Biomedical subjects

Mihrimah Ozkan

Publications and source records attributed to Mihrimah Ozkan.

13 recordsLinked to original sources

PubMed2007

High-throughput sorting and analysis of human sperm with a ring-shaped laser trap.

Sperm motility is an important concept in fertility research. To this end, single spot laser tweezers have been used to quantitatively analyze the motility of individual sperm. However, this method is limited with throughput (single sperm per spot), lacks the ability of in-situ sorting based on motility and chemotaxis, requires high laser power (hundreds of milliWatts) and can not be used to dynamically monitor changes in sperm swimming behavior under the influence of a laser beam. Here, we report a continuous 3-D ring-shaped laser trap which could be used for multi-level and high-throughput (tens to hundred sperm per ring) sperm sorting based on their motility and chemotaxis. Under a laser power of only tens of milliWatts, human sperm with low to medium velocity are slowed down, stopped, or forced to change their trajectories to swim along the ring due to the optical gradient force in the radial direction. This is the first demonstration of parallel sperm sorting based on motility with optical trapping technology. In addition, by making the sperm swimming along the circumference of the ring, the effect of laser radiation, optical force and external obstacles on sperm energetics are investigated in a more gentle and quantitative way. The application of this method could be extended to motility and bio-tropism studies of other self-propelled cells, such as algae and bacteria.

Cell Separation↗

PubMed2006

Size tunable three-dimensional annular laser trap based on axicons.

A three-dimensional (3D) ring-shaped laser trap has been built using axicons. The diameter of this laser trap ranges from 70 to 140 mum and is adjusted by simply changing the position of one axicon in the optical path. Parallel 3D trapping of 5 mum silica microspheres and 3D confinement of cells along the ring are demonstrated. In this system the special optical properties of axicons are used to create a continuous annular trap with high power efficiency and a constant numerical aperture. This new approach, without any mechanical scanning, offers significant potential for applications in cell motility analysis and biotropism studies.

Equipment Design↗

PubMed2006

Nano-oncology: drug delivery, imaging, and sensing.

Innovation in the last decade has endowed nanotechnology with an assortment of tools for delivery, imaging, and sensing in cancer research-stealthy nanoparticle vectors circulating in vivo, assembled with exquisite molecular control, capable of selective tumor targeting and potent delivery of therapeutics; intense and photostable quantum dot-based tumor imaging, enabling multicolor detection of cell receptors with a single optical excitation source; arrays of semiconducting nanowire and carbon nanotube sensor elements for selective multiplexed sensing of cancer markers without the need for probe labeling. These rapidly emerging tools are indicative of a burgeoning field ready to expand into medical applications. This review attempts to outline most of the current nanoparticle toolset for therapeutic release by liposomes, dendrimers, smart polymers, and virus-based systems. Advantages of nanoparticle-based imaging and targeting by use of nanoshells and quantum dots are also explored. Finally, emerging nanoelectronics-based sensing and a global discussion on the utility of each nanoparticle system addresses their fundamental advantages and shortcomings in cancer research.

Biosensing Techniques↗

PubMed2006

Association of different prediction methods for determination of the efficiency and selectivity on neuron-based sensors.

A technique has been developed to determine the efficiency and the selectivity of a single neuron-based sensor in identifying the nature of the chemical agents in an unknown sample. This has been achieved by exploiting the unique electrical identifiers, also known as "signature patterns", generated by the neuronal cell membrane. These were generated based on the variations to the extracellular electrical activity, due to the effect of a broad range of chemical agents. We demonstrate the prediction capability of the sensor in identifying the nature of an unknown test sample from a combination of three chemical agents, namely, ethanol, pyrethroid, and hydrogen peroxide. This was achieved through a two-step process. The first step was experimentally achieved by in situ recording of the changes to the extracellular electrical activity from the sensing sites or the array of microelectrodes that form the platform for patterning neurons. Simultaneous optical characterization of the cell array during the sensing process was performed to identify the associated physiological changes. The second step was mathematical and was based on developing a library of signature patterns for a set of concentrations of the various combinations of the three chemical agents. Two variants of the nearest neighbor algorithm scheme - (a) partial distance search method, and (b) search tree method, were implemented for the accurate detection of all the components with varying concentrations in the test samples of unknown nature. This technique exhibits reliability in identification up to parts-per-billion (ppb) sensitivity. The capability of standardization of this technique for potential commercial applications is also discussed.

Action Potentials↗

PubMed2006

Carbon nanotube-DNA nanoarchitectures and electronic functionality.

Biological molecules such as deoxyribonucleic acid (DNA) possess inherent recognition and self-assembly capabilities, and are attractive templates for constructing functional hierarchical material structures as building blocks for nanoelectronics. Here we report the assembly and electronic functionality of nanoarchitectures based on conjugates of single-walled carbon nanotubes (SWNTs) functionalized with carboxylic groups and single-stranded DNA (ssDNA) sequences possessing terminal amino groups on both ends, hybridized together through amide linkages by adopting a straightforward synthetic route. Morphological and chemical-functional characterization of the nanoarchitectures are investigated using scanning electron microscopy, transmission electron microscopy, atomic force microscopy, energy-dispersive X-ray spectroscopy, Raman spectroscopy, and Fourier-transform infrared spectroscopy. Electrical measurements (I-V characterization) of the nanoarchitectures demonstrate negative differential resistance in the presence of SWNT/ssDNA interfaces, which indicates a biomimetic route to fabricating resonant tunneling diodes. I-V characterization on platinum-metallized SWNT-ssDNA nanoarchitectures via salt reduction indicates modulation of their electrical properties, with effects ranging from those of a resonant tunneling diode to a resistor, depending on the amount of metallization. Electron transport through the nanoarchitectures has been analyzed by density functional theory calculations. Our studies illustrate the great promise of biomimetic assembly of functional nanosystems based on biotemplated materials and present new avenues toward exciting future opportunities in nanoelectronics and nanobiotechnology.

DNA↗

PubMed2005

Laser-tweezer-controlled solid immersion microscopy in microfluidic systems.

We describe the creation and implementation of a near-field scanning solid immersion microscope that is specifically tailored for use in microfluidic systems. The microscope comprises a newly fabricated Weierstrass solid immersion lens (SIL), which is detached from its substrate and is free floating in the fluid, and a laser optical tweezer, which serves both as a trapping beam for alignment and positioning of the SIL and as a near-field scanning beam that images the sample through the SIL. A discussion of the SIL's fabrication method is presented along with experimental results that demonstrate the effectiveness of our microscope design.

Equipment Design↗

PubMed2005

Counter-propagating optical trapping system for size and refractive index measurement of microparticles.

We propose and demonstrate a novel approach to measure the size and refractive index of microparticles based on two beam optical trapping, where forward scattered light is detected to give information about the particle. The counter-propagating optical trap measurement (COTM) system exploits the capability of optical traps to measure pico-Newton forces for microparticles' refractive index and size characterization. Different from the current best technique for microparticles' refractive index measurement, refractometry, a bulk technique requiring changing the fluid composition of the sample, our optical trap technique works with any transparent fluid and enables single particle analysis without the use of biological markers. A ray-optics model is used to explore the physical operation of the COTM system, predict system performance and aid system design. Experiments demonstrate the accuracy of refractive index measurement of Deltan=0.013 and size measurement of 3% of diameter with 2% standard deviation. Present performance is instrumentation limited, and a potential improvement by more than two orders of magnitude can be expected in the future. With further development in parallelism and miniaturization, the system offers advantages for cell manipulation and bioanalysis compatible with lab-on-a-chip systems.

Biopolymers↗

PubMed2005

Organic and inorganic nanoparticle hybrids.

Viruses are exemplary models in nanoassembly for their regular geometries, well characterized surface properties, and nanoscale dimensions. Armed with versatile tools aimed at site-directed mutagenesis to modify the virion's surface, conjugation chemistry for capsid coupling, and manipulation of nanoparticles, we have demonstrated nanoscale assembly of inorganic carbon nanotubes and quantum dots with engineered viruses to produce an intimate array of hybrid structures.

Capsid↗

PubMed2005

Two-beam optical traps: refractive index and size measurements of microscale objects.

A counter-propagating optical trap measurement (COTM) system is proposed and analyzed based on the ray-optics model. In this system, refractive index and size of trapped objects can be estimated by using forward scattered light from the two-beam laser trap with resolution Delta n = 0.013 for the refractive index measurements and 3.3% for the size measurements, which is comparable with current bulk techniques, such as refractometry, and flow cytometry. The unique advantage of the COTM system over conventional approaches lies in its capability of marker-free single-particle characterization in whatever transparent buffer required by living cell, eliminating the necessity of changing the fluid composition of the sample in refractometry, and of tagging target with toxic fluorescence dyes in flow cytometry. Noise analysis predicts a potential improvement in the system resolution by more than two orders of magnitude. This non-invasive and sterile tool complements lab-on-a-chips with single cell manipulation and analysis in living friendly ambient.

Biopolymers↗

PubMed2004

Quantum dots and other nanoparticles: what can they offer to drug discovery?

Nanocrystals (quantum dots) and other nanoparticles (gold colloids, magnetic bars, nanobars, dendrimers and nanoshells) have been receiving a lot of attention recently with their unique properties for potential use in drug discovery, bioengineering and therapeutics. In this review, structural, optical and biological assets of nanocrystals are summarized and their applications to drug discovery studies are discussed. Unique properties of these nanoparticles can offer new advancements in drug discovery.

Drug Design↗

PubMed2004

Neurons as sensors: individual and cascaded chemical sensing.

A single neuron sensor has been developed based on the interaction of gradient electric fields and the cell membrane. Single neurons are rapidly positioned over individual microelectrodes using positive dielectrophoretic traps. This enables the continuous extracellular electrophysiological measurements from individual neurons. The sensor developed using this technique provides the first experimental method for determining single cell sensitivity; the speed of response and the associated physiological changes to a broad spectrum of chemical agents. Binding of specific chemical agents to a specific combination of receptors induces changes to the extracellular membrane potential of a single neuron, which can be translated into unique "signature patterns" (SP), which function as identification tags. Signature patterns are derived using Fast Fourier Transformation (FFT) analysis and Wavelet Transformation (WT) analysis of the modified extracellular action potential. The validity and the sensitivity of the system are demonstrated for a variety of chemical agents ranging from behavior altering chemicals (ethanol), environmentally hazardous agents (hydrogen peroxide, EDTA) to physiologically harmful agents (pyrethroids) at pico- and femto-molar concentrations. The ability of a single neuron to selectively identify specific chemical agents when injected in a serial manner is demonstrated in "cascaded sensing".

Action Potentials↗

PubMed2004

Separation of individual neurons using dielectrophoretic alternative current fields.

Experimental investigations into the dynamics of neuronal networks are a fundamental step towards understanding how the nervous system works. Memory formation and development are associated with changes in the electrical activity of the neurons. To understand the changes in the electrical activity, it is essential to conduct in vitro studies on individual neurons. Hence, there is an enormous need to develop novel ways for isolating and localizing individual neurons. To this end, we designed and fabricated a 4x4 multiple microelectrode array system to spatially arrange neurons by generating dielectrophoretic traps using gradient alternating current (AC) fields. We characterized the electric field distribution inside our test platform by using three-dimensional finite element modeling (FEM) and estimated the location of neurons over the electrode array. As the first stage in forming a neuronal network, dielectrophoretic AC fields were employed to separate the neurons from the glial cells and to position individual neurons over single electrodes. The extracellular electrical activity from a single neuron was recorded. The frequency spectrum of the electrical activity was generated using fast Fourier transformation analysis (FFT) to determine the characteristic burst rates of individual neurons.

Action Potentials↗

PubMed2004

Neuron-based microarray sensors for environmental sensing.

We present a novel sensing scheme for detecting the effects of unburned fossil fuels by integrating microarray technology and dielectrophoresis to develop single-neuron arrays. These arrays have the capability to sense and identify the two fuels, at parts per billion (ppb) concentrations, as well to determine the associated physiological changes at the single-cell level. Identification is achieved through frequency domain analysis of the measured changes to the extracellular electrical activity due to the effect of the fossil fuels. This yields unique electrical identifiers known as "signature patterns". Simultaneous optical visualization to the physiological changes is obtained by specific fluorescent staining. The correlation between the signature patterns and the cellular biological behavior establishes the veracity of this identification technique.

Biosensing Techniques↗