Photonic ring resonance is a versatile platform for performing multiplex immunoassays in real time
Photonic ring resonance is a versatile platform for performing multiplex immunoassays in real time
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DOI：
10.1016/j.jim.2017.05.005
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发表时间：
2017-09-01
影响因子：
2.2
通讯作者：
Burlingame, Rufus W.
中科院分区：
文献类型：
--
作者：
Mudumba, Sasi;de Alba, Sophia;Burlingame, Rufus W.
光子环共振是光的一种性质，其中在某些情况下，特定波长被捕获在环形谐振器中。基于硅光子环谐振器的传感器通过检测传感器内部循环的光与沉积在传感器表面上的物质之间的相互作用来起作用。生物材料的结合导致传感器表面上折射率的局部变化，这影响延伸超出传感器边界的循环光场。也就是说，当环形谐振器周围的介质的折射率改变时，谐振波长将改变。环形谐振器可以被制造到小的硅芯片上，从而允许开发基于环形生物传感器的微型多路复用阵列。本文描述了这样一个系统的属性时，响应于折射率的变化，在一个简单而精确的方式通过改变周围介质的离子强度，并在一个更有用的方式通过大分子的结合到谐振器上方的表面。具体地，描述了一种捕获免疫测定法，其测量当具有抗SS-A自身抗体的患者血清样品流过用SSA抗原点样并用抗IgG扩增的芯片时共振波长的变化。该技术已被小型化并蚀刻到一个4 x 6 mm的硅芯片上，可以同时测量32个不同的反应。通过2 M盐测定法测量的芯片上128个环之间的变异性平均为0.6%CV。测定的输出是4个环的每个簇的平均偏移，并且簇之间的测定平均为0.5%CV。芯片之间的变异性平均为1.8%。在多台仪器上运行相同的阵列表明，在对波长参考系统进行一些改进后，13台不同仪器之间的变化上限为3%。免疫测定显示出比盐测定高约2%的变异性。这一制度有几个突出的特点。每个测试芯片上使用的抗原量约为200皮克，仅需几微升样品，
Photonic ring resonance is a property of light where in certain circumstances specific wavelengths are trapped in a ring resonator. Sensors based on silicon photonic ring resonators function by detecting the interaction between light circulating inside the sensor and matter deposited on the sensor surface. Binding of biological material results in a localized change in refractive index on the sensor surface, which affects the circulating optical field extending beyond the sensor boundary. That is, the resonant wavelength will change when the refractive index of the medium around the ring resonator changes. Ring resonators can be fabricated onto small silicon chips, allowing development of a miniature multiplex array of ring based biosensors. This paper describes the properties of such a system when responding to the refractive index changed in a simple and precise way by changing the ionic strength of the surrounding media, and in a more useful way by the binding of macromolecules to the surface above the resonators. Specifically, a capture immunoassay is described that measures the change of resonant wavelength as a patient serum sample with anti-SS-A autoantibodies is flowed over a chip spotted with SSA antigen and amplified with anti-IgG. The technology has been miniaturized and etched into a 4 x 6 mm silicon chip that can measure 32 different reactions in quadruplicate simultaneously. The variability between 128 rings on a chip as measured by 2 M salt assays averaged 0.6% CV. The output of the assays is the average shift per cluster of 4 rings, and the assays averaged 0.5% CV between clusters. The variability between chips averaged 1.8%. Running the same array on multiple instruments showed that after some improvements to the wavelength referencing system, the upper boundary of variation was 3% between 13 different instruments. The immunoassay displayed about 2% higher variability than the salt assays. There are several outstanding features of this system. The amount of antigen used on the chip for each test is around 200 picograms, only a few microliters of sample is necessary, and the assays take