microwaves are concerned, an opening, provided by the window  28 . 
     The space  30  contains a cylindrical pillar  32  of insulating material (e.g. PTFE) that acts as a brace between the window  28  and the flat face of the brass housing  26 . The diameter of the pillar  32  is stepped such that part  32   a  of the pillar has a smaller diameter than part  32   b . The axis of the pillar  32  is substantially coincident with the axis of the cylindrical housing  26 . Two metal rings  34  and  36  are mounted snugly on the pillar  32 , on parts  32   a  and  32 , respectively. It should therefore be apparent that the rings  34  and  36  are circular and that ring  34  has a smaller diameter than ring  36 . The axes of the rings  34  and  36  are coincident with the axes of the pillar  32  and the housing  26 . The rings  34  and  36  are spaced apart along the axis of the pillar  32 . The rings  34  and  36  are discontinuous. That is to say, each of rings  34  and  36  is broken by a small gap. 
     Diametrically opposed ports are provided in the curved wall of the housing  26  and the coaxial cables  18  and  20  extend through respective ones of these ports and a short way into the space  30 . Thus, cable  18  delivers microwaves to the space  30  and cable  20  receives microwaves from the space. The rings  34  and  36  are largely responsible for the coupling of microwaves from cable  18  into cable  20 , and dictate the principal features of the spectrum obtained from the sensor  12 . The central conductor of the coaxial cable  18  is, at the end of the cable that protrudes into the space  30 , formed into a loop  18   a . Likewise, the central conductor of the coaxial cable  20  is, at the end of the cable that protrudes into the space  30 , formed into a loop  20   a.    
     The sensor is in essence a microwave resonator. A typical spectrum obtained from sensor  12  in the absence of a subject is shown in  FIG. 3 . The spectrum shows two prominent resonant peaks  38  and  40  at frequencies f 1  and f 2 , respectively. Peak  38  is due to ring  34  and peak  40  is due to ring  36 . 
       FIG. 4  shows what happens to the spectrum from sensor  12  when the window  28  is placed against a subject. To aid comparison, the spectrum of  FIG. 3  is shown in  FIG. 4  as a dashed line. It is apparent from  FIG. 4  that peak  40  is largely unchanged and that peak  38  has become lower and broader and has moved down in frequency to f 3 . The height, width and centre frequency of peak  38  depends on the blood glucose level of the blood in the tissue in that part of the subject that is adjacent the sensor. Thus, the height, width and centre frequency of peak  38  can be monitored by periodically reacquiring the power versus frequency spectrum of the sensor  12  in order to discern changes in the subject&#39;s blood glucose level. 
     Peak  40 , on the other hand, acts as a reference peak since, as can be seen by comparing the parts of the solid and dashed traces in the region of f 2  in  FIG. 4 , its characteristics are largely unchanged by the presence or absence of a subject adjacent the sensor  12 . This insensitivity is due to the fact that the ring  36 , to which peak  40  corresponds, is located sufficiently distant from the subject (it is further from the window  28  than is ring  34 ) so as to be unperturbed by the subject. In contrast, from the perspective of ring  34 , the subject&#39;s tissue becomes an influential part of the microwave resonator that is the sensor  12 . Whilst peak  40  is not affected by the subject, it is still affected by systematic factors that affect both rings  34  and  36 . Examples of such systematic factors are temperature and humidity variations in the sensor&#39;s immediate environment, whether due to an adjacent subject or to the conditions of the wider environment. 
     With the aid of  FIG. 5 , we will now discuss in more detail the measurements that are made on a spectrum that is acquired by the computer  24  from the VNA  16 . In fact,  FIG. 5  reproduces the spectrum of  FIG. 3 , although it is now overlaid with various measurement parameters, which are:
         Δf, which is the difference in frequency between the frequency f 1  of resonant peak  38  due to ring  34  and the frequency f 2  of the resonant peak  40  due to ring  36 .   h 1 , which is the height of peak  38 .   h 2 , which is the height of peak  40 .   w 1 , which is the full width of peak  38  and its half-height.   w 2 , which is the full width of peak  40  and its half-height.       

     The computer  24  measures these parameters in a received spectrum. Then, in order to remove bias due to systematic errors of the kinds mentioned earlier, a normalised peak height h n =h 1 /h 2  and a width difference Δw=w 1 -w 2  are calculated. Moreover, a modified Q factor is calculated for peak  38 , Q=f 1 /Δw. The values Δf, h n , Δw and Q are then used together to address a look up table (LUT) in the memory of the computer  24  to retrieve a value of the blood glucose level of the subject at the time the spectrum was captured. 
     Of course, many variations of the embodiment described above are possible without departing from the scope of the present invention. Some of these will now be described. 
     In one variant, the LUT is addressed by just the Δf value in order to return a blood glucose level reading. In other embodiments, other subsets of Δf, h n , Δw and Q may be used to address the LUT. 
     For another class of embodiments, the NIBGM according to the invention is minaturised or “productised” or packaged for commercial use. Typically, this involves taking the functionality both of the VNA  16  that determines the microwave spectrum of the sensor  12  and also of computer  24  for determining a blood glucose level from a captured spectrum and putting that functionality into a smaller electronic package, where most, if not all of that functionality is provided by a single integrated circuit. In the same vein, a small and simple user interface would typically be provided, to enable a user to trigger an ad hoc blood glucose level measurement and to read off, e.g. from a small LCD screen, a most recently determined blood glucose level. 
     In other class of variants, the shape and/or the dimensions of the resonator that is the sensor  12  can be varied. For example, the reference ring  36  could be removed if compensation of systematic errors is unimportant or can be achieved through other means.