CN105241828A - CRDS acetone breath analyzer for noninvasively measuring blood ketone body level - Google Patents
CRDS acetone breath analyzer for noninvasively measuring blood ketone body level Download PDFInfo
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Abstract
The invention discloses a breath analyzer which can measure ketone body level through a noninvasive measurement method (breath analytic method) on the basis of the limitation of a ketone body level measurement method in the prior art. The breath analyzer can achieve real-time and accurate measurement on acetone concentration of human breath and directly display the blood ketone body level and reference blood glucose level. The breath analyzer also can synchronously upload data to network and displays the data on various electronic terminal devices. The breath analyzer allows diabetic patients, epileptic patients and other patients who need to measure the ketone body level and know the blood glucose level to know metabolism status themselves in real time, thereby promoting management and treatment of diseases and further significantly improving health condition and living quality.
Description
Technical field
The present invention relates to field of biomedicine technology, particularly relate to a kind of acetone scentometer measuring ketone body levels for hurtless measure.
Background technology
The present invention relates to a kind of acetone scentometer measuring ketone body levels for hurtless measure.This analyser is the cavity ring down spectroscopy technology (CRDS) based on hypersensitive, high selectivity.Need to monitor ketone body concentration mainly in diabetic and epileptic (human and animal) supervision and therapeutic process, and in current monitoring means, blood measuring needs to take blood sample, pain and easy infection, have a strong impact on quality of life, urine examination can only show half measures of quantization, reference accurately cannot be provided for the supervision of disease and treatment, thus invent the acetone scentometer based on CRDS technology that a kind of content by measuring volatile organic compounds (VOCs) acetone in respiratory component carrys out hurtless measure measurement ketone body levels.This invention belongs to biomedical sector.
Associated pathology investigation and research show, after the internal organs of human body or tissue damage or pathology, its change functionally correspondingly can cause the change of corresponding metabolic product, these metabolic products enter into blood will cause relatively increasing of some metabolite content, just can be diagnosed out the degree of injury of internal organs by the concentration detecting metabolic product.Therefore, diagnosed the illness by some special component in analyzing blood and become a kind of conventional means of modern medical diagnosis.And the metabolic product in blood can enter lung by ABB, and then cause the change of expiratory air component, some specific gas concentration excreted is raised, thus can as the biomarker of some diseases.
Along with improving constantly of living standards of the people, diabetes have become more and more serious public health problem.China is one of the fastest country of diabetic's number growth rate, ill more than 50,000,000.Diabetes can involve each histoorgan of whole body, cause multiple complications, and become the lethal main cause disabled.Ketoacidosis is serious Diabetic Acute complication, needs urgent hospitalization.Untreated or treatment ketoacidosis not in time can cause serious disease or death.
Easily there is diabetic ketoacidosis in type 1 diabetes patient, up to the Children and teenager generation ketoacidosis of 15% ~ 67% newly diagnosis.The consequence of ketoacidosis is very serious, but understands the symptom of this disease, adheres to Canonical management, carries out ketoboidies detection regularly and can help prevention.Ketoboidies (acetonebodies) is that fatty acid carries out at liver normally decomposing the special intermediate product generated, and the acetone (acetone) comprising beta-hydroxybutyric acid (β-hydroxybutyricacid accounts for 78%), acetoacetate (acetoaceticacid accounts for 28%) and minute quantity accounts for 2%.The blood ketone body levels of normal person is lower than 0.5mM, but in the routine inspection of type 1 diabetes patient routine, ketone body levels is very common at 1-2mM (1-2 μm of ol/mL), for serious ketosis patients blood plasma ketone body concentration even more than 25mmol/L.
The beta-hydroxybutyric acid measured in capillary lumen has become the routine inspection in a diabetes mellitus type routine monitoring.But existing detection method needs blood sampling, pain and easy infection, especially 1 type most patients be children or teenager, the quality of life of serious reduction patient.
Epilepsy is the chronic syndromes of one group of of short duration cerebral function imbalance caused by the unexpected paradoxical discharge of neuron.Wherein patient's prognosis of about 20% is bad, is incorporated into as intractable epilepsy.According to statistics, the cure rate of existing antiepileptic to intractable epilepsy is only 5%, and Long-Time Service easily causes hypophrenia, decrease of memory, personality and behavior change.The whole world about has the population of 1% (6,005 million people) to suffer from epilepsy, and the case of nearly 80% all occurs in developing country.
High fat diet, namely by controlling the food-intake of infant and diet ratio, mainly changing fat, ratio between protein and carbohydrates, mixing into the diet of high fat, low-carb and appropriate albumen.According to clinical experience, after a lot of drug therapy is invalid, high fat diet therapy really also effectively, for infantile spasms, efficiently reach 80%-90%, what wherein control outbreak completely has 40%, and major part is that (2 weeks) just reach and do not show effect in a short time.When high fat diet, infant will be in a kind of ketosis state, and the concentration level in vivo of ketoboidies will raise, although ketosis is not clear to the mechanism controlling epilepsy, need to measure ketone body concentration continually in high fat diet treatment.
Two kinds of methods of current detection ketoboidies: urine ketoboidies detects and blood ketone body detects.Blood ketone body test, for surveying beta-hydroxybutyric acid, needs to take blood sample, pain and easy infection, limits the frequency that ketoboidies measures.The test of urine ketoboidies is for surveying acetoacetate, and result is half measures of quantization, only can indicate high, medium and low or micro-.
Summary of the invention
The present invention is directed to the limitation (as introduced) measuring ketone body levels method at present above, invention one can measure the scentometer of ketone body levels by AT measuring method (breast rail method), this instrument can realize the real-time Measurement accuracy to human body respiration acetone concentration, direct display blood ketone body levels and reference blood sugar level, and data syn-chronization can be uploaded network and be presented at various terminal electronic device, this invention is for diabetic, epileptic and other patients needing measurement ketone body levels and understand blood sugar level, the metabolism status of oneself can be grasped in real time, promote disease supervision and treatment, and then its health status and quality of life are significantly improved.
The technical scheme adopted for realizing object of the present invention is: based on the acetone breast rail instrument system of CRDS technology, it is characterized in that system is formed primarily of optical table and Electronic Control two parts: optical table part mainly comprises laser instrument, gas sample chamber (optical resonator), detector and other annex etc., and its function is the acquisition realizing spectral signal.Wherein, gas sample chamber is not only for holding gaseous sample to be measured, and it is an optical resonator especially, and its two ends are two panels high reflectivity mirror, forms a stable resonator, laser back and forth can be propagated in chamber, realize the generation of cavity ring-down spectroscopy.This optical table part is fixed on the aluminium sheet of one piece of 600mm × 250mm × 10mm (length and width are thick), can move integrally and not need to readjust light path.Consider the size of the main devices such as adopted laser instrument, gas sample chamber and detector, this optical table part can be loaded in the cartridge type pressure-resistant seal cabin of an internal diameter Φ=200mm, length L=600mm.Electronic control part comprises laser controlling power supply, vacuum pump, oscillograph and computing machine etc., main settling signal collection, display and processing capacity.Wherein, vacuum pump is used for intracavity gas sample to pump, oscillograph is for showing cavity-type BPM signal and carrying out A/D conversion to the simulating signal collected, software again by loading in computing machine carries out data processing, and these three equipment can use micropump, data collecting card and PC/104 industrial computer to replace to realize miniaturization respectively.
According to the difference of used LASER Light Source, CRDS can be divided into the pulsating wave cavity ring-down spectroscopy (Pulsed-CRDS) using pulse laser and the continuous wave-cavity ring-down spectroscopy (CW-CRDS) using continuous laser, and wavelength coverage covers ultraviolet to infrared band.According to the difference of research object and demand, the kind of laser instrument is also different, such as neodymium-doped yttrium-aluminum garnet (Nd:YAG) laser instrument, titanium-doped sapphire (Ti:sapphire) laser instrument, the dye laser of Nd:YAG laser or excimer laser pumping and optical parametric oscillator (OPO), quantum cascade laser, semiconductor laser diode, etc.
The different qualities of laser, as pulsewidth and live width etc., all can have influence on cavity-type BPM waveform and quantitative detection result.
CRDS high sensitivity detection ability is mainly coming from the contribution of resonator cavity, just because of the roundtrip propagation of laser in resonator cavity, laser is made to have the increase doubly of several order of magnitude through the light path of absorbing material, compared to traditional absorption spectroscopy techniques, the detection sensitivity of CRDS also obtains corresponding raising.The stable cavity that modal resonator cavity is made up of two sides high reflectivity mirror.In addition, also have the resonator cavity of some other forms, such as, polygonal mirror, built-in Brewster angle reflecting plate, prism cavity and optical fiber loop chamber etc.The resonator cavity of these forms designs for different detected object, although in form different, its ultimate principle is all similar.When only analyzing resonator cavity formation, under not considering absorbing material situation, the parameter affecting cavity-type BPM time size is cavity length d and cavity mirrors reflectivity R.In general, conventional cavity length is between tens centimetres to tens centimetres.
After the reflection of two sides high reflectivity mirror, the laser intensity signal arriving detector is very faint, and the duration of cavity-type BPM signal usually nanosecond to musec order not etc., therefore, fast response time and highly sensitive photo-detector is needed to detect, general conventional photodiode and photomultiplier (PMT).When using wide wavelength laser to carry out scanning probe, photodiode array and photoelectric coupled device (CCD) can also be used as photodetector, in order to detect spectral signal that is quick, wideband simultaneously, system employs streak camera as photo-detector.
During actual measurement sample, consider atmospheric diurnal variation, consistent in order to ensure the gaseous sample volume be filled with at every turn, the pressure of gaseous sample indoor remains between low pressure 5Torr and high pressure 750Torr usually.The step measured experimental gas sample is as follows:
First nitrogen is used to rinse gas sample chamber.After flushing completes, in sample chamber, pressure remains on low pressure 5Torr, and now sample indoor gas is nitrogen, measures its cavity-type BPM time τ 0;
Nitrogen is filled in sample chamber, makes pressure rise to 750Torr, measure its ring-down time;
Repeat step 1,2, measure 2 ~ 3 times, get the mean value of measurement result as the ring-down time value τ 1 under this condition;
Pressure in sample chamber is reduced to 5Torr, is filled with gaseous sample to be measured, until pressure rises to 750Torr in sample chamber, measure its cavity-type BPM time; Extracted out by gas to be measured, and use nitrogen to carry out flushing 3 ~ 4 times to gaseous sample chamber, after having rinsed, sample indoor gas is nitrogen, and pressure is 5Torr;
Repeat step 4,5, the cavity-type BPM time of measurement same gaseous sample to be measured 2 ~ 3 times, average as the cavity-type BPM time τ 2 of certain gaseous sample under this condition:
Repeat step 4,5,6, measure the cavity-type BPM time τ 3, τ 4 of other gaseous samples to be measured ...;
After having tested, again gas sample chamber is rinsed.
Measurement to the expiratory air sample containing acetone: wherein, gas for collecting blood volatilization gas, and imports in optical resonator by described gas collector.Its collection method is after blood sample is carried out anti-freezing process, in injecting sample ware, then the bottom of gas collector is placed in, sealing gas gathering-device, the temperature maintaining gas collector is 40 degrees Celsius, by the delivery outlet valve open of gas collector after maintenance 2min, the top tank air containing blood volatilization gas is introduced in optical resonator and carries out CRDS spectral measurement.
Background subtraction is utilized to carry out data processing, adopt with the scheme of air gas as a setting: suppose in tidal air, only have acetone to create absorption to laser, and ignore the impact of other gas, the acetone concentration so obtained according to cavity-type BPM time and background subtraction should be the higher limit of acetone concentration in expiratory air.
Overdelicate cavity ring-down spectroscopy (CRDS) measuring method, not only can carry out at different wavelengths measuring thus obtain the optical information of abundant blood constituent, and having overdelicate accuracy of detection, its detection limit can be low to moderate ppm even ppb.Because Direct Analysis blood constituent has certain technical difficulty, thus the present invention adopts a kind of method of indirect analysis blood constituent, namely the VOCs content in blood volatilization gas is measured, thus extrapolate the content of each composition in blood, again by the parameter comparison of various dimensions, can identify different blood sample.
Accompanying drawing explanation
Figure 1 shows that the CRDS acetone breast rail instrument apparatus schematic diagram for non-invasive measurement blood ketone body levels.
Embodiment
Below in conjunction with specific embodiment, the present invention is described in further detail.Should be appreciated that specific embodiment described herein only in order to explain the present invention, be not intended to limit the present invention.
Embodiment:
A kind of CRDS acetone scentometer for non-invasive measurement blood ketone body levels, it is characterized in that comprising: optical table part and electronic control part, wherein optical table part comprises laser instrument, gas sample chamber, detector and optical resonator, and optical resonator two ends are two panels high reflectivity mirror; Electronic control part comprises laser controlling power supply, vacuum pump, oscillograph and computing machine.
Described laser instrument is a Q-switch Nd:YAG pulsed laser, and output wavelength is 266nm, is made up of control power supply and laser head two parts; The repetition frequency of described control Energy control output laser pulse changes in the scope of 1KHz to 100KHz, and exports a synchronizing signal with each laser pulse.
Described gas sample chamber is circular stainless-steel tube material, and length is 430mm, internal diameter 20mm, and its two ends are equipped with a pair catoptron fixed support, for stationary mirror; Described catoptron fixed support is furnished with three micrometer adjusting screws, the angle of fine setting catoptron; Described catoptron is a pair high reflectivity mirror, be assemblied in described catoptron fixed support respectively, form a stable resonator cavity, high reflection mirror two sides adopts spherical pad and corrugated gasket clamping plated film high reflective mirror respectively, spherical pad adds one deck annular shim again seal for cavity, simultaneously cavity outermost loads one piece of piece of stainless steel with optical window and seals, and adopts M6 stud to lock; The reflecting surface of described catoptron directly contacts with gaseous sample, together constitutes the good gas sample chamber of a sealing with stainless-steel tube.
Described gas sample chamber there are three gas IO interface, connect miniature pressure transducer, vacuum air pump and a T-valve respectively; Described T-valve connects the gas cylinder that nitrogen is housed and the Storage Time in Gas Collecting Bag that gaseous sample is housed respectively.
Cavity-type BPM signal is detected by a miniature photomultiplier, its diameter diameter of phi=16mm, length L=12mm, described laser instrument exports 266nm laser and is obtained to its two frequency multiplication by 532nm optical pumping, adds a slice 266nm bandpass filter in photomultiplier front end.
This optical table part is fixed on the aluminium sheet of one piece of 600mm × 250mm × 10mm (length and width are thick), can move integrally; This optical table part cargo shipment is in the cartridge type pressure-resistant seal cabin of an internal diameter Φ 200mm, length L600mm.
For a CRDS acetone measurement method for non-invasive measurement blood ketone body levels, comprise the following steps:
Step 1, first uses nitrogen to rinse gas sample chamber; After flushing completes, in sample chamber, pressure remains on low pressure 5Torr, and now sample indoor gas is nitrogen, measures its cavity-type BPM time τ 0;
Step 2, is filled into nitrogen in sample chamber, makes pressure rise to 750Torr, measures its ring-down time; Step 3, repeats step 1,2, measures 2 ~ 3 times, gets the mean value of measurement result as the ring-down time value τ 1 under this condition;
Step 4, reduces to 5Torr by pressure in sample chamber, is filled with gaseous sample to be measured, until pressure rises to 750Torr in sample chamber, measures its cavity-type BPM time;
Step 5, extracts out gas to be measured, and uses nitrogen to carry out flushing 3 ~ 4 times to gaseous sample chamber, and after having rinsed, sample indoor gas is nitrogen, and pressure is 5Torr;
Step 6, repeats step 4,5, the cavity-type BPM time of measurement same gaseous sample to be measured 2 ~ 3 times, averages as the cavity-type BPM time τ 2 of certain gaseous sample under this condition:
Step 7, repeats step 4,5,6, measures the cavity-type BPM time τ 3, τ 4 of other gaseous samples to be measured ...;
Step 8, after having tested, rinses gas sample chamber again;
Wherein, the instrument of described expiratory air sample collection is that respirator mask and gas sample sack couple together by use retaining valve, during collected specimens, face shield is covered and shut up and nose areas, expiratory air passes through this retaining valve by unidirectional, thus in collected sample sack, and by this retaining valve, person under inspection still can freely breathe.
System hardware is formed:
(1) laser instrument and control power supply: LASER Light Source is a Q-switch Nd:YAG pulsed laser (CrystaLaser), and output wavelength is 266nm, is made up of control power supply 2 and laser head 1 two parts.This laser controlling power supply 2 is of a size of 200mm × 200mm × 80mm (length, width and height), and the repetition frequency that it can control output laser pulse changes in the scope of 1KHz to 100KHz, and exports a synchronizing signal with each laser pulse.Laser head 1 has structure closely, and its size is similar to hand size, is only 185mm × 50mm × 36mm (length, width and height), and this is one of principal character of this laser instrument.The output beam of this laser instrument is TEM00 fundamental transverse mode, diameter 0.25mm, light beam multiplying power diffraction factor M2<1.3.When the repetition frequency of its output laser pulse is 1KHz, its output pulse width is 7ns, and single pulse energy is 2 μ J, and power stability is 5% (root-mean-square value), and interpulse fluctuation (pulsetopulsevariation) is ± 10%.
For off-line type metering system, breath sample gathers by breathing sampler bag.Collection capacity is about about 1L, after experimenter has a suck of gas deeply, by pulmonary gases by disposable blow gun incoming call sampler bag.Then close sampler bag outlet valve, be stored in portable heat-insulation box, prevent too high or too low for temperature, avoid strong illumination.After preserving a period of time, in the suitable time, take out sampler bag and measure.The general storage time is no more than 6h, is causing VOCs concentration to reduce to prevent breath sample due to chemical reaction or other factors.
For online metering system, experimenter is by disposable blow gun, and by pulmonary gases incoming call breath sample cushion chamber, breath sample is introduced sample chamber and measured by solenoid valve then by automatically controlling at once.
(2) gas sample chamber 8 and utility appliance: gas sample chamber is circular stainless-steel tube material, and length is 430mm, internal diameter 20mm, and its two ends are equipped with a pair catoptron fixed support, can be used for stationary mirror.Catoptron fixed support is furnished with three micrometer adjusting screws, the angle of fine-tuning catoptron.Two sides is assemblied in the high reflectivity mirror (LosGatosResearch in catoptron fixed support respectively, reflectivity R=99.8%, radius-of-curvature r=1m) constitute a stable resonator, simultaneously, the reflecting surface of this catoptron directly contacts with gaseous sample, together constitutes the good gas sample chamber of a sealing with stainless-steel tube.This gas sample chamber there are three gas IO interface, as shown in Figure 1, connect respectively: pressure transducer 6 (870BMicro-Baratron, MKSInstruments that (1) is miniature, Inc.), can gas pressure intensity in Real-Time Monitoring sample chamber; (2) vacuum air pump 7 (E2M18oil-sealedrotarypump, EdwardsLLC.), extracted out by sample indoor gas, low pressure can to 1.1 × 10-2Torr (about 1.47Pa, 1Torr=133.3Pa); (3) T-valve, connect respectively and the gas cylinder of nitrogen 10 are housed and the Storage Time in Gas Collecting Bag of laboratory sample gas 11 is housed.
Measuring principle is based on background deduction method.Measure the content of a certain VOC in breath sample, must with air as a setting, therefore, measure start before to measure the actual absorption of air.Also introduce sample chamber by air, measure ring-down time.Average after measuring 3 times, calculate the absorption of air, as a setting.Then sample measurement is carried out.After each measurement breath sample, vacuum pump being utilized to extract sample out sample chamber, for preventing remaining, also needing to use high pure nitrogen or dry air to clean.
(3) photo-detector 12 and band pass filter: cavity-type BPM signal is detected by a miniature photomultiplier (PMT, R74000U-09, Hamamatsu), and its size is only diameter of phi=16mm, length L=12mm.Its response speed can reach 0.78ns (rise time), is about 10mA/W in the cathode radiant sensitivity at 266nm place, and gain can reach 5 × 104 (voltage 800V).Obtained to its two frequency multiplication by 532nm optical pumping because laser instrument exports 266nm laser, so can with 532nm laser composition in output beam.Therefore, a slice 266nm band pass filter (CVIMellesGriot has been added in native system, diameter of phi=25.4mm), be placed in PMT incidence window front end, not only effectively prevent the interference of 532nm laser, and eliminate the impact of other parasitic light, experiment can be carried out under visible light conditions.
According to CRDS ultimate principle, after calculating the sample absorbance measured for each time, background deduction method need be adopted, draw the actual absorption of tested VOC.Then tested VOC concentration is determined according to pressure when measuring and molecule absorpting section.
Be illustrated in figure 1 the CRDS acetone breast rail instrument apparatus schematic diagram for non-invasive measurement blood ketone body levels, comprise:
(4) oscillograph 3 and computing machine 4: oscillograph 3 (TDS460A, Tektronix) for showing cavity-type BPM signal, and the function of data acquisition card, digital signal is converted to again after being averaged by the electric signal that PMT obtains, data processing is carried out by the CRDS software loaded in portable computer 4, mono-exponential fit is carried out to cavity-type BPM signal, obtains cavity-type BPM time parameter.
In this subsystem, be all fixed on the aluminium sheet 9 of one piece of thick about 10mm, length and width 600mm × 250mm as the laser head 1 of main optics, gas sample chamber 8, PMT and annex etc. thereof, constitute the optical table part of this experimental system.This part integrally can arbitrarily movement, and the Primary Component such as laser instrument and photo-detector owing to employing miniaturization, makes in its cartridge type pressure-resistant seal cabin that can be placed in an internal diameter Φ=200mm, length L=600mm, can meet the demands.
Nitrogen (99.2%, AirgasInc.) gas, cushion gas and the purge gas as a setting of technical grade purity is have employed in system.Use same gas gas as a setting, the impact of background gas change on experimental result can be eliminated, ensure that Experimental Background is consistent; As cushion gas, can be used for the dilution of gaseous sample; As purge gas, after the measurement at every turn completing a kind of sample, gas sample chamber is rinsed, eliminate gas residue, ensure the accuracy of each experiment.
When measuring beginning, high pure nitrogen first to be used to rinse gas sample chamber, to eliminate residual impurity gas.Detailed process is: first use vacuum air pump to be extracted out completely by gas original in sample chamber; Then by nitrogen insufflation gas sample chamber, pressure in sample chamber is made to rise to close to an atmospheric pressure; Re-use vacuum pump nitrogen is extracted out, until vacuum.Experiment shows, repeatedly carries out this process 3 ~ 4 times, can realize the flushing to sample chamber.Nitrogen, in the process being filled with and extracting out, make sample chamber internal gas pressure change slowly by the switch controlling gas valve, prevents pressure difference inside and outside sample chamber from changing and too acutely causes reflector position to change.
(5) optics cavity mirror
Adopt metal washer to fix high reflection mirror, the micro-displacement eliminating system chamber mirror may be caused declining swinging signal distortion; High reflection mirror two sides adopts spherical pad and corrugated gasket clamping plated film high reflective mirror respectively, spherical pad adds one deck annular shim again seal for cavity, simultaneously cavity outermost loads one piece of piece of stainless steel with optical window and seals, and adopts M6 stud to lock.Due to rigidity and the sealing of metal, this structure can be applicable to work in the vibration environment such as ocean, aviation, in breast rail process, thus have stability very reliably.In addition, the inside surface of sample chamber adopts special plated film technology, can effectively prevent the VOCs in breathing gas or air or other molecules from remaining, and can ensure that the long-term stability of cavity is run.
(6) chamber mirror life system
1) high pure nitrogen or dry air enter sample chamber by the air intake opening near chamber mirror, produce airflow scouring effect, constantly extracted out by intracavity gas by vacuum pump near cavity mirror face.The flow velocity that gas enters cavity is controlled by reduction valve.
2) meanwhile, the ring-type heating plate being attached to cavity two ends heats cavity mirror end (small size place), promotes the volatilization of the VOCs molecule of cavity mirror face adventitious deposit, is finally washed air-flow and takes cavity out of.Control system will ensure that heating-up temperature is no more than 60 DEG C.This functional device, without the need to frequent unlatching, only needs the maintenance carrying out increasing the service life when instrument long-time running.
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (7)
1. the CRDS acetone scentometer for non-invasive measurement blood ketone body levels, it is characterized in that comprising: optical table part and electronic control part, wherein optical table part comprises laser instrument, gas sample chamber, detector and optical resonator, and optical resonator two ends are two panels high reflectivity mirror; Electronic control part comprises laser controlling power supply, vacuum pump, oscillograph and computing machine.
2. a kind of CRDS acetone scentometer for non-invasive measurement blood ketone body levels according to claim 1, it is characterized in that described laser instrument is a Q-switch Nd:YAG pulsed laser, output wavelength is 266nm, is made up of control power supply and laser head two parts; The repetition frequency of described control Energy control output laser pulse changes in the scope of 1KHz to 100KHz, and exports a synchronizing signal with each laser pulse.
3. a kind of CRDS acetone scentometer for non-invasive measurement blood ketone body levels according to claim 1, it is characterized in that described gas sample chamber is circular stainless-steel tube material, length is 430mm, internal diameter 20mm, its two ends are equipped with a pair catoptron fixed support, for stationary mirror; Described catoptron fixed support is furnished with three micrometer adjusting screws, the angle of fine setting catoptron; Described catoptron is a pair high reflectivity mirror, be assemblied in described catoptron fixed support respectively, form a stable resonator cavity, high reflection mirror two sides adopts spherical pad and corrugated gasket clamping plated film high reflective mirror respectively, spherical pad adds one deck annular shim again seal for cavity, simultaneously cavity outermost loads one piece of piece of stainless steel with optical window and seals, and adopts M6 stud to lock; The reflecting surface of described catoptron directly contacts with gaseous sample, together constitutes the good gas sample chamber of a sealing with stainless-steel tube.
4. a kind of CRDS acetone scentometer for non-invasive measurement blood ketone body levels according to claim 1, it is characterized in that described gas sample chamber there are three gas IO interface, connect miniature pressure transducer, vacuum air pump and a T-valve respectively; Described T-valve connects the gas cylinder that nitrogen is housed and the Storage Time in Gas Collecting Bag that gaseous sample is housed respectively.
5. a kind of CRDS acetone scentometer for non-invasive measurement blood ketone body levels according to claim 4, is characterized in that cavity-type BPM signal is detected by a miniature photomultiplier, its diameter diameter of phi=16mm, length
l=12mm, described laser instrument exports 266nm laser and is obtained to its two frequency multiplication by 532nm optical pumping, adds a slice 266nm bandpass filter in photomultiplier front end.
6. a kind of CRDS acetone scentometer for non-invasive measurement blood ketone body levels according to claim 1, is characterized in that this optical table part is fixed in one piece of 600mm × 250mm × 10mm(length and width thick) aluminium sheet on, can move integrally; This optical table part cargo shipment is in an internal diameter Φ
=200mm, length
l=in the cartridge type pressure-resistant seal cabin of 600mm.
7., for a CRDS acetone measurement method for non-invasive measurement blood ketone body levels, it is characterized in that adopting the analyser described in any one of claim 1-6 to measure gaseous sample, comprise the following steps:
Step 1, first uses nitrogen to rinse gas sample chamber; After flushing completes, in sample chamber, pressure remains on low pressure 5Torr, and now sample indoor gas is nitrogen, measures its cavity-type BPM time τ 0;
Step 2, is filled into nitrogen in sample chamber, makes pressure rise to 750Torr, measures its ring-down time; Step 3, repeats step 1,2, measures 2 ~ 3 times, gets the mean value of measurement result as ring-down time value τ 1;
Step 4, reduces to 5Torr by pressure in sample chamber, is filled with gaseous sample to be measured, until pressure rises to 750Torr in sample chamber, measures its cavity-type BPM time;
Step 5, extracts out gas to be measured, and uses nitrogen to carry out flushing 3 ~ 4 times to gaseous sample chamber, and after having rinsed, sample indoor gas is nitrogen, and pressure is 5Torr;
Step 6, repeats step 4,5, the cavity-type BPM time of measurement same gaseous sample to be measured 2 ~ 3 times, averages as the cavity-type BPM time τ 2 of certain gaseous sample under this condition:
Step 7, repeats step 4,5,6, measures the cavity-type BPM time τ 3, τ 4 of other gaseous samples to be measured ...;
Step 8, after having tested, rinses gas sample chamber again;
Wherein, the instrument of expiratory air sample collection is that respirator mask and gas sample sack couple together by use retaining valve, during collected specimens, face shield is covered and shut up and nose areas, expiratory air passes through this retaining valve by unidirectional, thus in collected sample sack, and by this retaining valve, person under inspection still can freely breathe.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107463766A (en) * | 2017-06-23 | 2017-12-12 | 深圳市中识创新科技有限公司 | Generation method, device and the computer-readable recording medium of blood glucose prediction model |
| CN107655855A (en) * | 2017-11-13 | 2018-02-02 | 中国医学科学院生物医学工程研究所 | A kind of full-automatic haldane-Henderson gas analysis apparatus based on cavity ring down spectroscopy technology |
| CN108680748A (en) * | 2018-05-24 | 2018-10-19 | 歌尔股份有限公司 | Blood-sugar detecting instrument based on acetone sensor and its detection method |
| TWI816666B (en) * | 2017-04-06 | 2023-10-01 | 日商明治股份有限公司 | Monitoring device for the effectiveness of the ketogenic diet and management method for the ketogenic diet intake |
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| CN107655855A (en) * | 2017-11-13 | 2018-02-02 | 中国医学科学院生物医学工程研究所 | A kind of full-automatic haldane-Henderson gas analysis apparatus based on cavity ring down spectroscopy technology |
| CN108680748A (en) * | 2018-05-24 | 2018-10-19 | 歌尔股份有限公司 | Blood-sugar detecting instrument based on acetone sensor and its detection method |
| CN108680748B (en) * | 2018-05-24 | 2021-02-26 | 潍坊歌尔微电子有限公司 | Blood glucose detector based on acetone sensor and detection method thereof |
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