CN113546696B - Nano-fluid enrichment device, manufacturing method thereof, enrichment method and detection device - Google Patents
Nano-fluid enrichment device, manufacturing method thereof, enrichment method and detection device Download PDFInfo
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Abstract
The invention discloses a nanofluid enrichment device, a manufacturing method, an enrichment method and a detection device thereof, wherein the nanofluid enrichment device comprises: the nano-channel structure comprises a substrate base plate, a nano-channel layer and an electrode layer, wherein the nano-channel layer and the electrode layer are sequentially positioned on the substrate base plate; the nanochannel layer comprises: the device comprises an enrichment tank, a base liquid tank, a first channel and a second channel, wherein the enrichment tank and the base liquid tank are mutually independent; the electrode layer includes: a first electrode, a second electrode, and a third electrode; wherein the first electrode is electrically connected with the second electrode; the orthographic projection of the first electrode on the substrate base plate is positioned between the orthographic projection of the enrichment tank and the orthographic projection of the base liquid tank; the orthographic projection of the second electrode on the substrate is positioned on one side of the orthographic projection of the enrichment tank, which is far away from the orthographic projection of the substrate tank; the orthographic projection of the third electrode on the substrate is positioned on the orthographic projection side of the base liquid tank far away from the enrichment tank; the first electrode, the second electrode and the third electrode are configured to be loaded with alternating current signals so as to control the charged particles with different charge-to-mass ratios in the base liquid tank to be enriched in the enrichment tank in batches.
Description
Technical Field
The invention relates to the technical field of biological detection, in particular to a nanofluid enrichment device, a manufacturing method thereof, an enrichment method and a detection device.
Background
The nano-fluid enrichment technology has wide application scenes in the fields of trace detection, medicine purification, medical detection, environmental detection and the like. The technology realizes the selectivity of the charged particles by utilizing the electrostatic action of the charges on the wall surface of the nano fluid channel on the charged particles, thereby achieving the effect of enriching the charged particles. Although the conventional nanofluid enrichment device has different enrichment capacities for particles with different volume, mass and charge ratios, the enrichment effect of the conventional nanofluid enrichment device is to simultaneously enrich all charged particles with channel charged particle selectivity in a solvent, namely, the generated enrichment effect is non-specific enrichment, the particles with different volumes, masses and charges can be simultaneously enriched in an enrichment region, and the application is difficult for the applications requiring biological engineering, drug extraction and specific enrichment.
In bioengineering, for example, proteins produced or secreted by microorganisms are effective components to be extracted, and conventional enrichment methods may result in simultaneous enrichment of the microorganisms and the proteins, while the microorganisms are not substances to be purified, and pharmaceutical companies need to enrich proteins secreted by organisms and not enrich microorganisms. For example, in the process of detecting bacteria and viruses in blood, the conventional enrichment method may cause simultaneous enrichment of proteins, bacteria, viruses and even blood cells in different volumes in blood, which may affect each other and make it difficult to perform diagnostic observation, and pretreatment such as centrifugation is required to remove substances that are not desired to be observed.
Disclosure of Invention
In view of the above, embodiments of the present invention provide a nanofluid enrichment device, a manufacturing method thereof, an enrichment method thereof, and a detection apparatus thereof, so as to achieve selective enrichment effects of different types of particles.
Accordingly, an embodiment of the present invention provides a nanofluid enrichment device, including: the nano-channel structure comprises a substrate, a nano-channel layer and an electrode layer, wherein the nano-channel layer is positioned on the substrate, and the electrode layer is positioned on one side of the nano-channel layer, which is far away from the substrate; wherein the content of the first and second substances,
the nanochannel layer comprises: the device comprises an enrichment tank, a base liquid tank, a first channel and a second channel, wherein the enrichment tank and the base liquid tank are independent from each other;
the electrode layer includes: a first electrode, a second electrode, and a third electrode; wherein the first electrode is electrically connected to the second electrode;
the orthographic projection of the first electrode on the substrate base plate is positioned between the orthographic projection of the enrichment tank and the orthographic projection of the substrate liquid tank;
the orthographic projection of the second electrode on the substrate base plate is positioned on the orthographic projection side of the enrichment tank far away from the base liquid tank;
the orthographic projection of the third electrode on the substrate base plate is positioned on the orthographic projection side of the substrate liquid tank far away from the enrichment tank;
the first electrode, the second electrode and the third electrode are configured to be loaded with alternating current signals to control the charged particles with different charge-to-mass ratios in the base liquid tank to be enriched in batches in the enrichment tank.
In a possible implementation manner, in the nanofluid enrichment device provided in an embodiment of the present invention, a boundary of an orthogonal projection of the first electrode on the substrate, the boundary being on a side close to the enrichment tank, coincides with a boundary of an orthogonal projection of the first channel, the boundary being on a side close to the enrichment tank, and the boundary of an orthogonal projection of the first electrode on the substrate, the side close to the substrate tank, is located within an area defined by a boundary of an orthogonal projection of the first channel, the side close to the substrate tank.
In a possible implementation manner, in the nanofluid enrichment device provided in an embodiment of the present invention, the nanochannel layer further includes: the second channel is positioned on one side of the enrichment tank, which is far away from the base liquid tank, and the third channel is positioned on one side of the base liquid tank, which is far away from the enrichment tank; wherein, the first and the second end of the pipe are connected with each other,
an opening is formed in one end, close to the enrichment groove, of the second channel, one end, far away from the enrichment groove, of the second channel is closed, and the orthographic projection of the second channel on the substrate is completely overlapped with the orthographic projection of the second electrode;
an opening is formed in one end, close to the base liquid groove, of the third channel, one end, far away from the base liquid groove, of the third channel is closed, and the orthographic projection of the third channel on the substrate is completely overlapped with the orthographic projection of the third electrode.
In a possible implementation manner, in the nanofluid enrichment device provided in an embodiment of the present invention, the nanofluid enrichment device further includes: a support layer on a side of the electrode layer facing away from the nanochannel layer;
the supporting layer comprises a first through hole and a second through hole;
the orthographic projection of the first through hole on the substrate base plate covers the enrichment groove, the first electrode is close to the edge area of the enrichment groove, and the second electrode is close to the edge area of the enrichment groove;
the orthographic projection of the second through hole on the substrate covers the base liquid groove, and the third electrode is close to the edge area of the base liquid groove.
In a possible implementation manner, in the foregoing nanofluid enrichment device provided in an embodiment of the present invention, the apparatus further includes: the hard mask layer is positioned on one side, away from the electrode layer, of the supporting layer;
the hard mask layer includes: a third via that completely overlaps the first via, and a fourth via that completely overlaps the second via.
In a possible implementation manner, in the nanofluid enrichment device provided in an embodiment of the present invention, the nanofluid enrichment device further includes: the protective cover plate is positioned on one side, away from the supporting layer, of the hard mask layer;
the protective cover plate is provided with a fifth through hole communicated with the third through hole and a sixth through hole communicated with the fourth through hole;
the orthographic projection of the fifth through hole on the substrate base plate and the orthographic projection of the third through hole are not overlapped;
the orthographic projection of the sixth through hole on the substrate base plate and the orthographic projection of the fourth through hole are not overlapped.
Based on the same inventive concept, the embodiment of the invention provides a method for manufacturing a nanofluid enrichment device, which comprises the following steps:
providing a substrate base plate;
forming a nano-channel layer and an electrode layer on the substrate base plate;
the nanochannel layer comprising: the device comprises an enrichment tank, a base liquid tank, a first channel and a second channel, wherein the enrichment tank and the base liquid tank are independent from each other;
the electrode layer includes: a first electrode, a second electrode, and a third electrode; wherein the first electrode is electrically connected to the second electrode;
the orthographic projection of the first electrode on the substrate base plate is positioned between the orthographic projection of the enrichment tank and the orthographic projection of the substrate liquid tank;
the orthographic projection of the second electrode on the substrate base plate is positioned on the orthographic projection side of the enrichment tank far away from the base liquid tank;
the orthographic projection of the third electrode on the substrate base plate is positioned on the orthographic projection side of the substrate liquid tank far away from the enrichment tank;
the first electrode, the second electrode and the third electrode are configured to be loaded with alternating current signals to control the charged particles with different charge-to-mass ratios in the base liquid tank to be enriched in batches in the enrichment tank.
In a possible implementation manner, in the above manufacturing method provided in an embodiment of the present invention, after forming the electrode layer on the substrate and before forming the nano channel layer, the method further includes:
sequentially forming an organic insulating layer and an inorganic insulating layer on the electrode layer;
etching the inorganic insulating layer to form a third through hole and a fourth through hole which penetrate through the inorganic insulating layer and are independent of each other; wherein the third via exposes an edge region of the first electrode adjacent to the second electrode and an edge region of the second electrode adjacent to the first electrode; the fourth through hole exposes an edge area of the third electrode adjacent to the first electrode; the inorganic insulating layer having the third via hole and the fourth via hole constitutes a hard mask layer;
etching the organic insulating layer by taking the hard mask layer as a shield to form a first through hole completely superposed with the third through hole and a second through hole completely superposed with the fourth through hole; the organic insulating layer having the first and second via holes constitutes a support layer.
In a possible implementation manner, in the manufacturing method provided in an embodiment of the present invention, the forming a nano channel layer specifically includes:
forming a closed nanochannel on the substrate base plate;
and etching the closed nano channel by taking the hard mask layer and the electrode layer as shielding to form an enrichment groove between the first electrode and the second electrode, a base solution groove between the first electrode and the third electrode, a first channel between the enrichment groove and the base solution groove, a second channel at one side of the enrichment groove far away from the base solution groove, and a third channel at one side of the base solution groove far away from the enrichment groove, so as to obtain the nano channel layer.
Based on the same inventive concept, an embodiment of the present invention provides a nanofluid enrichment method of the nanofluid enrichment device, including:
loading a first signal which is opposite to the polarity of the wall surface charge of the nano channel layer and has a preset amplitude and a preset frequency to a first electrode and a second electrode which are electrically connected, loading a second signal which is opposite to the polarity of the first signal and has the preset amplitude and the preset frequency to a third electrode, so that first charged particles which are the same as the polarity of the wall surface charge of the nano channel layer in the base liquid tank and have the preset charge-to-mass ratio move from the base liquid tank to an enrichment tank through a first channel, and simultaneously vibrating second charged particles which are the same as the polarity of the wall surface charge of the nano channel layer and have the smaller charge-to-mass ratio in situ in the base liquid tank;
loading the second signal to the first electrode and the second electrode while loading the first signal to the third electrode such that the first charged particles stay in the enrichment tank and the second charged particles remain vibrated in situ.
Based on the same inventive concept, the embodiment of the invention provides a detection device, which comprises the nanofluid enrichment device.
The invention has the following beneficial effects:
the embodiment of the invention provides a nanofluid enrichment device, a manufacturing method thereof, an enrichment method and a detection device, wherein the nanofluid enrichment device comprises the following components: the nano-channel structure comprises a substrate, a nano-channel layer and an electrode layer, wherein the nano-channel layer is positioned on the substrate; wherein the nanochannel layer comprises: the device comprises an enrichment tank, a base liquid tank, a first channel and a second channel, wherein the enrichment tank and the base liquid tank are independent from each other; an electrode layer, comprising: a first electrode, a second electrode, and a third electrode; wherein the first electrode is electrically connected with the second electrode; the orthographic projection of the first electrode on the substrate base plate is positioned between the orthographic projection of the enrichment tank and the orthographic projection of the base liquid tank; the orthographic projection of the second electrode on the substrate is positioned on one side of the orthographic projection of the enrichment tank, which is far away from the orthographic projection of the substrate tank; the orthographic projection of the third electrode on the substrate is positioned on the orthographic projection side of the base liquid tank far away from the enrichment tank; the first electrode, the second electrode and the third electrode are configured to be loaded with alternating current signals so as to control the charged particles with different charge-to-mass ratios in the base liquid tank to be enriched in the enrichment tank in batches. The wall charges of the nanochannel layer act to selectively pass the first channel through charged particles of opposite electrical polarity to the wall charges. Taking the wall charges as negative charges, the first channel selectively passes through the positively charged particles. When the first electrode and the second electrode are loaded with positive voltage, and the third electrode is loaded with negative voltage, the positive voltage of the first electrode can inhibit the selectivity of the first channel to the positively charged particles, so that the negatively charged particles in the base liquid move from the base liquid tank to the enrichment tank under the action of electrophoresis. When the first electrode and the second electrode are connected with a loaded negative voltage and the third electrode is loaded with a positive voltage, the electrophoresis direction of the negatively charged particles points to the base solution tank from the enrichment tank, but the negative voltage of the first electrode can enhance the selectivity of the channel to the positively charged particles, so that the negatively charged particles cannot move from the enrichment tank to the base solution tank, and the effect of enriching the negatively charged particles in the enrichment tank is realized. Moreover, for negatively charged particles with large mass, large volume, small charge amount and slow movement, the negatively charged particles can be driven to move only by long voltage application time; for negatively charged particles with small mass, small volume, large charge quantity and high moving speed, the motion enrichment can be driven by short voltage application time. Therefore, the amplitude and the frequency of the loaded alternating current signal can be adjusted, so that the negatively charged particles with a charge-mass ratio higher than a certain charge-mass ratio can move to be enriched, and the negatively charged particles which do not meet the charge-mass ratio condition vibrate in situ, thereby realizing the selective enrichment effect on different types of negatively charged particles. Based on similar principles, the selective enrichment effect on different types of positively charged particles can be realized under the condition that wall charges are positive charges.
Drawings
Fig. 1 is a schematic top view of a nanofluid enrichment device according to an embodiment of the present invention;
FIG. 2 is a schematic cross-sectional view taken along the dotted line I-I' in FIG. 1;
FIG. 3 is one of the schematic diagrams of a nanofluid enrichment device provided in an embodiment of the present invention;
FIG. 4 is an enlarged schematic view of the region M in FIG. 3;
FIG. 5 is a second schematic diagram of a nanofluid enrichment device according to an embodiment of the present invention;
FIG. 6 is an enlarged schematic view of the region M in FIG. 5;
FIG. 7 is a graph showing the enrichment effect of a nanofluid enrichment device according to an embodiment of the present invention;
FIG. 8 is a second graph illustrating the enrichment effect of a nanofluid enrichment device according to an embodiment of the present invention;
FIGS. 9 to 23 are schematic structural diagrams of a nanofluid enrichment device according to an embodiment of the present invention during a fabrication process thereof;
FIG. 24 is a schematic diagram of optical detection of charged particles in an enrichment tank using a nanofluid enrichment device according to embodiments of the present invention;
FIG. 25 is a graph showing the fluorescence spectrum of the optical detection shown in FIG. 24.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the drawings of the embodiments of the present invention. The dimensions and shapes of the various figures in the drawings are not to scale and are merely intended to illustrate the invention. And like reference numerals refer to like or similar elements or elements having like or similar functions throughout. It is to be understood that the embodiments described are only a few embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the described embodiments of the invention without any inventive step, are within the scope of protection of the invention.
Unless defined otherwise, technical or scientific terms used herein shall have the ordinary meaning as understood by one of ordinary skill in the art to which this invention belongs. The terms "first," "second," and the like, as used in the description and in the claims, do not denote any order, quantity, or importance, but rather are used to distinguish one element from another. The word "comprising" or "comprises", and the like, means that the element or item listed before the word covers the element or item listed after the word and its equivalents, but does not exclude other elements or items. "inner", "outer", "upper", "lower", and the like are used merely to indicate relative positional relationships, and when the absolute position of the object being described is changed, the relative positional relationships may also be changed accordingly.
An embodiment of the present invention provides a nanofluid enrichment device, as shown in fig. 1 and 2, including: a substrate base plate 101, a nano-channel layer 102 positioned on the substrate base plate 101, and an electrode layer 103 positioned on the side of the nano-channel layer 102 away from the substrate base plate 101; wherein the content of the first and second substances,
the nanochannel layer 102 includes: the device comprises an enrichment tank A and a base liquid tank B which are independent of each other, and a first channel 1021 between the enrichment tank A and the base liquid tank B, wherein two ends of the first channel 1021 are provided with openings;
an electrode layer 103 including: a first electrode 1031, a second electrode 1032, and a third electrode 1033; wherein the first electrode 1031 is electrically connected to the second electrode 1032;
an orthographic projection of the first electrode 1031 on the substrate base plate 101 is positioned between an orthographic projection of the enrichment well a and an orthographic projection of the base liquid well B;
the orthographic projection of the second electrode 1032 on the substrate base plate 101 is positioned on the orthographic projection side of the enrichment groove A away from the base liquid groove B;
the orthographic projection of the third electrode 1033 on the substrate base plate 101 is positioned on the side of the orthographic projection of the substrate tank B, which is far away from the orthographic projection of the enrichment tank A;
the first electrode 1031, the second electrode 1032 and the third electrode 1033 are configured to be loaded with Alternating Current (AC) signals to control the charged particles of different charge-to-mass ratios in the base solution tank B to be batched for enrichment in the enrichment tank a.
In view of the fact that the surface of a substance such as a protein in the biological field is generally negatively charged, the following description will discuss screening negatively charged particles having different charge-to-mass ratios as an example.
Specifically, in the nanofluid enrichment device according to the present embodiment, the wall charges of the nanochannel layer 102 act to allow the first channel 1021 to selectively pass charged particles having an opposite electrical property to the wall charges. The wall charges of the silicon oxide nanochannel layer 102 are negative charges, and the first channel 1021 can selectively pass through positively charged particles under the action of the negative charges. When the first electrode 1031 and the second electrode 1032 are applied with a positive voltage by the ac power source 104, and the third electrode 1033 is applied with a negative voltage by the ac power source 104 (i.e. the nanofluid enrichment device is connected positively as shown in fig. 3), the positive voltage of the first electrode 1031 will inhibit the selectivity of the first channel 1021 to the positively charged particles, so that the positively charged particles in the base fluid will move from the base fluid tank B to the enrichment tank a under the selective action of the first channel 1021, and the negatively charged particles in the base fluid will move from the base fluid tank B to the enrichment tank a under the action of electrophoresis, as shown in fig. 4. When the first electrode 1031 and the second electrode 1032 are applied with a negative voltage by the ac power supply 104, and the third electrode 1033 is applied with a positive voltage by the ac power supply 104 (i.e. the nanofluid enrichment device is reversely connected as shown in fig. 5), the electrophoresis direction of the negatively charged particles is directed from the enrichment tank a to the base fluid tank B, but the negative voltage of the first electrode 1031 will enhance the selectivity of the channel to the positively charged particles, so that the positively charged particles move from the enrichment tank a to the base fluid tank B, and the negatively charged particles cannot move from the enrichment tank a to the base fluid tank B, as shown in fig. 6, thereby achieving the effect of enriching the negatively charged particles in the enrichment tank a. Based on a similar principle, the effect of the enrichment of the positively charged particles in the enrichment groove a can be achieved when the wall charges are positive charges (for example, the material of the nanochannel layer 102 is alumina).
Under a Direct Current (DC) signal, charged particles with different charge-to-mass ratios (i.e., charge-to-mass ratios) move electrophoretically along the direction of the electric field lines. Under the same electric field condition, for charged particles with large charge quantity and small mass, the charged particles are subjected to large electric field force and small inertia, can accelerate more quickly and can move for a large distance in a short time; for charged particles with small charge quantity and large mass, the electric field force is small, the inertia is large, and the charged particles can only slowly move for a small distance in a short time; for neutrally charged particles with very little charge, it is even impossible to displace. And when the charged particles with different charge-to-mass ratios work at a higher frequency of positive and negative electric field switching: for charged particles with large charge quantity and small mass, the device can have higher frequency response and fast motion, and can realize directional acceleration and deceleration motion under a reciprocating sinusoidal electric signal with positive amplitude larger than negative amplitude; for charged particles with small charge quantity and large mass, because the inertia is large and the electric field force is small, when the positive voltage does not enable the charged particles to move in a short time, the signals are switched to the negative voltage, namely the switching speed of the frequency is faster than the signal response speed of the charged particles, the charged particles can only do in-situ vibration in the solution, and the charged particles cannot move. Therefore, according to the amplitude and the frequency of an applied alternating current signal, charged particles higher than a certain charge-to-mass ratio can be controlled to move and be enriched in the device, and charged particles which do not meet the conditions are only vibrated in situ and cannot be enriched, so that selective enrichment of target particles is realized. Meanwhile, a channel transistor (TFT) in which the first electrode 1031 and the second electrode 1032 are electrically connected and are independent from the third electrode 1033 is formed in the nanofluid enrichment device, that is, a diode device is formed, and the diode device only allows one-way current conduction, so that even though a sinusoidal alternating current signal is conducted, after work is enriched in a positive half cycle of conduction work, the diode device is turned off in a negative half cycle, and the effect of the previous half cycle is not affected. Based on the above principle, the embodiments of the present disclosure can use a high-amplitude high-frequency ac signal to realize the enrichment of charged particles with large charge amount and small mass, as shown in fig. 7; and the low-amplitude low-frequency alternating current signal is used to realize the enrichment of the charged particles with small charge quantity and large mass, as shown in figure 8. In this way, the screening of charged particles with different charge-to-mass ratios can be realized.
It should be understood that, in the nanofluid enrichment device provided in the embodiments of the present invention, the charged particles may move from the base fluid tank B to the enrichment tank a in one cycle, or may move from the base fluid tank B to the enrichment tank a step by step through the action of multiple cycles, which is not limited herein. In addition, since the charged particles with different charge-to-mass ratios move at different speeds in the same electric field, in some embodiments, simultaneous enrichment of different charged particles at different positions can be achieved.
It should be noted that the ac power source 104 may be a built-in power source included in the nanofluid enrichment device provided in the embodiment of the present invention, or may be an external power source independent of the nanofluid enrichment device provided in the embodiment of the present invention, and is not limited herein. Generally, to save device cost, it is preferable to provide the ac power source 104 as an external power source.
Alternatively, in the nanofluid enrichment device according to the embodiment of the present invention, as shown in fig. 2, a boundary (i.e., left) of a side of the orthographic projection of the first electrode 1031 on the substrate 101 adjacent to the enrichment tank a coincides with a boundary (i.e., left) of a side of the orthographic projection of the first passage 1021 adjacent to the enrichment tank a, and a boundary (i.e., right) of a side of the orthographic projection of the first electrode 1031 on the substrate 101 adjacent to the substrate tank B is located within an area defined by a boundary (i.e., right) of a side of the orthographic projection of the first passage 1021 adjacent to the substrate tank B. In other words, the area of the first electrode 1031 is smaller than the area of the first passage 1021, and the left side of the first electrode 1031 is aligned with the left side of the first passage 1021.
As can be seen from the above, the voltage applied to the first electrode 1031 suppresses or enhances the selectivity of the first channel 1021 for the charged particles, so that the target charged particles move from the base solution tank B to the enrichment tank a and do not return from the enrichment tank a to the base solution tank B, thereby achieving the enrichment of the target charged particles. By providing the first electrode 1031 on a portion of the first passage 1021 adjacent to the enrichment tank a, the first electrode 1031 can be more effectively employed to suppress or enhance the selectivity of the first passage 1021 to charged particles. Of course, in practical implementation, the first electrode 1031 completely covering the first channel 1021 may be provided, and is not limited herein.
Optionally, in the nanofluid enrichment device provided in an embodiment of the present invention, as shown in fig. 2, the nanochannel layer 102 further includes: a second channel 1022 located on the side of the enrichment tank A away from the base solution tank B, and a third channel 1023 located on the side of the base solution tank B away from the enrichment tank A; wherein the content of the first and second substances,
one end (namely the right end) of the second channel 1022 close to the enrichment groove A is provided with an opening, the end (namely the left end) far away from the enrichment groove B is closed, and the orthographic projection of the second channel 1022 on the substrate base plate 101 is completely coincided with that of the second electrode 1032;
one end (i.e., the left end) of the third channel 1023 close to the substrate tank B is open, the end (i.e., the right end) far away from the substrate tank B is closed, and the orthographic projection of the third channel 1023 on the substrate 101 is completely overlapped with the orthographic projection of the third electrode 1033.
Since the feasibility of only arranging a channel with two open ends in the middle of one film layer is not high, in the invention, the nano-channel layer 102 with a closed nano-channel is formed, and then the enrichment groove A, the base liquid groove B, the first channel 1021, the second channel 1022 and the third channel 1023 are formed by slotting the middle part of the closed nano-channel. Therefore, the manufacturing difficulty of the device can be reduced. Also, since the second and third channels 1022 and 1023 are open only at a single end, charged particles cannot pass through the second and third channels 1022 and 1023, and thus the presence of the second and third channels 1022 and 1023 does not affect the effect of the enrichment of charged particles via the first channel 1021.
Optionally, in the nanofluid enrichment device provided in an embodiment of the present invention, as shown in fig. 2, the nanofluid enrichment device may further include: a support layer 105 on the side of electrode layer 103 facing away from nanochannel layer 102;
the support layer 105 includes a first through hole H 1 And a second through hole H 2 ；
First through hole H 1 An orthographic projection on the substrate base plate 101 covers the enrichment trench a, the first electrode 1031 is adjacent to the edge region t of the enrichment trench a, and the second electrode 1022 is adjacent to the edge region m of the enrichment trench a;
second via H 2 The orthographic projection on the substrate base plate 101 covers the base liquid tank B, and the third electrode 1033 is adjacent to an edge area n of the base liquid tank B.
Since the thickness of the nanochannel layer 102 and the electrode layer 103 is small, specifically, on a nanometer scale, in the process of injecting the base liquid into the base liquid tank B and injecting the solution containing the fluorescent molecules capable of being combined with the concentrate into the enrichment tank a, the liquid pressure may cause deformation of the nanochannel layer 102 and the electrode layer 103, the support layer 105 is disposed above the electrode layer 103 in the present disclosure, so as to avoid adverse effects of the liquid pressure on the electrode layer 103. Also, since the thickness of the electrode layer 103 is only in the order of nanometers, the contact resistance with the liquid is too large, and thus passes through the first through hole H 1 And the second through hole H 2 The staggered exposure of the first, second and third electrodes 1031, 1032 and 1033 is achieved such that the contact electrodes of the liquid with the first, second and third electrodes 1031, 1032 and 1033 are larger, thereby reducing the contact resistance. Optionally, the exposed first electrode 1031 is adjacent to the edge region t of the enrichment tank a, the second electrode 1032 is adjacent to the edge region m of the enrichment tank a, and the third electrode 1033 is adjacent to the edge region n of the substrate tank B, and the values of the three are in the range of 0.1 μm to 1mm, and the sizes of the three may be the same or different, which is not limited herein.
Optionally, in the nanofluid enrichment device provided in an embodiment of the present invention, as shown in fig. 2, the nanofluid enrichment device may further include: a hard mask layer 106 on the side of the support layer 105 facing away from the electrode layer 103;
a hard mask layer 106 comprising: and the first through hole H 1 Completely overlapped third through hole H 3 And with the second via hole H 2 Completely overlapped fourth through hole H 4 。
Since the pattern of the hard mask layer 106 is the same as the pattern of the support layer 105, the hard mask layer 106 serves as a mask, thereby realizing the etching of the support layer 105.
Optionally, in the nanofluid enrichment device provided in an embodiment of the present invention, as shown in fig. 2, the nanofluid enrichment device may further include: a protective cover plate 107 positioned on the side of the hard mask layer 106 away from the support layer 105;
the protective cover plate 107 has a third through hole H 3 Fifth through hole H for conduction 5 And with the fourth through-hole H 4 Sixth through hole H that conducts 6 ；
Fifth via hole H 5 Orthographic projection on the substrate base plate 101 and the third through hole H 3 The orthographic projections of the projection are not overlapped with each other;
sixth via H 6 Orthographic projection on the substrate base plate 101 and the fourth through hole H 4 Do not overlap each other.
Fifth through hole H of protective cover 107 5 Sixth through hole H 6 Third via holes H respectively connected with the hard mask layer 106 3 Fourth through hole H 4 Are staggered, so that the protective cover plate 107 is arranged in the fifth through hole H 5 Right side to third through hole H 3 Upper part S 1 Can block the third through hole H 3 The lower enrichment groove A, while protecting the cover plate 107 at the sixth through hole H 6 Left to fourth through hole H 4 Upper part S 2 Can block the fourth through hole H 4 The lower liquid base tank B is shown in figures 1 and 2, so that the influence of external particles on the enrichment and detection analysis effects is effectively avoided.
Based on the same inventive concept, embodiments of the present invention provide a method for manufacturing a nanofluid enrichment device, and since the principle of the manufacturing method for solving the problem is similar to the principle of the nanofluid enrichment device for solving the problem, the implementation of the manufacturing method provided by embodiments of the present invention can refer to the implementation of the nanofluid enrichment device provided by embodiments of the present invention, and repeated details are not repeated.
Specifically, the method for manufacturing a nanofluid enrichment device provided by the embodiment of the invention comprises the following steps:
providing a substrate base plate;
forming a nano-channel layer and an electrode layer on a substrate;
a nanochannel layer comprising: the device comprises an enrichment tank, a base liquid tank, a first channel and a second channel, wherein the enrichment tank and the base liquid tank are independent from each other;
an electrode layer, comprising: a first electrode, a second electrode, and a third electrode; wherein the first electrode is electrically connected with the second electrode;
the orthographic projection of the first electrode on the substrate base plate is positioned between the orthographic projection of the enrichment tank and the orthographic projection of the base liquid tank;
the orthographic projection of the second electrode on the substrate is positioned on one side of the orthographic projection of the enrichment tank, which is far away from the orthographic projection of the substrate tank;
the orthographic projection of the third electrode on the substrate is positioned on the orthographic projection side of the base liquid tank far away from the enrichment tank;
the first electrode, the second electrode and the third electrode are configured to be loaded with alternating current signals so as to control the charged particles with different charge-to-mass ratios in the base liquid tank to be enriched in the enrichment tank in batches.
Optionally, in the manufacturing method provided in the embodiment of the present invention, after the electrode layer is formed on the substrate and before the nano channel layer is formed, the following steps may be further performed:
sequentially forming an organic insulating layer and an inorganic insulating layer on the electrode layer;
etching the inorganic insulating layer to form a third through hole and a fourth through hole which penetrate through the inorganic insulating layer and are independent of each other; wherein the third via exposes an edge region of the first electrode adjacent to the second electrode and an edge region of the second electrode adjacent to the first electrode; the fourth through hole exposes the edge area of the third electrode close to the substrate liquid groove; an inorganic insulating layer having a third via hole and a fourth via hole constitutes a hard mask layer;
and etching the organic insulating layer by taking the hard mask layer as a shield to form a first through hole completely superposed with the third through hole and a second through hole completely superposed with the fourth through hole, wherein the organic insulating layer with the first through hole and the second through hole forms a supporting layer.
Optionally, in the manufacturing method provided in the embodiment of the present invention, forming the nano channel layer may be specifically implemented in the following manner:
forming a closed nano-channel on a substrate;
and etching the closed nano channel by taking the hard mask layer and the electrode layer as shielding to form an enrichment groove between the first electrode and the second electrode, a base liquid groove between the first electrode and the third electrode, a first channel between the enrichment groove and the base liquid groove, a second channel at one side of the enrichment groove far away from the base liquid groove, and a third channel at one side of the base liquid groove far away from the enrichment groove, so as to obtain the nano channel layer.
In order to understand the technical solution of the above manufacturing method provided by the embodiments of the present invention, the following detailed description will be given.
The first step is as follows: a silicon dioxide layer 102 'is formed on the substrate base plate 101 as shown in fig. 9, and a closed nanochannel 102 "is formed in the silicon dioxide layer 102' as shown in fig. 10 and 11. It should be noted that fig. 11 only shows the silicon dioxide layer 102' in the region of the first channel 1021 with the enrichment function.
The second step is that: forming a metal layer 103 'on the silicon dioxide layer 102' having the closed nanochannels 102 ", as shown in fig. 12 and 13; and patterning the metal layer 103' to form an electrode layer 103 including a first electrode 1031, a second electrode 1032 and a third electrode 1033, as shown in fig. 14 and 15; wherein the first electrode 1031 is electrically connected to the second electrode 1032.
The third step: an organic insulating layer 105 'and an inorganic insulating layer 106' are sequentially formed on the electrode layer 103, as shown in fig. 16 and 17; etching the inorganic insulating layer 106' to form third independent through holes H penetrating the inorganic insulating layer 106 3 And a fourth through hole H 4 (ii) a Wherein the third through hole H 3 Exposing an edge region t of the first electrode 1031 adjacent to the second electrode 1032, and an edge region m of the second electrode 1032 adjacent to the first electrode 1031; fourth via H 4 Exposing an edge region of the third electrode 1033 adjacent to the first electrode 1031n; having a third through hole H 3 And a fourth through hole H 4 The inorganic insulating layer 106' of (a) constitutes a hard mask layer 106, as shown in fig. 18 and fig. 19; using the hard mask layer 106 as a mask to etch the organic insulating layer 105', thereby forming a third via hole H 3 Completely coincident first through hole H 1 And with the fourth through-hole H 4 Completely coincident second through hole H 2 Having a first through hole H 1 And a second through hole H 2 The organic insulating layer 105' of (a) constitutes the support layer 105, as shown in fig. 20 and 21.
The fourth step: using the hard mask layer 106 and the electrode layer 103 as a mask, etching the closed nanochannel 102 ″ to form an enrichment trench a between the first electrode 1031 and the second electrode 1032, a base solution trench B between the first electrode 1031 and the third electrode 1032, a first channel 1021 between the enrichment trench a and the base solution trench B, a second channel 1022 on a side of the enrichment trench a away from the base solution trench B, and a third channel 1023 on a side of the base solution trench B away from the enrichment trench a, thereby obtaining the nanochannel layer 102, as shown in fig. 22 and 23.
The fifth step: providing a substrate having a fifth through hole H 5 And a sixth through hole H 6 The protective cover plate 107, the protective cover plate 107 is assembled to the hard mask layer 106 such that the fifth through hole H 5 Third via H to hard mask layer 106 3 Conducted and not overlapped with each other, a sixth through hole H 6 Fourth via H with hardmask layer 106 4 Conducting and not overlapping each other as shown in fig. 1 and 2.
Based on the same inventive concept, embodiments of the present invention provide a nanofluid enrichment method for the nanofluid enrichment device, and since the principle of the enrichment method for solving the problems is similar to the principle of the nanofluid enrichment device for solving the problems, the implementation of the enrichment method provided by embodiments of the present invention can refer to the implementation of the nanofluid enrichment device provided by embodiments of the present invention, and repeated details are omitted.
Specifically, the embodiment of the present invention provides a nanofluid enrichment method of the nanofluid enrichment device, which specifically includes the following steps:
loading a first signal which is opposite to the polarity of the wall surface charge of the nano channel layer and has a preset amplitude and a preset frequency to a first electrode and a second electrode which are electrically connected, loading a second signal which is opposite to the polarity of the first signal and has a preset amplitude and a preset frequency to a third electrode, so that first charged particles which are the same as the polarity of the wall surface charge of the nano channel layer in the liquid base tank and are more than or equal to a preset charge ratio move from the liquid base tank to the enrichment tank through the first channel, and simultaneously vibrating second charged particles which are the same as the polarity of the wall surface charge of the nano channel layer and are less than the preset charge ratio in situ in the liquid base tank;
and loading a second signal to the first electrode and the second electrode, and loading a first signal to the third electrode at the same time, so that the first charged particles stay in the enrichment tank, and the second charged particles keep vibrating in situ.
Based on the same inventive concept, the embodiment of the invention also provides a detection device, which comprises the nanofluid enrichment device provided by the embodiment of the invention. Because the principle of the detection device for solving the problems is similar to that of the nanofluid enrichment device, the implementation of the detection device can be referred to the embodiment of the nanofluid enrichment device, and repeated parts are not described again.
Specifically, as shown in fig. 24, in the detection of the charged particles in the enrichment tank a, the fifth through hole H 5 And adding a detection liquid which can be specifically combined with the charged particles in the enrichment tank A and has fluorescence performance into the enrichment tank A, and detecting the combined product in the enrichment tank A by adopting spectral analysis equipment such as an inverted fluorescence microscope 108 and the like. Then, the concentration content of the charged particles in the enrichment tank a is determined from the signal intensity of the detection spectrum, and the type of the charged particles in the enrichment tank a is identified from the signal frequency of the spectrum, as shown in fig. 25.
In the nanofluid enrichment device, the manufacturing method thereof, the enrichment method thereof and the detection apparatus provided in the embodiments of the present invention, the nanofluid enrichment device includes: the nano-channel structure comprises a substrate, a nano-channel layer and an electrode layer, wherein the nano-channel layer is positioned on the substrate; wherein the nanochannel layer comprises: the device comprises an enrichment tank, a base liquid tank, a first channel and a second channel, wherein the enrichment tank and the base liquid tank are independent from each other; an electrode layer, comprising: a first electrode, a second electrode, and a third electrode; wherein the first electrode is electrically connected with the second electrode; the orthographic projection of the first electrode on the substrate base plate is positioned between the orthographic projection of the enrichment tank and the orthographic projection of the base liquid tank; the orthographic projection of the second electrode on the substrate is positioned on one side of the orthographic projection of the enrichment tank, which is far away from the orthographic projection of the substrate tank; the orthographic projection of the third electrode on the substrate is positioned on the orthographic projection side of the base liquid tank far away from the enrichment tank; the first electrode, the second electrode and the third electrode are configured to be loaded with alternating current signals so as to control the charged particles with different charge-to-mass ratios in the base liquid tank to be enriched in the enrichment tank in batches. The wall charges of the nanochannel layer act to selectively pass the first channel through charged particles of opposite electrical polarity to the wall charges. Taking the wall charges as negative charges, the first channel selectively passes through the positively charged particles. When the first electrode and the second electrode are loaded with positive voltage, and the third electrode is loaded with negative voltage, the positive voltage of the first electrode can inhibit the selectivity of the first channel to the positively charged particles, so that the negatively charged particles in the base liquid move from the base liquid tank to the enrichment tank under the action of electrophoresis. When the first electrode and the second electrode are connected with a loaded negative voltage and the third electrode is loaded with a positive voltage, the electrophoresis direction of the negatively charged particles points to the base solution tank from the enrichment tank, but the negative voltage of the first electrode can enhance the selectivity of the channel to the positively charged particles, so that the negatively charged particles cannot move from the enrichment tank to the base solution tank, and the effect of enriching the negatively charged particles in the enrichment tank is realized. Moreover, for negatively charged particles with large mass, large volume, small charge amount and slow movement, the negatively charged particles can be driven to move only by long voltage application time; for negatively charged particles with small mass, small volume, large charge quantity and high moving speed, the motion enrichment can be driven by short voltage application time. Therefore, the amplitude and the frequency of the loaded alternating current signal can be adjusted, so that the negatively charged particles with a charge-mass ratio higher than a certain charge-mass ratio can move to be enriched, and the negatively charged particles which do not meet the charge-mass ratio condition vibrate in situ, thereby realizing the selective enrichment effect on different types of negatively charged particles. Based on similar principles, the selective enrichment effect on different types of positively charged particles can be realized under the condition that wall charges are positive charges.
It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, if such modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include such modifications and variations.
Claims (11)
1. A nanofluid enrichment device, comprising: the nano-channel structure comprises a substrate, a nano-channel layer and an electrode layer, wherein the nano-channel layer is positioned on the substrate, and the electrode layer is positioned on one side of the nano-channel layer, which is far away from the substrate; wherein the content of the first and second substances,
the nanochannel layer comprises: the device comprises an enrichment tank, a base liquid tank, a first channel and a second channel, wherein the enrichment tank and the base liquid tank are independent from each other;
the electrode layer includes: a first electrode, a second electrode, and a third electrode; wherein the first electrode is electrically connected to the second electrode;
the orthographic projection of the first electrode on the substrate base plate is positioned between the orthographic projection of the enrichment tank and the orthographic projection of the substrate liquid tank;
the orthographic projection of the second electrode on the substrate base plate is positioned on the orthographic projection side of the enrichment tank far away from the base liquid tank;
the orthographic projection of the third electrode on the substrate base plate is positioned on the orthographic projection side of the substrate liquid tank far away from the enrichment tank;
the first electrode, the second electrode and the third electrode are configured to be loaded with alternating current signals to control the charged particles with different charge-to-mass ratios in the base liquid tank to be enriched in batches in the enrichment tank.
2. The nanofluid enrichment device according to claim 1, wherein a boundary of an orthographic projection of the first electrode on the substrate base plate adjacent to a side of the enrichment tank coincides with a boundary of an orthographic projection of the first channel adjacent to a side of the enrichment tank, and the boundary of the orthographic projection of the first electrode on the substrate base plate adjacent to the side of the substrate tank is located within an area defined by the boundary of the orthographic projection of the first channel adjacent to the side of the substrate tank.
3. The nanofluidic enrichment device of claim 1, wherein the nanochannel layer further comprises: the second channel is positioned on one side of the enrichment tank, which is far away from the base liquid tank, and the third channel is positioned on one side of the base liquid tank, which is far away from the enrichment tank; wherein the content of the first and second substances,
an opening is formed in one end, close to the enrichment groove, of the second channel, one end, far away from the enrichment groove, of the second channel is closed, and the orthographic projection of the second channel on the substrate is completely overlapped with the orthographic projection of the second electrode;
an opening is formed in one end, close to the base liquid groove, of the third channel, one end, far away from the base liquid groove, of the third channel is closed, and the orthographic projection of the third channel on the substrate is completely overlapped with the orthographic projection of the third electrode.
4. The nanofluid enrichment device of claim 1, further comprising: a support layer on a side of the electrode layer facing away from the nanochannel layer;
the supporting layer comprises a first through hole and a second through hole;
the orthographic projection of the first through hole on the substrate base plate covers the enrichment groove, the first electrode is close to the edge area of the enrichment groove, and the second electrode is close to the edge area of the enrichment groove;
the orthographic projection of the second through hole on the substrate covers the base liquid groove, and the third electrode is close to the edge area of the base liquid groove.
5. The nanofluid enrichment device of claim 4, further comprising: the hard mask layer is positioned on one side, away from the electrode layer, of the supporting layer;
the hard mask layer includes: a third via that completely overlaps the first via, and a fourth via that completely overlaps the second via.
6. The nanofluid enrichment device of claim 5, further comprising: the protective cover plate is positioned on one side, away from the supporting layer, of the hard mask layer;
the protective cover plate is provided with a fifth through hole communicated with the third through hole and a sixth through hole communicated with the fourth through hole;
the orthographic projection of the fifth through hole on the substrate base plate and the orthographic projection of the third through hole are not overlapped;
the orthographic projection of the sixth through hole on the substrate base plate and the orthographic projection of the fourth through hole are not overlapped.
7. A method of fabricating a nanofluid enrichment device, comprising:
providing a substrate base plate;
forming a nano-channel layer and an electrode layer on the substrate base plate;
the nanochannel layer comprising: the device comprises an enrichment tank, a base liquid tank, a first channel and a second channel, wherein the enrichment tank and the base liquid tank are independent from each other;
the electrode layer includes: a first electrode, a second electrode, and a third electrode; wherein the first electrode is electrically connected to the second electrode;
the orthographic projection of the first electrode on the substrate base plate is positioned between the orthographic projection of the enrichment tank and the orthographic projection of the substrate liquid tank;
the orthographic projection of the second electrode on the substrate base plate is positioned on the orthographic projection side of the enrichment tank far away from the base liquid tank;
the orthographic projection of the third electrode on the substrate base plate is positioned on the orthographic projection side of the substrate liquid tank far away from the enrichment tank;
the first electrode, the second electrode and the third electrode are configured to be loaded with alternating current signals to control the charged particles with different charge-to-mass ratios in the base liquid tank to be enriched in batches in the enrichment tank.
8. The method of claim 7, further comprising, after forming the electrode layer on the substrate base plate and before forming the nanochannel layer:
sequentially forming an organic insulating layer and an inorganic insulating layer on the electrode layer;
etching the inorganic insulating layer to form a third through hole and a fourth through hole which penetrate through the inorganic insulating layer and are independent of each other; wherein the third via exposes an edge region of the first electrode adjacent to the second electrode and an edge region of the second electrode adjacent to the first electrode; the fourth through hole exposes an edge area of the third electrode adjacent to the first electrode; the inorganic insulating layer with the third through hole and the fourth through hole forms a hard mask layer;
etching the organic insulating layer by taking the hard mask layer as a shield to form a first through hole completely superposed with the third through hole and a second through hole completely superposed with the fourth through hole; the organic insulating layer having the first and second via holes constitutes a support layer.
9. The method of claim 8, wherein forming a nanochannel layer comprises:
forming a closed nanochannel on the substrate base plate;
and etching the closed nano channel by taking the hard mask layer and the electrode layer as shielding to form an enrichment groove between the first electrode and the second electrode, a base liquid groove between the first electrode and the third electrode, a first channel between the enrichment groove and the base liquid groove, a second channel at one side of the enrichment groove far away from the base liquid groove, and a third channel at one side of the base liquid groove far away from the enrichment groove, so as to obtain the nano channel layer.
10. A method of nanofluid enrichment for a nanofluid enrichment device according to any one of claims 1 to 6, comprising:
loading a first signal which is opposite to the polarity of the wall surface charge of the nano channel layer and has a preset amplitude and a preset frequency to a first electrode and a second electrode which are electrically connected, loading a second signal which is opposite to the polarity of the first signal and has the preset amplitude and the preset frequency to a third electrode, so that first charged particles which are the same as the polarity of the wall surface charge of the nano channel layer in the base liquid tank and have the preset charge-to-mass ratio move from the base liquid tank to an enrichment tank through a first channel, and simultaneously vibrating second charged particles which are the same as the polarity of the wall surface charge of the nano channel layer and have the smaller charge-to-mass ratio in situ in the base liquid tank;
loading the second signal to the first electrode and the second electrode while loading the first signal to the third electrode such that the first charged particles stay in the enrichment tank and the second charged particles remain vibrated in situ.
11. A test device comprising the nanofluid enrichment device of any one of claims 1-6.
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