Shashanka Ashili - Academia.edu (original) (raw)

Papers by Shashanka Ashili

Research paper thumbnail of Resonant optical circuits based on coupling between whispering gallery modes in dielectric microresonators

Conference on Lasers and Electro-Optics/International Quantum Electronics Conference and Photonic Applications Systems Technologies, 2004

The public reporting burden for this collection of information is estimated to average 1 hour per... more The public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information.

Research paper thumbnail of Encapsulated Microsphere Arrays for Applications in Photonic Circuits

Adaptive Optics: Analysis and Methods/Computational Optical Sensing and Imaging/Information Photonics/Signal Recovery and Synthesis Topical Meetings on CD-ROM, 2005

This paper describes the fabrication, characterization and spectroscopic properties of novel stru... more This paper describes the fabrication, characterization and spectroscopic properties of novel structures made from prearranged circuits of optically coupled polystyrene microspheres in a robust elastomeric polymer.

Research paper thumbnail of Optical Delay Lines Formed by Circuits of Spherical Cavities with Coupled Whispering Gallery Modes

Adaptive Optics: Analysis and Methods/Computational Optical Sensing and Imaging/Information Photonics/Signal Recovery and Synthesis Topical Meetings on CD-ROM, 2005

We propose a novel concept of optical delay lines where the tunable delay can be achieved by cont... more We propose a novel concept of optical delay lines where the tunable delay can be achieved by controlling the inter-resonator gap sizes in circuits of optically coupled microspheres.

Research paper thumbnail of Optical coupling and transport phenomena in long chains of slightly disordered spherical microresonators

Frontiers in Optics 2004/Laser Science XXII/Diffractive Optics and Micro-Optics/Optical Fabrication and Testing, 2004

It is shown that weak optical coupling between polystyrene spherical microresonators with size di... more It is shown that weak optical coupling between polystyrene spherical microresonators with size disorders allows creating optical waveguides with attenuation ~2-3 dB per sphere, which can be evanescently coupled to resonant sources of light and used in chip-scale photonic circuits. OCIS codes: (250.5300) Photonic integrated circuits; (230.3990) Microstructure devices Resonant optical coupling between cylindrical and spherical microresonators allows developing high order spectral filters [1] and coupled resonator optical waveguides (CROWs) [2]. The effectiveness of photon hopping transport

Research paper thumbnail of Optical coupling between spherical dielectric atoms

2005 Quantum Electronics and Laser Science Conference, 2005

It is shown that dielectric microspheres with strongly detuned whispering gallery modes can be ef... more It is shown that dielectric microspheres with strongly detuned whispering gallery modes can be effectively coupled. The transition from strong to weak coupling is demonstrated as a function of separation between nonidentical microspheres.

Research paper thumbnail of Observation of Light Propagation via Whispering Gallery Modes in 3D Networks of Coupled Spherical Cavities

Frontiers in Optics, 2006

We present spectroscopic evidence for efficient optical transport via coupled whispering gallery ... more We present spectroscopic evidence for efficient optical transport via coupled whispering gallery modes in 3D networks of slightly disordered spherical cavities with attenuation length in excess of 50 µm.

Research paper thumbnail of Optical Properties of Mesoscopic Systems of Coupled Microspheres

Research paper thumbnail of Percolation of light in 3D lattices of coupled microspheres

2007 Quantum Electronics and Laser Science Conference, 2007

Research paper thumbnail of Optical Transport Phenomena in Coupled Spherical Cavities

2007 9th International Conference on Transparent Optical Networks, 2007

The efficiency of optical transport is studied in one-dimensional (ID) chains and in 3D lattices ... more The efficiency of optical transport is studied in one-dimensional (ID) chains and in 3D lattices of coupled microspheres with -1-3% size disorder. To couple light into such structures we used sources of light formed by dye-doped fluorescent microspheres. Using techniques of spatially resolved scattering spectroscopy we observed large propagation losses (-3 dB per sphere) along the chain at the frequencies of whispering gallery modes (WGMs) in the source sphere. Away from the resonance with WGMs we observed much smaller losses (< 1 dB per sphere) due to formation of nanojet-induced modes. The propagation of light in 3D lattices of disordered coupled cavities with WGM resonances is interpreted in terms of percolation theory. In transmission spectra of such 3D structures we observed spectral signatures of strong coupling between multiple spheres with nearly resonant WGMs. The results indicate that the transmission properties can be significantly improved in 3D structures formed by more uniform spheres due to achieving an optical percolation threshold for WGM transport.

Research paper thumbnail of A physical sciences network characterization of non-tumorigenic and metastatic cells

Scientific Reports, 2013

To investigate the transition from non-cancerous to metastatic from a physical sciences perspecti... more To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences-Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.

Research paper thumbnail of <title>A novel method for multiparameter physiological phenotype characterization at the single-cell level</title>

Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues IX, 2011

Non-genetic intercellular heterogeneity has been increasingly recognized as one of the key factor... more Non-genetic intercellular heterogeneity has been increasingly recognized as one of the key factors in a variety of core cellular processes including proliferation, stimulus response, carcinogenesis and drug resistance. Many diseases, including cancer, originate in a single or a few cells. Early detection and characterization of these abnormal cells can provide new insights into the pathogenesis and serve as a tool

Research paper thumbnail of <title>Automated platform for multiparameter stimulus response studies of metabolic activity at the single-cell level</title>

Microfluidics, BioMEMS, and Medical Microsystems IX, 2011

We have developed a fully automated platform for multiparameter characterization of physiological... more We have developed a fully automated platform for multiparameter characterization of physiological response of individual and small numbers of interacting cells. The platform allows for minimally invasive monitoring of cell phenotypes while administering a variety of physiological insults and stimuli by means of precisely controlled microfluidic subsystems. It features the capability to integrate a variety of sensitive intra- and extra-cellular

Research paper thumbnail of Multiple sensor arrays for single cell metabolic analysis

2013 IEEE SENSORS, 2013

ABSTRACT We present the design, fabrication and characterization of multiple micro-pocket lid arr... more ABSTRACT We present the design, fabrication and characterization of multiple micro-pocket lid arrays used in live single cell metabolic analysis. In previous work we reported a platform for quantifying single cell oxygen consumption rates realized using a fused silica deep wet etching process. Here we extend that work to a dual-depth wet etching process for microfabrication of multiple sensor trapping (MST) lid arrays. Each lid comprises multiple micro-pockets. Oxygen, pH, other extra-cellular sensors, and reference dye were deposited in the pockets. In order to achieve simultaneous monitoring of multiple metabolic parameters, the lid array serves to hermetically seal arrays of microwells, each containing a single cell. The dual-depth etching process we developed can be easily applied to other glass-based microfabrication purposes requiring dual- or multiple-depth microstructures.

Research paper thumbnail of Integrated Circuits of Coupled Mircospheres for Optoelectronics Applications

2006 International Conference on Transparent Optical Networks, 2006

The paper is devoted to theoretical modeling, fabrication, and advanced spectroscopic characteriz... more The paper is devoted to theoretical modeling, fabrication, and advanced spectroscopic characterization of circuits of microspheres with high quality whispering gallery modes (WGMs). The discussion of results is based on three mechanisms of optical coupling between spherical cavities: (i) resonant coupling between WGMs in identical cavities, (ii) Fano resonance between a discrete energy state (true WGM excited in the source sphere) and a continuum of quasi-WGM states with distorted noncircular shape which can be induced in the receiving cavity, and (iii) photonic nanojet mechanism. For the case of identical cavities we present numerical modeling results demonstrating a good impedance matching, and a tunable nanosecond delay for propagating pulses. We experimentally studied optical coupling in size-mismatched bispheres with controllable inter-cavity separations, and showed the validity of mechanism based on Fano resonance. Finally, we observed photonic nanojets in extremely long chains of fluorescent microspheres with propagation losses less than 1 dB per sphere.

Research paper thumbnail of Micro-patterning and characterization of PHEMA-co-PAM-based optical chemical sensors for lab-on-a-chip applications

Sensors and Actuators B: Chemical, 2012

We report a novel method for wafer level, high throughput optical chemical sensor patterning, wit... more We report a novel method for wafer level, high throughput optical chemical sensor patterning, with precise control of the sensor volume and capability of producing arbitrary microscale patterns. Monomeric oxygen (O(2)) and pH optical probes were polymerized with 2-hydroxyethyl methacrylate (HEMA) and acrylamide (AM) to form spin-coatable and further crosslinkable polymers. A micro-patterning method based on micro-fabrication techniques (photolithography, wet chemical process and reactive ion etch) was developed to miniaturize the sensor film onto glass substrates in arbitrary sizes and shapes. The sensitivity of fabricated micro-patterns was characterized under various oxygen concentrations and pH values. The process for spatially integration of two sensors (Oxygen and pH) on the same substrate surface was also developed, and preliminary fabrication and characterization results were presented. To the best of our knowledge, it is the first time that poly (2-hydroxylethyl methacrylate)-co-poly (acrylamide) (PHEMA-co-PAM)-based sensors had been patterned and integrated at the wafer level with micron scale precision control using microfabrication techniques. The developed methods can provide a feasible way to miniaturize and integrate the optical chemical sensor system and can be applied to any lab-on-a-chip system, especially the biological micro-systems requiring optical sensing of single or multiple analytes.

Research paper thumbnail of Percolation of light through whispering gallery modes in 3D lattices of coupled microspheres

Optics Express, 2007

Using techniques of flow-assisted self-assembly we synthesized three-dimensional (3D) lattices of... more Using techniques of flow-assisted self-assembly we synthesized three-dimensional (3D) lattices of dye-doped fluorescent (FL) 5 μm polystyrene spheres with 3% size dispersion with well controlled thickness from one monolayer up to 43 monolayers. In FL transmission spectra of such lattices we observed signatures of coupling between multiple spheres with nearly resonant whispering gallery modes (WGMs). These include (i) splitting of the WGM-related peaks with the magnitude 4.0-5.3 nm at the average wavelength 535 nm, (ii) pump dependence of FL transmission showing that the splitting is seen only above the threshold for lasing WGMs, and (iii) anomalously high transmission at the WGM peak wavelengths compared to the background for samples with thickness around 25 μm. We propose a qualitative interpretation of the observed WGM transport based on an analogy with percolation theory where the sites of the lattice (spheres) are connected with optical "bonds" which are present with probability depending on the spheres' size dispersion. We predict that the WGM percolation threshold should be achievable in close packed 3D lattices formed by cavities with ~10 3 quality factors of WGMs and with ~1% size dispersion. Such systems can be used for developing next generation of resonant sensors and arrayed-resonator light emitting devices.

Research paper thumbnail of The effects of inter-cavity separation on optical coupling in dielectric bispheres

Optics Express, 2006

The optical coupling between two size-mismatched spheres was studied by using one sphere as a loc... more The optical coupling between two size-mismatched spheres was studied by using one sphere as a local source of light with whispering gallery modes (WGMs) and detecting the intensity of the light scattered by a second sphere playing the part of a receiver of electromagnetic energy. We developed techniques to control inter-cavity gap sizes between microspheres with ~30nm accuracy. We demonstrate high efficiencies (up to 0.2-0.3) of coupling between two separated cavities with strongly detuned eigenstates. At small separations (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1 microm) between the spheres, the mechanism of coupling is interpreted in terms of the Fano resonance between discrete level (true WGMs excited in a source sphere) and a continuum of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;quasi&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;-WGMs with distorted shape which can be induced in the receiving sphere. At larger separations the spectra detected from the receiving sphere originate from scattering of the radiative modes.

Research paper thumbnail of A statistical framework for multiparameter analysis at the single-cell level

Molecular BioSystems, 2012

Phenotypic characterization of individual cells provides crucial insights into intercellular hete... more Phenotypic characterization of individual cells provides crucial insights into intercellular heterogeneity and enables access to information that is unavailable from ensemble averaged, bulk cell analyses. Single-cell studies have attracted significant interest in recent years and spurred the development of a variety of commercially available and research-grade technologies. To quantify cell-to-cell variability of cell populations, we have developed an experimental platform for real-time measurements of oxygen consumption (OC) kinetics at the single-cell level. Unique challenges inherent to these single-cell measurements arise, and no existing data analysis methodology is available to address them. Here we present a data processing and analysis method that addresses challenges encountered with this unique type of data in order to extract biologically relevant information. We applied the method to analyze OC profiles obtained with single cells of two different cell lines derived from metaplastic and dysplastic human Barrett's esophageal epithelium. In terms of method development, three main challenges were considered for this heterogeneous dynamic system: (i) high levels of noise, (ii) the lack of a priori knowledge of single-cell dynamics, and (iii) the role of intercellular variability within and across cell types. Several strategies and solutions to address each of these three challenges are presented. The features such as slopes, intercepts, breakpoint or change-point were extracted for every OC profile and compared across individual cells and cell types. The results demonstrated that the extracted features facilitated exposition of subtle differences between individual cells and their responses to cell-cell interactions. With minor modifications, this method can be used to process and analyze data from other acquisition and experimental modalities at the single-cell level, providing a valuable statistical framework for single-cell analysis.

Research paper thumbnail of Method for physiologic phenotype characterization at the single-cell level in non-interacting and interacting cells

Journal of Biomedical Optics, 2012

Intercellular heterogeneity is a key factor in a variety of core cellular processes including pro... more Intercellular heterogeneity is a key factor in a variety of core cellular processes including proliferation, stimulus response, carcinogenesis, and drug resistance. However, cell-to-cell variability studies at the single-cell level have been hampered by the lack of enabling experimental techniques. We present a measurement platform that features the capability to quantify oxygen consumption rates of individual, non-interacting and interacting cells under normoxic and hypoxic conditions. It is based on real-time concentration measurements of metabolites of interest by means of extracellular optical sensors in cell-isolating microwells of subnanoliter volume. We present the results of a series of measurements of oxygen consumption rates (OCRs) of individual non-interacting and interacting human epithelial cells. We measured the effects of cell-to-cell interactions by using the system&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s capability to isolate two and three cells in a single well. The major advantages of the approach are: 1. ratiometric, intensity-based characterization of the metabolic phenotype at the single-cell level, 2. minimal invasiveness due to the distant positioning of sensors, and 3. ability to study the effects of cell-cell interactions on cellular respiration rates.

Research paper thumbnail of Optical coupling and transport phenomena in chains of spherical dielectric microresonators with size disorder

Applied Physics Letters, 2004

The optical transmission properties of chains or circuits of touching polystyrene microspheres wi... more The optical transmission properties of chains or circuits of touching polystyrene microspheres with sizes in the 3-20 mum range and a size dispersion of ~1% are studied. The dye-doped spheres with fluorescent peaks due to whispering gallery modes were attached to one end of the chains. The effects of optical transport were detected using spatially resolved scattering spectroscopy. The attenuation

Research paper thumbnail of Resonant optical circuits based on coupling between whispering gallery modes in dielectric microresonators

Conference on Lasers and Electro-Optics/International Quantum Electronics Conference and Photonic Applications Systems Technologies, 2004

The public reporting burden for this collection of information is estimated to average 1 hour per... more The public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information.

Research paper thumbnail of Encapsulated Microsphere Arrays for Applications in Photonic Circuits

Adaptive Optics: Analysis and Methods/Computational Optical Sensing and Imaging/Information Photonics/Signal Recovery and Synthesis Topical Meetings on CD-ROM, 2005

This paper describes the fabrication, characterization and spectroscopic properties of novel stru... more This paper describes the fabrication, characterization and spectroscopic properties of novel structures made from prearranged circuits of optically coupled polystyrene microspheres in a robust elastomeric polymer.

Research paper thumbnail of Optical Delay Lines Formed by Circuits of Spherical Cavities with Coupled Whispering Gallery Modes

Adaptive Optics: Analysis and Methods/Computational Optical Sensing and Imaging/Information Photonics/Signal Recovery and Synthesis Topical Meetings on CD-ROM, 2005

We propose a novel concept of optical delay lines where the tunable delay can be achieved by cont... more We propose a novel concept of optical delay lines where the tunable delay can be achieved by controlling the inter-resonator gap sizes in circuits of optically coupled microspheres.

Research paper thumbnail of Optical coupling and transport phenomena in long chains of slightly disordered spherical microresonators

Frontiers in Optics 2004/Laser Science XXII/Diffractive Optics and Micro-Optics/Optical Fabrication and Testing, 2004

It is shown that weak optical coupling between polystyrene spherical microresonators with size di... more It is shown that weak optical coupling between polystyrene spherical microresonators with size disorders allows creating optical waveguides with attenuation ~2-3 dB per sphere, which can be evanescently coupled to resonant sources of light and used in chip-scale photonic circuits. OCIS codes: (250.5300) Photonic integrated circuits; (230.3990) Microstructure devices Resonant optical coupling between cylindrical and spherical microresonators allows developing high order spectral filters [1] and coupled resonator optical waveguides (CROWs) [2]. The effectiveness of photon hopping transport

Research paper thumbnail of Optical coupling between spherical dielectric atoms

2005 Quantum Electronics and Laser Science Conference, 2005

It is shown that dielectric microspheres with strongly detuned whispering gallery modes can be ef... more It is shown that dielectric microspheres with strongly detuned whispering gallery modes can be effectively coupled. The transition from strong to weak coupling is demonstrated as a function of separation between nonidentical microspheres.

Research paper thumbnail of Observation of Light Propagation via Whispering Gallery Modes in 3D Networks of Coupled Spherical Cavities

Frontiers in Optics, 2006

We present spectroscopic evidence for efficient optical transport via coupled whispering gallery ... more We present spectroscopic evidence for efficient optical transport via coupled whispering gallery modes in 3D networks of slightly disordered spherical cavities with attenuation length in excess of 50 µm.

Research paper thumbnail of Optical Properties of Mesoscopic Systems of Coupled Microspheres

Research paper thumbnail of Percolation of light in 3D lattices of coupled microspheres

2007 Quantum Electronics and Laser Science Conference, 2007

Research paper thumbnail of Optical Transport Phenomena in Coupled Spherical Cavities

2007 9th International Conference on Transparent Optical Networks, 2007

The efficiency of optical transport is studied in one-dimensional (ID) chains and in 3D lattices ... more The efficiency of optical transport is studied in one-dimensional (ID) chains and in 3D lattices of coupled microspheres with -1-3% size disorder. To couple light into such structures we used sources of light formed by dye-doped fluorescent microspheres. Using techniques of spatially resolved scattering spectroscopy we observed large propagation losses (-3 dB per sphere) along the chain at the frequencies of whispering gallery modes (WGMs) in the source sphere. Away from the resonance with WGMs we observed much smaller losses (< 1 dB per sphere) due to formation of nanojet-induced modes. The propagation of light in 3D lattices of disordered coupled cavities with WGM resonances is interpreted in terms of percolation theory. In transmission spectra of such 3D structures we observed spectral signatures of strong coupling between multiple spheres with nearly resonant WGMs. The results indicate that the transmission properties can be significantly improved in 3D structures formed by more uniform spheres due to achieving an optical percolation threshold for WGM transport.

Research paper thumbnail of A physical sciences network characterization of non-tumorigenic and metastatic cells

Scientific Reports, 2013

To investigate the transition from non-cancerous to metastatic from a physical sciences perspecti... more To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences-Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.

Research paper thumbnail of <title>A novel method for multiparameter physiological phenotype characterization at the single-cell level</title>

Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues IX, 2011

Non-genetic intercellular heterogeneity has been increasingly recognized as one of the key factor... more Non-genetic intercellular heterogeneity has been increasingly recognized as one of the key factors in a variety of core cellular processes including proliferation, stimulus response, carcinogenesis and drug resistance. Many diseases, including cancer, originate in a single or a few cells. Early detection and characterization of these abnormal cells can provide new insights into the pathogenesis and serve as a tool

Research paper thumbnail of <title>Automated platform for multiparameter stimulus response studies of metabolic activity at the single-cell level</title>

Microfluidics, BioMEMS, and Medical Microsystems IX, 2011

We have developed a fully automated platform for multiparameter characterization of physiological... more We have developed a fully automated platform for multiparameter characterization of physiological response of individual and small numbers of interacting cells. The platform allows for minimally invasive monitoring of cell phenotypes while administering a variety of physiological insults and stimuli by means of precisely controlled microfluidic subsystems. It features the capability to integrate a variety of sensitive intra- and extra-cellular

Research paper thumbnail of Multiple sensor arrays for single cell metabolic analysis

2013 IEEE SENSORS, 2013

ABSTRACT We present the design, fabrication and characterization of multiple micro-pocket lid arr... more ABSTRACT We present the design, fabrication and characterization of multiple micro-pocket lid arrays used in live single cell metabolic analysis. In previous work we reported a platform for quantifying single cell oxygen consumption rates realized using a fused silica deep wet etching process. Here we extend that work to a dual-depth wet etching process for microfabrication of multiple sensor trapping (MST) lid arrays. Each lid comprises multiple micro-pockets. Oxygen, pH, other extra-cellular sensors, and reference dye were deposited in the pockets. In order to achieve simultaneous monitoring of multiple metabolic parameters, the lid array serves to hermetically seal arrays of microwells, each containing a single cell. The dual-depth etching process we developed can be easily applied to other glass-based microfabrication purposes requiring dual- or multiple-depth microstructures.

Research paper thumbnail of Integrated Circuits of Coupled Mircospheres for Optoelectronics Applications

2006 International Conference on Transparent Optical Networks, 2006

The paper is devoted to theoretical modeling, fabrication, and advanced spectroscopic characteriz... more The paper is devoted to theoretical modeling, fabrication, and advanced spectroscopic characterization of circuits of microspheres with high quality whispering gallery modes (WGMs). The discussion of results is based on three mechanisms of optical coupling between spherical cavities: (i) resonant coupling between WGMs in identical cavities, (ii) Fano resonance between a discrete energy state (true WGM excited in the source sphere) and a continuum of quasi-WGM states with distorted noncircular shape which can be induced in the receiving cavity, and (iii) photonic nanojet mechanism. For the case of identical cavities we present numerical modeling results demonstrating a good impedance matching, and a tunable nanosecond delay for propagating pulses. We experimentally studied optical coupling in size-mismatched bispheres with controllable inter-cavity separations, and showed the validity of mechanism based on Fano resonance. Finally, we observed photonic nanojets in extremely long chains of fluorescent microspheres with propagation losses less than 1 dB per sphere.

Research paper thumbnail of Micro-patterning and characterization of PHEMA-co-PAM-based optical chemical sensors for lab-on-a-chip applications

Sensors and Actuators B: Chemical, 2012

We report a novel method for wafer level, high throughput optical chemical sensor patterning, wit... more We report a novel method for wafer level, high throughput optical chemical sensor patterning, with precise control of the sensor volume and capability of producing arbitrary microscale patterns. Monomeric oxygen (O(2)) and pH optical probes were polymerized with 2-hydroxyethyl methacrylate (HEMA) and acrylamide (AM) to form spin-coatable and further crosslinkable polymers. A micro-patterning method based on micro-fabrication techniques (photolithography, wet chemical process and reactive ion etch) was developed to miniaturize the sensor film onto glass substrates in arbitrary sizes and shapes. The sensitivity of fabricated micro-patterns was characterized under various oxygen concentrations and pH values. The process for spatially integration of two sensors (Oxygen and pH) on the same substrate surface was also developed, and preliminary fabrication and characterization results were presented. To the best of our knowledge, it is the first time that poly (2-hydroxylethyl methacrylate)-co-poly (acrylamide) (PHEMA-co-PAM)-based sensors had been patterned and integrated at the wafer level with micron scale precision control using microfabrication techniques. The developed methods can provide a feasible way to miniaturize and integrate the optical chemical sensor system and can be applied to any lab-on-a-chip system, especially the biological micro-systems requiring optical sensing of single or multiple analytes.

Research paper thumbnail of Percolation of light through whispering gallery modes in 3D lattices of coupled microspheres

Optics Express, 2007

Using techniques of flow-assisted self-assembly we synthesized three-dimensional (3D) lattices of... more Using techniques of flow-assisted self-assembly we synthesized three-dimensional (3D) lattices of dye-doped fluorescent (FL) 5 μm polystyrene spheres with 3% size dispersion with well controlled thickness from one monolayer up to 43 monolayers. In FL transmission spectra of such lattices we observed signatures of coupling between multiple spheres with nearly resonant whispering gallery modes (WGMs). These include (i) splitting of the WGM-related peaks with the magnitude 4.0-5.3 nm at the average wavelength 535 nm, (ii) pump dependence of FL transmission showing that the splitting is seen only above the threshold for lasing WGMs, and (iii) anomalously high transmission at the WGM peak wavelengths compared to the background for samples with thickness around 25 μm. We propose a qualitative interpretation of the observed WGM transport based on an analogy with percolation theory where the sites of the lattice (spheres) are connected with optical "bonds" which are present with probability depending on the spheres' size dispersion. We predict that the WGM percolation threshold should be achievable in close packed 3D lattices formed by cavities with ~10 3 quality factors of WGMs and with ~1% size dispersion. Such systems can be used for developing next generation of resonant sensors and arrayed-resonator light emitting devices.

Research paper thumbnail of The effects of inter-cavity separation on optical coupling in dielectric bispheres

Optics Express, 2006

The optical coupling between two size-mismatched spheres was studied by using one sphere as a loc... more The optical coupling between two size-mismatched spheres was studied by using one sphere as a local source of light with whispering gallery modes (WGMs) and detecting the intensity of the light scattered by a second sphere playing the part of a receiver of electromagnetic energy. We developed techniques to control inter-cavity gap sizes between microspheres with ~30nm accuracy. We demonstrate high efficiencies (up to 0.2-0.3) of coupling between two separated cavities with strongly detuned eigenstates. At small separations (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1 microm) between the spheres, the mechanism of coupling is interpreted in terms of the Fano resonance between discrete level (true WGMs excited in a source sphere) and a continuum of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;quasi&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;-WGMs with distorted shape which can be induced in the receiving sphere. At larger separations the spectra detected from the receiving sphere originate from scattering of the radiative modes.

Research paper thumbnail of A statistical framework for multiparameter analysis at the single-cell level

Molecular BioSystems, 2012

Phenotypic characterization of individual cells provides crucial insights into intercellular hete... more Phenotypic characterization of individual cells provides crucial insights into intercellular heterogeneity and enables access to information that is unavailable from ensemble averaged, bulk cell analyses. Single-cell studies have attracted significant interest in recent years and spurred the development of a variety of commercially available and research-grade technologies. To quantify cell-to-cell variability of cell populations, we have developed an experimental platform for real-time measurements of oxygen consumption (OC) kinetics at the single-cell level. Unique challenges inherent to these single-cell measurements arise, and no existing data analysis methodology is available to address them. Here we present a data processing and analysis method that addresses challenges encountered with this unique type of data in order to extract biologically relevant information. We applied the method to analyze OC profiles obtained with single cells of two different cell lines derived from metaplastic and dysplastic human Barrett's esophageal epithelium. In terms of method development, three main challenges were considered for this heterogeneous dynamic system: (i) high levels of noise, (ii) the lack of a priori knowledge of single-cell dynamics, and (iii) the role of intercellular variability within and across cell types. Several strategies and solutions to address each of these three challenges are presented. The features such as slopes, intercepts, breakpoint or change-point were extracted for every OC profile and compared across individual cells and cell types. The results demonstrated that the extracted features facilitated exposition of subtle differences between individual cells and their responses to cell-cell interactions. With minor modifications, this method can be used to process and analyze data from other acquisition and experimental modalities at the single-cell level, providing a valuable statistical framework for single-cell analysis.

Research paper thumbnail of Method for physiologic phenotype characterization at the single-cell level in non-interacting and interacting cells

Journal of Biomedical Optics, 2012

Intercellular heterogeneity is a key factor in a variety of core cellular processes including pro... more Intercellular heterogeneity is a key factor in a variety of core cellular processes including proliferation, stimulus response, carcinogenesis, and drug resistance. However, cell-to-cell variability studies at the single-cell level have been hampered by the lack of enabling experimental techniques. We present a measurement platform that features the capability to quantify oxygen consumption rates of individual, non-interacting and interacting cells under normoxic and hypoxic conditions. It is based on real-time concentration measurements of metabolites of interest by means of extracellular optical sensors in cell-isolating microwells of subnanoliter volume. We present the results of a series of measurements of oxygen consumption rates (OCRs) of individual non-interacting and interacting human epithelial cells. We measured the effects of cell-to-cell interactions by using the system&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s capability to isolate two and three cells in a single well. The major advantages of the approach are: 1. ratiometric, intensity-based characterization of the metabolic phenotype at the single-cell level, 2. minimal invasiveness due to the distant positioning of sensors, and 3. ability to study the effects of cell-cell interactions on cellular respiration rates.

Research paper thumbnail of Optical coupling and transport phenomena in chains of spherical dielectric microresonators with size disorder

Applied Physics Letters, 2004

The optical transmission properties of chains or circuits of touching polystyrene microspheres wi... more The optical transmission properties of chains or circuits of touching polystyrene microspheres with sizes in the 3-20 mum range and a size dispersion of ~1% are studied. The dye-doped spheres with fluorescent peaks due to whispering gallery modes were attached to one end of the chains. The effects of optical transport were detected using spatially resolved scattering spectroscopy. The attenuation