A kind of real-time monitoring system and monitoring method of amniotic fluid embolism serological index
Technical field
The present invention relates to a kind of real-time monitoring systems and monitoring method of amniotic fluid embolism serological index.
Background technology
Amniotic fluid embolism is a kind of rare but extremely hazardous obstetric conditions, and morbidity is unexpected, and progression of the disease is swift and violent, and symptom is fierce
Danger, within morbidity a few minutes, patient can be critically ill.Therefore, relevant life is paid close attention in puerpera's production process
Sign, and when finding amniotic fluid embolism sign, emergent management is carried out in time, it is the key that rescue amniotic fluid embolism patient.However, mesh
Preceding medical staff can only just rescue when observing amniotic fluid embolism related symptoms, this undoubtedly shortens medical staff and locates to the ill
The time of reason increases the difficulty of rescue.
If can be detected to certain indexs related with amniotic fluid embolism in puerpera's body, just sent out when its appearance is abnormal pre-
Alert signal, reminds medical staff to carry out the preparation of reply amniotic fluid embolism, medical staff will be made to discover potential danger, get the jump on morbidity
It is preceding that patient is unfolded to give treatment to, the life of the puerpera of more burst amniotic fluid embolisms can be retrieved, or even them is allowed to obtain preferably
Prognosis.In recent years, it is checked for the specificity of amniotic fluid embolism related biochemical indicator, also becomes a kind of and amniotic fluid embolism is assisted
The means of diagnosis.Zinc coproporphyrin-I (ZnCp-I) is one of which amniotic fluid embolism correlation marker, it is more be present in amniotic fluid and
In meconium, concentration is extremely low in the blood of normal person, and when amniotic fluid blood vessel damaged at uterus enters blood circulation,
The concentration of ZnCp-I will significantly rise in blood.Therefore, ZnCp-I concentration in puerpera's blood is measured, has become needle at present
To a kind of aided diagnosis method of amniotic fluid embolism.At present for the detection method of ZnCp-I in blood, carried out to blood sample
After centrifugation and high performance liquid chromatography separation, carrying out the detection of induced fluorescence method, (a length of 405nm of excitation light wave detects fluorescence wave
A length of 580nm), single measurement sampling quantity is big, time-consuming, and tedious process, is not matched with the requirement monitored closely.Cause
This, it would be desirable to develop a kind of novel monitoring system, have single measurement sampling quantity it is low, take short, Highgrade integration, with
And the advantages of can taking multiple measurements, to adapt to the requirement monitored closely to ZnCp-I in blood.
Invention content
It is an object of the invention to overcome shortcoming and defect in the prior art, a kind of amniotic fluid embolism serological index is provided
Real-time monitoring system and monitoring method, ZnCp-I concentration indexs in its blood are supervised closely in puerpera's production process
It surveys.When detecting that the value of ZnCp-I in blood is more than secure threshold or excessively high speedup, alarm signal is just sent out, allows medical care people
Member pays close attention to the situation, and carries out emergent management, is gained time with being reached for puerpera and medical staff, improves the mesh of salvage success rate
's.
The present invention is achieved by the following technical solutions:A kind of real-time monitoring system of amniotic fluid embolism serological index,
It is characterized by comprising:Sampler, 405nm excitation light sources array, micro-fluidic chip detection platform, 580nm filter layers, double grid
Aurora thin film transistor array and signal processing circuit.
Bigrid photo tft is a kind of field-effect transistor, is a kind of sensor devices, the light intensity sensed
Variation causes its threshold voltage to change, so that the electric current between source-drain electrode changes, thus can believe light intensity
Number be converted into electric signal, have the characteristics that it is light, energy saving, be easily integrated.The bigrid optoelectronic film that WANG et al. is proposed is brilliant
Body pipe " intelligence " dot structure by sensing separate in traditional light detection pixel circuit, storage and reads three parts progress
It is integrated, sensing, storage and reading to detecting signal are completed by a bigrid photo tft, have pixel circuit simple
Single, saving space, low detection limit, low noise, simplifies preparation and integrated technique, reduces the advantages that production cost high sensitivity, ginseng
See reference document:K.Wang,H.Ou,J.Chen,"Dual-Gate Photosensitive Thin-Film Transistor-
Based Active Pixel Sensor for Indirect-Conversion X-Ray Imaging,"IEEE
Transactions on Electron Devices,vol.62,no.9,pp.2894-2899,2015.
We are integrated in miniflow using bigrid photo tft as core sensing element, by array way arrangement
Below the detection zone for controlling chip, 580nm filter layers are laid in its photosensitive gate surface, and lays 405nmLED above detection zone and swashs
Radiant array carries out induced fluorescence detection, it is intended to be sampled low, time-consuming short, frequency to the ZnCp-1 concentration in puerpera's blood plasma
The high real-time measurement of rate.Preferably, we select highly sensitive bigrid photo tft, such as " intelligence " dot structure
Bigrid photo tft.
Further, the sampler is connected with the micro-fluidic chip detection platform, the 405nm excitation light sources battle array
Row, micro-fluidic chip detection platform, 580nm filter layers and bigrid photo tft array are arranged from top to bottom successively.
580nm filter layers are layed in the photosensitive gate surface of the bigrid photo tft array, the signal processing circuit
It can be used for handling current changing signal between the drain electrode of the bigrid photo tft array.
Further, the 405nm excitation light sources array is 405nm laser source arrays or 405nm LED light source arrays.
As an implementation, the micro-fluidic chip detection platform includes blood sample intake passage, the interim runner of blood
With blood sprue, reference background signal acquisition area, waste liquid pool, real-time blood plasma optical detection zone and blood backflow channel.It is described
The interim runner of blood and blood sprue are gone out by blood sample intake passage branch and controlled by micro-valve respectively to be opened and closed, the back of the body
Scape reference signal obtains area both ends and is equipped with microfiltration membranes, and is connect respectively with the interim runner of the blood, the waste liquid pool with it is described
Blood interim runner connection, the real-time blood plasma optical detection zone both ends are equipped with microfiltration membranes, and respectively with the blood sprue
Connection, the blood backflow channel is located at the rear end of the blood sprue, and is controlled and opened and closed by micro-valve.
Further, reference background signal acquisition area is by the antibody fixed area and temporary detecting district's groups that set gradually
At being fixed with anti-ZnCp-I monoclonal antibodies in the antibody fixed area.
As another embodiment, the micro-fluidic chip detection platform includes blood sample intake passage, region of plasma, antibody
Fixed area, antibody-antigene dissociation solution input channel and waste liquid pool.Described region of plasma one end be equipped with microfiltration membranes, with the blood into
Sample channel connects, and is fixed with anti-ZnCp-I monoclonal antibodies in the antibody fixed area, is connected to the region of plasma other end, described anti-
Body-antigen dissociation solution input channel is connect with the antibody fixed area by micro-valve, the waste liquid pool and blood sample intake passage
Rear end is connected to the antibody fixed area.
The present invention also provides a kind of method of real-time of amniotic fluid embolism serological index, it is characterised in that including following several
A step:(1) micro blood is taken out of puerpera body by sampler, injects micro-fluidic chip detection platform, by ZnCp-I from
It is separated in blood;(2) it above micro-fluidic chip detection platform, is irradiated through micro-fluidic using 405nm excitation light source arrays
The ZnCp-I that chip detection platform is separated makes it generate fluorescence;(3) above-mentioned fluorescence is detected through the micro-fluidic chip again
580nm filter layers below platform;(4) only have the part that wavelength is 580nm in fluorescence to penetrate, and be irradiated into the 580nm filters
On bigrid photo tft array below photosphere;(5) it is brilliant to handle the bigrid optoelectronic film for signal processing circuit
Current changing signal between the drain electrode of body pipe array, and the anti-concentration for pushing away ZnCp-I in puerpera's blood.
As an implementation, puerpera's blood enters micro-fluidic chip by blood sample intake passage in described (1) step
Detection platform, and enter blood sprue, a channel for only allowing blood plasma to flow through is separated by microfiltration membranes, into real-time blood plasma
Optical detection zone does not detach and purifies to the blood plasma flowed through in the real-time blood plasma optical detection zone, directly subsequently walked
Rapid detection, the blood plasma detected converges through the blood of microfiltration membranes and blood sprue again returns to human body through blood return flow line
It is interior.But the disadvantage is that may have other materials (hereinafter referred to as impurity) can be under 450nm exciting lights photograph in addition to ZnCp-I in blood plasma
Generate 580nm fluorescence.
Further, a small amount of puerpera's blood is first taken to enter micro-fluidic chip by blood sample intake passage before (1) step
Detection platform is introduced into the interim runner of blood, separates a channel for only allowing blood plasma to flow through by microfiltration membranes, joins into background
Signal acquisition area is examined, all ZnCp-I in blood plasma are removed, to eliminating blood plasma 405nm excitation light sources and the 580nm of ZnCp-I
Filter layer carries out induced fluorescence detection, obtains reference background signal strength, while the part blood plasma is directly entered through microfiltration membranes
Waste liquid pool;Then each step for carrying out the method for real-time of amniotic fluid embolism serological index according to any one of claims 8 again, in step
Suddenly measured total signal strength is subtracted into reference background signal strength, ZnCp- as to be measured when (5) signal processing circuit calculates
The fluorescence intensity of I, to the anti-concentration for pushing away ZnCp-I in puerpera's blood.
As another embodiment, puerpera's blood enters micro-fluidic core by blood sample intake passage in (1) step
Piece detection platform, after isolating blood plasma with microfiltration membranes, into region of plasma, then blood plasma passes through antibody fixed area so that determinand
Matter ZnCp-I is fixed on antibody fixed area, and carries out subsequent step detection in antibody fixed area, and blood after testing is directly entered
Antibody-antigene dissociation solution input antibody fixed area is made antibody be regenerated, to carry out down by waste liquid pool before detect next time
One-time detection enters waste liquid pool with complete antibody-antigene dissociation solution.
The real-time monitoring system and monitoring method of the amniotic fluid embolism serological index of the present invention, for amniotic fluid embolism correlation mark
Object --- zinc coproporphyrin-I (ZnCp-I) is monitored note in real time in puerpera's blood plasma, and it is low, time-consuming to have single measurement sampling quantity
It is short, Highgrade integration, and multiple repairing weld can be carried out, repeatedly the advantages of measurement, ZnCp-I in blood is supervised in adaptation closely
The requirement of survey.The real-time monitoring system of the amniotic fluid embolism serological index of the present invention, not to the Monitoring lower-cut of ZnCp-I in blood
Higher than Plasma 1.6nmol/L, be conducive to carry out auxiliary diagnosis using ZnCp-I in blood.
Description of the drawings
Fig. 1 is the structural schematic diagram of the real-time monitoring system of the amniotic fluid embolism serological index of the present invention.
Fig. 2 is a kind of embodiment structure signal of the real-time monitoring system of the amniotic fluid embolism serological index of the present invention
Figure.
Fig. 3 be amniotic fluid embolism serological index of the present invention real-time monitoring system in micro-fluidic chip detection platform one kind
Embodiment structure schematic diagram.
Fig. 4 be amniotic fluid embolism serological index of the present invention real-time monitoring system in micro-fluidic chip detection platform it is another
Kind embodiment structure schematic diagram.
Wherein, each reference numeral expression is meant that:
1- samplers, 2-405nm excitation light source arrays, 3- micro-fluidic chip detection platforms, 31- blood sample intake passages,
The interim runner of 32- blood, 320- reference background signal acquisitions area, 321- antibody fixed areas, 322- temporary detectings area, 33- blood
Sprue, the real-time blood plasma optical detection zones 330-, 34- waste liquid pools, 35- blood backflows channel, 36- micro-valves, 37- microfiltration membranes;
31 '-blood sample intake passages, 32 '-region of plasma, 33 '-antibody fixed areas, 34 '-waste liquid pools, the input of 38 '-antibody-antigene dissociation solutions
Channel.
Specific implementation mode
Hereinafter, preferred embodiments of the present invention will be described with reference to the accompanying drawings, it should be understood that preferred reality described herein
Apply example only for the purpose of illustrating and explaining the present invention and is not intended to limit the present invention.
Embodiment 1
Referring to Fig. 1, it is the structural schematic diagram of the real-time monitoring system of the amniotic fluid embolism serological index of the present invention.Sheep
The real-time monitoring system of water embolism serological index includes sampler 1,405nm excitation light sources array 2, micro-fluidic chip detection
Platform 3,580nm filter layers 4, bigrid photo tft array 5 and signal processing circuit (not shown).Sampling dress
It sets 1 with micro-fluidic chip detection platform 3 to be connected, 405nm excitation light sources array 2, micro-fluidic chip detection platform 3,580nm filter
Layer 4 and bigrid photo tft array 5 are arranged from top to bottom successively, and signal processing circuit is for handling the bigrid
Current changing signal between the drain electrode of photo tft array.
Preferably, bigrid photo tft array 5 can be the bigrid optoelectronic film of " intelligence " dot structure
Transistor, in bibliography:K.Wang,H.Ou,J.Chen,"Dual-Gate Photosensitive Thin-Film
Transistor-Based Active Pixel Sensor for Indirect-Conversion X-Ray Imaging,"
It is mentioned in IEEE Transactions on Electron Devices, vol.62, no.9, pp.2894-2899,2015.
As an implementation, such as Fig. 2,405nm excitation light sources array 2 is 405nm LED light source arrays, by LED light
Array is obtained through 405nm filter coatings 6.405nm excitation light sources array 2 can also be 405nm laser source arrays.
Such as Fig. 3, micro-fluidic chip detection platform 3 includes blood sample intake passage 31, the interim runner 32 of blood and blood mainstream
Road 33, reference background signal acquisition area 320, waste liquid pool 34, real-time blood plasma optical detection zone 330 and blood backflow channel 35.Blood
The interim runner 32 of liquid and blood sprue 33 are gone out by 31 branch of blood sample intake passage and controlled by micro-valve 36 respectively to be opened and closed, background
Reference signal obtains 320 both ends of area and is equipped with microfiltration membranes 37, and is connect respectively with the interim runner of blood 32, and waste liquid pool 34 faces with blood
Shi Liudao 32 is connected to, and real-time 330 both ends of blood plasma optical detection zone are equipped with microfiltration membranes 37, and are connect respectively with blood sprue 33,
Blood backflow channel 35 is located at the rear end of blood sprue 33, and is controlled and opened and closed by micro-valve 36.Reference background signal acquisition area 320
It is made of the antibody fixed area 321 and temporary detecting area 322 that set gradually, it is mono- that anti-ZnCp-I is fixed in antibody fixed area 321
Clonal antibody.
Embodiment 2
Referring to Fig. 1, the real-time monitoring system of amniotic fluid embolism serological index includes sampler 1,405nm excitation light sources
Array 2, micro-fluidic chip detection platform 3,580nm filter layers 4, bigrid photo tft array 5 and signal processing
Circuit (not shown).Sampler 1 is connected with micro-fluidic chip detection platform 3,405nm excitation light sources array 2, micro-fluidic chip
Detection platform 3,580nm filter layers 4 and bigrid photo tft array 5 are arranged from top to bottom successively, signal processing electricity
Current changing signal between drain electrode of the road for handling the bigrid photo tft array.
Such as Fig. 4, micro-fluidic chip detection platform 3 include blood sample intake passage 31 ', region of plasma 32 ', antibody fixed area 33 ',
Antibody-antigene dissociation solution input channel 38 ' and waste liquid pool 34 '.32 ' one end of region of plasma is equipped with microfiltration membranes 37, logical with blood sample introduction
Road 31 ' connects, and is fixed with anti-ZnCp-I monoclonal antibodies in antibody fixed area 33 ', is connected to the 32 ' other end of region of plasma, antibody-
Antigen dissociation solution input channel 38 ' is connect with antibody fixed area 33 ' by micro-valve 36, waste liquid pool 34 ' and blood sample intake passage 31 '
Rear end be connected to antibody fixed area 33 '.
Embodiment 3
It please refers to Fig.1, Fig. 3, the method for real-time of amniotic fluid embolism serological index of the invention, including following step
Suddenly:(1) micro blood is taken out of puerpera body by sampler 1, injection micro-fluidic chip detection platform 3, by ZnCp-I from blood
It is separated in liquid;(2) it above micro-fluidic chip detection platform 3, is irradiated through micro-fluidic core using 405nm excitation light source arrays
The ZnCp-I that piece detection platform 3 is separated makes it generate fluorescence;(3) above-mentioned fluorescence is detected through the micro-fluidic chip again
The 580nm filter layers 4 of 3 lower section of platform;(4) only have the part that wavelength is 580nm in fluorescence to penetrate, and be irradiated into the 580nm
On the bigrid photo tft array 5 of 4 lower section of filter layer;(5) it is thin to handle the bigrid photoelectricity for signal processing circuit
Current changing signal between the drain electrode of film transistor array 5, and the anti-concentration for pushing away ZnCp-I in puerpera's blood.
Wherein, puerpera's blood enters micro-fluidic chip detection platform 3, micro-valve by blood sample intake passage 31 in (1) step
36 open and feed them into blood sprue 33, and separating one by microfiltration membranes 37 only allows the channel flowed through of blood plasma, into real-time
Blood plasma optical detection zone 330 does not detach and purifies to the blood plasma flowed through in real-time blood plasma optical detection zone 330, directly carries out
Subsequent (2) (3) (4) (5) step detects, and the blood plasma detected penetrates microfiltration membranes 37 again and the blood of blood sample intake passage 31 converges
It flows through blood backflow channel 35 and returns into the human body.
Embodiment 4
It please refers to Fig.1, Fig. 3, the method for real-time of amniotic fluid embolism serological index of the invention, the present embodiment is as real
The optimal enforcement example for applying example 3 further includes prior acquisition impurity fluorescence signal intensity, as reference background signal, then again
Carry out the real-time monitoring of amniotic fluid embolism serological index.It comprises the concrete steps that:
A small amount of puerpera's blood is first taken to enter micro-fluidic chip detection platform 3 by blood sample intake passage 31, micro-valve 36 is opened
It is introduced into the interim runner 32 of blood, a channel for only allowing blood plasma to flow through is separated by microfiltration membranes 37, believes into reference background
Number obtain area 320, antibody fixed area 321 and temporary detecting area 322 are sequentially entered, to eliminating the only impure of all ZnCp-I
Blood plasma in temporary detecting area 322 by induced fluorescence detection, obtain reference background signal strength, while the part blood plasma penetrates
Microfiltration membranes are directly entered waste liquid pool;Then each step of the method for real-time of the amniotic fluid embolism serological index of embodiment 3 is pressed again
It is rapid to carry out, measured total signal strength is subtracted into reference background signal strength when step (5) signal processing circuit calculates, as
The fluorescence intensity of ZnCp-I to be measured, to the anti-concentration for pushing away ZnCp-I in puerpera's blood.
Embodiment 5
It please refers to Fig.1, Fig. 4, the method for real-time of amniotic fluid embolism serological index of the invention, including following step
Suddenly:(1) micro blood is taken out of puerpera body by sampler 1, injection micro-fluidic chip detection platform 3, by ZnCp-I from blood
It is separated in liquid;(2) it above micro-fluidic chip detection platform 3, is irradiated through micro-fluidic core using 405nm excitation light source arrays
The ZnCp-I that piece detection platform 3 is separated makes it generate fluorescence;(3) above-mentioned fluorescence is detected through the micro-fluidic chip again
The 580nm filter layers 4 of 3 lower section of platform;(4) only have the part that wavelength is 580nm in fluorescence to penetrate, and be irradiated into the 580nm
On the bigrid photo tft array 5 of 4 lower section of filter layer;(5) it is thin to handle the bigrid photoelectricity for signal processing circuit
Current changing signal between the drain electrode of film transistor array 5, and the anti-concentration for pushing away ZnCp-I in puerpera's blood.
Wherein, puerpera's blood enters micro-fluidic chip detection platform 3 by blood sample intake passage 31 ' in (1) step, and use is micro-
After filter membrane 37 isolates blood plasma, into region of plasma 32 ', then blood plasma passes through antibody fixed area 33 ' so that test substance ZnCp-I
It is fixed on antibody fixed area 33 ', and subsequent induced fluorescence detection is carried out in antibody fixed area 33 ', blood after testing is direct
Into waste liquid pool 34 ', before detect next time, antibody is set to obtain again antibody-antigene dissociation solution input antibody fixed area 33 '
It is raw, to be detected next time, enter waste liquid pool 34 ' with complete antibody-antigene dissociation solution.
The invention is not limited in the above embodiments, if the various changes or deformation to the present invention do not depart from the present invention
Spirit and scope, if these changes and deformation belong within the scope of the claim and equivalent technologies of the present invention, then this hair
It is bright to be also intended to comprising these changes and deformation.