A kind of compound optoacoustic dynamic nondestructive blood-sugar detecting instrumentTechnical field
The present invention relates to a kind of detect the measuring instrument of blood sugar in diabetic patients level and in particular to a kind of be combined for medical scienceType optoacoustic dynamic nondestructive blood-sugar detecting instrument.
Background technology
A kind of hurtless measure, continuously can survey, and portable dynamic glucose detector has become as current blood glucose instrument development trend.International Diabetes Federation issues《Diabetes map》Display, the whole world in 2013 there are about 3.82 hundred million adults and suffers from diabetes,And China has become the most country of global diabetic, total patient of diabetes patient's number nearly 100,000,000, prediabetes numberReach 1.5 hundred million about.And diabetic, in order to control its PD, needs to measure its blood sugar level incessantly, withReach so that blood glucose value is maintained at the purpose of normal range (NR).
And the blood glucose monitoring system clinically commonly used at present is traumatic, bring certain misery to patient.Meanwhile, INotice that numerous enterprises are developing non-invasive determination method of blood sugar and detecting instrument, be wherein no lack of the big enterprise of ZoomlionIndustry, such as Microsoft, Google, Samsung propose in recent years and carry out the research and development of noninvasive glucose instrument, hurtless measureBlood glucose meter is once researched and developed successfully, and the pattern for existing " blood glucose meter is free, lean on test paper to make money " will be revolutionary progress.
On the other hand, we note that and have been disclosed for the multinomial patent of invention with regard to non-invasive blood sugar instrument up till now, such as《NoninvasiveFormula near-infrared electronic blood-glucose meter》(CN102198004A) utilize infrared light supply (600～2500nm) transmission finger, according to blood sugarAbsorption spectrum, the Mixture of expert algorithm using neutral net is weighted averagely to the signal of sensor each in infrared sensing arrayAfter obtain blood glucose value；《Non-invasive blood sugar monitor》(CN201295231Y) it is by two electrodes with patient contactThe capacitance of measurement patient is thus obtain the blood glucose value of patient；《Self-service non-wound blood sugar measurer》(CN1271562A) it is using infraredLight-emitting tube is as infrared light supply (wavelength：1000～2900nm), blood glucose value is measured using transmission-type.
The Chinese patent of Application No. 200710304706.7 discloses a kind of method of Woundless blood sugar quick detection and dressPut, it uses pulse laser, measurement is to be carried out using optoacoustic effect and light scattering effect, using pulse laser cost relativelyHeight, and it also cannot solve the problems, such as that blood sugar test is affected by environment.
The infra-red sepectrometry that above method adopts, is disturbed serious, high to environmental requirement.Affected by the ambient temperatureGreatly.Why non-invasive blood sugar instrument does not delay is researched and developed successfully, and tracing it to its cause is two aspects：(1) stability and accuracy are meshBottleneck (2) the hurtless measure dynamic glucose detector detection of front noninvasive glucose instrument is affected by environment big.
Content of the invention
It is an object of the present invention to provide a kind of hurtless measure measuring instrument detecting blood sugar in diabetic patients level for medical science, solveAffected by environment big, the problem especially being affected by other tissue fluid of noninvasive glucose instrument.
The technical scheme is that：A kind of compound optoacoustic dynamic nondestructive blood-sugar detecting instrument, it includes laser instrument, laserCollimation unit, focus lens group, cooling unit, finger lock chamber, piezoelectric transducer array, laser modulator, DSP microprocessorDevice, display module, lock-in amplifier and preamplifier；Cooling unit is attached on finger lock chamber；Laser instrument, laser alignmentUnit, focus lens group are in approximately the same plane；
Laser instrument is modulated by laser modulator, and the chirp signal that DSP microprocessor is produced is loaded into laser beamOn, chirp signal is sent to lock-in amplifier as reference signal simultaneously；Laser beam with chirp signal passes through laserAfter collimation unit, incide focus lens group so that laser beam focusing is in finger lock chamber, light energy is placed on fingerAfter skin histology in lock chamber absorbs, because optoacoustic effect forms ultrasonic wave, piezoelectric transducer array detects ultrasonic wave, willAcoustical signal is converted into electric signal, and the electric signal that piezoelectric transducer array collects is amplified by preamplifier, is input to lock and mutually putsBig device is detected, obtains the photoacoustce signal intensity of respective frequencies.
Further, laser instrument is modulated by laser modulator, by the chirp signal for 0.3M～11MHz for the frequency rangeModulate laser instrument, generate periodic intensity fluctuation.
Further, piezoelectric transducer array is made up of the Acoustic focusing transducer of at least two different center frequency, itsDetection frequency of sound wave covering frequence scope is 0.3M～11MHz, and the focal length of Acoustic focusing transducer is identical simultaneously, their focusOverlap with laser instrument incident light position, just fall on the focal plane of incident laser.
Further, cooling unit is made up of peltier cooling element and temperature sensor, carries out temperature to finger lock chamberDegree is adjusted so that its operating temperature is 15 ± 0.2 DEG C.
Further, finger lock chamber is mainly made up of optical lens, glass baffle plate and substrate, forms acoustic resonant cavity.
Further, centered on described laser instrument, wavelength is the near-infrared semiconductor continuous-wave laser of 980nm.
The present invention is used continuous-wave laser and is modulated using chirp signal, with respect to pulse laser, continuouslyExcept low price, our modulation system makes frequency spectrum of laser acoustics enrich to laser instrument, you can to cover 0.3M～11MHz'sSignal；And study discovery measuring point temperature and often raise 0.1 DEG C of light intensity causing and concentration of glucose reduction 3.68mmol/LQuite (bibliography：Liu Rong etc. University Of Tianjin journal .Vol.41No.12008), such temperature control is very important, can improvePrecision, it is to avoid using introducing human error after laser.
Compared with prior art, the invention has the beneficial effects as follows：
(1) it is based on chirped modulation signal and piezoelectric transducer array, there is the ability obtaining blood sugar fingerprint characteristic, Er QiejieStructure is simple, and certainty of measurement reaches more than 96.5%.
(2) effective control tested spot temperature change simultaneously, thus be prevented effectively from the impact of environment.
Brief description
Fig. 1 is the structural representation of the present invention；
Fig. 2 is finger control chamber structural representation；
The chirp signal figure that Fig. 3 uses for the present invention；
Fig. 4 is the deionized water and blood sugar solution (500mmol/L) optoacoustic spectrogram obtaining according to present system；
When Fig. 5 adopts optical maser wavelength for 980nm for the present invention, IDDM human blood carbohydrate density is measured with photoacoustic signal valueGraph of a relation in time.
When Fig. 6 adopts optical maser wavelength for 980nm for the present invention, type II diabetes human blood carbohydrate density is measured with photoacoustic signal valueGraph of a relation in time.
Fig. 7 is to measure for multiple, the linear coupling relation of blood sugar density and photoacoustic signal value.
In figure, 11 is laser instrument, and 12 is laser alignment unit, and 13 is focus lens group, and 14 is cooling unit, and 15 is fingerLock chamber, 16 is the whole array of PZT (piezoelectric transducer), and 17 is laser modulator, and 18 is DSP microprocessor, and 19 is display module, and 110 areLock-in amplifier, 111 is preamplifier, and 21 is finger chamber, and 22 is substrate, and 23 is lens fixed mount, and 24 is anti-reflection mirror, and 25 areConvex lens, 26 is glass baffle plate.
Specific embodiment
The invention will be further described below in conjunction with the accompanying drawings, and a kind of dual-wavelength difference near infrared no-wound hinders blood glucose meter：
The present invention is mainly characterized by：First, employ chirp signal as modulated signal, form photoacoustic spectrum to be detected；Second, control the temperature at tested position using cooling unit, it is to avoid the impact of environment temperature or measuring point temperature change；TheThree, using using Acoustic focusing transducer hence it is evident that improve sound wave detection efficiency.
Its structure is as shown in figure 1, it includes laser instrument 11, laser alignment unit 12, focus lens group 13, cooling unit14th, finger lock chamber 15, piezoelectric transducer array 16, laser modulator 17, DSP microprocessor 18, display module 19, lock are mutually putBig device 110 and preamplifier 111；Cooling unit 14 is attached on finger lock chamber 15；Laser instrument 11, laser alignment unit12nd, focus lens group 13 is in approximately the same plane.
Laser instrument 11 is subject to modulating of laser modulator 17, and the chirp signal that DSP microprocessor 18 is produced is loaded into sharpOn light light beam, chirp signal is sent to lock-in amplifier 110 as reference signal simultaneously；Laser beam with chirp signalAfter laser alignment unit 12, incide focus lens group 13 so that laser beam focusing is in finger lock chamber 15, luminous energyAfter the skin histology that amount is placed in finger lock chamber 15 absorbs, because optoacoustic effect forms ultrasonic wave, PZT (piezoelectric transducer) battle arrayRow detect ultrasonic wave, convert acoustic signals into electric signal, the electricity that piezoelectric transducer array 16 is collected by preamplifier 111Signal amplifies, and is input to lock-in amplifier 110 and is detected, obtain the photoacoustce signal intensity of respective frequencies, is input to the micro- place of DSPReason device 18 is shown by display module after processing.
Laser instrument 11 is subject to modulating of laser modulator 17, by the chirp signal modulation for 0.3M～11MHz for the frequency rangeTo laser instrument, generate periodic intensity fluctuation.Piezoelectric transducer array 16 is by the Acoustic focusing of at least two different center frequencyTransducer forms, and its detection frequency of sound wave covering frequence scope is 0.3M～11MHz, the focal length phase of Acoustic focusing transducer simultaneouslyWith their focus is overlapped with laser instrument 11 incident light position, just falls on the focal plane of incident laser.Cooling unit 14 byPeltier cooling element and temperature sensor composition, carry out temperature adjustment to finger lock chamber 15 so that its operating temperature is 15±0.2℃.Finger lock chamber is made up of optical lens, glass baffle plate 26 and substrate 22, forms acoustic resonant cavity.Finger chamber 21 isFor placing tested finger position；Anti-reflection mirror 24 effect is the effect that the near infrared light to 980nm plays narrow-band-filter, it is to avoid itsThe impact of the infrared light of his wavelength；Convex lens 25 can adjust focus point so that focus point just falls after glass baffle plate 26, away fromFrom glass baffle plate 262mm～3mm, the effect of glass baffle plate 26 be during detection finger plaster on glass baffle plate 26 so that laserFocus point just falls inside finger skin；The effect of substrate 22 has two, and one is fixed finger cavity, and another one acts onIt is to form acoustic resonant cavity with glass baffle plate 26.Centered on described laser instrument 11, the near-infrared semiconductor for 980nm for the wavelength connectsContinuous wave laser.
Setting up detection algorithm Mathematical Modeling is the theoretical foundation selecting optoacoustic spectral technology.The acoustical signal producing is in cell tissueIn propagation equation can be described with following formula：
Here I represents laser intensity, and v is sound wave spread speed in cell tissue, and α is the absorption coefficient of light, and β is thermal expansionCoefficient, CpIt is specific heat capacity, p is sound pressure.
The histiocytic situation for weak absorbing, sound pressure p can be written as：
Here k is system weighting constant, E0For incident intensity energy, n is experiment experience constant (between 1 and 2).
So using chirp signal as shown in Fig. 2 it includes the signal of frequency 0.01MHz～10MHz, time delay is0.1s, in 10 minutes sampling times, can calculate a blood glucose value every 30s, form kinetic measurement.
Give deionized water and blood sugar solution (500mmol/L) optoacoustic spectrogram in Fig. 4, from absorption spectrum it can be seen thatThere is the peak value of optoacoustic absorption spectra near 980nm, select the near-infrared laser of 980nm can realize accurately measuring the mesh of blood glucose value's.
When Fig. 5 and Fig. 6 represents using optical maser wavelength for 980nm respectively, IDDM human blood carbohydrate density and photoacoustic signal valueMeasurement graph of a relation and type II diabetes human blood carbohydrate density and the measurement of photoacoustic signal value in time graph of a relation in time, from relationIn figure can be clearly seen for I type and type II diabetes people, and photoacoustic signal value and blood sugar density have extraordinary linear relationship.
Fig. 7 is for the multiple blood glucose value V measuring, providing PA detectionPAWith medical measured value VClinicalBetween linear couplingConjunction relation is
VPA=0.965VClinical+12.65 (3)
Both correlations reach 96.5%, you can accurately measure blood glucose value, and certainty of measurement reaches more than 96.5%.
Embodiment described above only have expressed the specific embodiment of the application, and its description is more concrete and detailed, but simultaneouslyTherefore the restriction to the application protection domain can not be interpreted as.It should be pointed out that for those of ordinary skill in the artFor, on the premise of conceiving without departing from technical scheme, some deformation can also be made and improve, these broadly fall into thisThe protection domain of application.