Mohammed Sharif Murib

Heat-Transfer Resistance at Solid–Liquid Interfaces: A Tool for the Detection of Single-Nucleotide Polymorphisms in DNA

In this article, we report on the heat-transfer resistance at interfaces as a novel, denaturation-based method to detect single-nucleotide polymorphisms in DNA. We observed that a molecular brush of double-stranded DNA grafted onto synthetic diamond surfaces does not notably affect the heat-transfer resistance at the solid-to-liquid interface. In contrast to this, molecular brushes of single-stranded DNA cause, surprisingly, a substantially higher heat-transfer resistance and behave like a thermally insulating layer. This effect can be utilized to identify ds-DNA melting temperatures via the switching from low- to high heat-transfer resistance. The melting temperatures identified with this method for different DNA duplexes (29 base pairs without and with built-in mutations) correlate nicely with data calculated by modeling. The method is fast, label-free (without the need for fluorescent or radioactive markers), allows for repetitive measurements, and can also be extended toward array formats. Reference measurements by confocal fluorescence microscopy and impedance spectroscopy confirm that the switching of heat-transfer resistance upon denaturation is indeed related to the thermal on-chip denaturation of DNA.

Heat-transfer-based detection of SNPs in the PAH gene of PKU patients

Conventional neonatal diagnosis of phenylketonuria is based on the presence of abnormal levels of phenylalanine in the blood. However, for carrier detection and prenatal diagnosis, direct detection of disease-correlated mutations is needed. To speed up and simplify mutation screening in genes, new technologies are developed. In this study, a heat-transfer method is evaluated as a mutation-detection technology in entire exons of the phenylalanine hydroxylase (PAH) gene. This method is based on the change in heat-transfer resistance (Rth) upon thermal denaturation of dsDNA (double-stranded DNA) on nanocrystalline diamond. First, ssDNA (single-stranded DNA) fragments that span the size range of the PAH exons were successfully immobilized on nanocrystalline diamond. Next, it was studied whether an Rth change could be observed during the thermal denaturation of these DNA fragments after hybridization to their complementary counterpart. A clear Rth shift during the denaturation of exon 5, exon 9, and exon 12 dsDNA was observed, corresponding to lengths of up to 123 bp. Finally, Rth was shown to detect prevalent single-nucleotide polymorphisms, c.473G>A (R158Q), c.932T>C (p.L311P), and c.1222C>T (R408W), correlated with phenylketonuria, displaying an effect related to the different melting temperatures of homoduplexes and heteroduplexes.

Photonic detection and characterization of DNA using sapphire microspheres

Abstract. A microcavity-based deoxyribonucleic acid (DNA) optical biosensor is demonstrated for the first time using synthetic sapphire for the optical cavity. Transmitted and elastic scattering intensity at 1510 nm are analyzed from a sapphire microsphere (radius 500  μm, refractive index 1.77) on an optical fiber half coupler. The 0.43 nm angular mode spacing of the resonances correlates well with the optical size of the sapphire sphere. Probe DNA consisting of a 36-mer fragment was covalently immobilized on a sapphire microsphere and hybridized with a 29-mer target DNA. Whispering gallery modes (WGMs) were monitored before the sapphire was functionalized with DNA and after it was functionalized with single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). The shift in WGMs from the surface modification with DNA was measured and correlated well with the estimated thickness of the add-on DNA layer. It is shown that ssDNA is more uniformly oriented on the sapphire surface than dsDNA. In addition, it is shown that functionalization of the sapphire spherical surface with DNA does not affect the quality factor (Q≈104) of the sapphire microspheres. The use of sapphire is especially interesting because this material is chemically resilient, biocompatible, and widely used for medical implants.

Tunable Integrated Optical Filters Based on Sapphire Microspheres and Liquid Crystals

We present an integrated optical narrowband electrically tunable filter based on the whispering gallery modes of sapphire microspheres and double ion-exchanged channel BK7 glass waveguides. Tuning is provided by a liquid crystal infiltrated between the spheres and the glass substrate. By suitably choosing the radii of the spheres and of the circular apertures, upon which the spheres are positioned, arrays of different filters can be realized on the same substrate with a low cost industrial process. We evaluate the performance in terms of quality factor, mode spacing, and tuning range by comparing the numerical results obtained by the numerical finite element modeling approach and with the analytical approach of the Generalized Lorenz-Mie Theory for various design parameters. By reorienting the LC in an external electrical field, we demonstrate the tuning of the spectral response of the sapphire microsphere based filter. We find that the value of the mode spacing remains nearly unchanged for the different values of the applied electric field. An increase of the applied electric field strength, changes the refractive index of the liquid crystal, so that for a fixed geometry the mode spacing remains unchanged.

Whispering-gallery modes observed in elastic scattering from submerged high-refractive-index silica microspheres

Abstract. The effect of the discrete values of the refractive index of the surrounding medium on the spectral behavior of the whispering-gallery modes (WGMs) in the elastic scattering spectra of high-refractive-index silica microspheres submerged in fluids, such as air, water, and glycerol, is studied. The elastic scattering spectral measurements, as well as the spectral autocorrelation analysis of these elastic scattering spectra show that the spectral-mode spacing, the spectral-mode density, and the spectral-mode definition of the WGMs decrease as the refractive index of the surrounding fluid increases. We believe that this work opens up the way for optofluidic applications of high-refractive-index silica microsphere-based guided wave optics.

Fiber Optic Excitation of Silicon Microspheres in Amorphous and Crystalline Fluids

ABSTRACT This study investigates the optical resonance spectra of free-standing monolithic single crystal silicon microspheres immersed in various amorphous fluids, such as air, water, ethylene glycol, and 4-Cyano-4’-pentylbiphenyl nematic liquid crystal. For the various amorphous fluids, morphology-dependent resonances with quality factors on the order of 105 are observed at 1428 nm. The mode spacing is always on the order of 0.23 nm. The immersion in various amorphous fluids affects the spectral response of the silicon microsphere and heralds this technique for use in novel optofluidics applications. Even though the nematic liquid crystal is a highly birefringent, scattering, and high-index optical medium, morphology-dependent resonances with quality factors on the order of 105 are observed at 1300 nm in the elastic scattering spectra of the silicon microsphere, realizing a liquid-crystal-on-silicon geometry. The relative refractive index and the size parameter of the silicon microsphere are the parameters that affect the resonance structure. The more 4-Cyano-4’-pentylbiphenyl interacting with the silicon microsphere, the lower the quality factor of the resonances is. The more 4-Cyano-4’-pentylbiphenyl is interacting with the silicon microsphere, the lower the mode spacing Δλ of the resonances is. The silicon microspheres wetted with nematic liquid crystal can be used for optically addressed liquid-crystal-on-silicon displays, light valve applications, or reconfigurable optical networks.

Silicon microspheres for optoelectronics

Optoelectronic properties of silicon microspheres are explored. The IV characteristics show an electrical response similar to two back-to-back Schottky diodes. Optical resonances with Q-factors of 105 are observable in the elastic scattering spectra.

Optical modulation with a ruby microsphere in liquid crystal

Optical spectra of a hybrid device consisting of a ruby microsphere and nematic liquid crystal are calculated at different voltages applied to the liquid crystal. A wavelength shift of 0.11 nm is observed for resonances with mode spacing of 1.6 nm.

Electrooptical tuning of a ruby microsphere morphology dependent resonance in a liquid crystal medium

A simulation describing the shifts in resonant peaks of scattered light from a waveguide coupled microsphere resonator immersed in nematic liquid crystal is discussed.

Ruby microsphere and liquid cyrstal based tunable optical filter

A microsphere placed in a liquid crystal is used as an optical filter. By changing the refractive index of the liquid crystal, the resonance frequency of the sphere is controlled.