JP6211273B2 - Lipid bilayer device, lipid bilayer device array, lipid bilayer device manufacturing apparatus, and lipid bilayer device manufacturing method - Google Patents

Description

  The present invention provides a lipid bilayer device having a lipid bilayer membrane used in fields such as biotechnology, biochip, membrane protein analysis, drug discovery screening, or biosensor, and the lipid comprising a plurality of lipid bilayer membrane devices The present invention relates to a bilayer device array, a lipid bilayer device manufacturing apparatus for manufacturing the lipid bilayer device, and a method for manufacturing the lipid bilayer device.

  In order to understand the functions of membrane proteins involved in mass transport / information transmission in and out of biological membranes and apply them in engineering, the artificial lipid bilayer model experimental system incorporating isolated membrane proteins Need to build. However, skilled techniques are required to construct such an experimental system. For this reason, the constructed experimental system is not reproducible, and the construction throughput may not be high.

  The inventors have disclosed a lipid bilayer device 101 having a lipid bilayer membrane produced by the MEMS technique shown in FIG. 1 in Japanese Patent Application Laid-Open No. 2012-205536. The lipid bilayer device 101 provided improvements in construction throughput, miniaturization, shortened analysis time, a small amount of necessary reagents, and high reproducibility. The lipid bilayer membrane device 101 includes a main channel 113 and a micro diverticulum (microchamber) 114 that opens on the side wall of the main channel 113.

  A first liquid 130A made of an aqueous solution, a second liquid made of an oily solution in which lipid 121, which is a component of the lipid bilayer, is dissolved, and a third liquid 130B made of an aqueous solution are sequentially injected into the main channel 113. Then, a lipid bilayer membrane 122 is formed in the opening. That is, when the first liquid 130A is injected, the first liquid 130A fills the main channel 113 and the micro diverticulum 114. When the second liquid is injected, a monomolecular layer of lipid 121 is formed between the second liquid and the first liquid 130A left in the micro diverticulum 114 while the second liquid pushes the first liquid 130A in the main channel. Forming an interface. Next, when the third liquid 130B is injected, the second liquid in the main channel is pushed away. At this time, since the lipid 121 of the second liquid overlaps the already formed monomolecular layer, the lipid bilayer membrane 122 is formed at the interface between the first liquid 130A and the third liquid 130B.

  A desired membrane protein can be further incorporated into the lipid bilayer membrane 122. Then, a model experiment is performed by performing electrical measurement or fluorescence observation using the lipid bilayer membrane device 101.

  However, it may not be easy to form the lipid bilayer membrane 122 at the interface between the liquids. In addition, it may not be easy to stably hold the lipid bilayer membrane 122 formed at the liquid interface.

  On the other hand, JP-A-5-7770 discloses a lipid bilayer membrane 222 shown in FIG. 2 in which both surfaces are held by polymer gels 210A and 210B.

  The lipid bilayer membrane 222 held by the solid polymer gels 210A and 210B is considered to have high stability. However, although it is easy to form a monolayer lipid membrane on the surface of the polymer gels 210A and 210B by the LB (Langmuir Projet) method, the polymer gels 210A and 210B on which the monolayer lipid membrane is formed Bonding together to form the lipid bilayer membrane 222 is not easy.

JP, 2012-205536, A JP-A-5-7770

  Embodiments of the present invention provide a lipid bilayer device having a highly stable lipid bilayer membrane, the lipid bilayer membrane device array including a plurality of the lipid bilayer membrane devices, and the lipid bilayer membrane device easily. An object of the present invention is to provide a lipid bilayer device production apparatus that can be produced, and a method for producing the lipid bilayer device that can easily produce a lipid bilayer device having a highly stable lipid bilayer membrane.

The lipid bilayer membrane device of one embodiment of the present invention is a convex shape having a curved tip surface, and is a conductive water-containing material, in which protrusions made of gel or solid material and a conductive aqueous solution are stored , A storage tank in which an oily solution layer in which lipids are dissolved covers the liquid surface of the aqueous solution, a tip surface of the protrusion disposed above the oily solution layer, and the liquid surface of the aqueous solution And a lipid bilayer membrane composed of the lipid formed between the two.

In addition, the lipid bilayer membrane device array of one embodiment of the present invention is a convex shape having a curved tip surface, a conductive water-containing material, a protrusion made of a gel or a solid material , a conductive aqueous solution, An oily solution layer covering the liquid surface of the aqueous solution, in which lipids are dissolved, a tip surface of the protrusion disposed above the oily solution layer, and the liquid surface of the aqueous solution. And a plurality of lipid bilayer membrane devices each comprising the lipid bilayer membrane formed of the lipid.

Moreover, the lipid bilayer membrane device manufacturing apparatus according to one aspect of the present invention is a storage tank in which a conductive aqueous solution is stored , and an oily solution layer in which lipid is dissolved floats on the liquid surface of the aqueous solution ; A conductive water-containing material, which is made of a gel or a solid material, and has a protruding tip surface having a curved surface disposed above the oily solution layer, the tip surface of the protruding portion, and the aqueous solution And a drive part that moves either of the oily solution layers so that an interface between them and the oily solution layer are close to each other, and a lipid double layer is provided between the tip surface of the protrusion and the liquid surface of the aqueous solution. A film is formed .

Further, in the method for producing a lipid bilayer membrane device of one embodiment of the present invention, an oily solution in which lipid is dissolved is introduced so as to cover the liquid surface of the conductive aqueous solution in the liquid storage tank, and the oily solution layer A projecting tip surface formed of a curved surface of a protruding portion made of a gel or a solid material, and a driving portion. A step of forming a lipid bilayer composed of the lipid by moving the tip surface of the protrusion and the interface between the aqueous solution and the oily solution layer in proximity to each other. .

  According to an embodiment of the present invention, a lipid bilayer device having a highly stable lipid bilayer membrane, the lipid bilayer membrane device array including a plurality of the lipid bilayer membrane devices, and the lipid bilayer membrane device An apparatus for producing a lipid bilayer membrane device that can be easily produced and a method for producing the lipid bilayer membrane device capable of easily producing a lipid bilayer membrane device having a highly stable lipid bilayer membrane can be provided.

It is a top view of the conventional lipid bilayer membrane device. It is sectional drawing of the conventional lipid bilayer membrane device. It is a figure for demonstrating the structure of the lipid bilayer membrane device manufacturing apparatus of 1st Embodiment. It is a figure for demonstrating the structure of the lipid bilayer membrane device of 1st Embodiment. It is a flowchart for demonstrating the manufacturing method of the lipid bilayer membrane device of 1st Embodiment. It is a figure for demonstrating the manufacturing method of the lipid bilayer membrane device of 1st Embodiment. It is a figure for demonstrating the structure of the lipid bilayer membrane device of the modification 1 of 1st Embodiment. It is a figure for demonstrating the manufacturing method of the lipid bilayer membrane device of the modification 1 of 1st Embodiment. It is a figure for demonstrating the manufacturing method of the lipid bilayer membrane device of the modification 2 of 1st Embodiment. It is a figure which shows the electric current measurement by the lipid bilayer membrane device of the modification 2 of 1st Embodiment. It is a figure for demonstrating the structure of the lipid bilayer membrane device manufacturing apparatus of 2nd Embodiment. It is a figure for demonstrating the structure of the lipid bilayer membrane device manufacturing apparatus of 2nd Embodiment.

<First Embodiment>
As shown in FIGS. 3 and 4, the lipid bilayer device (hereinafter also referred to as “LB device”) 1 of the present embodiment includes a protrusion 10 and a liquid storage tank 40. The liquid storage tank 40 is made of resin such as PDMS (polydimethylsiloxane) or fluororesin, silicon, Pyrex (registered trademark) glass, or the like. The protrusion 10 is a convex shape having a curved end surface and is made of a conductive water-containing material. In the liquid storage tank 40, a conductive aqueous solution 30 in which the oil solution layer 20 covers the liquid surface is stored. A lipid 21 is dissolved in the oily solution layer 20. A lipid bilayer membrane 22 made of lipid 21 is formed between the tip surface of the protrusion 10 and the liquid surface of the aqueous solution 30.

  An electrode 62 is disposed on the protrusion 10, and an electrode 63 is disposed on the liquid storage tank 40. The electrodes 62 and 63 constitute a pair of electrodes for measuring the electrical resistance between the protrusion 10 and the aqueous solution 30.

  And the manufacturing apparatus 2 of the lipid bilayer membrane device of this embodiment comprises the LB device 1, the pump 50 which is a drive part, and the detection part 61. FIG. The pump 50 is an aqueous solution injection part that injects the aqueous solution 30 into the liquid storage tank 40 to raise the liquid level. In other words, the pump 50 is a drive unit that changes the relative positions of the tip surface 10SA of the protrusion 10 and the interface between the aqueous solution 30 and the oil solution layer 20 so as to be close to each other. The pump 50A supplies an oily solution.

  The detection unit 61 is a power source that measures the electrical resistance by applying electricity between the pair of electrodes 62 and 63. The constant voltage control detector 61 measures current, and the constant voltage drive detector 61 measures voltage. That is, the detection unit 61 does not measure the electrical resistance itself, but indirectly measures the electrical resistance by measuring a current or a voltage.

  Next, the manufacturing method of the lipid bilayer membrane device 1 using the lipid bilayer membrane device manufacturing apparatus 2 is demonstrated along the flowchart of FIG.

<Step S11>
The aqueous solution 30 is introduced into the liquid storage tank 40. The aqueous solution 30 may be poured through a pump 50 or may be poured from an opening at the top of the liquid storage tank 40.

  The aqueous solution 30 may contain any component as long as it is a conductive aqueous solution as long as it does not affect the formation of the lipid bilayer membrane. As the aqueous solution 30, a pH buffered physiological saline was used.

<Step S12>
The oily solution is introduced by the pump 50A, and the oily solution layer 20 that covers the liquid surface of the aqueous solution 30 is formed. The oily solution is preferably supplied from above the liquid level 30 SA of the aqueous solution 30 to the liquid level of the aqueous solution 30 along the wall surface of the liquid storage tank 40, for example. The lipid 21 is dissolved in the oily solvent of the oily solution layer 20.
When covered with the oily solution layer 20, the liquid level 30 SA of the aqueous solution 30 becomes an interface 30 SA with the oily solution layer 20.

  As shown in FIG. 6A, the lipid 21 of the oily solution layer 20 forms a monomolecular film having a hydrophilic group directed to the aqueous solution 30 at the interface 30SA with the aqueous solution 30.

  The lipid 21 is a lipid bilayer membrane-forming component and has a hydrophilic group (hydrophilic atomic group) and a hydrophobic group (hydrophobic atomic group). The lipid 21 is appropriately selected from, for example, phospholipid, glycolipid, cholesterol, or other compounds according to the lipid bilayer to be formed. The phospholipid is phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin and the like. The glycolipid is cerebroside, ganglioside or the like.

  On the other hand, the oily solvent for dissolving the lipid 21 is selected from various organic solvents such as hexadecane and squalene. The oily solvent is insulative.

  For example, an oily solution layer 20 composed of an oily solution in which 5-20 mg / mL of phosphasidylcholine (DPhPC, 850356C, Avanti Polar Lipids INC, Funakoshi Co., Ltd.) was added as a lipid to an oily solvent hexadecane was formed.

<Step S13>
As shown in FIG. 6 (A), the protrusion 10 is disposed above the liquid storage tank 40, that is, above the oily solution layer 20. The distance between the tip surface of the protrusion 10 and the interface 30SA between the aqueous solution 30 and the oil solution layer 20 is defined as d. Of course, step S13 may be performed before step S11.

  The protrusion 10 is a solid made of a water-containing material. The water-containing material is appropriately selected from solid materials that can contain water, such as sponge, glass fiber sheet, polymer gel, or paper. The water content of the protrusion 10 is preferably 30% by weight or more and 99% by weight or less, and particularly preferably 80% by weight or more and 99% by weight or less. Within the above range, moderate rigidity and imparting electrical conductivity are easy.

  The protrusion part 10 of embodiment consists of agarose which is a polymer gel. Specifically, the protrusion 10 is obtained by heating a dispersed aqueous solution of agarose, dissolving agarose, adding a conductive component such as sodium salt or potassium salt, and then pouring into a hollow mold and solidifying at room temperature. Produced. The electrode 62 may be inserted or joined to the solidified protrusion 10 or may be inserted before solidification.

  As the polymer gel, a material that gels at a physiological temperature such as polyacrylamide or methylcellulose may be used.

  In FIG. 6A and the like, the tip end of the rod-like protrusion 10 is illustrated in a substantially hemispherical shape for the sake of explanation. However, as will be described later, at least the tip surface 10SA is a convex shape having a curved surface. Good.

  Further, the protruding portion 10 may be configured by forming a thin agarose layer on the surface of the tip surface 10SA of the electrode 62 by using, for example, a dipping method, using the convex electrode 62 whose tip surface 10SA is a curved surface. Good.

<Step S14>
The detection unit 61 starts measuring the electrical resistance between the electrode 62 and the electrode 63, that is, the electrical resistance between the protrusion 10 and the aqueous solution 30. When the tip surface of the protrusion 10 is above the oily solution layer 20, the air layer is interposed, so that the resistance is very high because the electrodes are insulated.

  The voltage or current applied between the electrodes is selected according to the specification. An AC signal may be applied.

  3 illustrates the electrode 63 disposed on the bottom surface of the liquid storage tank 40, the electrode 63 may be disposed on the side surface of the liquid storage tank 40 as long as the electrode 63 is in contact with the aqueous solution 30. . Further, the liquid storage tank 40 may be made of a conductor, and the function of the electrode 63 may be provided.

<Step S15>
The aqueous solution 30 is additionally injected little by little from below the oily solution layer 20 by the pump 50. That is, since the volume of the aqueous solution 30 inside the liquid storage tank 40 increases, the interface between the aqueous solution 30 and the oily solution layer 20 moves upward little by little. That is, the distance d between the aqueous solution 30 and the interface 30SA between the oily solution layer 20 decreases. As the pump 50, a syringe pump capable of accurately controlling a small flow rate is particularly preferable.

As shown in FIG. 6 (B), when the tip surface of the protrusion 10 is immersed in the oily solution layer 20, the lipid 21 of the oily solution layer 20 causes the protrusion of the hydrophilic group on the tip surface 10SA of the protrusion 10. A monomolecular film directed to 10 is formed.

Even if the tip surface of the protrusion 10 is immersed in the oily solution layer 20, since there is an insulating oily solvent between the electrodes 62 and 63, the resistance is so high that it cannot be measured by a general-purpose evaluation machine. .
<Step S16>
The aqueous solution 30 is continuously injected (S15) until the electrical resistance detected by the detection unit 61 decreases rapidly.

<Step S17>
When the aqueous solution 30 is further injected as shown in FIG. 6C, the lipid bilayer membrane 22 is formed between the protrusion 10 and the liquid surface 30SA of the aqueous solution 30. When the lipid bilayer membrane 22 is formed, the electrical resistance between the electrodes 62 and 63 is rapidly reduced to a measurable order of several gigaohms.

  When the detection unit 61 detects the formation of the lipid bilayer membrane 22, the injection of the aqueous solution 30 ends. By introducing the membrane protein 31 into the aqueous solution 30 after the formation of the lipid bilayer membrane 22, the membrane protein 31 can be incorporated into the lipid bilayer membrane 22.

  The thickness of the lipid bilayer membrane 22, that is, the distance d between the protrusion 10 and the liquid surface 30SA of the aqueous solution 30, varies depending on the type of lipid 21, but is, for example, 5 nm or more and 20 nm or less.

  For this reason, it is very important that the front end surface 10SA of the protrusion 10 is a convex shape having a curved surface. For example, if the tip surface 10SA is a flat surface, it is not easy to control the distance d to the thickness of the lipid bilayer membrane 22. On the other hand, in the convex projection having the tip surface 10SA made of a curved surface, even if the distance d is slightly smaller than the thickness of the lipid bilayer membrane 22, a ring-shaped lipid bilayer is formed on a part of the tip surface 10SA. A heavy film 22 can be formed.

  That is, in the lipid bilayer membrane device 1, the lipid bilayer membrane 22 is not formed on the entire surface of the distal end surface 10SA, but is formed only on a part of the distal end surface 10SA. The allowable range is widened.

  The curvature radius of the curved surface of the tip surface 10SA is preferably D or more and 100D or less when the radius of the protrusion 10 is D. If it is less than the above range, the area of the lipid bilayer membrane 22 is small, and if it exceeds the above range, the allowable range of the distance d becomes large.

  The lipid bilayer membrane 22 of the lipid bilayer device 1 is formed between the protrusion 10 that is a solid and the liquid surface of the aqueous solution 30 that is a liquid. For this reason, the lipid bilayer membrane 22 is less susceptible to disturbances and the like and has high stability. The lipid bilayer membrane 22 can be easily manufactured by using the lipid bilayer device manufacturing apparatus 2.

<Variation 1 of the first embodiment>
Next, the lipid bilayer membrane device 1A, the lipid bilayer membrane device manufacturing apparatus 2A, and the like according to the first modification of the first embodiment will be described. Since the lipid bilayer membrane device 1A is similar to the lipid bilayer membrane device 1, components having the same function are denoted by the same reference numerals and description thereof is omitted.

  The lipid bilayer device 1 has a pump 50 that can easily realize ultra-low speed movement as a drive unit for changing the distance d between the protrusion 10 and the liquid level 30SA of the aqueous solution 30. However, you may use the drive part which descends the projection part 10, or the drive part which raises the liquid storage tank 40. FIG. In other words, the drive unit only needs to be able to move either the tip surface 10SA of the protrusion 10 and the interface 30SA between the aqueous solution 30 and the oil solution layer 20 in proximity to each other.

  As shown in FIG. 7, the drive unit 50A of the lipid bilayer device 1A is a mechanical drive unit that pushes down the protrusion 10A. That is, the drive unit 50A pushes down the push rod 11 that contacts the upper surface of the protrusion 10A. The push rod 11 is preferably made of a conductive material such as copper, but may be a non-conductive material as long as it is electrically connected to the protrusion 10A by a conductive wire or the like.

  The liquid storage tank 40A has a hole at the top where the protrusion 10A can be inserted without any gap. As shown in FIG. 8A, monomolecular films of lipids 21 are formed on the upper and lower surfaces of the oily solution layer 20 inside the pores. When the protruding portion 10A is pushed down, the oily solution layer 20 is gradually discharged from the discharging portion, and as shown in FIG. 8B, a lipid bilayer membrane 22 is formed at the interface between the protruding portion 10A and the aqueous solution 30. .

  The modified lipid bilayer membrane device 1A (lipid bilayer membrane device manufacturing apparatus 2A) has the same effects as the lipid bilayer membrane device 1.

<Modification 2 of the first embodiment>
Next, a lipid bilayer membrane device 1B and a lipid bilayer membrane device manufacturing apparatus 2B according to Modification 2 of the first embodiment will be described. Since the lipid bilayer membrane device 1B is similar to the lipid bilayer membrane device 1, components having the same function are denoted by the same reference numerals and description thereof is omitted.

  In the first embodiment, pH buffered saline is used for the aqueous solution 30. On the other hand, the lipid bilayer membrane 22 in which the membrane protein is incorporated can be produced by using an aqueous solution in which the membrane protein is dissolved.

  That is, in the lipid bilayer device 1B, after the lipid bilayer membrane 22 is formed, when the aqueous solution in which the membrane protein is dissolved is injected so as to push the aqueous solution 30 out of the waste liquid port (not shown), Membrane proteins are incorporated into the membrane 22. The lipid bilayer device 1B may include a discharge pump that discharges the aqueous solution 30.

  For example, as shown in FIG. 9, when hemocillin is used as the membrane protein 31, the incorporated hemolysin forms a heptamer 31 </ b> S and a micropore penetrating the lipid bilayer membrane 22 is formed.

  As an aqueous solution 30, 1 μg / mL of α-hemolysin (H9395—0.5 mg, Sigma-Aldrich Japan) was added to Hanks buffered salt solution (Ca +) 14025 (Life Technologies Japan).

  FIG. 10 shows the time change of current when the detection unit 61 applies a constant voltage signal of 60 mV between the electrodes (62, 63). At time t1, the current increases sharply by 25 pA. This increase in current confirms formation of the lipid bilayer membrane 22 and incorporation of hemocillin into the lipid bilayer membrane 22.

  The reason that the current once decreased at time t2 is that the incorporated hemocillin was detached but immediately incorporated again. The reason why the current further increased by 25 pA at the time t3 is that hemosperin heptamer was incorporated at two locations of the lipid bilayer membrane 22 and two through holes were formed.

When the detection unit 61 applied a low voltage signal of 30 mV, the current increase pitch was about 12 pA, and when the detection unit 61 applied a 90 mV low voltage signal, the current increase pitch was about 37 pA. That is, the resistance value of the through-hole formed by the hemomerin heptamer is about 2.5 × 10 ⁶ ohms.

  The electrical resistance of the lipid bilayer membrane 22 in which the membrane protein is incorporated is very small as compared with the case where the membrane protein is not incorporated. For this reason, in the lipid bilayer membrane device 1B (lipid bilayer membrane device manufacturing apparatus 2B) of a modification, formation of a lipid bilayer membrane can be detected more reliably.

Second Embodiment
Next, the lipid bilayer device array 3 and the lipid bilayer device array manufacturing apparatus 2C according to the second embodiment will be described. Since the lipid bilayer device array 3 and the like are similar to the lipid bilayer device 1, the same reference numerals are given to components having the same function, and description thereof is omitted.
As shown in FIGS. 9 and 10, the lipid bilayer device array 3 of the present embodiment includes a plurality of lipid bilayer devices 1C1 to 1C3.

  In addition, in FIG. 9 etc., the state where three lipid bilayer membrane devices 1C1 to 1C3 are arranged one-dimensionally, that is, linearly, is illustrated for explanation. However, it is preferable that a plurality of lipid bilayer membrane devices are arranged two-dimensionally, for example, 10 to 100.

  The plurality of lipid bilayer devices 1C1 to 1C3 of the lipid bilayer device array 3 can be separated. That is, the liquid storage tank 40C is manufactured by fitting the three liquid storage tanks 40C1 to 40C3 into the recesses of the substrate 40C4.

  The lipid bilayer membrane devices 1C1 to 1C3 can separate the storage tanks 40C1 to 40C3 together with the protrusions 10C1 to 10C3 from the substrate 40C4 after forming the lipid bilayer membranes 22C1 to 22C3 by the manufacturing method described above. Needless to say, the inlet of the aqueous solution 30 is sealed before the separation.

  The separated lipid bilayer membrane devices 1C1 to 1C3 can be used, for example, as environmental monitor sensors by moving to the respective measurement locations.

In the lipid bilayer device array 3 shown in FIG. 9 and the like, the detection unit 61 detects the electrical resistance between the electrode 62C2 of one protrusion 10C2 and the electrode 63C2, and the lipid bilayer membrane 22C2 Detecting formation.
However, the electrical resistance may be measured by connecting the electrodes of the lipid bilayer membrane devices 1C1 to 1C3 in parallel.

  Moreover, you may form the lipid bilayer membrane in which membrane protein is integrated using the aqueous solution which membrane protein melt | dissolved like the lipid bilayer membrane device of the modification of 1st Embodiment.

  In addition, although it may not be easy to arrange | position correctly the position (height) of the front end surface of the protrusion part 10, even if it is not yield 100% but yield 50%, a lipid bilayer membrane device The array 3 can simultaneously produce a large number of lipid bilayer membrane devices 1C.

  In addition, the lipid bilayer membrane devices 1C1 to 1C3 may be formed with lipid bilayer membranes 22C1 to 22C3 having different lipids or different areas. That is, the types of lipids in the oily solution layers 20C1 to 20C3 may be different. Further, the shapes of the protrusions 10C1 to 10C3 may be different.

  According to the lipid bilayer membrane device array 3 of the present embodiment, a plurality of lipid bilayer membrane devices 1C1 to 1C3 can be manufactured simultaneously and collectively. And each lipid bilayer membrane device 1C1-1C3 has the effect of the lipid bilayer membrane device 1 already demonstrated.

  The present invention is not limited to the above-described embodiments, and various changes and modifications can be made without departing from the scope of the present invention.

DESCRIPTION OF SYMBOLS 1, 1A, 1B, 1C1-1C3 ... Lipid bilayer device, 2 ... Lipid bilayer device manufacturing apparatus, 3 ... Lipid bilayer device array, 10 ... Protrusion part, 20 ... Oil solution layer, 21 ... Lipid, DESCRIPTION OF SYMBOLS 22 ... Lipid bilayer membrane, 30 ... Aqueous solution, 30SA ... Liquid surface (interface), 31 ... Membrane protein, 40 ... Reservoir, 50 ... Pump, 61 ... Detection part, 62 ... Electrode, 63 ... Electrode

Claims (15)

The tip surface is a convex shape consisting of a curved surface, a conductive water-containing material, and a protrusion made of a gel or a solid material,
A liquid storage tank in which a conductive aqueous solution is stored and an oily solution layer in which lipids are dissolved covers the liquid surface of the aqueous solution ;
It comprises a lipid bilayer membrane composed of the lipid formed between the tip surface of the protrusion disposed above the oily solution layer and the liquid surface of the aqueous solution. Lipid bilayer device.   The lipid bilayer device according to claim 1, further comprising a pair of electrodes for measuring an electric resistance between the protrusion and the aqueous solution. Injection into the reservoir of the aqueous solution by a pump, or by increase of the storage tank by the driving unit, the liquid level of the aqueous solution, by raising, with the front end surface is the liquid level of the aqueous solution The lipid bilayer device according to claim 1, wherein the lipid bilayer membrane is formed adjacent to each other. Membrane protein is dissolved in the aqueous solution,
The lipid bilayer device according to claim 1, wherein the membrane protein is incorporated into the lipid bilayer membrane. The tip surface is a convex shape having a curved surface, and is an electrically conductive water-containing material, which is a gel or solid material projection, an electrically conductive aqueous solution, and covers the liquid surface of the aqueous solution. An oily solution layer, a tip end surface of the protrusion disposed above the oily solution layer, and a lipid bilayer membrane made of the lipid formed between the liquid surface of the aqueous solution, respectively A lipid bilayer membrane device array comprising a plurality of lipid bilayer membrane devices. The tip surface of the aqueous solution rises as the liquid level of the aqueous solution rises due to the injection of the aqueous solution by a pump into the liquid storage tank in which the aqueous solution is stored or the rise of the liquid storage tank by a drive unit. lipid bilayer device array of claim 5, in proximity to the liquid surface, and wherein the lipid bilayer is formed.   6. The lipid bilayer device array according to claim 5, wherein the lipid bilayer device array is separable into each lipid bilayer device.   The lipid bilayer membrane device array according to claim 5, wherein at least one of the lipid bilayer membranes and / or areas of the plurality of lipid bilayer membrane devices are different. A liquid storage tank in which a conductive aqueous solution is stored and an oily solution layer in which lipids are dissolved floats on the liquid surface of the aqueous solution ;
A conductive water-containing material, made of a gel or solid material, and a protruding tip surface having a curved surface disposed above the oily solution layer; and
A drive unit that moves the tip surface of the projection so that the interface between the aqueous solution and the oily solution layer is close to each other, and the tip surface of the projection and the aqueous solution A lipid bilayer device manufacturing apparatus, wherein a lipid bilayer membrane is formed between the liquid level and the liquid surface .   The apparatus for producing a lipid bilayer membrane device according to claim 9, further comprising a detection unit that measures an electrical resistance between the protrusion of the lipid bilayer membrane device and the aqueous solution. The said drive part is an aqueous solution injection | pouring part which forms the said lipid bilayer membrane by inject | pouring the said aqueous solution into the said storage tank with a pump, and raising the said liquid level of the said aqueous solution. An apparatus for producing a lipid bilayer membrane device according to 1. A step in which an oily solution in which lipids are dissolved is introduced so as to cover the liquid surface of the conductive aqueous solution in the liquid storage tank, and an oily solution layer is formed;
A conductive water-containing material, wherein a convex tip surface formed of a curved surface of a protrusion made of a gel or a solid material is disposed above the oily solution layer; and
A step of forming a lipid bilayer composed of the lipid by moving the tip end surface of the protrusion and the interface between the aqueous solution and the oily solution layer close to each other by a driving unit; A method for producing a lipid bilayer membrane device, comprising: 13. The lipid bilayer according to claim 12, wherein the lipid double membrane is formed by raising the interface by injecting the aqueous solution into the liquid storage tank by a pump as the driving unit. Manufacturing method of membrane device.   The lipid bilayer device according to claim 13, wherein the detection unit detects the formation of the lipid bilayer membrane based on a change in electrical resistance between the protrusion and the aqueous solution. Production method.   The method for producing a lipid bilayer device according to claim 14, wherein a membrane protein is dissolved in the aqueous solution, and a lipid bilayer membrane in which the membrane protein is incorporated is formed.

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