For monitoring and prevention of lifestyle diseases, we have investigated development of non-invasive ear-clip type blood glucose sensors that can be used by individuals in daily life. Because mid-infrared light (λ = 8–14 μm) is absorbed strongly by water, it is difficult to detect transmitted light from human bodies. We propose that an ultrasonic-assisted method, which can actively produce a reflection plane at a blood vessel (depth of around 100 μm), could be used to detect internal reflected light from biological tissues. An ultrasonic standing wave produced near the skin surface by an ultrasonic vibrator can form refractive index boundaries between areas of high and low density. Additionally, we can use a low ultrasonic frequency (1 MHz) that does not suffer from heavy damping by parametric standing waves, which appear in non-rigid samples and produce reflection planes at the same depth when using a high frequency (10 MHz). At the refractive index boundary nearest the skin surface, the light from inside biological tissues is reflected and can be used to obtain information of biological components. The optical path length can be set by changing the measurement depth by altering the ultrasonication frequency. We measured internal reflected light from the ears of mice (blood glucose level = 120 mg/dL) non-invasively using our unique mid-infrared spectroscopic imager and obtained absorption peaks for blood glucose (λ = 9.3 μm and 9.7 μm). Mid-infrared spectroscopy can be applied to measurements in samples with high water contents.
We propose the point one-shot mid-infrared Fourier spectroscopic imager, which is composed of only a single Ge lens (diameter: 6 mm; thickness: 5 mm) and a two-dimensional array device. The lens is a nonspherical lens on the front side and a dual-axis inclined wedge prism at the rear side. The objective beams, which have different optical path lengths because of the effects of the prism, are imaged using the array device and we obtain a two-dimensional spatial fringe pattern. We can improve the wavelength resolution analytically by connecting the same optical path difference (OPD) pixels of the horizontal lines at different rows, even though we use low-resolution cameras.
The use of the wide-field-stop and beam-expansion method for sensitivity enhancement of one-shot Fourier spectroscopy is proposed to realize health care sensors installed in smartphones for daily monitoring. When measuring the spectral components of human bodies noninvasively, diffuse reflected light from biological membranes is too weak for detection using conventional hyperspectral cameras. One-shot Fourier spectroscopy is a spatial phase-shift-type interferometer that can determine the one-dimensional spectral characteristics from a single frame. However, this method has low sensitivity, so that only the spectral characteristics of light sources with direct illumination can be obtained, because a single slit is used as a field stop. The sensitivity of the proposed spectroscopic method is improved by using the wide-field-stop and beam-expansion method. The use of a wider field stop slit width increases the detected light intensity; however, this simultaneously narrows the diffraction angle. The narrower collimated objective beam diameter degrades the visibility of interferograms. Therefore, a plane-concave cylindrical lens between the objective plane and the single slit is introduced to expand the beam diameter. The resulting sensitivity improvement achieved when using the wide-field-stop and beam-expansion method allows the spectral characteristics of hemoglobin to be obtained noninvasively from a human palm using a midget lamp.
We proposed the ultrasonic-assisted spectroscopic imaging for the realization of blood-glucose-level monitoring during dialytic therapy. Optical scattering and absorption caused by blood cells deteriorate the detection accuracy of glucose dissolved in plasma. Ultrasonic standing waves can agglomerate blood cells at nodes. In contrast, around anti-node regions, the amount of transmitted light increases because relatively clear plasma appears due to decline the number of blood cells. Proposed method can disperse the transmitted light of plasma without time-consuming pretreatment such as centrifugation. To realize the thumb-size glucose sensor which can be easily attached to dialysis tubes, an ultrasonic standing wave generator and a spectroscopic imager are required to be small. Ultrasonic oscillators are ∅30[mm]. A drive circuit of oscillators, which now size is 41×55×45[mm], is expected to become small. The trial apparatus of proposed one-shot Fourier spectroscopic imager, whose size is 30×30×48[mm], also can be little-finger size in principal. In the experiment, we separated the suspension mixed water and micro spheres (Θ10[mm) into particles and liquid regions with the ultrasonic standing wave (frequency: 2[MHz]). Furthermore, the spectrum of transmitted light through the suspension could be obtained in visible light regions with a white LED.
We propose one-shot Fourier-spectroscopic tomography as a method of ultraminiature spectroscopic imaging. The apparatus used in this technique consists solely of a glass slab with a portion of its surface polished at a certain inclination angle—a device we term a relative-inclination phase shifter—simply mounted on an infinite-distance-corrected optical imaging system. For this reason, the system may be ultraminiaturized to sizes on the order of a few tens of millimeters. Moreover, because our technique uses a near-common-path wavefront-division phase-shift interferometer and has absolutely no need for a mechanical drive unit, it is highly robust against mechanical vibrations. In addition, because the proposed technique uses Fourier-transform spectroscopy, it offers highly efficient light utilization and an outstanding signal-to-noise ratio compared to devices that incorporate distributed or hyperspectral acousto-optical tunable filters. The interferogram, which is a pattern formed by interference of waves at all wavelengths, reflects the spatial variation in the intensity of the interference depending on the magnitude of the phase shift. We first discuss the design of the phase shifter and the results of tests to validate the principles underlying one-shot Fourier-spectroscopic tomography. We then report the results of one-dimensional spectroscopic imaging using this technique.
For blood glucose level measurement of dialysis machines, we proposed AAA-battery-size ATR (Attenuated total reflection) Fourier spectroscopy in middle infrared light region. The proposed one-shot Fourier spectroscopic imaging is a near-common path and spatial phase-shift interferometer with high time resolution. Because numerous number of spectral data that is 60 (= camera frame rare e.g. 60[Hz]) multiplied by pixel number could be obtained in 1[sec.], statistical-averaging improvement realize high-accurate spectral measurement. We evaluated the quantitative accuracy of our proposed method for measuring glucose concentration in near-infrared light region with liquid cells. We confirmed that absorbance at 1600[nm] had high correlations with glucose concentrations (correlation coefficient: 0.92). But to measure whole-blood, complex light phenomenon caused from red blood cells, that is scattering and multiple reflection or so, deteriorate spectral data. Thus, we also proposed the ultrasound-assisted spectroscopic imaging that traps particles at standing-wave node. Thus, if ATR prism is oscillated mechanically, anti-node area is generated around evanescent light field on prism surface. By elimination complex light phenomenon of red blood cells, glucose concentration in whole-blood will be quantify with high accuracy. In this report, we successfully trapped red blood cells in normal saline solution with ultrasonic standing wave (frequency: 2[MHz]).
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