LED-based Interferometric Reflectance Imaging Sensor for quantitative dynamic monitoring of biomolecular interactions

Daaboul, George G.; Vedula, Rahul S.; Ahn, Sunmin; Lopez, Carlos A.; Reddington, Alex; Özkumur, Emre; Ünlü, M. Selim

doi:10.1016/j.bios.2010.09.038

Cited by 96 publications

(93 citation statements)

References 20 publications

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“…The glass top-layer facilitates the use of well-established surface chemistries. [23][24][25] In addition, the layered design produces an interference signal to enable IRIS measurements 16,17 and shows fluorescence enhancement factors beyond available glass substrates. 26 Cretich and Reddington et al demonstrate an approach to assay development through the implementation of a 2 thickness SiO 2 /Si slide, which is optimized for both IRIS (500 nm SiO 2 ) and fluorescence enhancement (100 nm SiO 2 ) in a single experiment.…”

Section: A Slide Designmentioning

confidence: 99%

“…16 A more simplistic system with four unpolarized discrete LEDs, to circumvent imaging issues associated with wide-field laser imaging like speckle, has shown to achieve the same sensitivity with a 500 nm SiO 2 layer and on-chip fiducial marks for intensity monitoring. 17,28 The modeling for the tunable laser can be described by the Fresnel reflection of a two-interface system when assuming a near-normal (paraxial approximation), single-wavelength illumination: 29…”

Section: B High Na Interferometric Reflectance Imaging Sensormentioning

confidence: 99%

“…Utilizing optical interference and a silicon oxide on silicon (SiO 2 /Si) slide, IRIS has shown multiplexed, high-throughput, high sensitivity, and dynamic detection capabilities for molecular surface binding. 16,17 Additionally, the layered structure required for IRIS does not have a detrimental effect on the fluorescence readout, and the structure can be adjusted to enhance the fluorescence signal beyond glass slides.…”

Section: Introductionmentioning

confidence: 99%

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Integrated imaging instrument for self-calibrated fluorescence protein microarrays

Reddington

Monroe

Ünlü

2013

Review of Scientific Instruments

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Protein microarrays, or multiplexed and high-throughput assays, monitor multiple protein binding events to facilitate the understanding of disease progression and cell physiology. Fluorescence imaging is a popular method to detect proteins captured by immobilized probes with high sensitivity and specificity. Reliability of fluorescence assays depends on achieving minimal inter-and intra-assay probe immobilization variation, an ongoing challenge for protein microarrays. Therefore, it is desirable to establish a label-free method to quantify the probe density prior to target incubation to calibrate the fluorescence readout. Previously, a silicon oxide on silicon chip design was introduced to enhance the fluorescence signal and enable interferometric imaging to self-calibrate the signal with the immobilized probe density. In this paper, an integrated interferometric reflectance imaging sensor and widefield fluorescence instrument is introduced for sensitive and calibrated microarray measurements.

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Section: A Slide Designmentioning

confidence: 99%

Section: B High Na Interferometric Reflectance Imaging Sensormentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Integrated imaging instrument for self-calibrated fluorescence protein microarrays

Reddington

Monroe

Ünlü

2013

Review of Scientific Instruments

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“…17 and spectral reflectance imaging biosensors. 41 The example that we demonstrated was virus isolation on-chip, which can facilitate HIV viral load testing in resource-constrained settings since the viral load is defined as the free circulating viruses in plasma. The microchip platform can also be modified to provide sample processing for a host of other applications.…”

Section: Recovery (%)mentioning

confidence: 99%

Simple filter microchip for rapid separation of plasma and viruses from whole blood

Wang¹,

Chen²,

Huang³

et al. 2012

IJN

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Sample preparation is a significant challenge for detection and sensing technologies, since the presence of blood cells can interfere with the accuracy and reliability of virus detection at the nanoscale for point-of-care testing. To the best of our knowledge, there is not an existing on-chip virus isolation technology that does not use complex fluidic pumps. Here, we presented a lab-on-a-chip filter device to isolate plasma and viruses from unprocessed whole blood based on size exclusion without using a micropump. We demonstrated that viruses (eg, HIV) can be separated on a filter-based chip (2-µm pore size) from HIV-spiked whole blood at high recovery efficiencies of 89.9% ± 5.0%, 80.5% ± 4.3%, and 78.2% ± 3.8%, for viral loads of 1000, 10,000 and 100,000 copies/mL, respectively. Meanwhile, 81.7% ± 6.7% of red blood cells and 89.5% ± 2.4% of white blood cells were retained on 2 µm pore-sized filter microchips. We also tested these filter microchips with seven HIV-infected patient samples and observed recovery efficiencies ranging from 73.1% ± 8.3% to 82.5% ± 4.1%. These results are first steps towards developing disposable point-of-care diagnostics and monitoring devices for resource-constrained settings, as well as hospital and primary care settings.

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“…The idea of thin film interference has been studied since 19 th century [8] and applied to biochemical sensors more than 20 years ago [9]. We have developed the concept of Interferometric Reflectance Imaging Sensor (IRIS) [10,11] for multiplexed biodetection using functionalized immunocapture surfaces on reflecting substrates with thin dielectric layers. In this article, we will focus on the single-particle modality of IRIS (SP-IRIS) and discuss the principles as well as results on detection of viruses and applications to digital biomolecular assays.…”

Section: Introductionmentioning

confidence: 99%

Digital Detection of Nanoparticles: Viral Diagnostics and Multiplexed Protein and Nucleic Acid Assays

Ünlü

2015

MRS Proc.

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Synthetic nanoparticles have made significant impact across a broad range of technological applications including optical nanoantennas, ultra-sensitive imaging and sensing, and diagnostics and therapeutics. Natural nanoparticles such as viruses and pollutants are major concerns for human health. High-throughput characterization of nanoparticles in terms of their size and shape is crucial for practical applications of synthetic nanoparticles and highly sensitive pathogen identification. Recently, we have demonstrated Interferometric Reflectance Imaging Sensor (IRIS) with the ability to detect single nanoscale particles [1,2].In single-particle modality of IRIS (SP-IRIS), the interference of light reflected from the sensor surface is modified by the presence of particles producing a distinct signal that reveals the size of the particle. In our approach, the dielectric layered structure acts as an optical antenna optimizing the elastic scattering characteristics of nanoparticles for sensitive detection and analysis. We have demonstrated identification of virus particles in complex samples for various viruses in multiplexed format. Size discrimination of the imaged nanoparticles (virions) allows differentiation between modified viruses having different genome lengths and facilitates a reduction in the counting of non-specifically bound particles to achieve a limit-of-detection (LOD) of 5x10 3 pfu/mL for the Ebola and Marburg VSV pseudotypes. We have demonstrated the simultaneous detection of multiple viruses in serum or whole blood as well as in samples contaminated with high levels of bacteria [3]. Single nanoparticle detection with IRIS has shown promising results for protein [4] and DNA arrays with attomolar detection sensitivity.

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LED-based Interferometric Reflectance Imaging Sensor for quantitative dynamic monitoring of biomolecular interactions

Cited by 96 publications

References 20 publications

Integrated imaging instrument for self-calibrated fluorescence protein microarrays

Integrated imaging instrument for self-calibrated fluorescence protein microarrays

Simple filter microchip for rapid separation of plasma and viruses from whole blood

Digital Detection of Nanoparticles: Viral Diagnostics and Multiplexed Protein and Nucleic Acid Assays

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