Dual-Capillary Backscatter Interferometry for High-Sensitivity Nanoliter-Volume Refractive Index Detection with Density Gradient Compensation

Wang, Zhanling; Bornhop, Darryl J.

doi:10.1021/ac050752h

Cited by 45 publications

(64 citation statements)

References 16 publications

(49 reference statements)

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“…in a frequency range of 10 −1 -10 0 Hz. This result is comparable to the best refractive-index detection limit reported so far, which was achieved with a microinterferometic backscattering detection system [25].…”

Section: Analysis Of Resultssupporting

confidence: 87%

Refractometry with Ultralow Detection Limit Using Anisotropic Whispering-Gallery-Mode Resonators

Weng¹,

Anstie²,

Luiten³

2015

Phys. Rev. Applied

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The intrinsic sensitivity of whispering-gallery-mode resonators aimed at measuring refractive index can be extremely high, although their practical performance is compromised by temperature fluctuations that masquerade as refractive-index changes. We present a triple-mode approach that delivers simultaneous and independent sensing of temperature and refractive-index changes in the same resonator. The frequency difference between two orthogonally polarized modes is used to sense temperature which is then actively stabilized to ∼1 μK over 15 minutes. We then detect a frequency difference between two modes of different wavelengths to obtain a refractive-index measurement that is free of temperature fluctuations. This triple-mode technique delivers a state-of-the-art detection limit of 8 × 10 −9 refractive-index units, despite the resonator size being 100 times larger than that typically used for sensitive refractometric sensing.

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Section: Analysis Of Resultssupporting

confidence: 87%

Refractometry with Ultralow Detection Limit Using Anisotropic Whispering-Gallery-Mode Resonators

Weng¹,

Anstie²,

Luiten³

2015

Phys. Rev. Applied

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“…1) in the backscattered direction. Depending on configuration, tracking the position of the fringes enables RI changes to be quantified in the range from 10 −4 to 10 −9 (60,61), within picoliter to nanoliter probe volumes. A long effective path length results from multiple reflections at the fluidchannel interface and leads to the unprecedented sensitivity in constrained volumes (62).…”

Section: Conformation and Hydration Changes Are The Origin Of Free-somentioning

confidence: 99%

Origin and prediction of free-solution interaction studies performed label-free

Bornhop

Kammer

Kussrow

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Interaction/reaction assays have led to significant scientific discoveries in the biochemical, medical, and chemical disciplines. Several fundamental driving forces form the basis of intermolecular and intramolecular interactions in chemical and biochemical systems (London dispersion, hydrogen bonding, hydrophobic, and electrostatic), and in the past three decades the sophistication and power of techniques to interrogate these processes has developed at an unprecedented rate. In particular, label-free methods have flourished, such as NMR, mass spectrometry (MS), surface plasmon resonance (SPR), biolayer interferometry (BLI), and backscattering interferometry (BSI), which can facilitate assays without altering the participating components. The shortcoming of most refractive index (RI)-based label-free methods such as BLI and SPR is the requirement to tether one of the interaction entities to a sensor surface. This is not the case for BSI. Here, our hypothesis is that the signal origin for freesolution, label-free determinations can be attributed to conformation and hydration-induced changes in the solution RI. We propose a model for the free-solution response function (FreeSRF) and show that, when quality bound and unbound structural data are available, FreeSRF correlates well with the experiment (R 2 > 0.99, Spearman rank correlation coefficients >0.9) and the model is predictive within ∼15% of the experimental binding signal. It is also demonstrated that a simple mass-weighted dη/dC response function is the incorrect equation to determine that the change in RI is produced by binding or folding event in free solution.backscattering interferometry | assay methodology | molecular interactions | conformation change | hydration change C ontemporary assays enabling single-molecule detection (1,2) have accelerated the sequencing of the human genome (3) and facilitated imaging with extraordinary resolution without labels (4). To most closely approximate the natural state, an interaction assay methodology would interrogate the processes (reaction, molecular interaction, protein folding event, etc.) without perturbation. Label-free chemical and biochemical investigations (5, 6) transduce the desired signal without an exogenous label (fluorescent, radioactive, or otherwise) representing an essential step toward this goal. Many label-free methods require one of the interacting species to be either tethered or immobilized to the sensor surface, introducing a potential perturbation to the natural state of the species (7,8). However, back-scattering interferometry (BSI) is a free-solution label-free technique with the added benefit of sensitivity that rivals fluorescence (9). There are other techniques performed in free solution, such as MS (10, 11) and NMR (12,13) and the widely used isothermal titration calorimetry (ITC) (14, 15). As with NMR, ITC has many advantages, but exhibits modest sensitivity and often requires large sample quantities. Another increasingly popular free-solution approach is microscale thermophoresis (...

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“…A universal optical detector based on dual capillary backscatter interferometry with density gradient compensation has been constructed for refractive index measurements in nanoliter volume for microchip CE with sensitivity at the femtomole level [165].…”

Section: Uv Absorption and Interferometrymentioning

confidence: 99%

Recent developments in CE and CEC of peptides

Kašička

2007

Electrophoresis

118

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The article brings a comprehensive survey of recent developments and applications of high-performance capillary electromigration methods, zone electrophoresis, ITP, IEF, affinity electrophoresis, EKC, and electrochromatography, to analysis, preparation, and physicochemical characterization of peptides. New approaches to the theoretical description and experimental verification of electromigration behavior of peptides and to methodology of their separations, such as sample preparation, adsorption suppression, and detection, are presented. Novel developments in individual CE and CEC modes are shown and several types of their applications to peptide analysis are presented: conventional qualitative and quantitative analysis, purity control, determination in biomatrices, monitoring of chemical and enzymatical reactions and physical changes, amino acid and sequence analysis, and peptide mapping of proteins. Some examples of micropreparative peptide separations are given and capabilities of CE and CEC techniques to provide important physicochemical characteristics of peptides are demonstrated.

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Dual-Capillary Backscatter Interferometry for High-Sensitivity Nanoliter-Volume Refractive Index Detection with Density Gradient Compensation

Cited by 45 publications

References 16 publications

Refractometry with Ultralow Detection Limit Using Anisotropic Whispering-Gallery-Mode Resonators

Refractometry with Ultralow Detection Limit Using Anisotropic Whispering-Gallery-Mode Resonators

Origin and prediction of free-solution interaction studies performed label-free

Recent developments in CE and CEC of peptides

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