WO2018068237A1 - 液晶液滴及制备方法、生物传感器和检测生物样品的方法 - Google Patents

液晶液滴及制备方法、生物传感器和检测生物样品的方法 Download PDF

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WO2018068237A1
WO2018068237A1 PCT/CN2016/101933 CN2016101933W WO2018068237A1 WO 2018068237 A1 WO2018068237 A1 WO 2018068237A1 CN 2016101933 W CN2016101933 W CN 2016101933W WO 2018068237 A1 WO2018068237 A1 WO 2018068237A1
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liquid crystal
crystal droplets
molecules
dna
droplets
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French (fr)
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杨忠强
刘冬生
梁晓
田艺
董原辰
张懿暘
周京生
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Tsinghua University
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/21—Polarisation-affecting properties
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/41—Refractivity; Phase-affecting properties, e.g. optical path length

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  • the present invention relates to the field of materials, and in particular, to liquid crystal droplets and methods of making, biosensors, and methods of detecting samples.
  • the liquid crystal state is a "soft state" between a solid crystal and a disordered liquid.
  • Liquid crystal molecules have long-range order and optical anisotropy and have been widely used in the field of flat display.
  • the Abbott Research Group of the University of Wisconsin in the United States used liquid crystal molecules to construct biosensors for the first time, opening up a new field of liquid crystal applications.
  • the liquid crystal biosensor is easy to realize miniaturization and array, and has the advantages of simple structure, simple and rapid detection, and has broad application prospects in the fields of life science, clinical medicine and food safety.
  • the basic principle of the liquid crystal sensor is: the orientation of the liquid crystal molecules is changed after the combination with the analyte, thereby changing the refractive power of the liquid crystal molecules, and the polarization change of the liquid crystal molecules is detected by a polarizing microscope to realize the detection of the object to be tested.
  • the liquid crystal droplets with sensing function prepared by the conventional method often have the following problems: the obtained liquid crystal droplets are not uniform in size and insufficient in number, and it is impossible to observe sufficient liquid crystal droplets in the field of view of the polarizer. In turn, the sensing effect is affected; when there is a sample in the environment, the orientation change of the liquid crystal droplets is not obvious, that is, the obvious change of the liquid crystal droplets cannot be observed under the polarizing microscope, thereby affecting the detection.
  • the inventors have conducted extensive experiments and in-depth research and found that this is because the current liquid crystal droplet preparation method cannot obtain liquid crystal droplets of uniform size and sufficient quantity.
  • liquid crystal droplets need to be used for biosensing
  • the prepared liquid crystal droplets are often mixed with the amphiphilic molecules having the sensing function, so that the parent molecules and the liquid crystal molecules in the liquid crystal droplets self-assemble to form a parent.
  • Molecular liquid crystal droplets Molecular liquid crystal droplets.
  • liquid crystal molecules and amphiphilic molecules cannot form an effective assembly, or the number of liquid crystal droplets capable of forming an effective assembly is insufficient, thereby causing liquid crystal droplets to fail to be tested in the environment. Conduct sensitive, fast and efficient testing.
  • the present invention aims to solve at least one of the technical problems in the related art to some extent.
  • the invention proposes a method of preparing liquid crystal droplets.
  • the method comprises: mixing liquid crystal molecules and amphiphilic molecules to form a mixture; and placing an ultrasonic wave emitting source in the mixture, and emulsification treating the mixture to obtain the liquid crystal droplets.
  • the liquid crystal molecules and the amphiphilic molecules can be effectively assembled, and the obtained liquid crystal droplets have a large number and uniformity, and can quickly, sensitively and effectively detect the substance to be tested in the environment in which the liquid crystal droplets are located, wherein , the analyte can be generated with the parent molecule Combine.
  • the liquid crystal molecules have a liquid crystal phase at room temperature.
  • the liquid crystal droplets can complete the detection of the object to be tested in an environment without heating or cooling treatment, thereby facilitating the application of the liquid crystal droplets.
  • the liquid crystal molecules comprise 5CB.
  • the liquid crystal molecules can be assembled directly with the amphiphilic molecules by direct phacoemulsification at normal temperature, thereby further improving the efficiency and effect of the liquid crystal droplets of the method.
  • the amphiphilic molecule comprises at least one selected from the group consisting of a biosensing amphiphilic molecule, SDS, CTAB, and DTAB.
  • the above-mentioned amphiphilic molecule can be effectively assembled with the liquid crystal molecules, and when there is a substance to be tested which can be combined with the above-mentioned parent molecules in the environment, the liquid crystal droplets can be significantly changed in the ability to refract light, thereby facilitating the use of the method.
  • the obtained liquid crystal droplets are used in the field of sensing detection.
  • the biosensing amphiphilic molecule comprises at least one selected from the group consisting of a DNA single-stranded amphiphilic molecule and a phospholipid.
  • the liquid crystal droplets can be used for sensing detection of the biological sample.
  • the DNA single-chain amphiphilic molecule comprises at least one of DNA-C18, DNA-G2CL, DNA-PS, and DNA-PPO.
  • the DNA single-chain amphiphilic molecule modified by the above lipophilic group (C18, G2CL, PS, etc.) can be assembled directly with liquid crystal molecules by direct phacoemulsification treatment at normal temperature, thereby further improving the specific liquid crystal droplets of the method. Efficiency and effectiveness.
  • a volume ratio of the liquid crystal molecules to the amphiphilic molecules is (1:3) to (1:8).
  • the volume ratio of the liquid crystal molecules to the amphiphilic molecules is 1:5.
  • the frequency of the phacoemulsification treatment is from 2 KH to 20 KH.
  • the frequency of the phacoemulsification treatment is from 3 KH to 10 KH.
  • the phacoemulsification treatment time is from 15 to 45 s.
  • the phacoemulsification treatment is carried out using an ultrasonic cell disrupter.
  • the liquid crystal molecules and the amphiphilic molecules can be easily assembled efficiently, and the number of liquid crystal droplets obtained is large and uniform.
  • the invention provides a liquid crystal droplet.
  • the liquid crystal droplets were prepared by the method described above. Thereby, the liquid crystal droplets have effectively assembled liquid crystal molecules and amphiphilic molecules, and the liquid crystal droplets have good uniformity, and can quickly, sensitively and effectively detect the analytes capable of binding with the amphiphilic molecules.
  • the invention provides a biosensor.
  • the biosensor includes liquid crystal droplets, The liquid crystal droplets were prepared by the method described above. Thereby, it is possible to perform rapid, sensitive and effective detection with the object to be tested.
  • the invention provides a method of detecting a sample.
  • the method comprises: (1) providing liquid crystal droplets prepared by the method described above; (2) observing an optical signal of the liquid crystal droplets under a polarizing microscope (3) mixing the sample with the liquid crystal droplets; and (4) observing an optical signal passing through the mixed liquid crystal droplets under a polarizing microscope, and liquid crystal droplets that have not been subjected to the mixing The images are compared to detect the sample. Since the method performs the detection by using the liquid crystal droplets prepared by the method described above, the detection of the sample to be tested can be completed quickly, sensitively and efficiently by observation under a polarizing mirror.
  • FIG. 1 is a schematic view showing the principle of change of light refraction of liquid crystal droplets in the present invention
  • FIG. 3 is a micrograph of a liquid crystal droplet according to Embodiment 1 of the present invention before and after being combined with a DNA single-stranded chain;
  • Figure 4 shows a micrograph of liquid crystal droplets of Comparative Example 1 according to the present invention
  • Figure 5 shows a micrograph of liquid crystal droplets of Comparative Example 2 according to the present invention
  • Fig. 6 is a schematic view showing the principle of combining liquid crystal droplets and DNA single-stranded chains of Example 1 of the present invention.
  • the invention proposes a method of preparing liquid crystal droplets.
  • the liquid crystal droplets prepared by the method have the advantages of uniform size, large number of liquid crystal droplets obtained, large yield, and can effectively assemble the amphiphilic molecules and the liquid crystal molecules, and can be used for at least one of the advantages of sensing and the like.
  • the method comprises: mixing liquid crystal molecules and amphiphilic molecules, placing an ultrasonic wave emitting source in the above mixture, and subjecting the mixture to phacoemulsification to obtain liquid crystal droplets.
  • liquid crystal molecules and the amphiphilic molecules can be effectively assembled, and the obtained liquid crystal droplets have a large number and uniformity, and can quickly, sensitively and effectively detect the object to be tested, wherein the object to be tested is liquid crystal liquid.
  • the specific types of the liquid crystal molecules and the amphiphilic molecules to be used are not particularly limited as long as the two can be effectively self-assembled under the above conditions, and liquid crystal droplets can be formed.
  • the liquid crystal molecules may be liquid crystal molecules having a liquid crystal phase at room temperature.
  • the orientation of the liquid crystal droplets containing the liquid crystal molecules can be changed at room temperature with changes in the content of the surfactant (a parent molecule and a substance to be tested which can specifically bind to the amphiphilic molecule) in the environment, thereby changing the liquid crystal liquid.
  • room temperature and normal temperature specifically mean an ambient temperature which does not require additional heating or cooling treatment, and the specific temperature range thereof is not particularly limited.
  • room temperature and normal temperature refer to an ambient temperature at the time of usual preparation and detection of a test object, and specifically, may be 10 to 30 degrees Celsius.
  • the following is a description of the change in the refractive power of the light generated when the liquid crystal droplets have a sufficient amount of a surfactant (a parent molecule and a substance capable of binding to the amphiphilic molecule) in the environment.
  • a surfactant a parent molecule and a substance capable of binding to the amphiphilic molecule
  • FIG. 1 in the absence of a sufficient amount of surfactant in the environment in which the liquid crystal droplets are located, in the white light field of the microscope (refer to FIG. 1A) and the polarized field of view (refer to FIG. 1B), in the liquid crystal droplets
  • the liquid crystal molecules are arranged in a bipolar state (refer to FIG. 1C), and have characteristic defects unique to the bipolar state (defects indicated by arrows in FIGS.
  • the liquid crystal droplet prepared by the method used in the present invention assembles an appropriate amount of amphiphilic molecules and liquid crystal molecules by a one-step method to form liquid crystal droplets, and when there is a substance capable of specifically binding to the above-mentioned parent molecule in the environment, the substance
  • the binding to the liquid crystal droplets by binding with the amphiphilic molecules is equivalent to increasing the content of the surfactant in the liquid crystal droplet environment, thereby causing the arrangement of the liquid crystal molecules in the liquid crystal droplets to change, and the ability to refract light. Change, and this change can be easily observed by a polarizing microscope to realize the detection of the object to be tested.
  • the term "preparation" should be understood in a broad sense, and a substance prepared by the method may be used as long as it contains liquid crystal droplets. That is to say, the present invention proposes a method for obtaining a liquid crystal material, which can be obtained by combining the surfactant (a parent molecule and a substance which can be combined with a parent molecule) by the method proposed by the present invention, and before and after the combination Liquid crystal droplets whose refractive index changes.
  • the liquid crystal droplets can be dispersed in the solution, and the above-mentioned use function of the liquid crystal droplets can be realized without actually separating the liquid crystal droplets in the solution and the solvent in the solution during actual use.
  • the "liquid crystal droplet" prepared by the above method refers specifically to a liquid crystal molecule and a substance obtained after the assembly of the amphiphilic molecule, the substance may contain a plurality of liquid crystal molecules and a parent molecule assembled therewith, and the liquid crystal liquid When a parent molecule or a substance capable of specifically binding to a parent molecule is dropped in the environment, the ability to refract light can be changed.
  • the amount of liquid crystal molecules and amphiphilic molecules contained in the liquid crystal droplets is not particularly limited.
  • the amphiphilic molecule may comprise a substance selected from the group consisting of biosensing amphiphiles, SDS (sodium dodecyl sulfate), CTAB (cetyltrimethylammonium bromide), and DTAB (dodecyl group). At least one of trimethylammonium bromide).
  • the above-mentioned amphiphilic molecule can be efficiently assembled with the liquid crystal molecules, and when the liquid crystal droplets formed by the assembly have a substance to be tested which can be combined with the above-mentioned parent molecule in the environment, the liquid crystal droplet can be specifically combined with the substance to be tested, thereby making the liquid crystal
  • the ability of the droplet to reflect light is significantly changed, which is beneficial to the application of liquid crystal droplets obtained by this method in the field of sensing detection.
  • the biosensing amphiphilic molecule comprises at least one selected from the group consisting of a DNA single-stranded amphiphilic molecule and a phospholipid.
  • the liquid crystal droplets can be used for sensing detection of the biological sample. For example, detection of DNA capable of pairing with a DNA single-stranded amphiphilic molecule can be utilized.
  • the volume ratio of the liquid crystal molecules to the amphiphilic molecules is 1: (3 to 8).
  • the volume ratio of liquid crystal molecules to amphiphilic molecules may be 1:5.
  • the inventors have intensively studied that the current method for preparing liquid crystal droplets cannot obtain liquid crystal droplets of uniform size and sufficient quantity, mainly because the current method usually acts on an intermediate medium by using an ultrasonic wave source, for example, water, and then water.
  • the intermediate medium acts on the liquid crystal molecules to obtain liquid crystal droplets.
  • the above process often fails to obtain liquid crystal droplets of uniform size, and the amount of liquid crystal droplets in the obtained solution is also very limited.
  • the inventors have conducted intensive research and a large number of experiments and found that when an ultrasonic wave source is directly applied to a mixture containing liquid crystal molecules and amphiphilic molecules (for example, in the present invention, the ultrasonic wave source is directly placed in the mixture), the liquid crystal molecules and the amphiphilic molecules Effective self-assembly can occur, and the number of liquid crystal droplets obtained is large and the size is relatively uniform.
  • the inventors have found through extensive experiments that the conventional method for preparing liquid crystal droplets (the intermediate medium acts on the mixture) can not obtain the present invention even if the frequency of the ultrasonic wave source is adjusted to be much larger than the ultrasonic wave source used in the present invention. The effect obtained by the proposed method.
  • the frequency of the ultrasonic wave source may be 2 KH to 20 KH during the phacoemulsification process.
  • an ultrasonic transmission source having a frequency of 3 kHz to 10 kHz may also be employed.
  • phacoemulsification can be performed at a frequency of 4 KH.
  • the timing of the phacoemulsification process described above is related to the frequency of the ultrasonic source.
  • the time of the above phacoemulsification treatment may be 15 to 45 s.
  • the above mixture can be treated with an ultrasonic cell disrupter.
  • the probe of the ultrasonic cell disrupter can be directly inserted into the mixture for phacoemulsification treatment.
  • the liquid crystal molecules and the DNA single-chain amphiphilic molecules can be efficiently assembled, and the quality of the obtained liquid crystal droplets can be further improved.
  • the specific kind of the DNA single-chain amphiphilic molecule is not particularly limited.
  • a person skilled in the art can select an appropriate DNA single-chain amphiphilic molecule according to the specific kind of liquid crystal molecules and the condition of the analyte to be detected.
  • linear liquid crystal molecules 5CB may be selected as liquid crystal molecules
  • DNA-C18, DNA-G2CL, DNA-PS or DNA-PPO may be selected as a DNA single-chain amphiphilic molecule.
  • the DNA sequence selected may be (TGG TGA AGT AGA TGT GTA).
  • the invention provides a liquid crystal droplet.
  • the liquid crystal droplets were prepared by the method described above.
  • the liquid crystal droplets have all of the features and advantages of the liquid crystal droplets prepared by the method described above, and are not described herein.
  • the liquid crystal droplets contain effectively assembled liquid crystal molecules and amphiphilic molecules, and the liquid crystal droplets have good uniformity, and can quickly, sensitively and effectively detect the analytes capable of binding with the parent molecules. .
  • the invention provides a biosensor.
  • the biosensor comprises liquid crystal droplets prepared by the method described above.
  • the biosensor has all of the features and advantages of the liquid crystal droplets prepared by the method described above, and will not be described herein.
  • rapid, sensitive, and effective detection of a test substance capable of binding to a parent molecule contained in a liquid crystal droplet can be performed.
  • the above biosensor may further contain other components or components capable of realizing the sensing function, and those skilled in the art may select the above-mentioned essential components or components according to specific substances to be detected.
  • the invention provides a method of detecting a sample.
  • the method comprises:
  • the liquid crystal droplets are prepared by the method described above.
  • the liquid crystal droplets contain amphiphilic molecules, whereby detection of a sample capable of specifically binding to the amphiphilic molecule can be achieved.
  • an image of liquid crystal droplets which are not combined with the object to be tested is observed and recorded using a polarizing microscope for subsequent comparative use.
  • the sample in this step, is mixed with liquid crystal droplets.
  • the sample is specifically bound to the amphiphilic molecules in the liquid crystal droplets to change the arrangement direction of the liquid crystal molecules in the liquid crystal droplets, thereby changing the image of the liquid crystal droplets in the microscope.
  • the optical signal of the liquid crystal droplet is observed and compared with the image of the liquid crystal droplet that is not in contact with the sample to be tested to complete the detection of the sample.
  • the image of the liquid crystal droplet will change.
  • the method performs the detection using the liquid crystal droplets prepared by the method described above, the detection of the sample to be tested can be completed quickly, sensitively and efficiently by observation under a polarizing mirror.
  • the invention is illustrated by the following specific examples.
  • the following specific examples are intended to be illustrative only and not to limit the scope of the invention in any way, and unless otherwise specified,
  • the conditions or steps are all conventional and the reagents and materials employed are commercially available.
  • the cell The crusher was QSonica Sonicators, NO: 63736T-07-11.
  • liquid crystal droplets 10 ⁇ L of 5CB was added to 50 ⁇ L of 20 ⁇ M DNA single-stranded amphiphilic DNA-C18, and emulsified by a cell disrupter at 20% power for 30 s to prepare liquid crystal droplets.
  • the number of liquid crystal droplets prepared is numerous and relatively uniform in size.
  • a DNA strand capable of pairing with DNA-C18 was added to the environment of the above liquid crystal droplets.
  • DNA-C18 is successfully assembled with the liquid crystal molecule 5CB
  • DNA strand can agglomerate and bind a plurality of liquid crystal molecules through DNA-C18.
  • the basic principle is shown in Fig. 6.
  • the liquid crystal droplets prepared in Example 1 contained liquid crystal molecules (LC) and DNA-C18 (having a 3' end and a 5' end, wherein the 5' end was attached to the LC).
  • the DNA strand structure employed is a double-stranded DNA having an R1+R2 structure, wherein the R1 end and the R2 end can be complementary to a DNA-C18, respectively.
  • the liquid crystal molecules are efficiently assembled with DNA-C18, and the liquid crystal droplets are agglomerated under the regulation of the presence of the double-stranded DNA having the R1+R2 structure.
  • Example 2 The liquid crystal droplets prepared in Example 1 and the above solution containing the DNA (R1+R2) solution were respectively diluted by 50 times, and the experimental phenomenon was observed by a polarizing microscope.
  • the experimental results are shown in FIG. 3a and 3b are white light microscope images and polarized microscope images of liquid crystal droplets prepared in Example 1;
  • FIG. 3c and FIG. 3d are white light microscope images and polarizing microscopes of liquid crystal droplets added with DNA (R1+R2). image. It is not difficult to see that liquid crystal droplets have a clear agglomeration phenomenon.
  • the single-stranded DNA-parent molecule is assembled on the liquid crystal droplets, so that the single-stranded DNA-parent molecules on the liquid crystal droplets are complementaryly paired, so that a large amount of agglomeration occurs in the liquid crystal droplets, thereby demonstrating single-stranded DNA-
  • the amphiphilic molecules self-assemble on the liquid crystal droplets.
  • Fig. 4 A microscopic image of the obtained liquid crystal droplets is shown in Fig. 4 (Fig. 4a is an image in a white light field of view, and Fig. 4b is an image in a polarized field of view). Among them, the number of liquid crystal droplets is significantly less, and the size of the liquid crystal droplets is also very uneven.

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Abstract

提出了液晶液滴及制备方法、生物传感器和检测生物样品的方法。该方法包括：将液晶分子以及双亲分子混合以便形成混合物；以及将超声波发射源置于所述混合物中，超声乳化处理所述混合物，以便获得所述液晶液滴。

Description

液晶液滴及制备方法、生物传感器和检测生物样品的方法 技术领域
本发明涉及材料领域，具体地，本发明涉及液晶液滴及制备方法、生物传感器和检测样品的方法。
背景技术
液晶态是一种处于固态晶体和无序液体之间的“软物质态”。液晶分子具有长程有序性和光学各向异性，已被广泛应用于平面显示领域。1998年美国威斯康星大学Abbott研究组首次利用液晶分子构建生物传感器，开辟了液晶应用新领域。液晶生物传感器易于实现微型化和阵列化，具备结构简单、检测简便快速等优点，在生命科学、临床医学和食品安全领域具有广阔的应用前景。液晶传感器的基本原理是：液晶分子与待测物结合后取向发生变化，从而改变液晶分子对光线的折射能力，应用偏光显微镜检测液晶分子的折射变化，即可实现对待测物的检测。
然而，目前制备液晶液滴的方法以及液晶生物传感器仍有待改进。
发明内容
本申请是基于发明人对以下事实和问题的发现和认识作出的：
目前利用传统方法制备的带有传感功能的液晶液滴，常常存在以下问题：获得的液晶液滴大小不均匀、数量不充足，导致无法在偏光镜的视野中观察到足够的液晶液滴，进而影响传感检测效果；在环境中存在待测物时，液晶液滴的取向变化不明显，即无法在偏光显微镜下观察到液晶液滴的明显变化，从而影响检测。发明人经过大量实验以及深入研究发现，这是由于目前的液晶液滴制备方法无法获得大小均一、数量充足的液晶液滴。并且，在需要利用液晶液滴进行生物传感时，常常利用制备好的液晶液滴与具有传感功能的双亲分子混合，使上述双亲分子与液晶液滴中的液晶分子自组装，形成具有双亲分子的液晶液滴。然而目前的液晶液滴中液晶分子与双亲分子之间不能够形成有效的组装，或是能够形成有效组装的液晶液滴数目不足，进而导致了液晶液滴不能够对其环境中的待测物进行灵敏、快速、有效的检测。
本发明旨在至少在一定程度上解决相关技术中的技术问题之一。
在本发明的第一方面，本发明提出了一种制备液晶液滴的方法。根据本发明的实施例，该方法包括：将液晶分子以及双亲分子混合以便形成混合物；以及将超声波发射源置于所述混合物中，超声乳化处理所述混合物，以便获得所述液晶液滴。由此，可以使液晶分子以及双亲分子发生有效的组装，获得的液晶液滴数量多、均一性好，能够对该液晶液滴所在环境中的待测物质进行快速、灵敏、有效的检测，其中，待测物之能够与双亲分子发生 结合。
根据本发明的实施例，所述液晶分子在室温下具有液晶相。由此，该液晶液滴可以在不加热或者冷却处理的环境中，完成对待测物的检测，从而便于该液晶液滴的应用。
根据本发明的实施例，所述液晶分子包括5CB。上述液晶分子可以在常温下较好地通过直接超声乳化处理，与双亲分子进行组装，从而可以进一步提高该方法之比液晶液滴的效率以及效果。
根据本发明的实施例，所述双亲分子包括选自生物传感双亲分子、SDS、CTAB以及DTAB的至少之一。上述双亲分子可以有效地与液晶分子发生组装，在环境中存在能够与上述双亲分子发生结合的待测物质时，可以使该液晶液滴对光线的折射能力发生显著变化，从而有利于利用该方法获得的液晶液滴应用于传感检测领域。
根据本发明的实施例，所述生物传感双亲分子包括选自DNA单链双亲分子以及磷脂的至少之一。由此，可以利用该液晶液滴进行生物样品的传感检测。
根据本发明的实施例，所述DNA单链双亲分子包括DNA-C18、DNA-G2CL、DNA-PS以及DNA-PPO的至少之一。上述亲油基团(C18、G2CL、PS等)修饰的DNA单链双亲分子可以在常温下较好地通过直接超声乳化处理，与液晶分子进行组装，从而可以进一步提高该方法之比液晶液滴的效率以及效果。
根据本发明的实施例，所述混合物中，所述液晶分子与所述双亲分子的体积比为(1:3)～(1:8)。由此，可以进一步提高形成的液晶液滴的均一性以及质量。
根据本发明的实施例，所述混合物中，所述液晶分子与所述双亲分子的体积比为1:5。由此，可以进一步提高形成的液晶液滴的均一性以及质量。
根据本发明的实施例，所述超声乳化处理的频率为2KH～20KH。由此，可以进一步提高液晶分子以及双亲分子进行组装的效率以及效果。
根据本发明的实施例，所述超声乳化处理的频率为3KH～10KH。由此，可以进一步提高液晶分子以及双亲分子进行组装的效率以及效果。
根据本发明的实施例，所述超声乳化处理的时间为15～45s。由此，可以使液晶分子以及DNA单链双亲分子发生有效的组装，从而可以进一步提高获得的液晶液滴的质量。
根据本发明的实施例，所述超声乳化处理是采用超声波细胞破碎仪实现的。由此，可以简便地使液晶分子以及双亲分子发生有效的组装，获得的液晶液滴数量多、均一性好。
在本发明的另一方面，本发明提出了一种液晶液滴。该液晶液滴是利用前面所述的方法制备的。由此，该液晶液滴中具有有效组装了的液晶分子以及双亲分子，该液晶液滴的均一性好，可以对能够与双亲分子结合的待测物进行快速、灵敏、有效的检测。
在本发明的又一方面，本发明提出了一种生物传感器。该生物传感器包括液晶液滴，该 液晶液滴是由前面所述的方法制备的。由此，可以对能够与待测物进行快速、灵敏、有效的检测。
在本发明的又一方面，本发明提出了一种检测样品的方法。根据本发明的实施例，该方法包括：(1)提供液晶液滴，所述液晶液滴是利用前面所述的方法制备的；(2)在偏光显微镜下观察所述液晶液滴的光学信号；(3)将所述样品与所述液晶液滴混合；以及(4)在偏光显微镜下观察经过所述混合的所述液晶液滴的光学信号，并与未经过所述混合的液晶液滴的像进行比较，以便检测所述样品。由于该方法利用前面描述的方法制备的液晶液滴完成检测，因此可以简便地通过在偏光镜下进行观察，快速、灵敏、有效的完成对待测样品的检测。
附图说明
图1显示了本发明中的液晶液滴对光线折射情况的变化原理示意图；
图2显示了根据本发明实施例1的液晶液滴的显微镜照片；
图3显示了根据本发明实施例1的液晶液滴与DNA单链链结合前后的显微镜照片；
图4显示了根据本发明对比例1的液晶液滴的显微镜照片；
图5显示了根据本发明对比例2的液晶液滴的显微镜照片；以及
图6显示了本发明实施例1的液晶液滴与DNA单链链结合的原理示意图。
具体实施方式
下面详细描述本发明的实施例，所述实施例的示例在附图中示出。下面通过参考附图描述的实施例是示例性的，旨在用于解释本发明，而不能理解为对本发明的限制。
在本发明的第一方面，本发明提出了一种制备液晶液滴的方法。该方法制备的液晶液滴具有尺寸均一、获得的液晶液滴数量多，产量大、能够有效使双亲分子与液晶分子进行组装，可以用于传感检测等优点的至少之一。具体地，根据本发明的实施例，该方法包括：将液晶分子以及双亲分子混合，将超声波发射源置于上述混合物中，对该混合物进行超声乳化处理，以便获得液晶液滴。由此，可以使液晶分子以及双亲分子发生有效的组装，获得的液晶液滴数量多、均一性好，能够对待测物进行快速、灵敏、有效的检测，其中，待测物为可以与液晶液滴中的双亲分子发生结合的物质。
需要说明的是，在该方法中，选用的液晶分子以及双亲分子的具体类型不受特别限制，只要二者能够在上述条件下有效自组装，并形成液晶液滴即可。例如，根据本发明的实施例，液晶分子可以为在室温下具有液晶相的液晶分子。由此，含有上述液晶分子的液晶液滴的取向在常温下即可随环境中表面活性剂(双亲分子以及能够与双亲分子特异性结合的待测物质)含量的改变而改变，从而改变液晶液滴对光线的折射情况，由此，该液晶液滴 可以在不加热或者冷却处理的环境中完成对待测物的检测，便于该液晶液滴的应用。需要说明的是，在本发明中，术语“室温”、“常温”特指不需要额外进行加热或者冷却处理的环境温度，而其具体温度范围不受特别限制。例如，“室温”、“常温”指通常情况下进行制备以及待测物检测等操作时的环境温度，具体地，可以为10～30摄氏度。
为了方便理解，下面首先对液晶液滴在环境中存在足量的表面活性剂(双亲分子及能够与双亲分子进行结合的物质)时，发生的对光线的折射能力的变化情况进行说明。具体地，参考图1，当液晶液滴所在的环境中不存在足量的表面活性剂时，在显微镜的白光视野(参考图1A)以及偏光视野(参考图1B)中，液晶液滴中的液晶分子排列为双极状态(参考图1C)，具有双极状态特有的特征缺陷(图1A以及图1B中箭头所指处，defect)。而当环境中存在足量的表面活性剂时，液晶液滴中液晶分子的排列取向发生变化，从而导致液晶液滴对光线的折射能力发生变化，此时在显微镜的白光视野(参考图1D)以及偏光视野(参考图1E)中，液晶液滴中的液晶分子排列为辐射状态(参考图1F)。本发明采用的方法制备的液晶液滴，通过一步法将适量的双亲分子与液晶分子进行组装，形成液晶液滴，而当环境中具有能够与上述双亲分子进行特异性结合的物质时，该物质通过与双亲分子结合而结合到该液晶液滴中，相当于增加了液晶液滴环境中的表面活性剂的含量，进而导致该液晶液滴中液晶分子的排列方式发生改变，对光线的折射能力改变，而这一改变可以方便地通过偏光显微镜观察出来，进而实现对待测物的检测。需要说明的是，在该方法中，术语“制备”应做广义理解，利用该方法制备而得到的物质中只要含有液晶液滴即可。也即是说，本发明提出了一种获得液晶材料的方法，利用本发明所提出的方法能够获得可以与表面活性剂(双亲分子及可以与双亲分子结合的物质)进行结合，并且结合前后对光线的折射率发生改变的液晶液滴。该液晶液滴可以分散在溶液中，在实际使用过程中，无需对该溶液中的液晶液滴以及溶液中的溶剂进行分离，即可实现该液晶液滴的上述使用功能。在本发明中，利用上述方法制备的“液晶液滴”特指液晶分子以及双亲分子发生组装之后获得的物质，该物质可以含有多个液晶分子以及与其组装在一起的双亲分子，且该液晶液滴在环境中双亲分子或能够与双亲分子特异性结合的物质时，对光线的折射能力能够发生改变。而液晶液滴中所含有的液晶分子、双亲分子的量不受特别限制。
根据本发明的实施例，双亲分子可以包括选自生物传感双亲分子、SDS(十二烷基磺酸钠)、CTAB(十六烷基三甲基溴化铵)以及DTAB(十二烷基三甲基溴化铵)的至少之一。上述双亲分子可以有效地与液晶分子发生组装，且组装形成的液晶液滴在环境中存在能够与上述双亲分子发生结合的待测物质时，可以特异性地与待测物质结合，从而使该液晶液滴对光线的折射能力发生显著变化，有利于利用该方法获得的液晶液滴应用于传感检测领域。
根据本发明的实施例，生物传感双亲分子包括选自DNA单链双亲分子以及磷脂的至少之一。由此，可以利用该液晶液滴进行生物样品的传感检测。例如，可以利用具有DNA单链双亲分子进行能够与之配对的DNA的检测。
根据本发明的实施例，在上述液晶分子以及双亲分子的混合物中，液晶分子与双亲分子的体积比为1：(3～8)。例如，根据本发明的具体实施例，液晶分子与双亲分子的体积比可以为1：5。由此，可以使适量的双亲分子与液晶分子进行组装形成液晶液滴，从而可以进一步提高形成的液晶液滴的质量。
发明人经过深入研究，目前制备液晶液滴的方法无法获得大小均一、数量充足的液晶液滴，主要是由于目前的方法通常是通过超声波发射源作用于中间介质，例如，水，然后再利用水等中间介质作用于含有液晶分子以获得液晶液滴。而上述过程常常不能够获得大小均匀的液晶液滴，且获得的溶液中液晶液滴的数量也十分有限。发明人经过深入研究以及大量实验发现，当采用超声波发射源直接作用于含有液晶分子以及双亲分子的混合物(例如在本发明中，直接将超声波发射源置于混合物中)时，液晶分子以及双亲分子能够发生有效的自组装，获得的液晶液滴数量较多，尺寸较为均一。发明人经过大量实验发现，利用传统的制备液晶液滴的方法(中间介质作用于混合物)，即便是将超声波发射源的频率调节至远大于本发明所采用的超声波发射源，也无法获得本发明所提出的方法获得的效果。根据本发明的实施例，在超声乳化处理过程中，超声波发射源的频率可以为2KH～20KH。根据本发明的另一些实施例，还可以采用频率为3KH～10KH的超声波发射源。例如，可以采用4KH的频率进行超声乳化处理。发明人经过大量实验发现，当处理功率不足时，无法形成数目足够、尺寸均一的液晶液滴，且形成的液晶液滴中，双亲分子与液晶分子也无法有效地组装在一起，从而在后续的待测物检测过程中，严重影响检测的可靠性。而当处理功率过大时，双亲分子与液晶分子也无法有效地组装在一起形成液晶液滴。本领域技术人员能够理解的是，上述超声乳化处理的时间与超声波发射源的频率有关。具体地，根据本发明的实施例，在上述超声乳化处理的时间可以为15～45s。为了方便操作，可以采用超声波细胞破碎仪处理上述混合物。由此，可以简便地获得质量较好的液晶液滴。具体地，可以将超声细胞破碎仪的探头直接伸入到混合物中进行超声乳化处理。由此，可以使液晶分子以及DNA单链双亲分子发生有效的组装，从而可以进一步提高获得的液晶液滴的质量。
需要说明的是，在本发明中，DNA单链双亲分子的具体种类不受特别限制。本领域技术人员可以根据液晶分子的具体种类，以及需要检测的待测物的情况选择适当的DNA单链双亲分子。例如，根据本发明的具体实施例，可以选择线性液晶分子5CB作为液晶分子，选择DNA-C18、DNA-G2CL、DNA-PS或者DNA-PPO作为DNA单链双亲分子。所选择的DNA序列可以为(TGG TGA AGT AGA TGT GTA)。
在本发明的另一方面，本发明提出了一种液晶液滴。该液晶液滴是利用前面所述的方法制备的。由此，该液晶液滴具有利用前面描述的方法制备的液晶液滴的全部特征以及优点，在此不再赘述。总的来说，该液晶液滴中，含有有效组装了的液晶分子以及双亲分子，该液晶液滴的均一性好，可以对能够与双亲分子结合的待测物进行快速、灵敏、有效的检测。
在本发明的又一方面，本发明提出了一种生物传感器。该生物传感器包括液晶液滴，该液晶液滴是由前面所述的方法制备的。由此，该生物传感器具有利用前面描述的方法制备的液晶液滴的全部特征以及优点，在此不再赘述。总的来说，可以对能够与液晶液滴中含有的双亲分子结合的待测物进行快速、灵敏、有效的检测。本领域技术人员能够理解的是，上述生物传感器中还可以含有能够实现传感功能的其余成分或部件，本领域技术人员可以根据需要检测的具体物质，对上述必须成分或部件进行选择。
在本发明的又一方面，本发明提出了一种检测样品的方法。根据本发明的实施例，该方法包括：
(1)提供液晶液滴
根据本发明的实施例，该液晶液滴是利用前面描述的方法制备的。具体地，该液晶液滴中含有双亲分子，由此，可以实现对能够与该双亲分子进行特异性结合的样品的检测。关于该液晶液滴的具体特征以及优点，前面已经进行了详细的描述，在此不再赘述。
(2)观察液晶液滴
根据本发明的实施例，在该步骤中，利用偏光显微镜，观察未与待测物结合时的液晶液滴的像并记录，以便后续对比使用。
(3)混合；
根据本发明的实施例，在该步骤中，将样品与液晶液滴混合。使样品与液晶液滴中的双亲分子特异性结合，改变液晶液滴中液晶分子的排布方向，从而改变液晶液滴在显微镜中的像。
(4)观察经过混合的液晶液滴
根据本发明的实施例，在该步骤中，观察上述液晶液滴的光学信号，并与未接触待测样品的液晶液滴的像进行比较，以便完成样品的检测。当样品中存在目标待测物时，液晶液滴的像将会发生变化。
总的来说，由于该方法利用前面描述的方法制备的液晶液滴完成检测，因此可以简便地通过在偏光镜下进行观察，快速、灵敏、有效的完成对待测样品的检测。
下面通过具体实施例对本发明进行说明，需要说明的是，下面的具体实施例仅仅是用于说明的目的，而不以任何方式限制本发明的范围，另外，如无特殊说明，则未具体记载条件或者步骤的方法均为常规方法，所采用的试剂和材料均可从商业途径获得。其中，细胞 破碎仪采用QSonica Sonicators,NO:63736T-07-11。
实施例1：液晶液滴的制备
将10μL 5CB加入到50μL 20μM DNA单链双亲分子DNA-C18中，用细胞破碎仪20％功率乳化30s以制备液晶液滴。参考图2，制备得到的液晶液滴数目众多，尺寸相对均一。
为了验证双亲分子DNA-C18成功地与液晶分子5CB发生了组装，在上述液晶液滴的环境中加入能够与DNA-C18配对的DNA链。如DNA-C18成功地与液晶分子5CB发生了组装，则在环境中存在能够与DNA-C18配对的DNA链时，上述DNA链能够通过DNA-C18使多个液晶分子之间发生团聚结合。基本原理如图6所示：实施例1中制备的液晶液滴含有液晶分子(LC)以及DNA-C18(具有3’端以及5’端，其中5’端与LC相连)。采用的DNA链结构为具有R1+R2结构的双链DNA，其中R1端以及R2端分别可以与一个DNA-C18互补配对。由此，如实施例1中制备的液晶液滴中，液晶分子与DNA-C18发生了有效的组装，则在具有R1+R2结构的双链DNA存在的调节下，上述液晶液滴将发生团聚。
具体操作如下：
1、取10μL实施例1中制备的液晶液滴置于低吸PC管中，再加入10μL 20μM的DNA(R1+R2)溶液，静置5min左右让其自主装。
2、分别取实施例1制备的液晶液滴以及上述含有DNA(R1+R2)溶液的溶液，格稀释50倍，通过偏光显微镜观察实验现象，实验结果如图3所示。其中，图3a以及图3b为实施例1中制备的液晶液滴的白光显微镜像以及偏光显微镜像；图3c以及图3d为加入DNA(R1+R2)的液晶液滴的白光显微镜像以及偏光显微镜像。不难看出，液晶液滴出现了明显的团聚现象。说明单链DNA-双亲分子组装在了液晶液滴上，使液晶液滴上的单链DNA-双亲分子之间互补配对，故此使液晶液滴出现了大量团聚现象，从而证明了单链DNA-双亲分子自组装在了液晶液滴上。
对比例1
将10μL 5CB加入到1mL PBS缓充液中，30秒超声，30秒涡流震荡仪作为一个周期，经过10—12个周期，以制备液晶液滴。在制备好的液晶液滴中加入单链DNA双亲分子DNA-C18，使其与液晶液滴进行组装。获得的液晶液滴的显微镜图像如图4所示(图4a为白光视场下的像，图4b为偏光视场下的像)。其中，液晶液滴的数目明显较少，且液晶液滴的尺寸也十分不均一。
对比例2
先将10μL 5CB与50μL 20μM单链DNA双亲分子DNA-C18混和，然后30秒超声，30秒涡流震荡仪作为一个周期，经过10—12个周期，以制备液晶液滴。获得的液晶液滴的显微镜图像如图5所示(图5a为白光视场下的像，图5b为偏光视场下的像)。其中，液晶 液滴的数目较对比例1多，但明显少于实施例1，且液晶液滴的尺寸也十分不均一。
在本说明书的描述中，参考术语“一个实施例”、“一些实施例”、“示例”、“具体示例”、或“一些示例”等的描述意指结合该实施例或示例描述的具体特征、结构、材料或者特点包含于本发明的至少一个实施例或示例中。在本说明书中，对上述术语的示意性表述不必须针对的是相同的实施例或示例。而且，描述的具体特征、结构、材料或者特点可以在任一个或多个实施例或示例中以合适的方式结合。此外，在不相互矛盾的情况下，本领域的技术人员可以将本说明书中描述的不同实施例或示例以及不同实施例或示例的特征进行结合和组合。
尽管上面已经示出和描述了本发明的实施例，可以理解的是，上述实施例是示例性的，不能理解为对本发明的限制，本领域的普通技术人员在本发明的范围内可以对上述实施例进行变化、修改、替换和变型。

Claims (15)

  1. 一种制备液晶液滴的方法，其特征在于，包括：
    将液晶分子以及双亲分子混合以便形成混合物；以及
    将超声波发射源置于所述混合物中，超声乳化处理所述混合物，以便获得所述液晶液滴。
  2. 根据权利要求1所述的方法，其特征在于，所述液晶分子在室温下具有液晶相。
  3. 根据权利要求1所述的方法，其特征在于，所述液晶分子包括5CB。
  4. 根据权利要求1所述的方法，其特征在于，所述双亲分子包括生物传感双亲分子、SDS、CTAB以及DTAB的至少之一。
  5. 根据权利要求1所述的方法，其特征在于，所述生物传感双亲分子包括选自DNA单链双亲分子以及磷脂的至少之一。
  6. 根据权利要求4所述的方法，其特征在于，所述DNA单链双亲分子包括DNA-C18、DNA-G2CL、DNA-PS以及DNA-PPO的至少之一。
  7. 根据权利要求1所述的方法，其特征在于，所述混合物中，所述液晶分子与所述双亲分子的体积比为(1:3)～(1:8)。
  8. 根据权利要求7所述的方法，其特征在于，所述混合物中，所述液晶分子与所述双亲分子的体积比为1:5。
  9. 根据权利要求1所述的方法，其特征在于，所述超声乳化处理的频率为2KH～20KH。
  10. 根据权利要求9所述的方法，其特征在于，所述超声乳化处理的频率为3KH～10KH。
  11. 根据权利要求9所述的方法，其特征在于，所述超声乳化处理的时间为15～45s。
  12. 根据权利要求1所述的方法，其特征在于，所述超声乳化处理是采用超声波细胞破碎仪实现的。
  13. 一种液晶液滴，所述液晶液滴是利用权利要求1～12任一项所述的方法制备的。
  14. 一种生物传感器，其特征在于，包括液晶液滴，所述液晶液滴是由权利要求1～12任一项所述的方法制备的。
  15. 一种检测样品的方法，其特征在于，包括：
    (1)提供液晶液滴，所述液晶液滴是利用权利要求1～12任一项所述的方法制备的；
    (2)在偏光显微镜下观察所述液晶液滴的光学信号；
    (3)将所述样品与所述液晶液滴混合；以及
    (4)在偏光显微镜下观察经过所述混合的所述液晶液滴的光学信号，并与未经过所述混合的液晶液滴的像进行比较，以便检测所述样品。
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1346866A (zh) * 2000-10-10 2002-05-01 索尼国际(欧洲)股份有限公司 液晶混合物和液晶单元及带偶极的染料对混合物的应用
CN102414554A (zh) * 2009-04-22 2012-04-11 威斯康星校友研究基金会 采用液晶的分析物检测
CN102526745A (zh) * 2012-02-02 2012-07-04 西安交通大学 一种用微电场控制溶致液晶担载药物分子的缓释方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1346866A (zh) * 2000-10-10 2002-05-01 索尼国际(欧洲)股份有限公司 液晶混合物和液晶单元及带偶极的染料对混合物的应用
CN102414554A (zh) * 2009-04-22 2012-04-11 威斯康星校友研究基金会 采用液晶的分析物检测
CN102526745A (zh) * 2012-02-02 2012-07-04 西安交通大学 一种用微电场控制溶致液晶担载药物分子的缓释方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BRAKE, JEFFREY M. ET AL.: "An Experimental System for Imaging the Reversible Adsorption of Amphiphiles at Aqueous-Liquid Crystal Interfaces", LANGMUIR, vol. 18, 27 June 2002 (2002-06-27), pages 6101 - 6109, XP055604322 *

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