Invention content
In order to solve the above technical problem, the present invention provides biomarker in a kind of quick, accurate acquisition determinand is dense
Biological marker object detecting method, the apparatus and system based on surface plasma resonance technology of degree.
The used to solve above-mentioned technical problem technical solution of the present invention is:Life based on surface plasma resonance technology
Object marker detection method, includes the following steps:
S1, optical receiver module receive the reflected beams, and set the initial position of its spectrum received, record light-receiving mould
Block exports the initial value of electric signal;
Spectral position when S2, the adjusting of spectral position regulating device have determinand on optical receiver module, moves it to just
Beginning position;
S3, control module calculate biomarker concentration in detectable substance according to the amount of movement of the spectrum on optical receiver module.
For the biological marker object detecting method based on surface plasma resonance technology above-mentioned in the present invention, as into one
The setting of step further includes step S0 before step S1, assembles the light beam after reflection, is sent to light later
Receiving module.
For the biological marker object detecting method based on surface plasma resonance technology above-mentioned in the present invention, as into one
The setting of step before step S0, further includes step S00, the reflected beams at sensor chip is carried out primary event.
Biomarker detecting system based on surface plasma resonance technology, the biomarker detecting system include
Optical receiver module, control module, spectral position regulating device and power module,
The optical receiver module is electrically connected with the control module, for receiving the reflected beams at sensing chip, and
Corresponding output electric signal, control module is sent to by electric signal;
The spectral position regulating device is electrically connected with the control module, the power module, for receiving electricity
The current information of source module and the position for changing the spectrum on the optical receiver module, while the current information is sent to
Control module;
The power module is electrically connected with the control module, the spectral position regulating device, for receiving
The instruction of the control module, according to described instruction into the spectral position regulating device input current;
The control module for recording the change in electric information on optical receiver module, and issues instructions to power supply
Module, and the current information that recording power module is passed through to spectral position regulating device, by its electricity with optical receiver module output
Signal contrast obtains the biomarker concentration information in detectable substance.
For the biomarker detecting system based on surface plasma resonance technology above-mentioned in the present invention, as
The further setting of optical receiver module, the optical receiver module include the first optical receiver module, the second optical receiver module and
Third optical receiver module.
For the biomarker detecting system based on surface plasma resonance technology above-mentioned in the present invention, as
A kind of specific embodiment of spectral position regulating device, the spectral position regulating device include batten, mirror, transmission
Mechanism, coil, magnet and pedestal, the mirror setting are fixed on described on batten at the transmission mechanism one
On batten, another place is fixed on the pedestal, and the coil is fixed on the transmission mechanism, and the magnet leans on
The nearly coil so that it can pass through the transmission mechanism band under the action of the magnet after being powered into the coil
Move the batten movement.
For the biomarker detecting system based on surface plasma resonance technology above-mentioned in the present invention, as
A kind of optional embodiment of its transmission mechanism, the transmission mechanism include intermeshing rack and pinion, the tooth
Item is fixed on the batten, and the gear is rotatably fixed on the pedestal.
For the biomarker detecting system based on surface plasma resonance technology above-mentioned in the present invention, as
A kind of optional embodiment of its transmission mechanism, the transmission mechanism include intermeshing worm gear and worm screw, the snail
Bar is fixed on the batten, and the worm gear is rotatably fixed on the pedestal.
For the biomarker detecting system based on surface plasma resonance technology above-mentioned in the present invention, described
Balancing device is additionally provided on transmission mechanism, the balancing device is distributed in the both sides of the transmission mechanism with the coil.
For the biomarker detecting system based on surface plasma resonance technology above-mentioned in the present invention, the light
Spectral position regulating device further includes spring, and the batten is by the spring supporting.
The technique effect that the present invention is brought is:Use the biological marker analyte detection side based on surface plasma resonance technology
Method receives special spectrum information using optical receiver module, forms spectrum, and set dead-center position, and adjustment determinand is in light-receiving
Spectral position in module calculates the concentration value information of the biomarker in determinand by regulated quantity correspondence, can
Easily and fast, the concentration of the biomarker in determinand is accurately detected;Detecting system in the present invention, including control
Module, optical receiver module, spectral position regulating device and power module, wherein, optical receiver module is used to receive at sensing chip
The reflected beams, after forming spectrum above, export electric signal, and electric signal be sent to control module;Power module receives
The control of control module, and the input current into spectral position regulating device, spectral position regulating device receive power module
Electric current simultaneously operates the position for changing the spectrum on optical receiver module, while the size of current information of its own is transferred to control mould
Block;Change in electric information on control module record optical receiver module, and instructed according to this delivering to power module, control
Power module processed makes it be passed through electric current into spectral position regulating device, and recording power module is led into spectral position regulating device
The electric current entered, and the electric signal comparing calculation that it is sent out with optical receiver module, obtain the biological marker in detected substance
The concentration information of object;The spectral position adjusting apparatus for biological marker analyte detection in the present invention, passes through the coil that can be powered
With the active force of magnet, and pass through transmission mechanism drive mirror motion, so as to adjust the position of the spectrum on optical receiver module, knot
Structure is simple, and cost of manufacture is cheap, and very easy to use.
Specific embodiment
Purpose, technical scheme and advantage to make the embodiment of the present invention are clearer, below in conjunction with the embodiment of the present invention
In attached drawing, the technical solution in the embodiment of the present invention is explicitly described, it is clear that described embodiment be the present invention
Part of the embodiment, instead of all the embodiments.Based on the embodiments of the present invention, those of ordinary skill in the art are not having
All other embodiments obtained under the premise of creative work are made, shall fall within the protection scope of the present invention.
Fig. 1 be the present invention relates to surface plasma resonance technology fundamental diagram, be the prior art, such as figure institute
Show, using the process of surface plasma resonance technology detection biomarker concentration, first, 300 He of flow channel is set
Sensing chip 400 sets one layer of golden film on sensing chip 400, and the one side part that sensing chip 400 is made to be equipped with golden film is located at
In flow channel 300 so that the object to be detected flowed into flow channel 300 can touch the sensing chip 400 with golden film,
During measurement, the object to be detected with biomarker is passed through flow channel 300 so that object to be detected is contacted with sensing chip,
One layer of antibody molecule is modified in reaction interface in advance, after target antigen and antibody identification, the refractive index of golden film surface dielectric
It changes, SPR resonance angles can change with the change of refractive index, the variation and the life with being incorporated in metal surface of refractive index
The variation of object macromolecular quality is directly proportional, and the size of formant displacement will reflect the change for being fixed on metal surface biotinylated molecular weight
Change, and then realize immunoassay.In Fig. 1, light beam is sent out by light source 600, be irradiated on sensing chip 400, after its reflection
By optical detection unit 700 (present invention in will by the use of optical receiver module be used as optical detection unit) reception, pass through optical detection list
Member 700 senses the variation of the beam information received by it, obtains the change information and object biomarker concentration to be detected
Correspondence finally obtains biomarker concentration value in object to be detected from the change information.For light source 600, can be used
Monochromatic source, such as infrared beams light source, effect are preferable.
Work flow diagram such as Fig. 2 of the biological marker object detecting method based on surface plasma resonance technology in the present invention
It is shown, include the following steps:
S1, optical receiver module receive the reflected beams, and set the initial position of its spectrum received, record light-receiving mould
Block exports the initial value of electric signal;
Spectral position when S2, the adjusting of spectral position regulating device have determinand on optical receiver module, moves it to just
Beginning position;
S3, control module calculate biomarker concentration in detectable substance according to the amount of movement of the spectrum on optical receiver module.
Further, the present invention can also carry out the above process perfect, for this purpose, providing second of more perfect implementation
Example, work flow diagram is as shown in figure 3, include the following steps:
S00, the reflected beams at sensor chip are subjected to primary event;
S0, the light beam after reflection is assembled, is sent to optical receiver module later;
S1, optical receiver module receive the reflected beams, and set the initial position of its spectrum received, record light-receiving mould
Block exports the initial value of electric signal;
Spectral position when S2, the adjusting of spectral position regulating device have determinand on optical receiver module, moves it to just
Beginning position;
S3, control module calculate biomarker concentration in detectable substance according to the amount of movement of the spectrum on optical receiver module.
The present invention is on the basis of surface plasma resonance technology, first using the object for not containing biomarker to be measured
Matter after homogeneous beam irradiates, receives light beam with optical receiver module, is set as initial position at this time, records its output electricity
The initial value of signal as the initial position value of spectrum, is treated detectable substance and is measured later, because containing biology mark in determinand
Will object, the position of spectrum and its dark space on optical receiver module change, the telecommunications exported on corresponding optical receiver module
Number size also accordingly change, by adjusting the position of spectrum, may be such that the electric signal size exported on optical receiver module
Identical during with initial position, for the adjusting process of spectral position, different adjusting methods can all be realized, but each adjusting method
Regulated quantity there are one-to-one relationships with the amount of movement of spectral position, the biomarker in detectable substance can be calculated with this
Concentration.
Under the principle of above-mentioned detection process, what setting one on the basis of the above of the invention helped out is used for biology
The spectral position adjusting apparatus of marker detection, for adjust reflected light harness optical detection unit 700 (in the present invention
Optical receiver module is corresponding) on position, can react the concentration information of biomarker in object to be detected to obtain.The device
Overall structure diagram as shown in figure 4, including batten 2, mirror 3, spring 4, gear 7, coil 9 and magnet 10, the one of batten 2
End is fixed in articulated manner, and the other end is fixedly connected with rack 6, and on the side of rack 6, setting is there are one gear 7, gear 7 and
Rack 6 is in meshing state, and gear 7 is rotatably fixed on axis 8, and axis 8 is fixed on stent 11, for convenience in batten 2
Batten 2 can be set as the two parts being fixedly connected by upper stationary rack 6, and a part is straightway 21, and another part is bending segment
22, one end of straightway 21 is fixed by the way of hinged, and the other end is fixedly connected with bending segment 22, and causes straightway 21
(in the majority with acute angle under normal circumstances) is a certain included angle with horizontal direction, mirror 3 is fixed on straightway 21, for reflecting
Infrared light during biomarker is detected, bending segment 22 is in 90 degree of bending-likes, and horizontal component is fixedly connected with straightway,
It is of course also possible to set rack structure in the vertical section, rack and bending segment 22 are arranged to for vertical portion stationary rack 6
In comparison integral structure, sets rack structure in the vertical portion of bending segment 22, that is, the structure for being made of one formula is being made
It can be more convenient when making, install and using.
Rack structure or fixed rack 6 on batten 2 are in meshing state with gear 7, when gear 7 is in the work of external force
During with lower rotation, rack structure or rack 6 on batten 2 are rotated with the rotation of gear 7, so as to which batten 2 be driven to transport
It is dynamic.In order to control/the rotation of adjustment gear 7, the coil 9 of a closure is fixed on gear 7, which will extend gear 7
Ontology, and a distance that extends outwardly, with 9 one fixed magnet 10 of side setting of coil, a part for coil 9 with
Magnet 10 is overlapped, in this way since, when being passed through electric current on coil 9, coil 9 in closed state forms returning for closure
Road, when have in the circuit of this closure electric current by when, its own generates magnetic field under electromagnetic induction effect, what coil 9 generated
The magnetic field of magnetic field and magnet 10 is had an effect power between each other, can be at this point, changing size of current/direction for being passed through in coil 9
Change magnetic field intensity and magnetic direction caused by coil 9, since the size and Orientation in magnetic field caused by magnet 10 is solid
Fixed, therefore, when changing size of current and/or the direction in coil 9, under the action of the magnetic field of magnet 10, coil 9 occurs
Rotation, since coil 9 is integrally fixed on gear 7, when coil 9 starts rotation, gear 7 is as coil 9 rotates and turns
Dynamic, gear 7 is engaged with the rack structure on batten 2 or rack 6, therefore rack structure on batten 2 or rack 6 are with gear 7
Rotation and move (in figure move for vertical direction), final batten 2 can also be moved with the variation of electric current in coil 9, right
In batten 2, due to its straightway 21 be it is fixed in articulated manner, be passed through electric current in batten 2 is with coil 9
Variation and when changing, the straightway 21 of batten 2 will also change therewith with the angle of horizontal direction, and then, be fixed on batten 2
On mirror 3 and horizontal direction angle also just with change, the angle of reflection light above can also change therewith.
As shown in figure 4, in order to further improve the adjusting sensitivity of the horizontal sextant angle of the mirror 3 on batten 2, in batten 2
One spring 4 of upper connection, the other end of spring 4 are fixed, and set an initial position so that spring 4 is whole in the initial position
A device is in a zero, can be by the elastic force of spring 4 so that mirror 3 is more when needing to adjust the horizontal sextant angle of mirror 3
Add and easily return back to initial position.Above-mentioned detailed process is shown as:When being passed through electric current into coil 9, magnetic field is generated in coil,
Under the action of magnet 10, rotated under the active force that coil 9 interacts in magnetic field around axis 8, while gear 7 also begins to rotate, on batten 2
Rack structure or fixed installation rack 6 under the rotation of gear 7 rise/fall, and then drive batten 2 rise overally/under
Drop, when batten 2 begins to ramp up/declines, also begins to stretching/compressing spring 4 simultaneously, when need to make batten 2 and its mirror above
When son 3 returns back to the position of initial position or required setting, size of current or direction in coil 9 are passed through when corresponding change,
For batten 2 when being moved accordingly with the rack structure above it or rack 6, spring 4 can provide convergent force or drawing accordingly
Stretch so that batten 2 can it is sensitiveer under the assistance of the active force of spring 4, quickly return back to initial position or required
Position.
Setting for 4 position of spring, can refer to Fig. 4, will be one end of which is fixed on bending segment 22, and the other end is fixed on phase
The position (such as platform or rack first-class) answered.
In Fig. 4, one end of batten 2 is hingedly fixed, be can be used herein more including hinge, hinged ball etc.
Kind articulated mounting and hinged fixed form need to only ensure that batten 2 can be rotated around supporting point 1 with relatively low frictional force.
As shown in Figure 4, for the shape of magnet 10 is in scheme, in vertical direction, (this direction is intuitive direction in figure, tool
The setting orientation of body material object is not limited thereto) setting magnet 10, and make its N pole and its S poles reasonable layout so that 9 energy of coil
It is enough to be moved between the N poles of magnet 10 and S poles in the sphere of action in 10 magnetic field of magnet, for magnet 10, in order to can
Generate sufficiently strong magnetic field, it is preferred to use neodium magnet can obtain stronger magnetic field, can strength promote be powered after
The movement of coil 9.
Further, as shown in Figure 4, in order to improve stability of the coil 9 on gear 7, and coil 9 is further improved
Adjusting sensitivity, a balancing device 5 is fixed on gear 7, the balancing device 5 be mounted on gear 7 on, position will and line
Circle 9 corresponds to, i.e., so that balancing device 5 and coil 9 are located at the both sides of gear respectively, and the two is made to be located at same level height,
Certain balanced action is played each other, here, can balancing device 5 be arranged to coiled type, can extend its part
Go out gear 7, can so mitigate the weight of balancing device 5, meanwhile, balancing device 5 can also be by its own gravity, in thick stick
Play good balanced action to the position height of coil 9 under bar effect, i.e., when coil 9 by magnet 10 magnetic field force to up/down
When (only referring to orientation in figure, actual direction is without being limited thereto) moves, under the action of balancing device 5,9 need of coil overcome very little
Power can break away from stationary state and be moved, likewise, when that need to adjust coil 9 to initial position, need to only overcome smaller
Resistance can be realized, i.e., the position adjustment to coil 9 can be realized without the electric current that significantly variation is passed through in coil 9.
For the axis 8 in Fig. 4, it can be fixed by stent 11, in the present invention, the fixation end of batten 2, spring
4 fixing end and the bearing of stent 11 are the platform with supporting role, such as:Desk-top workbench or setting
Package unit however, it is also possible to add a rack or shell, is fixed on rack or outer by support platform in rack etc.
On shell.
The spectral position adjusting apparatus for biological marker analyte detection in the present invention, for the turning on axis 8 of gear 7
Dynamic fixed form can be used the prior art and be solved, and gear 7 is sleeved on the outer ring of bearing for example, can be used, makes it can
It is rotated around bearing, then the inner ring of bearing is fixed on axis 8, axis 8 is fixed on stent 11;In addition, gear 7 also can be straight
It connects using Bearing gear, is directly anchored on axis 8;The mode of other existing rotation connections, such as hinged, socket, etc.
Can realize gear 7 it is rotatable it is fixed in the present invention can be within practical range.
With reference to Fig. 4, using incident ray therein as the infrared external reflection light of the detectable substance detected, using its emergent light as light
The light of 12 actual received of receiving module, when need to be adjusted to the dark space position of the spectrum formed on optical receiver module 12,
When further relating to the details of biomarker to obtain, change size of current or/and the direction being passed through in coil 9, close
The intensity in magnetic field caused by the coil 9 of conjunction or/and direction change also with sending, in this way since, under the action of magnet 10,
Coil 9 rotates with moving gear 7 and (is easier the magneticaction in magnet 10 in the balancing brake effect lower coil 9 of balancing device 5
Lower movement), and then gear 7 drives rack structure on batten 2 or rack 6 to move, and batten 2 also begins to move, mirror 3 with it is horizontal
The angle in direction changes with the movement of batten 2, so that the incidence angle for the incident light being irradiated on mirror 3 occurs
Variation, correspondingly, the angle of emergence also changes, the angle that emergent light is irradiated on optical receiver module 12 also changes, therefore
The position of dark space that the infrared ray reflected by detectable substance is formed on optical receiver module 12 can also change, i.e., according to adjustment
The size of electric current or/and direction in coil 9 are passed through, it is corresponding to control the position of dark space formed on optical receiver module 12, pass through
The change of the dark space position and the change for the electric current being passed through in coil 9 obtain required metrical information.
It should be strongly noted that the spectral position adjusting apparatus for biological marker analyte detection in the present invention is implemented simultaneously
Above-mentioned embodiment is not limited to, for example, wherein realizing the tooth on the gear 7 moved of batten 2 and the batten 2 engaged
Structure or rack 6, can by intermeshing turbine, worm screw or the nut of installation can be socketed, screw rod carries out whole replacement,
And the corresponding position on demand by required change is modified, such as worm screw or nut are fixed on batten 2, by snail
Wheel and screw rod are fixed on pedestal, for its of those skilled in the art and the existing machinery field common knowledge of combination
Its field personnel very can readily make above-mentioned variation;Moreover, in the present invention, the position of spring 4 is also not limited to figure
Shown in position, can also be moved near supporting point 1, the function and effect of such spring 4 may be more preferable.
In Fig. 4, the incident ray on mirror 3 is irradiated to from the light reflected at sensing chip 400 in Fig. 1
Beam.The spectral position adjusting apparatus for biological marker analyte detection in the present invention reflects for adjusting at sensing chip 400
And irradiating angle (incidence angle and the angle of emergence) of the light beam come on mirror 3.
The present invention is to set first using containing biomarker concentration in the biomarker concentration for measuring object to be detected
The detectable substance of definite value (may generally be zero), the flow channel 300 being passed into Fig. 1 modify one layer of antibody in reaction interface
Molecule does not have target antigen in object to be detected, and the refractive index of golden film surface dielectric will not change, at this point, by prism 500
Do not become substantially after light beam (generally using monochromatic light, such as infrared beam) outgoing being irradiated to after refraction on sensing chip 400
Change, emergent light is irradiated to optical receiver module 12 after the reflection of mirror 3, and the light with dark space is formed on optical receiver module 12
It composes, optical receiver module 12 exports an electric signal in such cases, and the electric signal is as an initial value (zero), if light-receiving
Dark space position in module 12 shifts, and the intensity of received light changes above, by measuring light-receiving mould
The variation of the electric signal exported on block 12, it can be seen that whether the dark space position of the spectrum formed on optical receiver module 12 changes, from
And learn the presence or absence of the biomarker in detected substance.
After above-mentioned dead-center position determines, the spectrum formed on optical receiver module 12 as shown in Figure 5, it is first can to set this
Beginning position, and determine the intensity of electric signal exported from optical receiver module 12, the electrical signal intensity value as initial position.
After above-mentioned dead-center position determines, when the biomarker concentration to test substance is needed to be detected, it will want
The substance of detection is passed into flow channel 300, due to the antibody molecule on the target antigen and reaction interface in object to be detected
With reference to the refractive index of golden film surface dielectric changes, correspondingly, being irradiated on sensing chip 400 after the refraction of prism 500
Beam exit after also accordingly change so that be irradiated to the spectrum of the light beam on optical receiver module 12 dark space position occur
Change, as shown in Figure 6, wherein Fig. 6 a, Fig. 6 b are respectively the spectrum and its dark space being likely to occur on optical receiver module 12
Situation of movement, since during mirror 3 is adjusted, moving direction of the dark space position on optical receiver module 12 can not be learnt
It is uncertain so that different variations, the telecommunications exported occur for received whole light intensity on optical receiver module 12
Number it can also occur to change accordingly.
A kind of embodiment of the method for biomarker in the above-mentioned object to be detected of detection provided in the present invention is to work as inspection
When measuring the electric signal exported on optical receiver module 12 and the initial position difference of setting, biomarker is used for into Fig. 4
Electric current is passed through in the coil 9 of the spectral position adjusting apparatus of detection, coil 9 is made to generate magnetic field, in magnetic field caused by magnet 10
Under the action of, the rotation of 9 stress of coil and is rotated with moving gear 7, gear 7 drive rack structure on the batten 2 engaged or
Rack 6 drives batten 2 to be rotated centered on its hinged supporting point 1, so as to change the angle of the mirror 3 on batten 2, passes through tune
The angle of whole mirror 3 adjusts the angle for being irradiated to the incident light (shown in Fig. 4) on mirror 3, so as to adjust optical receiver module 12
The position of the dark space of the spectrum of upper formation, when dark space position is adjusted to set dead-center position, record is passed through line at this time
Size of current in circle 9, and by the concentration pair of the biomarker in the size of current being passed through in coil 9 and the substance that is detected
It should get up, you can find the concentration of the biomarker in detected substance.
In the present invention, further, in the angle of above-mentioned adjusting mirror 3 to obtain biomarker in object to be detected
During the corresponding electric current being passed through in coil 9 of concentration, as shown in Figure 6, the light formed on optical receiver module 12
The movement in the position of the dark space of spectrum direction during adjusting it is possible that as shown in wherein a, b, this causes in adjusting process
In the size of electric current that is passed through in coil 9 and/or direction will be difficult to determine, can be by optical receiver module in order to avoid such case
12 be arranged to as shown in Figure 7 it is multiple (for three in scheming, respectively the first optical receiver module 121, the second light-receiving
Module 122 and third optical receiver module 123), mould of the setting positioned at the first intermediate optical receiver module 121 where initial position
During block, i.e. initial position, the dark space of spectrum is on the first optical receiver module 121, at this time on the first optical receiver module 12
The electric signal of output is initial value, and during measurement, when changing the electric current that is passed through in coil 9, the angle of mirror 3 changes, spectrum
The position of dark space may be moved to the second optical receiver module 122 or third optical receiver module 123, and according to acquisition, it is exported above
Electric signal it can be learnt that the mobile message of dark space, so as to judge accordingly the size for the electric current that be passed through in coil 9 and/or
Dark space so as to obtain faster is adjusted to the size of current being passed through in coil 9 needed for initial position, learns detectable substance by direction
The concentration of middle biomarker.
Fig. 8 is the structure diagram of the biomarker detecting system in the present invention, as shown in the figure, it includes control module
13rd, optical receiver module 12, spectral position regulating device 14 and power module 15, wherein, optical receiver module 12 senses for receiving
The reflected beams at chip after forming spectrum above, export electric signal, and electric signal is sent to control module 13;Power supply
Module 15 receives the control of control module 13, and the input current into spectral position regulating device 14, spectral position regulating device
The electric currents of 14 reception power modules 15 simultaneously operate the position for changing the spectrum on optical receiver module 12, while by the electric current of its own
Size information is transferred to control module 13;Change in electric information on the record optical receiver module 12 of control module 13, and according to
This delivering is instructed to power module 15, and control power module 15 makes it be passed through electric current into spectral position regulating device 14,
The electric current that recording power module 15 is passed through into spectral position regulating device, and the electric signal that it is sent out with optical receiver module 12
Comparing calculation obtains the concentration information of the biomarker in detected substance.
Further, in addition the present invention can also set concentration module so that the light beam being irradiated on optical receiver module 12 obtains
With aggregation, optical receiver module 12 is enable preferably to receive light beam.
The specific embodiment of the present invention is explained in detail above in conjunction with attached drawing, but the present invention is not limited to above-mentioned
Embodiment, can also be under the premise of present inventive concept not be departed from the knowledge having in those skilled in the art
Various changes can be made.