Chiral molecular sensor based on metal nanosphere trimer and identification method

Abstract

The present invention relates to a chiral molecule sensor based on a metal nanosphere trimer and an identification method, comprising two units: a metal nanosphere trimer and a substrate. The sensor units are respectively a substrate and a metal nanosphere trimer from bottom to top. The metal nanosphere trimer is made of one of gold or silver, and the substrate is made of one of silicon, quartz or sapphire. The metal nanosphere trimer is made by self-assembly of a single metal nanosphere through a colloid chemical method. The resonance peak of the metal nanosphere trimer structure proposed by the present invention is in the visible light to near-infrared band, and its CD spectrum is also in the visible light to near-infrared band. A chiral molecule solution is combined with the metal nanosphere trimer, and the chiral molecule enantiomer can be distinguished through the asymmetric movement of the trimer CD spectrum, thereby realizing the identification of the chiral molecule enantiomer in the visible light to near-infrared band. The method has a simple process and is easy to operate. Compared with electron beam lithography technology, it has the characteristics of low price and easy promotion.

Description

Technical Field

[0001] The invention belongs to the field of micro-nano optics and biomedical sensing, and relates to a chiral molecule sensor based on a metal nanosphere trimer and an identification method. Background Art

[0002] Chirality is a property that exists universally in nature. Just like a human hand, the mirror image of a chiral structure cannot overlap with itself. Objects with opposite chirality are called enantiomers. Enantiomers usually have the same chemical and physical properties. They are consistent in molecular formula, molar mass, density, phonon vibration, etc., but enantiomers can induce different chemical and biological results. This phenomenon has a profound impact on biomedicine. A famous example is the drug thalidomide, one of its enantiomers is used for sedation and analgesia, while the other enantiomer can cause limb defects in newborns after being ingested by pregnant women. There are many chiral drugs like this. At present, there are more than 100 chiral drugs in China without clear chirality distinction, facing a huge risk of toxic side effects of chiral drugs. Therefore, the identification of chiral molecular enantiomers is crucial.

[0003] Chiral molecules have different absorption cross sections (circular dichroism) for left-handed circularly polarized light and right-handed circularly polarized light, so optical analysis technology is very suitable for detecting and identifying chiral molecules. Chiral molecules have significant circular dichroism (CD) response in the ultraviolet band, but the ultraviolet band is optically transparent and the detection difficulty is much greater than that in the visible light band. Furthermore, in the visible light band, the scale of chiral molecules is much smaller than the scale of light waves, and its asymmetry factor is generally less than 10 -3 , so the CD response is weaker. In summary, in order to achieve the identification of chiral molecular enantiomers, the weak CD response of chiral molecules must be enhanced first.

[0004] Metal nanostructures have excellent plasmon properties. Their large local field enhancement and superchiral near-field provide an ideal platform for enhancing the CD response of chiral molecules. In order to achieve the enhancement of chiral response, researchers have designed various chiral or non-chiral metal nanostructures to construct superchiral near-fields. Because the superchiral field has a stronger chiral field than circularly polarized light, when chiral molecules combine with the superchiral field, they will show a stronger CD response than the interaction with circularly polarized light. At present, many chiral nanostructures are prepared by electron beam lithography technology, which has the advantage of arbitrary structural design, but its limited scalability and high processing cost limit the wide application of this technology. In comparison, the self-assembly of the structure by chemical means to achieve chiral nanostructures has the characteristics of simple preparation, low price and easy promotion. Among many metal nanostructures, metal nanospheres are widely favored by researchers for their simple structure, easy preparation, stable performance and easy self-assembly. In recent years, chiral dimers of metal nanospheres constructed by self-assembly have been used for chiral molecule sensing, but the field of self-assembly of achiral single metal nanospheres to form chiral trimers to generate CD signals and be used for chiral molecule enantiomer identification is still a blank. Summary of the invention

[0005] Technical issues to be solved

[0006] In order to avoid the shortcomings of the prior art, the present invention proposes a chiral molecule sensor based on a metal nanosphere trimer and an identification method, which improves the weak CD response of chiral molecules to achieve the identification of chiral molecule enantiomers. A chiral molecule sensor based on a metal nanosphere trimer provides a method for identifying chiral molecule enantiomers using the CD signal of a metal nanosphere trimer. The sensor has a detection range from visible light to near-infrared, a simple structure and is easy to prepare.

[0007] Technical Solution

[0008] A chiral molecular sensor based on metal nanosphere trimers, characterized in that it includes metal nanosphere trimers and a substrate; three metal nanosphere trimers are located on the substrate, wherein the diameter of a single metal nanosphere is 100-300nm, the trimer configuration covers various angles such as right angles, obtuse angles, and acute angles, the substrate thickness is 200-2000μm, and the length and width are 0.5-2cm.

[0009] The metal nanosphere trimer is made of gold or silver.

[0010] The substrate is made of silicon, quartz or sapphire.

[0011] A method for enantiomer identification using the chiral molecular sensor based on metal nanosphere trimer, characterized by the following steps:

[0012] Step 1: Drop deionized water on the left-handed (LH) and right-handed (RH) gold nanosphere trimer chiral molecular sensors, use obliquely incident left-handed and right-handed circularly polarized light as excitation light, and measure the dark field scattering spectrum of the sensor through the dark field scattering system; remove the deionized water, and then drop the chiral molecule solution on the LH and RH gold nanosphere trimer chiral molecular sensors to obtain the corresponding dark field scattering spectrum.

[0013] Step 2: Normalize the dark field scattering spectrum to obtain the right-handed excitation scattering spectrum Scat RCP and the scattering spectrum of left-handed excitation Scat LCP , the circular difference scattering spectrum is obtained by the following formula:

[0014] CDS=Scat RCP -Scat LCP

[0015] Step 3: The chirality of the chiral molecule enantiomer is identified by the positive or negative asymmetry factor of the CDS spectrum. When the asymmetry factor is positive, the chirality of the chiral molecule is right-handed. When the asymmetry factor is negative, the chirality of the chiral molecule is left-handed.

[0016] The chiral molecule solution is a right-handed phenylalanine D-phenylalanine, D-PA, and a left-handed phenylalanine L-phenylalanine, L-PA molecule solution.

[0017] The normalization of the obtained dark field scattering spectrum is processed by MATLAB, Origin or Excel.

[0018] Beneficial Effects

[0019] The present invention proposes a chiral molecular sensor based on a metal nanosphere trimer and an identification method, comprising two units: a metal nanosphere trimer and a substrate. The sensor units are respectively a substrate and a metal nanosphere trimer from bottom to top. The metal nanosphere trimer is made of one of gold or silver, and the substrate is made of one of silicon, quartz or sapphire. The metal nanosphere trimer is made of a single metal nanosphere self-assembled by a colloidal chemical method, wherein the diameter of the single metal nanosphere is 100-300nm, the thickness of the substrate is 200-2000μm, and the length and width are 0.5-2cm.

[0020] Compared with the prior art, the advantages of the present invention are:

[0021] 1. The present invention uses metal nanospheres of a hundred nanometers to self-assemble to form chiral metal nanosphere trimers. The method is simple in process and easy to operate. Compared with electron beam lithography, it is inexpensive and easy to promote. The present invention has simple structural excitation conditions, small size, and no biological toxicity, and is more suitable for label-free biomolecule detection.

[0022] Second, the present invention assembles achiral metal nanospheres into trimers, and excites the trimers with obliquely incident circularly polarized light to generate very strong electromagnetic field enhancement and superchiral field, providing a favorable platform for enhancing the CD response of chiral molecules.

[0023] 3. The resonance peak of the metal nanosphere trimer structure proposed by the present invention is in the visible light to near infrared band, and its CD spectrum is also in the visible light to near infrared band. By combining the chiral molecule solution with the metal nanosphere trimer, the chiral molecule enantiomers can be distinguished through the asymmetric shift of the trimer CD spectrum, realizing the identification of chiral molecule enantiomers in the visible light to near infrared band. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 Example of self-assembly result of gold nanosphere trimer

[0025] Figure 2 : A three-dimensional schematic diagram of the geometric structure of the rectangular gold nanosphere trimer chiral molecular sensor described in the embodiment

[0026] Figure 3 : A top view of the left and right hand structures of the rectangular gold nanosphere trimer chiral molecular sensor described in the embodiment

[0027] Figure 4 Figure 2 is a graph showing the CDS changes of the rectangular gold nanosphere trimer chiral molecular sensor described in the embodiment after contacting deionized water and L-PA molecules respectively.

[0028] Figure 5 Figure 2 is a graph showing the CDS changes of the rectangular gold nanosphere trimer chiral molecular sensor described in the embodiment after contacting deionized water and D-PA molecules respectively.

[0029] Figure 6 A comparison of the asymmetry factors of the CDS spectra of the right-angle gold nanosphere trimer chiral molecular sensor described in the embodiment after contact with the phenylalanine enantiomer

[0030] Figure 7 : A comparison of the asymmetry factors of the CDS spectra of the 120° blunt-angle gold nanosphere trimer chiral molecular sensor described in the embodiment after contact with the phenylalanine enantiomer DETAILED DESCRIPTION

[0031] The present invention will now be further described with reference to the embodiments and the accompanying drawings:

[0032] Figure 1 The SEM image of the gold nanosphere trimer self-assembled by the colloidal chemistry method of the present invention includes right-angle, acute-angle and obtuse-angle trimers. Figure 2 The invention provides a right-angle gold nanosphere trimer chiral molecular sensor, which is composed of a trimer 1 and a substrate 2. The trimer 1 is made of gold, and the substrate 2 is made of quartz. Figure 3 for Figure 2 Top views of the left-handed (LH) structure and the right-handed (RH) structure of the structure.

[0033] The trimer 1 and substrate 2 of the present invention are easy to purchase and inexpensive, so the preparation cost of the present invention is low.

[0034] Furthermore, the diameter of the gold nanospheres in the trimer 1 is 100-300 nm, the trimer configuration covers right angles, obtuse angles, and acute angles, the thickness of the substrate 2 is 200-2000 μm, and the length and width are 0.5-2 cm.

[0035] Example 1: The diameter of the gold nanospheres constituting trimer 1 is 160 nm, the configuration of trimer 1 is right angle, the thickness of substrate 2 is 500 μm, and the length and width are 0.7 cm. The chiral molecular sensing with the above parameters is used to perform enantiomer identification experiments.

[0036] A 2 mg / ml solution of right-handed phenylalanine (D-PA) and left-handed phenylalanine (L-PA) was used as the chiral sensing analysis solution, and deionized water was used as the control. Deionized water was dropped on the right-angle gold nanosphere trimer chiral molecular sensor, and the dark field scattering spectrum of the sensor was measured by the dark field scattering system using oblique incident left-handed and right-handed circularly polarized light as the excitation light, and then the normalized right-handed excited scattering spectrum (Scat RCP ) and the scattering spectrum of left-handed excitation (Scat LCP ), and further obtain the circular differential scattering (CDS) spectrum:

[0037] CDS=Scat RCP -Scat LCP

[0038] Similarly, the chiral molecule solution was dropped onto the right-angle gold nanosphere trimer chiral molecule sensor, and the CDS spectrum was obtained according to the above steps. Figure 4The changes of CDS spectra of LH and RH right-angle gold nanosphere trimers in aqueous solution and L-PA molecular solution were shown, among which the red shift of CDS spectrum peak position of RH structure Δλ RH =4nm, the red shift of the peak position of the CDS spectrum of the LH structure Δλ LH =6nm. Figure 5 is the change of CDS spectra of LH and RH right-angle gold nanosphere trimers in aqueous solution and D-PA molecular solution respectively, where the red shift of CDS spectrum peak position of RH structure Δλ RH =12nm, the red shift of the peak position of the CDS spectrum of the LH structure Δλ LH =4nm. The adsorption of chiral molecules on the chiral structure causes asymmetric modification of the local refractive index, which leads to an asymmetric shift of the CDS spectrum peak under LCP and RCP light excitation. The asymmetric shift of the CDS spectrum peak is defined as the asymmetry factor of the CDS spectrum (ΔΔλ = Δλ RH -Δλ LH ), Figure 6 The statistical graphs of the asymmetry factors of the CDS spectra after combining multiple groups of right-angle chiral gold nanosphere trimers with L-PA and D-PA chiral molecular solutions are shown. For L-PA, ΔΔλ=-4.3±2nm, and for D-PA, ΔΔλ=5±2.2nm. Therefore, the chirality of the chiral molecular enantiomers can be identified by the positive or negative asymmetry factors of the CDS spectra.

[0039] Example 2: The diameter of the gold nanospheres constituting trimer 1 is 160 nm, the trimer configuration is an obtuse angle of 120°, the thickness of substrate 2 is 500 μm, and the length and width are 0.7 cm. The chiral molecular sensing with the above parameters is used to perform enantiomer identification experiments.

[0040] A 2 mg / ml solution of right-handed phenylalanine (D-PA) and left-handed phenylalanine (L-PA) was used as a chiral sensing analysis solution, and deionized water was used as a control. According to the steps described in Example 1, the CDS spectra of the gold nanosphere trimer chiral molecular sensor in the deionized water environment and the chiral molecular solution environment were obtained. Figure 7 The statistical graphs of the asymmetry factors of the CDS spectra after combining multiple groups of right-angle chiral gold nanosphere trimers with L-PA and D-PA chiral molecular solutions are shown. For L-PA, ΔΔλ=-4.3±2nm, and for D-PA, ΔΔλ=11.2±0.85nm. The chirality of chiral molecular enantiomers can also be identified by the positive and negative asymmetry factors of the CDS spectra.

[0041] The metal nanosphere trimer chiral molecular sensor proposed in the present invention is easy to prepare, flexible and adjustable, and is cheaper and easier to promote than the sensor obtained by electron beam lithography. The asymmetry factor obtained by the chiral molecular enantiomer identification method proposed in the present invention is close to the asymmetry factor obtained by using a planar chiral metamaterial, and is several times the asymmetry factor obtained by using a dielectric chiral structure. Therefore, the method of the present invention has greater potential for use in enantiomer identification in the field of biochemistry.

[0042] The embodiments of the present invention are described in detail above, but the present invention is not limited to the described embodiments. For those skilled in the art, various changes, modifications, substitutions and variations of these embodiments are still within the scope of protection of the present invention without departing from the principles and spirit of the present invention.

Claims

1. A method for enantiomer identification of chiral molecular sensors based on metal nanosphere trimers, characterized in that: The chiral molecular sensor based on metal nanosphere trimer includes metal nanosphere trimer and substrate; three metal nanosphere trimers are located on the substrate, wherein the diameter of a single metal nanosphere is 100-300nm, the trimer configuration covers right angles, obtuse angles, and acute angles, the substrate thickness is 200-2000μm, and the length and width are 0.5-2cm; The metal nanosphere trimer is made of gold or silver; The substrate is made of silicon, quartz or sapphire; The method for identifying enantiomers of the chiral molecular sensor comprises: Step 1: Drop deionized water on the left-handed (LH) and right-handed (RH) gold nanosphere trimer chiral molecular sensors, use obliquely incident left-handed and right-handed circularly polarized light as excitation light, and measure the dark field scattering spectrum of the sensor through a dark field scattering system; remove the deionized water, and then drop the chiral molecule solution on the LH and RH gold nanosphere trimer chiral molecular sensors to obtain the corresponding dark field scattering spectrum; Step 2: Normalize the dark field scattering spectrum to obtain the right-handed excitation scattering spectrum Scat RCP and the scattering spectrum of left-handed excitation Scat LCP , the circular difference scattering spectrum is obtained by the following formula: CDS=Sact RCP -Scat LCP Step 3: Identify the chirality of the chiral molecule enantiomer by the positive or negative asymmetry factor of the CDS spectrum. When the asymmetry factor is positive, the chirality of the chiral molecule is right-handed; when the asymmetry factor is negative, the chirality of the chiral molecule is left-handed; The chiral molecular solution is a molecular solution of right-handed phenylalanine D-phenylalanine, D-PA, and left-handed phenylalanine L-phenylalanine, L-PA.

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