CN110133047A - The detection method of detection unit, detection device and memebrane protein diffusion rate - Google Patents
The detection method of detection unit, detection device and memebrane protein diffusion rate Download PDFInfo
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- CN110133047A CN110133047A CN201910464994.5A CN201910464994A CN110133047A CN 110133047 A CN110133047 A CN 110133047A CN 201910464994 A CN201910464994 A CN 201910464994A CN 110133047 A CN110133047 A CN 110133047A
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Abstract
The embodiment of the present invention provides a kind of detection unit, the detection method of detection device and memebrane protein diffusion rate, is related to detection technique field, can continuous, real-time, duplicate detection memebrane protein diffusion rate.A kind of detection unit, comprising: first electrode, p type semiconductor layer, n type semiconductor layer and the second electrode being cascading;The detection unit further includes heat-conducting layer, and the heat-conducting layer is set at an at least side surface for the p type semiconductor layer and the n type semiconductor layer, and is contacted with the p type semiconductor layer and the n type semiconductor layer;The surface far from the p type semiconductor layer and the n type semiconductor layer of the heat-conducting layer is provided with adhesion layer, and the adhesion layer is for making cell adherence on it.
Description
Technical field
The present invention relates to detection technique field more particularly to a kind of detection units, detection device and memebrane protein diffusion rate
Detection method.
Background technique
Albumen contained by biomembrane is memebrane protein.Memebrane protein plays very important in many vital movements of organism
Effect, such as the proliferation and differentiation, energy conversion, signal transduction and matter transportation of cell.
Memebrane protein can move freely in lipid bilayer, have certain fluidity.In the prior art, fluorescent bleach can be passed through
Restore (Fluorescence Photo bleaching Recovery, FPR) technical research memebrane protein mobility.For example, with glimmering
Then signal memebrane protein uses a certain region in laser beam irradiating cell surface, keeps the fluorescent quenching in illuminated area dimmed.Due to film
The mobility of albumen, the brightness that region is quenched can gradually increase again, be finally restored to it is equal with the fluorescence intensity of surrounding, further according to
The speed that fluorescence restores can calculate the diffusion velocity of membrane protein.
The above method needs to carry out fluorescein label to memebrane protein in advance, complicated for operation, at high cost, secondly, fluorescein mark
Remember that will cause certain chemistry to cell poisons, it is difficult to supermatic detection is realized, moreover, laser beam irradiation has cell
Damage is not suitable for the follow-up test of cell.
Summary of the invention
The embodiment of the present invention provides the detection method of a kind of detection unit, detection device and memebrane protein diffusion rate, can
Continuously, in real time, duplicate detection memebrane protein diffusion rate.
In order to achieve the above objectives, the embodiment of the present invention adopts the following technical scheme that
It on the one hand, include: the first electrode being cascading, P the embodiment provides a kind of detection unit
Type semiconductor layer, n type semiconductor layer and second electrode;The detection unit further includes heat-conducting layer, and the heat-conducting layer is set to institute
At at least side surface for stating p type semiconductor layer and the n type semiconductor layer, and partly with the p type semiconductor layer and the N-type
Conductor layer contacts;The surface far from the p type semiconductor layer and the n type semiconductor layer of the heat-conducting layer, is provided with viscous
Attached layer, the adhesion layer is for making cell adherence on it.
Optionally, the adhesion layer is modified to obtain by the surface to the heat-conducting layer.
Optionally, detection unit further include be set to it is intrinsic between the p type semiconductor layer and the n type semiconductor layer
Semiconductor layer;The heat-conducting layer is contacted with the p type semiconductor layer, the intrinsic semiconductor layer and the n type semiconductor layer.
Optionally, the material of the heat-conducting layer includes the ceramics or metal that thermal conductivity is more than or equal to 200W/mK.
In another aspect, the embodiment of the present invention also provides a kind of detection device, including substrate, it is multiple it is spaced as above
The detection unit and the detection circuit for corresponding and being electrically connected with the detection unit;The detection circuit setting
Yu Yuqi correspondingly the detection unit close to the side of the substrate;The detection circuit is used in the detection unit
After upper adherent cell, the voltage difference between the first electrode and second electrode of the detection unit is detected.
Optionally, the detection circuit includes switching transistor and voltmeter;The grid of the switching transistor and scanning
Line is connected, and the first pole is connected with data line, and the second pole is connected with the first electrode of the detection unit;The electricity
The both ends of pressure table are connected to the first electrode and the second electrode of the detection unit.
Optionally, the first electrode in the detection unit, the p type semiconductor layer, the n type semiconductor layer and
The second electrode, the thickness direction along the substrate are set gradually;Gap between the detection unit is greater than a cell
Diameter.
Optionally, the first electrode in the detection unit, the p type semiconductor layer, the n type semiconductor layer and
The second electrode, the thickness direction along the vertical substrate are set gradually.
Optionally, detection device further includes the second insulating layer being set between the detection unit.
On the other hand, the embodiment of the present invention also provides a kind of detection method of memebrane protein diffusion rate, comprising: will be as above
The detection device is placed on temperature platform, records the initial temperature of setting, and obtain the initial temperature by voltmeter
The voltage difference of lower detection unit, as initial junction voltage;The adherent cell in the detection unit, and pass through the voltage
Table obtains the voltage difference for adhering to the detection unit of cell, as the corresponding junction voltage of the cell;According to acquisition
The relationship slope and the initial temperature of junction voltage and sensing temperature, the initial junction voltage and the corresponding junction voltage of cell,
The temperature of cell is calculated;According to the relationship of temperature and memebrane protein diffusion rate, the memebrane protein for obtaining each cell expands
Dissipate rate.
Optionally, according to the relationship slope and the initial temperature of the junction voltage of acquisition and sensing temperature, described initial
Junction voltage and the corresponding junction voltage of cell, are calculated the temperature of cell, comprising: pass throughIt is calculated thin
The temperature of born of the same parents;Wherein, T0For the initial temperature, VF0For the initial junction voltage, K is that the relationship of junction voltage and sensing temperature is oblique
Rate, VFiFor the corresponding junction voltage of cell, TiFor the temperature of cell.
Optionally, according to electric method, the relationship slope of junction voltage and sensing temperature is obtained.
The embodiment of the present invention provides a kind of detection unit, the detection method of detection device and memebrane protein diffusion rate, leads to
Cross the setting heat-conducting layer at least one of p type semiconductor layer and n type semiconductor layer side surface, and heat-conducting layer and P-type semiconductor
Layer and n type semiconductor layer contact, so that the temperature conduction on heat-conducting layer is to PN junction, thus when detecting cell, detection unit
The sensing temperature for detecting PN junction is equivalent to detect the temperature of cell.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described, it should be apparent that, the accompanying drawings in the following description is only this
Some embodiments of invention for those of ordinary skill in the art without creative efforts, can be with
It obtains other drawings based on these drawings.
Fig. 1 is a kind of structural schematic diagram of detection unit provided in an embodiment of the present invention;
Fig. 2 is the structural schematic diagram of another detection unit provided in an embodiment of the present invention;
Fig. 3 is the structural schematic diagram of another detection unit provided in an embodiment of the present invention;
Fig. 4 is the structural schematic diagram of another detection unit provided in an embodiment of the present invention;
Fig. 5 is a kind of structural schematic diagram of detection device provided in an embodiment of the present invention;
Fig. 6 is the structural schematic diagram of another detection device provided in an embodiment of the present invention;
Fig. 7 is the structural schematic diagram of another detection device provided in an embodiment of the present invention;
Fig. 8 is the structural schematic diagram of another detection device provided in an embodiment of the present invention;
Fig. 9 is the structural schematic diagram of another detection device provided in an embodiment of the present invention;
Figure 10 is the detection circuit schematic diagram in detection device provided in an embodiment of the present invention;
Figure 11 is a kind of flow chart of the detection method of memebrane protein diffusion rate provided in an embodiment of the present invention;
Figure 12 is the schematic diagram that junction voltage provided in an embodiment of the present invention changes with sensing temperature;
Figure 13 is the schematic diagram that memebrane protein provided in an embodiment of the present invention forms that the percentage of chimera varies with temperature.
Appended drawing reference
1- detection device;2- detection unit;10-P type semiconductor layer;11- first electrode;20-N type semiconductor layer;21-
Two electrodes;30- heat-conducting layer;40- adhesion layer;50- intrinsic semiconductor layer;100- substrate;200- detection circuit;201- voltmeter;
The first insulating layer of 301-;302- second insulating layer.
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts every other
Embodiment shall fall within the protection scope of the present invention.
The embodiment of the present invention provides a kind of detection unit 2, as shown in figures 1 and 3, comprising: to be cascading
One electrode 11, p type semiconductor layer 10, n type semiconductor layer 20 and second electrode 21;It further include heat-conducting layer 30, heat-conducting layer 30 is arranged
At at least one side surface of p type semiconductor layer 10 and n type semiconductor layer 20, and with p type semiconductor layer 10 and N-type semiconductor
Layer 20 contacts.
The separate p type semiconductor layer 10 of heat-conducting layer 30 and the surface of n type semiconductor layer 20, are additionally provided with adhesion layer 40, glue
Attached layer 40 is for making cell adherence on it.
Wherein, first electrode 11, p type semiconductor layer 10, n type semiconductor layer 20 and second electrode 21 can be along the vertical direction
It is cascading, can also be cascading in the horizontal direction.
For example, as shown in Figure 1, first electrode 11, p type semiconductor layer 10, n type semiconductor layer 20 and second electrode 21 can be with
It is to be cascading from top to bottom, it is of course also possible to be to be cascading from top to bottom.On this basis, heat-conducting layer 30
Can be set at least one lateral position in p type semiconductor layer 10 and n type semiconductor layer 20, and with p type semiconductor layer 10 and N-type
Semiconductor layer 20 contacts.
Alternatively, as shown in figure 3, first electrode 11, p type semiconductor layer 10, n type semiconductor layer 20 and second electrode 21 can be with
It is from left to right to be cascading, it is of course also possible to be to be cascading from right to left.On this basis, heat-conducting layer 30
It can be set at the upper surface and/or lower surface of p type semiconductor layer 10 and n type semiconductor layer 20, and/or, heat-conducting layer 30 can
To be set at leading flank and/or the trailing flank of p type semiconductor layer 10 and n type semiconductor layer 20.
The material of first electrode 11 and second electrode 21 can be metal or alloy etc..
The material of p type semiconductor layer 10 and n type semiconductor layer 20 may include silicon (Si), gallium nitride (GaN) etc..Example
, triad (such as boron element) is mixed in silicon, forms p type semiconductor layer 10, pentad (such as phosphorus member is mixed in silicon
Element), form n type semiconductor layer 20.
It should be noted that there are many hole and electronics is seldom in p type semiconductor layer 10, it is electric in n type semiconductor layer 20
There are many son and hole is seldom.When p type semiconductor layer 10 and n type semiconductor layer 20 contact, there are electrons and holes in intersection
Concentration difference, formed electronics from the area N to the area P, diffusion of the hole from the area P to the area N, wherein the area N is located in n type semiconductor layer 20
Close to the side of p type semiconductor layer 10, the area P is located at the side in p type semiconductor layer 10 close to n type semiconductor layer 20.Lose electricity
Negatively charged ion is left in the area P of son, loses and leaves positively charged ion in the area N in hole, between positive and negative charge
Interaction forms built in field again, and built in field makes electronics drift to the area N from the area P again, and hole drifts to the area P from the area N.
Wherein, it is directed to electrons and holes respectively, drift bearing is opposite with dispersal direction.
When drift and diffusion reach dynamic equilibrium, two surfaces of p type semiconductor layer 10 and the contact of n type semiconductor layer 20
The space-charge region being formed about is referred to as PN junction (region of the A instruction in such as Fig. 1 and Fig. 3).
PN junction has unilateral conduction.PN junction adds forward voltage, and (p type semiconductor layer 10 connects the anode of additional power source, N-type half
Conductor layer 20 connects cathode) when be connected, PN junction adds backward voltage, and (n type semiconductor layer 20 connects the anode of additional power source, P-type semiconductor
Layer 10 connects cathode) when end.
Based on this, when PN junction is connected under forward voltage, certain temperature can be generated, which is referred to as junction temperature.
Since heat-conducting layer 30 has good heating conduction, heat-conducting layer 30 is set to p type semiconductor layer 10 and N
It, can be at least one side surface of type semiconductor layer 20, and when being contacted with p type semiconductor layer 10 and n type semiconductor layer 20
By the junction temperature of PN junction by heat-conducting layer 30 transfer out come.Certainly, the transmitting of this temperature is also possible to reversed.That is, by thermally conductive
Temperature conduction on layer 30 senses PN junction, which is referred to as the sensing temperature of PN junction to PN junction.
It is that the temperature for the cell being adhered on adhesion layer 40 is conducted to PN by heat-conducting layer 30 in the embodiment of the present invention
Knot, in the case, the sensing temperature of the PN junction is the temperature of cell.
Wherein, relative to heat-conducting layer 30 is only contacted with p type semiconductor layer 10 or is only contacted with n type semiconductor layer 20,
The case where sensing temperature for PN junction occur is different from the temperature of heat-conducting layer 30.Heat-conducting layer 30 is set to p type semiconductor layer 10 and N
At at least one side surface of type semiconductor layer 20, and when being contacted with p type semiconductor layer 10 and n type semiconductor layer 20, the PN
Knot is directly contacted with heat-conducting layer 30, so that the sensing temperature of PN junction is identical as the temperature on heat-conducting layer 30.
It should be noted that the side on the surface of 20 side of separate p type semiconductor layer 10 and n type semiconductor layer of adhesion layer 40
It is long, it need to be at least more than the diameter for being equal to a cell.So that a detection unit 2 can at least detect a cell.
The embodiment of the present invention provides a kind of detection unit 2, by p type semiconductor layer 10 and n type semiconductor layer 20
Heat-conducting layer 30 is set at least one side surface, and heat-conducting layer 30 is contacted with p type semiconductor layer 10 and n type semiconductor layer 20,
So that the temperature conduction on heat-conducting layer 30 is to PN junction, so that detection unit 2 detects the sensing temperature of PN junction when detecting cell
Degree, is equivalent to detect the temperature of cell.
Optionally, adhesion layer 40 is modified to obtain by the surface to heat-conducting layer 30.
Heat-conducting layer 30 is surface modified far from the surface of 20 side of p type semiconductor layer 10 and n type semiconductor layer, makes this
Surface is modified, forms adhesion layer 40.For example, surface modification is chemical modification, there is spy by fixed on 30 surface of heat-conducting layer
Chemical gene such as the methods of the hydroxyl, amino acid or protein for determining function, the specificity for influencing cell and 30 surface of heat-conducting layer are viscous
It is attached.
Wherein, specific adhesion refers to that adhesion layer 40 can only adhere to a kind of cell.When modified obtained adhesion layer 40
When adhesion property difference, the cell category of adherency can be different.
It is understood that the heat-conducting layer 30 of each detection unit 2 passes through surface modification when there is multiple detection units 2
Adhesion layer 40 is formed afterwards, and adhesion layer 40 can be with a kind of cell of specific adhesion.And a kind of this cell can be a cell, it can also
To be multiple cells.When multiple detection units 2 are by different surface modifications, different types of cell can be adhered to.
Optionally, the material of heat-conducting layer 30 includes the ceramics or metal that thermal conductivity is more than or equal to 200W/mK.
Optionally, as shown in Figure 2 and Figure 4, above-mentioned detection unit 2 further includes being set to p type semiconductor layer 10 and N-type is partly led
Intrinsic semiconductor layer 50 between body layer 20;Heat-conducting layer 30 and p type semiconductor layer 10, intrinsic semiconductor layer 50 and N-type semiconductor
Layer 20 contacts.
For example, as shown in Fig. 2, first electrode 11, p type semiconductor layer 10, intrinsic semiconductor layer 50, n type semiconductor layer 20
It can be with second electrode 21 and be cascading from top to bottom, of course, it is possible to be to be cascading from top to bottom.In this base
On plinth, at least one in p type semiconductor layer 10, intrinsic semiconductor layer 50 and n type semiconductor layer 20 is can be set in heat-conducting layer 30
Lateral position.
Alternatively, as shown in figure 4, first electrode 11, p type semiconductor layer 10, intrinsic semiconductor layer 50, n type semiconductor layer 20
It can be with second electrode 21 and be from left to right cascading, it is of course also possible to be to be cascading from right to left.Herein
On the basis of, heat-conducting layer 30 can be set in the upper surface of p type semiconductor layer 10, intrinsic semiconductor layer 50 and n type semiconductor layer 20
And/or at lower surface, and/or, heat-conducting layer 30 can be set in p type semiconductor layer 10, intrinsic semiconductor layer 50 and N-type semiconductor
At the leading flank of layer 20 and/or trailing flank.
More than, regardless of p type semiconductor layer 10, intrinsic semiconductor layer 50 and n type semiconductor layer 20 is arranged in heat-conducting layer 30
Which side is contacted with p type semiconductor layer 10, intrinsic semiconductor layer 50 and n type semiconductor layer 20.
The material of intrinsic semiconductor layer 50 also may include silicon (Si), gallium nitride (GaN) etc., still, intrinsic semiconductor layer
Non-impurity-doped in 50, close to pure semiconductor.
It should be noted that when p type semiconductor layer 10, intrinsic semiconductor layer 50 and 20 three of n type semiconductor layer contact, this
There is no space charge in sign semiconductor layer 50, still, near the close intrinsic semiconductor layer 50 in p type semiconductor layer 10, meeting
It loses electronics and leaves negatively charged ion, in n type semiconductor layer 20 near intrinsic semiconductor layer 50, hole can be lost
Leave positively charged ion.Therefore, it will be distributed over p type semiconductor layer 10 close to the side of intrinsic semiconductor layer 50 and N-type half
The space-charge region that conductor layer 20 is formed close to the side of intrinsic semiconductor layer 50, and intermediate intrinsic semiconductor layer 50 are referred to as
For PIN junction (region of the B instruction in such as Fig. 2 and Fig. 4).
PIN junction also has unilateral conduction, and PIN junction adds forward voltage, and (p type semiconductor layer 10 meets the anode of additional power source, N
Type semiconductor layer 20 connects cathode) when be connected, PIN junction adds backward voltage, and (n type semiconductor layer 20 connects the anode of additional power source, p-type half
Conductor layer 10 connects cathode) when end.
Based on this, when PIN junction is connected under forward voltage, certain temperature can be also generated, which is referred to as junction temperature.
Since heat-conducting layer 30 has good heating conduction, heat-conducting layer 30 is set to p type semiconductor layer 10, sheet
At at least one side surface for levying semiconductor layer 50 and n type semiconductor layer 20, and with p type semiconductor layer 10, intrinsic semiconductor layer
50 and n type semiconductor layer 20 when contacting, can by the junction temperature of PIN junction by heat-conducting layer 30 transfer out come, certainly, this temperature
Transmitting be also possible to it is reversed.That is, sensing PIN junction to PIN junction the temperature conduction on heat-conducting layer 30, which claims
The sensing temperature for PIN junction.It is the temperature for the cell that will be adhered on adhesion layer 40 by thermally conductive in the embodiment of the present invention
Layer 30 is conducted to PIN junction, and the sensing temperature of the PIN junction is the temperature of cell in the case.
Wherein, relative to heat-conducting layer 30 is only contacted with p type semiconductor layer 10 or is only contacted with intrinsic semiconductor layer 50
Or only contacted with n type semiconductor layer 20, occur PIN junction sensing temperature be different from heat-conducting layer 30 temperature the case where.It will lead
Thermosphere 30 is set at least one side surface of p type semiconductor layer 10, intrinsic semiconductor layer 50 and n type semiconductor layer 20, and
When contacting with p type semiconductor layer 10, intrinsic semiconductor layer 50 and n type semiconductor layer 20, which directly connects with heat-conducting layer 30
Touching, so that the sensing temperature of PIN junction is identical as the temperature on heat-conducting layer 30.
The embodiment of the present invention also provides a kind of detection device 1, as shown in figure 5, including substrate 100, the setting of multiple intervals
Detection unit as described above 2, and correspond with detection unit 2 and the detection circuit 200 that is electrically connected.
Detection circuit 200 is corresponded and is electrically connected with detection unit 2, and each detection circuit 200 is individually controlled
Make a corresponding detection unit 2.
Wherein, multiple spaced detection units 2, can be arranged with array.
As shown in figure 5, detection circuit 200 is set to its one-to-one detection unit 2 close to the side of substrate 100;
Detection circuit 200 is used to detect the voltage difference between the first electrode 11 and second electrode 21 of corresponding detection unit 2.
As shown in Figure 10, detection device 1 further includes multiple data lines (as shown in D1, D2, D3 in Figure 10) and a plurality of sweeps
Line (as shown in S1, S2, S3 in Figure 10) is retouched, the detection unit 2 positioned at same a line may be coupled to same scan line, be located at
The detection unit 2 of same row can connect same data line.
On the basis of the above, optionally, as shown in Figure 10, detection circuit 200 includes switching transistor T and voltmeter 201,
The grid of switching transistor T is connected with scan line, and the first pole is connected with data line, the second pole and the first of detection unit 2
Electrode 11 is connected;The both ends of voltmeter 201 are connected to the first electrode 11 and second electrode 21 of detection unit 2.
As shown in Figure 10, the second electrode 21 of detection unit 2 can be for example electrically connected with ground.Under the control of scan line,
When switching transistor in detection circuit 200 is opened, voltage is written in data line, is provided constant current for detection unit 2, is made to detect
Unit 2 is in normal operating conditions, at this point, the junction temperature that detection unit 2 itself generates is smaller, can be ignored.Then, work as inspection
It surveys on unit 2 after adhering to cell, detection unit 2 senses the temperature of cell, so that junction voltage changes, then passes through voltage
Table 201 reads the voltage difference between the first electrode 11 and second electrode 21 of detection unit 2.
Wherein, the first of switching transistor T extremely can be the source electrode of switching transistor T, and the second of switching transistor T is extremely
The drain electrode of switching transistor T.
It should be noted that whithin a period of time, when the cell temperature variation that adhesion layer 40 adheres to, passing through heat-conducting layer 30
Conduction, the sensing temperature of PN junction changes therewith, thus the electricity between the first electrode 11 in detection unit 2 and second electrode 21
Pressure difference also changes therewith.The detection device 1 can detect the temperature of cell, while the detection device 1 continuously, in real time as a result,
Damage, the temperature of recursive detection cell are not will cause to cell.
The embodiment of the present invention provides a kind of detection device 1, by being arranged in detection unit 2 close to the side of substrate 100
One-to-one detection circuit 200, allows each detection circuit 200 individually to control a corresponding detection unit 2.Together
When, it is that detection unit 2 provides constant current by detection circuit 200, makes its normal work, and adhere to carefully in detection unit 2
After born of the same parents, the voltage difference between the first electrode 11 of the detection unit 2 and second electrode 21 is detected.The detection device 1 can connect as a result,
The temperature of continuous, real-time, duplicate detection cell, obtains the voltage difference being stained in the detection unit 2 of cell, so as to basis
Voltage difference obtains the temperature of cell, and then obtains the diffusion rate of memebrane protein in cell.
Optionally, as shown in Fig. 6, Fig. 7, Fig. 8, Fig. 9, detection device 1 further includes being set to detection circuit 200 and detection list
The first insulating layer 301 between member 2.
The material of first insulating layer 301 can be inorganic material, or organic material, the present invention is to this without limit
It is fixed.
It can be with when being provided with the first insulating layer 301 between detection circuit 200 and detection unit 2, on the first insulating layer 301
Multiple via holes are set, so that detection unit 2 and one-to-one detection circuit 200 are carried out by the filler being filled in via hole
Electrical connection.Wherein, the material of the filler in via hole can be metal, alloy etc..
Optionally, as shown in Figure 6 and Figure 7, the first electrode 11 in detection unit 2, p type semiconductor layer 10, N-type semiconductor
Layer 20 and second electrode 21, the thickness direction along substrate 100 are set gradually.On this basis, the gap between detection unit 2 is big
In the diameter (such as Fig. 6 and d shown in fig. 7) of a cell.
Since heat-conducting layer 30 and adhesion layer 40 are arranged at the side surface of p type semiconductor layer 10 and n type semiconductor layer 20, and
It is contacted with p type semiconductor layer 10 and n type semiconductor layer 20, therefore, the gap between two detection units 2 should be greater than one
The diameter of cell cell adherence can be allowed in a detection unit 2, and does not influence adjacent detection unit 2.
On this basis, it should be noted that when the heat-conducting layer 30 being arranged in two detection units 2 close to when, for example, its
In heat-conducting layer 30 be located at the right side of p type semiconductor layer 10 and n type semiconductor layer 20 in corresponding detection unit 2, it is another
A heat-conducting layer 30 is located at the left side of p type semiconductor layer 10 and n type semiconductor layer 20 in corresponding detection unit 2.Two detections
Gap between unit 2 should be greater than the diameter of two cells, cell adherence can be allowed in each detection unit 2, and not
Influence adjacent detection unit 2.
Wherein, " left side ", " right side " are only used for indicating positional relationship, after the absolute position of description object changes,
Then the relative positional relationship may also change accordingly.
Optionally, as shown in Figure 8 and Figure 9, the first electrode 11 in detection unit 2, p type semiconductor layer 10, N-type are partly led
Body layer 20 and second electrode 21, the thickness direction along vertical substrates 100 are set gradually.
On this basis, since p type semiconductor layer 10 and n type semiconductor layer 20 is arranged in heat-conducting layer 30 and adhesion layer 40
Upper surface, and contacted with p type semiconductor layer 10 and n type semiconductor layer 20, the size of cell does not interfere with other inspections at this time
Unit 2 is surveyed, it is therefore not necessary to limit the spacing between detection unit 2, the gap between detection unit 2 can be according to need
It sets, the present invention is without limiting.
Wherein, " upper surface " is only used for indicating positional relationship, and after the absolute position of description object changes, then this is with respect to position
The relationship of setting may also change accordingly.
Optionally, as shown in Figure 8 and Figure 9, when first electrode 11, p type semiconductor layer 10, the N-type in detection unit 2 are partly led
Body layer 20 and second electrode 21, when setting gradually along the thickness direction perpendicular to substrate 100, detection device 1 further includes being set to
Second insulating layer 302 between detection unit 2.
Second insulating layer 302 is set between detection unit 2, the first electrode 11 in multiple detection units 2 can be made
With 21 mutually insulated of second electrode, avoid mutually having an impact between first electrode 11, second electrode 21.
Wherein, the material of second insulating layer 302 can be identical as the material of the first insulating layer 301, can also be different, this hair
It is bright to this without limit.
The present invention also provides a kind of detection methods of memebrane protein diffusion rate, as shown in figure 11, comprising:
S10, above-mentioned detection device 1 is placed on temperature platform, the initial temperature of record temperature platform setting, and passed through
Voltmeter 201 obtains the voltage difference of detection unit under the initial temperature, as initial junction voltage.
It is conducted by the heat-conducting layer 30 in detection unit 2, it is single that the initial temperature of temperature platform setting can pass to detection
PN junction in member 2, at this point, the sensing temperature of PN junction is identical as initial temperature.Under the initial temperature, the first of detection unit 2
The voltage difference that electrode 11 and second electrode 21 generate is initial junction voltage.
Exemplary, the GaAsP/InP that the PN junction of detection unit 2 is gallium arsenide phosphide (GaAsP) and indium phosphide (InP) is constituted is different
Matter PN junction, when being in normal operating conditions, operating current 0.8mA, the junction temperature itself generated be can be ignored.At this point, if
The initial temperature that temperature platform is set is T0, by the conduction of heat-conducting layer 30, the sensing temperature of the PN heterojunction becomes T0, thus
First electrode 11 and second electrode 21 generate voltage difference, and reading the voltage difference by voltmeter 201 is VF0, that is, initial junction voltage
For VF0。
S20, as shown in Fig. 6, Fig. 7, Fig. 8 and Fig. 9, the adherent cell in detection unit 2, and being obtained by voltmeter 201
The voltage difference for adhering to the detection unit 2 of cell, as the corresponding junction voltage of the cell.
It should be noted that the diffusion rate Yu temperature of memebrane protein have close relationship in cell, temperature is high, memebrane protein
For diffusion rate with regard to fast, temperature is low, and the diffusion rate of memebrane protein is with regard to slow.Therefore, according to this characteristic, cell adherence can examined
It surveys on device 1, when the diffusion rate difference of memebrane protein, the temperature of cell is different, and is conducted by heat-conducting layer 30, detection unit
The sensing temperature of PN junction in 2 is changed to the temperature of cell.At this point, the voltage difference of first electrode 11 and second electrode 21 will therewith
Variation is generated, the voltage difference after the variation got by voltmeter 201 is used as the corresponding junction voltage of the cell.
S30, according to the junction voltage of acquisition and the relationship slope of sensing temperature and the initial temperature, the initial knot
Voltage and the corresponding junction voltage of cell, are calculated the temperature of cell.
Optionally, according to electric method, the relationship slope of junction voltage and sensing temperature is obtained.
Electric method, i.e. end voltage parameter method, are a kind of current most common measurement methods, the most commonly used is low current K systems
Number method.
The main process of low current k-factor method is the k-factor for obtaining PN junction under low current.Small electricity is tested for example, applying
PN junction is arranged at a temperature of two or more known environments stream, measures junction voltage under relevant temperature, obtains COEFFICIENT K.
It is exemplary, test low current is applied to PN junction, the junction temperature of itself can be ignored, when environment temperature is T1When,
The sensing temperature of PN junction is T1, it is V that measurement, which obtains the corresponding voltage difference in PN junction both ends,F1, when environment temperature is T2When, PN junction
Sensing temperature is T2, it is V that measurement, which obtains the corresponding voltage difference in PN junction both ends,F2.Pass throughIt is calculated
The voltage difference at PN junction both ends and the relationship slope of temperature, i.e. the relationship slope K value of the junction voltage of PN junction and temperature, unit is mv/
K。
On this basis, multiple environment temperatures and corresponding junction voltage can be measured, it is oblique to improve calculated relationship
The precision of rate K value.
Exemplary, as shown in figure 12, PN junction is GaAsP/InP PN heterojunction, applies the test of 0.2mA to the PN heterojunction
Low current, the junction temperature itself generated can be ignored, and the temperature of temperature platform setting is gradually increasing, so that the sensing of PN junction
Temperature is gradually increasing, and the voltage difference at PN junction both ends also changes therewith, is based on this, for example, it is poor every 10 DEG C of acquisition primary voltages, it can
To obtain the voltage difference at multiple temperature spots.It is then possible to which it is corresponding to obtain 0.2mA test low current by linear difference method
Junction voltage and temperature relationship slope K0.2。
Similarly, as shown in figure 12, the test such as 0.3mA, 0.5mA, 0.8mA, 1mA, 2mA, 3mA and 4mA is successively respectively obtained
The relationship slope K of low current, corresponding junction voltage and sensing temperature0.3、K0.5、K0.8、K1、K2、K3And K4。
It should be noted that the PN junction pressure drop that temperature change is brought is millivolt level, test electric current must be sufficiently small, in order to avoid
It is produced from heating during the test, influences the accuracy of test.
Optionally, in S30, according to the junction voltage of acquisition and the relationship slope and initial temperature of sensing temperature, it is described just
Beginning junction voltage and the corresponding junction voltage of cell, are calculated the temperature of cell, comprising:
Pass throughThe temperature of cell is calculated;
Wherein, T0For initial temperature, VF0For initial junction voltage, K is the relationship slope of junction voltage and temperature, VFiFor cell pair
The junction voltage answered, TiFor the temperature of cell.
On the basis of the above, according to the example in S10, the PN junction of detection unit is GaAsP/InP PN heterojunction, and work
Making electric current is 0.8mA, and the relationship slope for obtaining junction voltage and temperature as a result, is K0.8.Then, according to initial temperature T0, initial to tie
Voltage VF0And the corresponding junction voltage of cell obtained in S20 is VFi, further according to formulaThis is calculated
When the corresponding sensing temperature of PN junction be Ti, i.e. the temperature of cell is Ti。
S40, according to the relationship of temperature and memebrane protein diffusion rate, obtain the memebrane protein diffusion rate of cell.
The relationship of temperature and memebrane protein diffusion rate can be obtained by people, the experiment of mouse cell fusion.For example, with difference
The antibody of fluorescent dye marks the memebrane protein of people, mouse cell, and after a period of time, two kinds of memebrane proteins are by diffusion motion, in hybrid
It is uniformly distributed to form chimera on cell membrane.As shown in figure 13, between 0 to 15 DEG C, diffusion motion is slower, and it is several to form chimera
Constant, between 15 to 35 DEG C, diffusion motion is speeded, formed chimera percentage increase, thus, it is possible to obtain temperature with
Memebrane protein is diffused with direct relation.Based on this, setting at a temperature of, using fluorescence recovery after photo- bleaching technology, calculate corresponding
Memebrane protein diffusion rate, so as to be fitted to obtain the relationship of temperature Yu memebrane protein diffusion rate.
It is exemplary, it is T according to the temperature that the example in S30 acquires celli, by being T by temperatureiSubstitution fits
Temperature and memebrane protein diffusion rate relational expression in, obtain corresponding memebrane protein diffusion rate.It follows that passing through detection dress
The 1 corresponding junction voltage of temperature for measuring cell is set, the temperature of cell can be calculated according to the relationship of junction voltage and temperature,
The relationship of temperature and memebrane protein diffusion rate further according to cell, so that it may obtain the memebrane protein diffusion rate of cell.
The embodiment of the present invention provides a kind of detection method of memebrane protein diffusion rate, is placed in by will test device 1
Temperature platform records the initial temperature and the corresponding initial junction voltage of detection device 1 of setting, then the detection in detection device 1
After adhering to cell on unit 2, the corresponding junction voltage of temperature of cell is obtained, then according to the pass of the junction voltage of acquisition and temperature
It is slope, the temperature that the corresponding temperature of the junction voltage is cell is calculated, further according to the pass of temperature and memebrane protein diffusion rate
System, obtains the memebrane protein diffusion rate of cell.As a result, by the detection method can continuous, real-time, duplicate detection cell, obtain
Take the corresponding memebrane protein diffusion rate of cell.
The above description is merely a specific embodiment, but scope of protection of the present invention is not limited thereto, any
Those familiar with the art in the technical scope disclosed by the present invention, can easily think of the change or the replacement, and should all contain
Lid is within protection scope of the present invention.Therefore, protection scope of the present invention should be based on the protection scope of the described claims.
Claims (12)
1. a kind of detection unit characterized by comprising first electrode, p type semiconductor layer, the N-type being cascading partly are led
Body layer and second electrode;
The detection unit further includes heat-conducting layer, and the heat-conducting layer is set to the p type semiconductor layer and the n type semiconductor layer
An at least side surface at, and contacted with the p type semiconductor layer and the n type semiconductor layer;
The surface far from the p type semiconductor layer and the n type semiconductor layer of the heat-conducting layer, is provided with adhesion layer, described
Adhesion layer is for making cell adherence on it.
2. detection unit according to claim 1, which is characterized in that the adhesion layer passes through the surface to the heat-conducting layer
It is modified to obtain.
3. detection unit according to claim 1, which is characterized in that further include being set to the p type semiconductor layer and institute
State the intrinsic semiconductor layer between n type semiconductor layer;
The heat-conducting layer is contacted with the p type semiconductor layer, the intrinsic semiconductor layer and the n type semiconductor layer.
4. detection unit according to claim 1-3, which is characterized in that the material of the heat-conducting layer includes thermally conductive
Rate is more than or equal to the ceramics or metal of 200W/mK.
5. a kind of detection device, which is characterized in that described in any item including substrate, multiple spaced claim 1-4
Detection unit and the detection circuit for corresponding and being electrically connected with the detection unit;
The detection circuit is set to its one-to-one detection unit close to the side of the substrate;The detection electricity
Road is used in the detection unit after adherent cell, is detected between the first electrode and second electrode of the detection unit
Voltage difference.
6. detection device according to claim 5, which is characterized in that the detection circuit includes switching transistor and voltage
Table;
The grid of the switching transistor is connected with scan line, and the first pole is connected with data line, the second pole and the detection
The first electrode of unit is connected;
The both ends of the voltmeter are connected to the first electrode and the second electrode of the detection unit.
7. detection device according to claim 5, which is characterized in that the first electrode, institute in the detection unit
P type semiconductor layer, the n type semiconductor layer and the second electrode are stated, the thickness direction along the substrate is set gradually;
Gap between the detection unit is greater than the diameter of a cell.
8. detection device according to claim 5, which is characterized in that the first electrode, institute in the detection unit
P type semiconductor layer, the n type semiconductor layer and the second electrode are stated, the thickness direction along the vertical substrate is set gradually.
9. detection device according to claim 8, which is characterized in that further include be set between the detection unit
Two insulating layers.
10. a kind of detection method of memebrane protein diffusion rate characterized by comprising
It will be placed on temperature platform such as the described in any item detection devices of claim 5-9, and record the initial temperature of setting, and
The voltage difference that detection unit under the initial temperature is obtained by voltmeter, as initial junction voltage;
The adherent cell in the detection unit, and the electricity for adhering to the detection unit of cell is obtained by the voltmeter
Pressure difference, as the corresponding junction voltage of the cell;
According to the relationship slope and the initial temperature of the junction voltage of acquisition and sensing temperature, the initial junction voltage and thin
The corresponding junction voltage of born of the same parents, is calculated the temperature of cell;
According to the relationship of temperature and memebrane protein diffusion rate, the memebrane protein diffusion rate of each cell is obtained.
11. the detection method of memebrane protein diffusion rate according to claim 10, which is characterized in that according to the knot of acquisition electricity
The relationship slope and the initial temperature, the initial junction voltage and the corresponding junction voltage of cell of pressure and sensing temperature calculate
Obtain the temperature of cell, comprising:
Pass throughThe temperature of cell is calculated;
Wherein, T0For the initial temperature, VF0For the initial junction voltage, K is the relationship slope of junction voltage and sensing temperature, VFi
For the corresponding junction voltage of cell, TiFor the temperature of cell.
12. the detection method of memebrane protein diffusion rate according to claim 10, which is characterized in that according to electric method, obtain
Take the relationship slope of junction voltage and sensing temperature.
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