Microfluidic Enzyme Immunoassay Using Silicon Microchip with Immobilized Antibodies and Chemiluminescence Detection

Yakovleva, Julia; Davidsson, Richard; Lobanova, Anna; Bengtsson, Martin; Eremin, Sergei A.; Laurell, Thomas; Emnéus, Jenny

doi:10.1021/ac015645b

Cited by 315 publications

(198 citation statements)

References 76 publications

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“…4͑a͔͒ and results from radiation loss. The maximum quality factor achieved in H 2 O was 2.3ϫ 10 8 and in D 2 O was 1.3ϫ 10 8 . These values are notable as they represent the highest Q-factors reported to date for operation in an aqueous environment.…”

Section: Figmentioning

confidence: 91%

“…Additionally, the surface of silica-based microcavities is easily sensitized using silanization agents, 6 amines, carbohydrates, the biotin-streptavidin system, 7 or antibodies. 8 For example, silica microsphere resonators, with a properly sensitized surface, were recently used to distinguish between two strands of DNA. 9 However, while detailed studies have been performed to determine the limits of a resonator's quality factor in air, [10][11][12] no comparable studies have been performed in water.…”

mentioning

confidence: 99%

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Ultra-high-Q microcavity operation in H2O and D2O

Armani

Min

et al. 2005

Applied Physics Letters

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Optical microcavities provide a possible method for boosting the detection sensitivity of biomolecules. Silica-based microcavities are important because they are readily functionalized, which enables unlabeled detection. While silica resonators have been characterized in air, nearly all molecular detections are performed in solution. Therefore, it is important to determine their performance limits in an aqueous environment. In this letter, planar microtoroid resonators are used to measure the relationship between quality factor and toroid diameter at wavelengths ranging from visible to near-IR in both H 2 O and D 2 O, and results are then compared to predictions of a numerical model. Quality factors ͑Q͒ in excess of 10 8 , a factor of 100 higher than previous measurements in an aqueous environment, are observed in both High-Q and ultra-high-Q ͑UHQ͒ silica optical microcavities can perform as highly sensitive detectors; 1-3 they derive their excellent transduction abilities from long photon lifetimes within the whispering gallery of the microcavity. Unlike their optical waveguide counterparts, wherein the photon interacts with a functionalized surface only once, 4,5 recirculation within the microcavity allows photons to interact with the surface many times. Additionally, the surface of silica-based microcavities is easily sensitized using silanization agents, 6 amines, carbohydrates, the biotin-streptavidin system, 7 or antibodies. 8 For example, silica microsphere resonators, with a properly sensitized surface, were recently used to distinguish between two strands of DNA. 9 However, while detailed studies have been performed to determine the limits of a resonator's quality factor in air, 10-12 no comparable studies have been performed in water. Because most detection experiments are performed in a water-based solution, it is important to thoroughly understand the impact of this environment on the relationship between the diameter of the microtoroid resonator and the operational wavelengths of interest.To this end, UHQ silica microtoroid resonators were fabricated over a wide range ͑50-250 m͒ of major toroid diameters as shown in Fig. 1. 13 Experiments were performed in both water ͑H 2 O͒ and deuterium oxide ͑D 2 O͒. The D 2 O was purchased from Aldrich. D 2 O was chosen as the second liquid because it has the same refractive index and, in turn, the same radiation loss as H 2 O. However, its absorption at all wavelengths tested is significantly less. 14 This allowed for selective probing of the absorption-loss mechanism and verification of the model developed to describe this system.The model used finite element analysis to predict the Q-factor of microtoroid resonators immersed in water or D 2 S and accounted for two loss mechanisms: radiation loss and absorption loss. The absorption loss was numerically calculated at ͑680, 1300, 1570͒ nm using published values of H 2 O ͑0.0045, 1.12, 8.79͒ cm −1 and D 2 O ͑2.46 ϫ 10 −4 , 0.105, 0.327͒ cm −1 . 14 The modeling of radiation loss uses a fully vectorial two-dimensio...

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Section: Figmentioning

confidence: 91%

mentioning

confidence: 99%

Ultra-high-Q microcavity operation in H2O and D2O

Armani

Min

et al. 2005

Applied Physics Letters

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“…The development of miniaturization technology is increasing, due to the well-known advantages and the crucial need for micrometer scale measurements with improved detection sensitivity [1][2][3]. Hence, micro-total analysis systems ( TAS) are usually designed for a well-defined analytical task [4].…”

Section: Introductionmentioning

confidence: 99%

Polymer microchip impedance spectroscopy through two parallel planar embedded microelectrodes: Understanding the impedance contribution of the surrounding polymer on the measurement accuracy

Kechadi

Gamby

Chaal

et al. 2013

Electrochimica Acta

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a b s t r a c tThe present work describes a new methodology for contact free impedance of a solution in a polymer microchip taking into account the role played by the surrounding polymer on the impedance accuracy. Measurements were carried out using a photoablated polyethylene terephthalate (PET) microchannel above two embedded microband electrodes. The impedance diagrams exhibit a loop from high frequencies to medium frequencies (1 MHz-100 Hz) and a capacitive behavior at low frequencies (100-1 Hz). The impedance diagrams were corrected by eliminating from the global microchip response the contribution of the impedance of the PET layer between the two microband electrodes. This operation enables a clear observation of the impedance in the microchannel solution, including the bulk solution contribution and the interfacial capacitance related to the surface roughness of the photoablated microchannel. Models for the impedance of solutions of varying conductivity showed that the capacitance of the polymer-solution interface can be modeled by a constant phase element (CPE) with an exponent of 0.5. The loop diameter was found to be proportional to the microchannel resistivity, allowing a cell constant around 4.93 × 10 5 m −1 in contactless microelectrodes configuration.

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“…[22][23][24] One key advantage of our chip is that it does not require an enzymatic amplification step to achieve high sensitivity, but rather uses fluorescently labeled detection antibodies (phycoerythrin), which helps reduce the cost and complexity of the assay.…”

Section: Benchmark Of Elisa Vs Serum Analyzer Chipmentioning

confidence: 99%

A 1024-sample serum analyzer chip for cancer diagnostics

García-Cordero

Maerkl

2014

Lab Chip

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We present a platform that combines microarrays and microfluidic techniques to measure four protein biomarkers in 1024 serum samples for a total of 4096 assays per device. Detection is based on a surface fluorescence sandwich immunoassay with a limit of detection of~1 pM for most of the proteins measured: PSA, TNF-α, IL-1β, and IL-6. To validate the utility of our platform, we measured these four biomarkers in 20 clinical human serum samples, 10 from prostate cancer patients and 10 female and male controls. We compared the results of our platform to a conventional ELISA and found a good correlation between them. However, compared to a classical ELISA, our device reduces the total cost of reagents by 4 orders of magnitude while increasing throughput by 2 orders of magnitude. Overall, we demonstrate an integrated approach to perform low-cost and rapid quantification of protein biomarkers from over one thousand serum samples. This new high-throughput technology will have a significant impact on disease diagnosis and management.

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Microfluidic Enzyme Immunoassay Using Silicon Microchip with Immobilized Antibodies and Chemiluminescence Detection

Cited by 315 publications

References 76 publications

Ultra-high-Q microcavity operation in H2O and D2O

Ultra-high-Q microcavity operation in H2O and D2O

Polymer microchip impedance spectroscopy through two parallel planar embedded microelectrodes: Understanding the impedance contribution of the surrounding polymer on the measurement accuracy

A 1024-sample serum analyzer chip for cancer diagnostics

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