CN1643379A - 具有可变的发射强度与发射频率的发光球形非自发光硅胶颗粒 - Google Patents
具有可变的发射强度与发射频率的发光球形非自发光硅胶颗粒 Download PDFInfo
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- CN1643379A CN1643379A CN03807087.1A CN03807087A CN1643379A CN 1643379 A CN1643379 A CN 1643379A CN 03807087 A CN03807087 A CN 03807087A CN 1643379 A CN1643379 A CN 1643379A
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Abstract
本发明涉及一种通过在硅胶基体中包封一种或多种不同发光物质制备的,具有高发光性的球形透明硅胶颗粒。通过改变发光物质的浓度和通过包封具有不同发射频率的物质,该颗粒可以在生物分析和诊断中作为复合编码和生物标记体系被使用。
Description
技术领域
本发明涉及一种发光强度可变的发光、球形微米或纳米颗粒,及该颗粒的制备方法和应用。
发光被定义为通过能量吸收而被预先激发的物质在全部光谱范围内的光发射。荧光和磷光也在此范围内。
当前发光物质以荧光或磷光物质的形式在生物化学和医学分析与诊断的整个领域内被常规地用于鉴别如蛋白质、肽、毒素或核酸的分析物,并且用作标记显示细胞、细胞小室,或检测生物学过程。
背景技术
一种对发光方法十分有趣和创新的使用是用于鉴别生物分子的所谓的芯片技术。在当今的生物分析和诊断领域中,芯片技术作为以栅格形排列有大量具有已知结构的生物分子传感器(核酸、蛋白质或肽)的平的、玻璃或聚合物载体或者基质,也称作生物芯片,而被熟知。通过与生物芯片一起孵育先前由例如组织或细胞获得的发光标记的蛋白质或核酸样品,在其表面上具有与样品互补的化学-物理结构的点上形成特异性结合。由于样品的发光标记会引起在形成结合的点上具有可检测的发光,因而对样品的化学和物理结构提供了直接的信息。由于大量的传感器被固定在芯片上,芯片技术对于在医药开发过程中测试分子库是一种很有用的工具。
由于芯片技术的品质和适用性直接依赖于发光标记的检测灵敏度和光谱特异性,已往进行了大量开发以制造新的、改进的发光体系,从而使得生物鉴定的检测极限被显著地降低。发光物质的开发集中于两类物质。一类是发光分子,这类发光分子中最普通的是Fluorescein、Rhodamin、Phycoerythrin、Coumarin、Cy3、Cy5、TAMRA、ROX、Oregon Green、Ethidiumbromid、Texas Red和Dabcyl(这些均为商品名称)。另一类化合物主要为由周期系中IIB和VIA族、IIIA和VA族或IVA族的半导体纳米晶体,这类纳米晶体中最普通的为CdS、CdSe、CdTe、ZnS和ZnSe。这些半导体纳米晶体的一个独特特征是一方面高的量子效率,另一方面又不象常规发光染色那样易于退色。更值得注意的使得在文献中称作为“量子点”的该化合物成为常规荧光染色的有趣替代的一点是量子点的吸收和发射性能取决于其大小。具体地是指随着颗粒尺寸的减小,发射光谱向短波范围移动,反之亦然。
对于使用发光效应的生物测定的发展,开启了不仅基于物质的选择而且基于颗粒大小进行不同发光标记的另外的可能性。这也为生物芯片领域中生物分子的光学编码提供了理想的基础。
在生物分析中荧光标记的应用在许多相关文献中已有叙述。
美国专利4,777,123描述了一种免疫测定原理,该原理揭示了两种不同荧光团标记的受体的应用,从而在检测的配体的存在下由第一个被激发的荧光团转移到第二个荧光团的能量减少。
美国专利5,324,633的主题为使用光子计数器或共焦显微镜检测与生物高聚物结合的荧光标记受体的生物芯片法。
美国专利5,066,580中描述了在被标记的抗体的协助下用于细胞检测的具有450~650nm的激发频率的氧杂蒽(xanthene)荧光染料。在美国专利3,998,943、3,996,345、4,174,384、4,199,559和4,261,968中公开了配体受体测定,该测定的基本原理为用发射性能依靠于配体-受体结合的荧光染色标记受体和/或配体。
美国专利5,319,209公开了其中适于测量细胞中离子浓度的苯并呋喃-异酞酸酯形式的荧光传感器。
具有相应的光学特性的半导体纳米晶体和/或量子点的制备是现有技术并在相关的文献中以不同方式被报道:Kortan等,美国化学学会杂志(J.Am.Chem.Soc.)Vol 112,1327,1990;Colvin等,自然(Nature),Vol.370,354,1994;Murray等,美国化学学会杂志(J.Am.Chem.Soc.)Vol.115,8706,1993;Hirai等,物理化学B杂志(J.Phys.Chem.B),Vol.103,4228,1999;Dabbousi等,物理化学B杂志(J.Phys.Chem.B),Vol.101,9463,1997;Hines等,物理化学杂志(J.Phys.Chem.)Vol.100,468,1996;Danek等,化学材料(Chem.Mater.)Vol.8,173,1996;Steigerwald等,美国化学学会杂志(J.Am.Chem.Soc.)(1988)110:3046-3050和Lianos等,化学物理快报(Chem.Phys.Lett.)Vol.125,299,1986。
但是,对于在生物分析中发光物质的使用而言,仅实际的合成并不是决定性的,重要的是在发光标记和相应生物物质之间的共价键的可能性。使用发光染料,首先以N-羟基琥珀酰亚胺基酯或异硫氰酸酯的形式被引入的功能基团起到与生物分子的氨基结合的作用。另一方面,量子点总是按照两种方法被功能化:一方面,表面用如巯基丙酸、二氢硫辛酸、巯基乙酸、巯基硅烷的功能巯基化合物转化,该化合物随后优选通过羧基功能与相应的生物分子连接(Gerion等,物理化学杂志(J.Phys.Chem.)Vol.105,8861,2001);Mattoussi等,美国化学学会杂志(J.Am.Chem.Soc.)Vol.122,12142,2000);Chan等,科学(Science)Vol 281,2016,1998);Mitchell等,美国化学学会杂志(J.Am.Chem.Soc.)Vol.121,8122,1999)),或者量子点被包封在聚合物基质或枝形聚合物(dendrimer)中(“覆盖”)。Lemon等,(美国化学学会杂志(J.Am.Chem.Soc.)Vol.122,12886,2000),Sooklal等,(先进材料(Adv.Mater.)Vol.10,1083,1998)和Lakowicz等,(物理化学杂志(J.Phys.Chem.)Vol.103,7613,1999)描述了在聚酰胺胺枝形聚合物的协助下半导体纳米晶体的包封。使用共聚苯乙烯乙烯(polystyrene-co-vinyl)吡啶、聚苯乙烯、硅胶或聚月桂酰甲基丙烯酸酯的包封由以下文献公开:Zhao等,(化学材料(Chem.Mater.)Vol.14,1418,2002);Han等,(自然生物技术(Nature Biotech.),Vol.19,631,2001);Correa-Duarte等,(化学物理快报(Chem.Phys.Letters,)Vol.286,497,1998);Chang等,(美国化学学会杂志(J.Am.Chem.Soc.)Vol.116,6739,1994)和Lee等,(先进材料(Adv.Mater.),Vol.12,1102,2000)。美国专利6,114,038和5,906,670的主要内容为被包封在含巯基的组分和二氨基羧酸中的量子点以及用喷射***在气相中制备的半导体纳米晶体。
美国专利6,207,397、5,251,018、5,751,018、5,262,357和5,505,928涉及了能够与亲和性配体结合的III-V族和II-VI族半导体纳米晶体的制备。
美国专利6,326,144和6,207,229的主要内容为具有与生物成分的亲和键的被包覆的半导体纳米晶体以及用ZnS、ZnSe、CdS或CdSe包覆的单分散的光发射纳米晶体。
美国专利5,293,050和5,354,707涉及用于电路的硅的光发射半导体层,其中第二硅层含有至少一个量子点。
美国专利5,525,377描述了用于阴极射线管或电致发光显示器的被聚甲基丙烯酸甲酯涂敷的掺杂半导体化合物的20~100纳米颗粒。
美国专利5,537,000中涉及了使用ZnS、ZnSe、ZnTe、CdS、CdSe、CdTe、HgS、HgSe、HgTe、GaS、InAs、InP和InSb形式的半导体纳米晶体作为电子传输介质制备电致发光设备,当被施加电压后,该电致发光设备可以发射出不同波长的可见光。美国专利5,541,948的主要内容为包含II和VI族元素的掺杂了过渡金属的激光强化晶体。
美国专利5,585,640公开了掺杂了发光纳米晶体的玻璃基质。制备掺杂的预制玻璃形式需要超过1000℃的温度。
美国专利5,770,299公开了用作绘画的颜料的包含CdS和/或III-V族组分的半导体纳米晶体或II-VI族半导体纳米晶体。
美国专利5,789,162公开了在商业硅胶小球上的荧光标记的肽库的固相合成。
美国专利5,990,479涉及涂敷硅烷衍生物并能够与亲和性分子键合的生物应用发光半导体纳米晶体传感器。
美国专利5,043,265公开了作为免疫球蛋白和聚核苷酸的标记的ZnS-Ag和Y2O2S-Eu形式的发光颗粒。
美国专利5,985,353的主要内容为在分散于核酸或蛋白质形式的惰性凝胶聚合物中的阳离子交换剂存在下由过渡金属、镧系元素或锕系元素制备纳米颗粒。与交换剂键合的阳离子通过加入相应的阴离子被沉淀为纳米颗粒。
美国专利4,666,862和Oi等(J.Cell.Biol.Vol.93,891 1982)公开了能够降低激发和发射频率之间的光谱重叠程度,相当于显著的斯托克司频移(Stokes shift),的藻胆蛋白标记物。
另外一组光发射物质是所谓的上转换磷光颗粒(up-convertingphosphor),其独特特征为发射与激发辐射相反的短波辐射。这种类型的物质主要地包含氧和/或硫和/或氟与镧系元素或钇的化合物。
如果被用于生物测定中,则这些物质具有吸收和发射频率不受如载体颗粒或微量滴定载玻片的载体***的自身荧光干扰的优点。当使用任何类型的载体***时,在当今的生物分析中该自身荧光现象仍会引起问题。
美国专利5,674,698和5,698,397公开了通过激光激发被用于生物学和其他测定中的一系列掺杂上转换磷光颗粒形式如氟化钠钇、氟化镧、氟化钆和氧硫化钇的分子传感器。
美国专利5,132,242中公开了密封在聚丙烯酸酯微载体中的上转换磷光颗粒,该微载体对于激发和发射频率是透明的并且能够通过功能基团而加入与蛋白质的共价键。
Corstjens等,(Clin.Chem.Vol.47,1885,2001)和Niedbala等,(分析生物化学(Anal.Biochem.)Vol.293,22,2001)公开了用于测定核酸序列和免疫测定的上转换磷光颗粒。Hampl等,(分析生物化学(Anal.Biochem.)Vol.288,176,2001)公开了硅烷涂敷的上转换磷光颗粒。
美国专利6,004,530的主要内容为可被用作检测生物物质的发光金属卟啉。
在现有技术水平中已知的单一分子或纳米晶体形式的发光标记具有缺陷,即该发光标记的使用,尤其是在生物测定中,在所需的时间和步骤方面需要复杂的制备。因而与复杂步骤相关的合成或制备时间为几小时到几天(参见美国专利5,132,242):在氮气惰性气氛中操作,蒸馏,在有机介质中操作。因而,这些在任何情况下均存在有机聚合物的产物具有显著的自身荧光,参见上面列出的Han等的参考文献。
已知的发光体系的最严重的局限是对每个要被标记的生物分子,一般地只有一个或很少的几个发光颗粒(半导体纳米晶体或上转换磷光颗粒晶体)可以被键合。结果,这种限制显著地降低了生物测定的检测灵敏度。对于发光分子情况也相似,同样仅有少数发光颗粒可与每个生物分子键合,所以很难检测到从被标记的生物分子发射出的信号。此外,连接发光物质到生物分子(如,抗体)上可能会引起后者失活。然而,已经被开发为替代物的发光标记的微粒或纳米颗粒均具有与难以生产、使用和检测的颗粒的表面相连接的发光标记,参见Fornusek和Vetvicka,在CRC Critical Reviews in Therapeutic Drug Carrier Systems,2,pp.137-174,1986中的“用于细胞表面标记示踪的作为诊断工具的聚合小球(Polymeric Microspheres as Diagnostic Tools for Cell SurfaceMarker Tracing)”。该文献对这种技术做了综合性的评述,其他引用文献为:Kaplan等(Biochimica et Biophysica Acta,Vol.728,112,1983)以及美国专利3,853,987、4,035,316、4,105,598、4,108,972、4,224,198和4,326,008。
发明内容
本发明的目的之一是避免已知现有技术水平的发光载体体系的缺点并提供包含复合发光物质的具有适当多孔性的透明、非自发荧光的微粒和亚微颗粒。由于可以在分子和纳米颗粒或胶体两种形式中包封大量的发光剂,在生物分析和诊断中生物分子的检测灵敏度已经被极大地提高,甚至达到可以检测单个分子的水平。然而,几种具有可变发射性能的发光物质的包封使得生物分子的光学编码有多种变化。
该目标按照本发明通过在不会影响基本物质的实质发光性能的硅胶透明基质中包封发光物质而实现。
更进一步,该目标按照本发明通过反向悬浮法(inverse suspensionmethod)完成,因而含有硅胶溶胶和发光物质的混合物被分散在不与水混溶的有机相中,然后被缩聚。通过该方法可以制备出包含包封的发光物质的立体交联的、珠状聚合物载体。
具体实施方式
硅溶胶根据普遍已知的现有技术的方法,即在稀释的无机酸的帮助下通过烷氧基硅烷的水解而被制备出来(Dave等ImmobilizedBiomolecules in Analysis,编辑Cass和Ligler,Oxford University出版社,1998;WO 02/09125 A1)。脂肪醇的硅原酸酯可被用作烷氧基硅烷,优选为甲基、乙基或丙基酯,单独或以混合物的形式。相应的发光物质在第二个步骤中被加入到硅溶胶中。为了能够更均匀地混合异质的溶胶-发光物质混合物,反应在超声浴中进行或使用超声极(ultrasonicsonotrode),处理通常持续半分钟。由这种方法获得的胶体分散混合物然后一般通过搅拌被分散在与水不混溶的有机溶剂中。形成的珠状溶胶滴然后通过随后加入稀释的碱缩聚成为立体交联硅胶。
溶胶和有机分散相的极性特征被选择一方面能够制备稳定的悬浮液,另一方面使得添加的发光物质对溶胶具有高亲合力,以至于在溶胶和有机相之间有清晰的分界,结果使加入的发光化合物只被均匀的分散在溶胶相中。
根据配方,包括硅胶溶胶制备的整个制备方法需要约20~50分钟。
发光颗粒的合成开始于按照已知方法通过在酸性水溶性的环境中水解适当的烷氧基硅烷制备的硅溶胶。具有C1到C3酯基的原硅酸被优选地用于该方法及产物。令人惊异的是,这与具有确定浓度的硅烷一起使得完全透明颗粒得以制备。在最初的配方中烷氧基硅烷的浓度为40~90%体积,优选的为65~80%体积。在酸性水溶液的存在下使硅烷受到超声的作用从而制备澄清的溶胶,该酸性水溶液在硅烷配方中的体积百分比一般在10~40%并且其浓度一般在0.01到0.5摩尔/升之间。超声处理的时间依赖酸浓度确定为5~20分钟。通过该方法获得的硅溶胶可以在深冷温度下(大约-18℃)中储存多天,或者也可以被立即处理。
本发明的硅胶技术的另一个特点是所获得颗粒的多孔性可以在宽的范围内变动,这是一个任何其它已知现有技术不具备的特点。
颗粒载体介质的多孔性对于所有的生物检测或分离过程中起到决定性作用,这是因为分析物的特异性的检测能力依赖于其与固定在载体上的配体和/或受体的结合。这种结合过程的程度和质量直接受载体的可接近表面的影响。后者直接由载体的多孔性决定。令人惊异的是,这可以借助于按照本发明的产物和方法通过向溶胶加入特定物质加以调节。这些一般被称为生孔剂(porogen)的物质在分散前被加入到溶胶中。被作为添加物使用的物质优选是不影响载体的吸收-发射性能的物质。这些物质的例子包括:聚乙二醇、聚乙烯醇、聚丙烯酸、聚氨基酸、多糖,蛋白质或聚乙烯吡咯烷酮,本发明不局限于这些物质。它们在分散和交联过程中被包封在球形颗粒中。相对于溶胶相而言,以1~10%水溶液存在的有机聚合物溶液的体积百分比为1~20%。
另外用于调节多孔性的参数源于对各种二、三或四取代的硅烷组分的组合的选择。从而,纯粹四取代酯的凝胶通常具有比通过添加二或三取代酯化合物而制备的溶胶或凝胶更低的多孔性。二或三功能酯基化合物的选择性混合物使孔径在50~200nm之间。相对于整个硅烷浓度,二和三功能硅烷的浓度一般在1~10%,优选为1~5%体积。
本发明的产物和方法的另一个重要方面是可以同时通过机械搅拌的类型和方式以及硅溶胶的粘度来控制颗粒的大小。众所周知,颗粒的大小是在悬浮聚合期间通过搅拌速度加以调节,其调节方式为颗粒尺寸问题随搅拌速度的增加而下降。这些因素的相互关系也适用于本发明,即>1000rpm的搅拌速度一般会使得颗粒尺寸<50μm,搅拌速度>5000rpm则颗粒尺寸<10μm。为了获得更细的亚微米级颗粒,就需要例如根据转子-定子原理(rotor-stator principle)工作并且转子速度>10000rpm(例如,Ultra-Turrax)的分散工具。超声处理也使颗粒尺寸在0.5~10μm的范围内。
除了纯粹的机械因素,溶胶的粘度对颗粒的大小也有决定性的影响。降低溶胶粘度一般会导致颗粒大小类似的降低,反之亦然:升高粘度导致颗粒尺寸的增加。获得按照本发明的具有0.5~50μm的理想颗粒尺寸的产物所需的粘度在5~300cp之间。
在制备了具有理想特性的溶胶后,相应的发光标记物在下一步骤中被加入并与溶胶均匀地混合,优选应用超声波处理。这些可以在吸收了一定波长的辐射后以不同于吸收频率的频率发射出光子并且能够达到与硅胶溶胶的均匀混合的化合物可以被用作发光物质。
多种这类物质已经在所列的参考文献中被描述。发光分子和标记的例子有:荧光黄(Fluorescein)、若丹明(Rhodamin)、香豆素(Coumarin)、丹磺酰氯(Dansylchlorid)、溴乙菲啶(Ethidiumbromid)、Texas Red、藻红蛋白、Oregon Green或Cascade Blue以及具有下列商品名的化合物:BODIPY、SYBR Green、TOTO-1或YOYO-1以及这些产品的衍生物,本发明的产物并不局限于此。例如MgS、MgSe、MgTe、CaS、CaSe、CaTe、SrS、SrSe、SrTe、BaS、BaSe、BaTe、ZnS、ZnSe、ZnTe、CdS、CdSe,CdTe,HgS,HgSe或HgTe的II-VI族系列化合物以及例如GaAs、InGaAs、InP或InAs的III-V族纳米晶体均可被用作半导体纳米晶体。例如锗的IVA族半导体也是适合的。
上转换磷光颗粒的适当例子为稀土或IIIB族元素的化合物,例如氟化钠钇、氟化镧、硫氧化镧、硫氧化钇、氟化钇、镓酸钇、氟化钆、氟化钡钇、硫氧化钆以及掺杂了活化剂对(activator pair)如镱/铒、镱/铥或镱/钬的上述类型的化合物。其它适合的上转换磷光颗粒包括铒、钕、铥、钬和镨的螯合化合物。发光蛋白质如视紫红蛋白质、绿荧光蛋白质(GFP)和金属卟啉也可以相似的方式被用作发光物质。
被加入的发光物质的浓度可以依据相应生物分析或诊断的要求在宽范围内变化。为了实现清楚地发光,为标记物质的1~10%重量的浓度通常就足够了。这些浓度超过了常规测定中每个分析物可使用的发光标记浓度的几个数量级。
硅溶胶与多种物质极佳的可混溶性意外地使得磁性胶体和/或纳米颗粒形式的磁性化合物可以与发光物质一起同时被包封。这产生了可同时起到发光效果和磁性分离的作用的全新的特性组合。这就为高效生物测定的发展开辟了全新的前景,通过该高效生物测定使得以前只在聚合物或玻璃基质上进行的先前的阵列无法测定的极大量的生物分子(“分子库”)得以被测定。可以被使用的磁性物质为已知的含亚铁、含铁或超顺磁性物质以及铁磁流体,其中许多已经在相关的文献中被描述:巴西专利1439031,Shinkai等,生物催化(Biocatalysis)Vol 5,61,1991;Kondo等,微生物生物技术应用(Appl.Microbiol.Biotechn.)Vol.41,99,1994。磁性胶体的浓度全部经过挑选以使得涉及到发光标记的吸收和发射性能的颗粒的透明性不会受到影响。其一般在相对于硅胶颗粒重量的10~30%。
在该方法的第三个步骤中,硅胶-发光标记混合物通过搅拌被分散在有机相中。这些不与水互溶且可以使硅溶胶稳定分散的溶剂是合适的分散剂。这类分散剂从现有技术可知并在以下文献中被描述:WO02/09125以及Laane等(“有机介质中的生物催化(Biocatalysis inOrganic Media)”,Laane等,编辑,Elsevier,Amsterdam,pp 65,1987)。符合这些要求的溶剂包括己烷、三氯乙烯、石油醚、甲苯、氯仿、1,1,1-三氯乙烷、四氯化碳、庚烷。密度大约为1g/cm3的上述溶液的混合物也很适于分散。有机相与水溶胶的体积比例一般在8∶1~30∶1。
考虑到更窄的颗粒大小分布和更好的分散性能,一种或多种表面活性剂、分散稳定剂或乳化剂型的表面活性物质可以被加入到有机相中。这些物质的例子包括:丙烯氧化物-乙烯氧化物的嵌段共聚物、聚羟基脂肪酸-聚乙二醇嵌段共聚物、聚乙二醇-醚衍生物、脱水山梨糖醇脂肪酸酯、蓖麻油衍生物的嵌段共聚物、聚乙二醇-蓖麻油衍生物、聚氧乙烯脱水山梨糖醇脂肪酸酯、烷基苯基聚乙二醇衍生物、聚丙三醇酯、改性聚酯、聚氧丙烯乙二胺嵌段共聚物、聚乙二醇、聚氧乙烯衍生物、聚氧乙烯醇衍生物。这种类型的物质在市场上的商品名为:Renex、Estol、Prisorine、Hypermer、Pluronic、Tween、Eumulgin、Pripol、Tetronic、Brij、Lameform、Arlacel、Span、Dehymuls、Synperonic或Triton。有关颗粒的产生的表面活性剂的浓度在体积和/或重量的0.1~15%之间,优选地为0.5~6%。
在该方法的最后一个步骤中,在分散过程中溶胶与稀释的碱混合,所以前者浓缩聚合为固体凝胶。溶胶一般在数秒钟(3~20秒)内被固定成预期的凝胶颗粒。因此,机械分散处理只进行几秒钟。所选的碱浓度越高,凝胶化和同时的机械分散处理就越短。1~12%水溶液形式的氨被优选地用作碱,其它的碱如NaOH、二乙胺或KOH也可以使用。碱与溶胶的体积比一般在1∶2~1∶4之间。
非常快速的凝胶化反应的结果是,包括发光标记包封的整个颗粒制备过程可以在一个小时内完成。这相对于全部制备发光颗粒的常规方法节省了高达90%的时间。
制备过程后用乙醇和水洗涤数次。所获得的磁性载体一般被储存在水中。所获得的硅胶颗粒可以被直接用于进一步的功能化。
为了使发光颗粒与所有作为目标物质的相应的生物分子,如蛋白质、抗体、肽、酶、核酸、低聚糖,受体、生物配体或分析物传感器相结合,使用了普通已知的硅胶和/或硅烷化载体的活化和连接方法。这些方法包括与具有例如氨基、环氧基、含巯基的、异硫氰酸酯、丙烯酸或卤素基团的功能烷氧基硅烷反应。这种活化和连接剂的例子包括:3-氨基丙基-三乙氧基硅烷、3-氨基丙基-三甲氧基硅烷、3-缩水甘油基-丙氧基三甲氧基硅烷、3-缩水甘油基丙氧基甲基二乙氧基硅烷、3-巯基丙基三甲氧基硅烷、3-异氰硫基丙基三乙氧基硅烷、甲基丙烯基丙氧基三乙氧基硅烷、氯丙基三乙氧基硅烷。通过使用氨基羧酸、戊二醛对前面所述的烷氧基硅烷的衍化或者以酸或碱水解环氧基团向羟基衍生物引入羧基、羟基或醛基的方法已被现有技术所公开。相似地,按照已知方法环氧活化的载体与羧酸、亚硫酸、硫代硫酸、氨基取代的羧酸如次氮基三乙酸或亚胺基乙酰乙酸之间的反应也会产生金属螯合物载体。通过光活化剂,如含有芳基叠氮(arylazine)或偶氮甲烷(diazirin)功能团的,活化硅胶颗粒是较容易做到的,该光活化剂首先通过紫外光照射被连接到载体上,然后可与生物配体和/或生物分子反应。该类型的物质包括:N-羟基琥珀酰亚胺基-4-叠氮苯甲酸、[2-硝基-4-[3-(三氟甲基)-3H-偶氮甲烷-3-基]苯氧基]乙酰基-N-羟基琥珀酰亚胺酸、N-羟基琥珀酰亚胺基-(4-叠氮苯基)-1,3`-二硫代丙酸、N-[m-[3-(三氟甲基)偶氮甲烷-3-基]苯基]-4-顺丁烯二酰亚胺丁酰胺(maleimidobutyramide)。
在这里不需要对各种活化、功能化和连接进行详细描述,因为特定的反应方法是普遍已知的并可以在任何时候被本领域技术人员所使用(参见,Vansant等,“二氧化硅表面的特性和化学修饰(Characterizationand Chemical Modification of the Silica Surface)”,由Delmon和Yates编辑,Elsevier,Amsterdam,1997;“磁性载体的科学与临床应用(Scientificand Clinical Applications of Magnetic Carriers)”,Hfeli等(编者),PlenumPress,New York,1997;Shriver-Lake,“分析中的固定生物分子(Immobilized Biomolecules in Analysis)”,Cass和Ligler,编辑,OxfordUniversity Press,1998;WO 99/01766;Lottspeich和Zorbas编辑,“Bioanalytik”,Spektrum Verlag,Heidelberg,1998)。基本实施例不应被看作是公开范围的限制。
按照本发明的发光颗粒的应用覆盖所有使用显色反应、发光或放射性以检测或定量特定物质或分析物的生物分析和诊断的领域。其例子包括放射或酶免疫形式的免疫分析、核酸检测、蛋白质组分析、DNA测序、噬菌体显示(phage display)、细胞标记、核酸阵列或细胞标记。此外,颗粒发光标记物可被用于流式细胞仪或被荧光激活细胞分选仪(FACS)或用于测试DNA或蛋白质库。
随后的实施例更详细地叙述了本发明的产物和方法,但本发明并不仅限于这些实施例。
实施例1
室温下5ml四甲氧基硅烷和2ml的0.05M HCl一同在超声浴中置于超声波下10分钟,所获得的2ml澄清的溶胶与1ml的0.05%若丹明B溶液混合,混合物然后被加入到含有0.4ml的Korantin(BASF)的25ml己烷中。该配比用分散装置(Ultra-Turrax)以20000rpm分散3秒钟。在加入1ml的1%的氨水溶液后再分散5秒钟。5分钟后颗粒通过两分钟的离心被沉淀。过量的部分被倾析掉并用乙醇,丙酮和水漂洗三次,每次大约10ml。得到了颗粒大小为1~3μm的发光颗粒。
获得的颗粒随后用无水甲苯洗涤数次,然后在氩气气氛中与5ml无水甲苯和2ml的3-缩水甘油基丙氧基三甲氧基硅烷在90℃搅拌下反应3小时。然后用甲苯和丙酮漂洗5次。100mg所获得的产物再用0.5摩尔pH为8.5的磷酸缓冲液洗涤三次,并且随后在溶解有10mg链霉抗生物素蛋白的2ml相同的缓冲液中40℃下孵育5小时。然后产物经离心步骤每次用0.05M pH为7.2的磷酸缓冲液洗涤5次。为了阻断任何剩余的环氧基团,被结合的产物在包含0.1%血清白蛋白的1%乙醇胺溶液中室温下储存24小时。然后用pH为8.0的0.05 Tris/HCl缓冲液洗涤数次。
从而制备出能够用于结合或标记生物素化的生物分子的产物。
实施例2
与实施例1类似地制备的2ml硅溶胶与根据Sooklal等(Adv.Mater.,Vol.10,1083,1998)的说明合成的平均颗粒大小为138nm的10mgCdS半导体纳米晶体混合,然后在室温下置于超声波中2分钟。混合物在溶解有2.5%体积的Span 60和溶解有0.5%体积的Tween 80的25ml甲苯中用Ultra-Turrax在20000rpm下被分散5秒钟。加入1ml 6%氨水溶液后,被继续分散5秒钟。然后类似于实施例1,颗粒被分离并制备。获得了发射最大值为510nm的平均颗粒大小为3.6μm的发光颗粒。
为了活化颗粒,在[2-硝基-4-[3-(三氟甲基)-3H-偶氮甲烷-3-基]苯氧基]乙酰基-N-羟基琥珀酰亚胺酸(配比:5mg溶解于0.5ml乙醇-水(1∶1)中)的存在下用stratalinker UV 2400(Stratagene)照射75mg发光颗粒20分钟。包含氨基的生物分子、配体或受体例如核酸、蛋白质或抗体都可根据已知方法(Matson和Little,J.Chromatogr.,Vol.458,67,1988)在用乙醇和水洗涤之后与活化的产物结合。
实施例3
0.5ml四乙氧基硅烷与0.1ml的水和0.08ml的0.1M HCl混合,在室温下超声浴中置于超声波下10分钟。所获得的0.2ml的溶胶与根据Hampl的描述(Anal.Biochem.,Vol.288,176,2001)制备的5mg(YYbEr)2O2S混合,并在超声浴中处理5分钟。然后加入30mg磁性粉末(Bayferrox 318M,Bayer,FRG)到混合物中。混合物再被置于超声波下2分钟。混合物然后通过在12000rpm的搅拌(Ultra-Turrax)被分散于溶解有2%体积的Dehymuls HRE7和0.5%体积的Prisorine 3700的3ml三氯乙烯中。0.08ml的6%氨水溶液在分散中被加入。化合物再搅拌5秒钟。获得的发光颗粒的分离和制备与实施例1类似。
得到了平均颗粒大小为6.7μm的发光颗粒。
在各次磁性分离之后,产物在被用干燥甲苯洗涤5次之前被真空干燥3小时,随后在加入3ml甲苯和0.25ml的3-丙氨基三乙氧基硅烷后沸腾回流12小时。磁性颗粒被再次磁性分离并用大约5ml的甲苯和氯仿洗涤3次。然后该磁性颗粒在真空中干燥数小时。然后35℃下在4ml的pH为9.0的0.1M碳酸钠缓冲液中,氨基修饰的产物用6%戊二醛溶液转化。然后该产物用pH为7.2的0.1M磷酸缓冲液彻底地漂洗。
根据已知方法,具有氨基基团的生物分子例如蛋白质、肽、核酸或在5′端有取代氨基的低聚核苷酸,能够与所获得的醛基功能化的发光颗粒结合。以这种方式被功能化的发光颗粒可以在蛋白质或核酸阵列中被用作传感器。
Claims (25)
1、发光硅胶颗粒,在透明硅胶基质中包含一种或多种发光物质。
2、根据权利要求1的颗粒,其特征在于该颗粒不是自发光的。
3、根据权利要求1或2的颗粒,其特征在于所述的发光物质被包封在该颗粒中。
4、根据前面权利要求任意一项的颗粒,其特征在于发光物质选自显示荧光、磷光、化学发光、电致发光或能量转换发光的物质的组。
5、根据前面权利要求任意一项的颗粒,其特征在于发光物质的浓度为1~10wt%。
6、根据前面权利要求任意一项的颗粒,其特征在于发光物质显示不同的发射频率。
7、根据前面权利要求任意一项的颗粒,其特征在于发光物质是激发频率高于发射频率的分子。
8、根据权利要求1到6中任意一项的颗粒,其特征在于发光物质包括IIIA和VA族,IIB和VIA族或IVA族的元素形成的半导体纳米晶体。
9、根据权利要求8的颗粒,其特征在于发光半导体纳米晶体被加入铜和/或银添加剂。
10、根据权利要求1到6中任意一项的颗粒,其特征在于发光物质具有比发射频率低的激发频率。
11、根据权利要求10的颗粒,其特征在于发光物质是稀土和/或钇与第VIA和/或VIIA族元素的微晶化合物。
12、根据前面权利要求中任意一项的颗粒,其特征在于发光物质是金属螯合化合物,其中心原子选自VIII,IB,IIB族或稀土族。
13、根据前面权利要求中任意一项的颗粒,其特征在于发光物质为吡咯染料。
14、根据权利要求1到6的颗粒,其特征在于发光物质为发光蛋白质。
15、根据权利要求1到14中任意一项的颗粒,其中额外包含或包封了磁性胶体。
16、根据权利要求15的颗粒,其特征在于磁性胶体选自包含亚铁、铁和超顺磁性化合物以及铁磁流体的组。
17、根据权利要求15或16的颗粒,其特征在于磁性胶体以相对颗粒重量10~50%的浓度存在。
18、根据前面权利要求中任意一项的颗粒,其特征在于硅胶具有可以与选自包含蛋白质、肽、细胞受体、核酸、核酸片断、多聚糖、低聚糖、抗体、抗体片断、链霉抗生物素蛋白、抗生物素蛋白、生物素和酶的组的生物分子结合的功能基团,或者能够与一种或多种这些生物分子联合的功能基团。
19、制备根据权利要求1到18中任意一项的发光硅胶颗粒的方法,其特征在于
a)由稀释的酸和烷氧基硅烷构成的混合物被浓缩为澄清的硅溶胶;
b)澄清硅溶胶被均匀地与一种或多种发光物质混合;
c)溶胶-发光物质混合物被分散在不与水混溶的有机相中;和
d)溶胶-发光物质混合物通过在分散过程中或分散之后加入碱被交联。
20、根据权利要求19的发光透明硅胶颗粒的制备方法,其特征在于10~50%重量的含亚铁、含铁或超顺磁性的物质被加入到溶胶-发光物质混合物中。
21、根据权利要求19和20的发光硅胶颗粒的制备方法,其特征在于不与水混溶的有机相包含0.1~15%体积浓度的一种或多种表面活性物质。
22、根据权利要求19到21中任意一项的发光硅胶颗粒的制备方法,其特征在于溶胶与有机相的体积比为1∶5到1∶30。
23、根据权利要求19到22中任意一项的发光硅胶颗粒的制备方法,其特征在于分散交联过程需要2~30秒。
24、根据权利要求19到23中任意一项的发光硅胶颗粒的制备方法,其特征在于1~20%体积比的有机聚合物、多聚糖或蛋白质的水溶液在分散前与溶胶混合。
25、根据权利要求1到18中的任意一项的发光硅胶颗粒在核酸、核酸片断、蛋白质、肽、抗体、抗体片断、细胞、细胞受体、生物素化的生物分子的分析和/或诊断,以及在芯片技术中作为传感器测试蛋白质或核酸库,或者在核酸测序中的应用。
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NZ565662A (en) | 2005-08-09 | 2010-10-29 | Univ Sunderland | Fingerprint analysis using mass spectrometry |
JP5400297B2 (ja) * | 2005-12-27 | 2014-01-29 | 古河電気工業株式会社 | 蛍光ナノシリカ粒子、ナノ蛍光材料、それを用いたバイオチップ及びそのアッセイ法 |
JPWO2008035569A1 (ja) * | 2006-09-19 | 2010-01-28 | コニカミノルタエムジー株式会社 | 生体分子検出用試薬及びそれを用いた生体分子検出方法 |
US8053744B2 (en) * | 2009-04-13 | 2011-11-08 | Src, Inc. | Location analysis using nucleic acid-labeled tags |
FR2952436B1 (fr) * | 2009-11-10 | 2014-10-31 | Commissariat Energie Atomique | Materiau et procede pour pieger, detecter et quantifier des composes aromatiques heterocycliques et autres. |
US8877505B2 (en) | 2010-02-02 | 2014-11-04 | Ventana Medical Systems, Inc. | Composition and method for stabilizing fluorescent particles |
WO2011100334A1 (en) * | 2010-02-09 | 2011-08-18 | Sri International | Chemical synthesis using up-converting phosphor technology and high speed flow cytometry |
US8703493B2 (en) | 2010-06-15 | 2014-04-22 | Src, Inc. | Location analysis using fire retardant-protected nucleic acid-labeled tags |
US8716027B2 (en) | 2010-08-03 | 2014-05-06 | Src, Inc. | Nucleic acid-labeled tags associated with odorant |
FR2993798B1 (fr) * | 2012-07-25 | 2015-03-06 | Commissariat Energie Atomique | Procede de marquage d'un substrat metallique par incorporation de particules inorganiques luminescentes |
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CN105419777B (zh) * | 2015-12-22 | 2018-08-14 | 莫婉玲 | 一种含有脂肪酸脂的量子点复合材料及其制备方法 |
CN105419778B (zh) * | 2015-12-22 | 2017-11-14 | 重庆益新阳工贸有限公司 | 一种含有石蜡的量子点复合材料及其制备方法 |
CN108701521B (zh) | 2016-02-29 | 2020-12-04 | 洛德公司 | 用于磁流变流体的添加剂 |
US10941057B2 (en) * | 2017-04-28 | 2021-03-09 | U.S. Environmental Protection Agency | Highly tunable fluorescent core-shell particles for environmental release simulation and tracking applications |
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Family Cites Families (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3853987A (en) * | 1971-09-01 | 1974-12-10 | W Dreyer | Immunological reagent and radioimmuno assay |
US3998943A (en) * | 1973-10-02 | 1976-12-21 | Syva Company | Double receptor fluorescent immunoassay |
US4108972A (en) * | 1974-03-15 | 1978-08-22 | Dreyer William J | Immunological reagent employing radioactive and other tracers |
DE2426919C3 (de) * | 1974-06-04 | 1981-07-16 | Philippe Edouard Jean Leon Alexis Puteaux Gravisse | PhotolumineszierendesBaumaterial und ein Verfahren zu dessen Herstellung |
US3996345A (en) * | 1974-08-12 | 1976-12-07 | Syva Company | Fluorescence quenching with immunological pairs in immunoassays |
US4199559A (en) * | 1974-08-12 | 1980-04-22 | Syva Company | Fluorescence quenching with immunological pairs in immunoassays |
US4174384A (en) * | 1975-06-30 | 1979-11-13 | Syva Company | Fluorescence quenching with immunological pairs in immunoassays |
US4035316A (en) * | 1975-11-24 | 1977-07-12 | California Institute Of Technology | Cell specific, variable density, polymer microspheres |
US4326008A (en) * | 1976-08-27 | 1982-04-20 | California Institute Of Technology | Protein specific fluorescent microspheres for labelling a protein |
US4235869A (en) * | 1978-05-16 | 1980-11-25 | Syva Company | Assay employing a labeled Fab-fragment ligand complex |
US4224198A (en) * | 1978-05-26 | 1980-09-23 | California Institute Of Technology | Protein specific polymeric immunomicrospheres |
US4261968A (en) * | 1979-05-10 | 1981-04-14 | Syva Company | Fluorescence quenching with immunological pairs in immunoassays |
US4666862A (en) * | 1984-08-14 | 1987-05-19 | Ortho Diagnostic Systems Inc. | Fluorescent energy transfer with phycobiliproteins |
JPS61246748A (ja) * | 1985-04-24 | 1986-11-04 | Konishiroku Photo Ind Co Ltd | ハロゲン化銀カラ−写真感光材料 |
EP0232357B1 (en) * | 1985-08-05 | 1991-01-30 | Rijksuniversiteit Leiden | Labelled macromolecules; a process for their preparation and their use for immunological or immunocytochemical assays |
US5132242A (en) * | 1987-07-15 | 1992-07-21 | Cheung Sau W | Fluorescent microspheres and methods of using them |
US5066580A (en) * | 1988-08-31 | 1991-11-19 | Becton Dickinson And Company | Xanthene dyes that emit to the red of fluorescein |
KR930011971B1 (ko) * | 1991-01-29 | 1993-12-23 | 삼성전자 주식회사 | 색신호 경계면 보정장치 |
WO1993006121A1 (en) * | 1991-09-18 | 1993-04-01 | Affymax Technologies N.V. | Method of synthesizing diverse collections of oligomers |
JP2970967B2 (ja) * | 1991-11-20 | 1999-11-02 | 浜松ホトニクス株式会社 | 蛍光性プローブ試薬を用いた細胞内イオン濃度測定法 |
US5505928A (en) * | 1991-11-22 | 1996-04-09 | The Regents Of University Of California | Preparation of III-V semiconductor nanocrystals |
WO1993010564A1 (en) * | 1991-11-22 | 1993-05-27 | The Regents Of The University Of California | Semiconductor nanocrystals covalently bound to solid inorganic surfaces using self-assembled monolayers |
US5262357A (en) * | 1991-11-22 | 1993-11-16 | The Regents Of The University Of California | Low temperature thin films formed from nanocrystal precursors |
US5324633A (en) * | 1991-11-22 | 1994-06-28 | Affymax Technologies N.V. | Method and apparatus for measuring binding affinity |
US5698397A (en) * | 1995-06-07 | 1997-12-16 | Sri International | Up-converting reporters for biological and other assays using laser excitation techniques |
US5674698A (en) * | 1992-09-14 | 1997-10-07 | Sri International | Up-converting reporters for biological and other assays using laser excitation techniques |
US5293050A (en) * | 1993-03-25 | 1994-03-08 | International Business Machines Corporation | Semiconductor quantum dot light emitting/detecting devices |
US6048616A (en) * | 1993-04-21 | 2000-04-11 | Philips Electronics N.A. Corp. | Encapsulated quantum sized doped semiconductor particles and method of manufacturing same |
GB9323498D0 (en) * | 1993-11-15 | 1994-01-05 | Isis Innovation | Making particles of uniform size |
US5527711A (en) * | 1993-12-13 | 1996-06-18 | Hewlett Packard Company | Method and reagents for binding chemical analytes to a substrate surface, and related analytical devices and diagnostic techniques |
US5537000A (en) * | 1994-04-29 | 1996-07-16 | The Regents, University Of California | Electroluminescent devices formed using semiconductor nanocrystals as an electron transport media and method of making such electroluminescent devices |
US5541948A (en) * | 1994-11-28 | 1996-07-30 | The Regents Of The University Of California | Transition-metal doped sulfide, selenide, and telluride laser crystal and lasers |
US5985353A (en) * | 1994-12-01 | 1999-11-16 | University Of Massachusetts Lowell | Biomolecular synthesis of quantum dot composites |
US5585640A (en) * | 1995-01-11 | 1996-12-17 | Huston; Alan L. | Glass matrix doped with activated luminescent nanocrystalline particles |
DE19541028C2 (de) * | 1995-11-05 | 1998-01-22 | Daimler Benz Ag | Effektlack mit Pigmenten, die eine Kennzeichnung tragen, sowie Verfahren zu seiner Herstellung |
US6207397B1 (en) * | 1996-04-18 | 2001-03-27 | Ariad Pharmaceuticals, Inc. | In vitro fluorescence polarization assay |
US6004530A (en) * | 1996-06-04 | 1999-12-21 | Roche Diagnostics Gmbh | Use of metallo-porphyrin conjugates for the detection of biological substances |
DE19730359A1 (de) * | 1997-07-15 | 1999-01-21 | Boehringer Mannheim Gmbh | Integriertes Verfahren und System zur Amplifizierung und zum Nachweis von Nukleinsäuren |
US7348181B2 (en) * | 1997-10-06 | 2008-03-25 | Trustees Of Tufts College | Self-encoding sensor with microspheres |
US6322901B1 (en) * | 1997-11-13 | 2001-11-27 | Massachusetts Institute Of Technology | Highly luminescent color-selective nano-crystalline materials |
US5990479A (en) * | 1997-11-25 | 1999-11-23 | Regents Of The University Of California | Organo Luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes |
US6326144B1 (en) * | 1998-09-18 | 2001-12-04 | Massachusetts Institute Of Technology | Biological applications of quantum dots |
US6114038A (en) * | 1998-11-10 | 2000-09-05 | Biocrystal Ltd. | Functionalized nanocrystals and their use in detection systems |
-
2002
- 2002-03-30 DE DE10214019A patent/DE10214019A1/de not_active Withdrawn
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2003
- 2003-03-27 AU AU2003223998A patent/AU2003223998A1/en not_active Abandoned
- 2003-03-27 EP EP03720372A patent/EP1490691B1/de not_active Expired - Lifetime
- 2003-03-27 WO PCT/EP2003/003163 patent/WO2003083481A2/de active Application Filing
- 2003-03-27 AT AT03720372T patent/ATE421696T1/de not_active IP Right Cessation
- 2003-03-27 CN CN03807087.1A patent/CN1643379A/zh active Pending
- 2003-03-27 DE DE50311117T patent/DE50311117D1/de not_active Expired - Lifetime
- 2003-03-27 US US10/509,712 patent/US20050147974A1/en not_active Abandoned
- 2003-03-27 JP JP2003580862A patent/JP2005528466A/ja active Pending
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US10167499B2 (en) | 2013-12-05 | 2019-01-01 | Capitalbio Technoloogy Corporation | Luminophore-labeled molecules coupled with particles for microarray-based assays |
US10982267B2 (en) | 2013-12-05 | 2021-04-20 | Capitalbio Technology Corporation | Luminophore-labeled molecules coupled with particles for microarray-based assays |
WO2021017904A1 (en) * | 2019-07-31 | 2021-02-04 | Auiset Biotechnology Co. Ltd. | Fabrication of fluorescent nanoparticles and their conjugates for in vitro and in vivo diagnostics |
CN114032086A (zh) * | 2020-12-25 | 2022-02-11 | 武汉大学 | 一种长余辉纳米探针组合在检测细菌生物被膜中的应用 |
CN114032086B (zh) * | 2020-12-25 | 2023-11-17 | 武汉大学 | 一种长余辉纳米探针组合在检测细菌生物被膜中的应用 |
CN115261013A (zh) * | 2022-07-01 | 2022-11-01 | 西安邮电大学 | 一种稀土发光材料及其制备方法与应用 |
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DE10214019A1 (de) | 2003-10-16 |
EP1490691A2 (de) | 2004-12-29 |
AU2003223998A1 (en) | 2003-10-13 |
ATE421696T1 (de) | 2009-02-15 |
DE50311117D1 (de) | 2009-03-12 |
US20050147974A1 (en) | 2005-07-07 |
WO2003083481A2 (de) | 2003-10-09 |
EP1490691B1 (de) | 2009-01-21 |
AU2003223998A8 (en) | 2003-10-13 |
JP2005528466A (ja) | 2005-09-22 |
WO2003083481A3 (de) | 2004-03-25 |
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