Browsing by Author "Hanay, M. Selim"

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Open Access
Atmospheric pressure mass spectrometry of single viruses and nanoparticles by nanoelectromechanical systems
(American Chemical Society, 2022-01-04) Erdogan, R. Tufan; Alkhaled, Mohammed; Kaynak, Batuhan E.; Alhmoud, Hashim; Pisheh, Hadi Sedaghat; Kelleci, Mehmet; Karakurt, Ilbey; Yanik, C.; Şen, Zehra Betül; Sari, B.; Yagci, A. M.; Özkul, A.; Hanay, M. Selim
Mass spectrometry of intact nanoparticles and viruses can serve as a potent characterization tool for material science and biophysics. Inaccessible by widespread commercial techniques, the mass of single nanoparticles and viruses (>10MDa) can be readily measured by nanoelectromechanical systems (NEMS)-based mass spectrometry, where charged and isolated analyte particles are generated by electrospray ionization (ESI) in air and transported onto the NEMS resonator for capture and detection. However, the applicability of NEMS as a practical solution is hindered by their miniscule surface area, which results in poor limit-of-detection and low capture efficiency values. Another hindrance is the necessity to house the NEMS inside complex vacuum systems, which is required in part to focus analytes toward the miniscule detection surface of the NEMS. Here, we overcome both limitations by integrating an ion lens onto the NEMS chip. The ion lens is composed of a polymer layer, which charges up by receiving part of the ions incoming from the ESI tip and consequently starts to focus the analytes toward an open window aligned with the active area of the NEMS electrostatically. With this integrated system, we have detected the mass of gold and polystyrene nanoparticles under ambient conditions and with two orders-of-magnitude improvement in capture efficiency compared to the state-of-the-art. We then applied this technology to obtain the mass spectrum of SARS-CoV-2 and BoHV-1 virions. With the increase in analytical throughput, the simplicity of the overall setup, and the operation capability under ambient conditions, the technique demonstrates that NEMS mass spectrometry can be deployed for mass detection of engineered nanoparticles and biological samples efficiently.
Open Access
Classification of dielectric microparticles by microwave impedance cytometry
(Cold Spring Harbor Laboratory, 2022-09-28) Hanay, M. Selim; Sarı, Burak; Tefek, Uzay
AbstractCoulter counters and impedance cytometry are commonly used for counting microscopic objects, such as cells and microparticles flowing in a liquid, as well as to obtain their size distribution. However, the ability of these techniques to provide simultaneous material information — via dielectric permittivity measurements — has been limited so far. The challenge stems from the fact that the signals generated by microparticles of identical size, but different material composition, are close to each other. The similarity in impedance signals arises because the material-dependent factor is determined mainly by the volume of aqueous solution displaced by the microparticles, rather than the microparticles themselves. To differentiate between materially distinct particles with similar geometry and size, another measurement mode needs to be implemented. Here, we describe a new microfluidics-based sensor that provides material classification between microparticles with similar sizes by integrating impedance cytometry with microwave resonator sensors on the same chip. While low-frequency impedance cytometry provides the geometric size of particles, the microwave sensor operating at three orders-of-magnitude higher frequency provides their electrical size. By combining these two measurements, the Clausius-Mossotti factors of microparticles can be calculated to serve as a differentiation parameter. In addition to distinguishing dielectric materials from cells and metals, we classified two different dielectric microparticles with similar sizes and electrical characteristics: polystyrene and soda lime glass, with 94% identification accuracy. The proposed technique can serve as an automated monitoring system for quality control of manufactured microparticles and facilitate environmental microplastic screening.
Open Access
Design and fabrication of CSWAP gate based on nano-electromechanical systems
(Springer, Cham, 2016) Yüksel, Mert; Erbil, Selçuk Oğuz; Arı, Atakan B.; Hanay, M. Selim
In order to reduce undesired heat dissipation, reversible logic offers a promising solution where the erasure of information can be avoided to overcome the Landauer limit. Among the reversible logic gates, Fredkin (CSWAP) gate can be used to compute any Boolean function in a reversible manner. To realize reversible computation gates, Nano-electromechanical Systems (NEMS) offer a viable platform, since NEMS can be produced en masse using microfabrication technology and controlled electronically at high-speeds. In this work-in-progress paper, design and fabrication of a NEMS-based implementation of a CSWAP gate is presented. In the design, the binary information is stored by the buckling direction of nanomechanical beams and CSWAP operation is accomplished through a mechanism which can selectively allow/block the forces from input stages to the output stages. The gate design is realized by fabricating NEMS devices on a Silicon-on-Insulator substrate. © Springer International Publishing Switzerland 2016.
Open Access
Fundamental sensitivity limitations of nanomechanical resonant sensors due to thermomechanical noise
(IEEE, 2020) Demir, A.; Hanay, M. Selim
Nanomechanical resonators are used as high performance sensors of physical stimuli such as force and mass changes. Any such physical stimulus produces a shift in the resonance frequency of the nanomechanical structure, which can be measured accurately by using a feedback system that locks the frequency of a signal generator to the resonance. Closed-loop frequency tracking is the most prevalent technique in the fields of nanomechanical sensors and non-contact atomic force microscopy. Ultimate performance of sensors is limited by various nonideal effects such as temperature variations, radiation, electromagnetic interference, and noise arising from inherent physical mechanisms. Here, we consider the noise performance of nanomechanical resonant sensors, which has so far eluded explanation with conflicting results reported in the literature. We present a precise theory for these ubiquitous sensors based on nanomechanical resonators under feedback in order to decipher the fundamental sensitivity limitations due to thermomechanical noise. The results we obtain, when the performance is limited by the thermomechanical noise of the resonator, are in complete agreement with the ones from stochastic simulations. Our findings shed light on recent results in the literature and resolve a critical problem regarding the frequency noise of nanomechanical sensors under feedback. Our results have applications in nanomechanics, atomic force microscopy, microwave and suspended microchannel resonators.
Open Access
High resolution dielectric characterization of single cells and microparticles using integrated microfluidic microwave sensors
(Institute of Electrical and Electronics Engineers, 2023-03-01) Seçme, Arda; Tefek, Uzay; Sarı, Burak; Pisheh, Hadi Sedaghat; Uslu, H. Dilara; Akbulut, Özge; Küçükoğlu, Berk; Erdogan, R. Tufan; Alhmoud, Hashim; Şahin, Özgür; Hanay, M. Selim
Microwave sensors can probe intrinsic material properties of analytes in a microfluidic channel at physiologically relevant ion concentrations. While microwave sensors have been used to detect single cells and microparticles in earlier studies, the synergistic use and comparative analysis of microwave sensors with optical microscopy for material classification and size tracking applications have been scarcely investigated so far. Here we combined microwave and optical sensing to differentiate microscale objects based on their dielectric properties. We designed and fabricated two types of planar sensor: a Coplanar Waveguide Resonator (CPW) and a Split-Ring Resonator (SRR). Both sensors possessed sensing electrodes with a narrow gap to detect single cells passing through a microfluidic channel integrated on the same chip. We also show that standalone microwave sensors can track the relative changes in cellular size in real-time. In sensing single 20-micron diameter polystyrene particles, Signal-to-Noise ratio values of approximately 100 for CPW and 70 for SRR sensors were obtained. These findings demonstrate that microwave sensing technology can serve as a complementary technique for single-cell biophysical experiments and microscale pollutant screening.
Open Access
High resolution dielectric characterization of single cells and microparticles using integrated microfluidic microwave sensors
(Institute of Electrical and Electronics Engineers, 2023-03-01) Seçme, Arda; Tefek, Uzay; Sarı, Burak; Pisheh, Hadi Sedaghat; Uslu, H. Dilara; Akbulut, Özge; Küçükoğlu, Berk; Erdoğan, R. Tufan; Alhmoud, Hashim; Şahin, Özgür; Hanay, M. Selim
Microwave sensors can probe intrinsic material properties of analytes in a microfluidic channel at physiologically relevant ion concentrations. While microwave sensors have been used to detect single cells and microparticles in earlier studies, the synergistic use and comparative analysis of microwave sensors with optical microscopy for material classification and size tracking applications have been scarcely investigated so far. Here we combined microwave and optical sensing to differentiate microscale objects based on their dielectric properties. We designed and fabricated two types of planar sensor: a Coplanar Waveguide Resonator (CPW) and a Split-Ring Resonator (SRR). Both sensors possessed sensing electrodes with a narrow gap to detect single cells passing through a microfluidic channel integrated on the same chip. We also show that standalone microwave sensors can track the relative changes in cellular size in real-time. In sensing single 20-micron diameter polystyrene particles, Signal-to-Noise ratio values of approximately 100 for CPW and 70 for SRR sensors were obtained. These findings demonstrate that microwave sensing technology can serve as a complementary technique for single-cell biophysical experiments and microscale pollutant screening.
Open Access
Intermodal coupling as a probe for detecting nanomechanical modes
(American Physical Society, 2018) Arı, Atakan B.; Karakan, M. Çağatay; Yanık, C.; Kaya, I. I.; Hanay, M. Selim
Nanoelectromechanical systems provide ultrahigh performance in sensing applications. The sensing performance and functionality can be enhanced by utilizing more than one resonance mode of a nanoelectromechanical-systems device. However, it is often challenging to measure mechanical modes at high frequencies or modes that couple weakly to output transducers. In this paper, we propose the use of intermodal coupling as a mechanism to enable the detection of such modes. To implement this method, a probe mode is continuously driven and monitored using a phase-locked loop, while an auxiliary drive signal scans for other modes. Each time the auxiliary drive signal excites the corresponding mode by matching the mechanical frequency, the effective tension within the structure increases, which in turn causes a frequency shift in the probe mode. The location and width of these frequency shifts can be used to determine the frequency and quality factor of mechanical modes indirectly. Intermodal coupling can be used as a tool to obtain the spectrum of a mechanical structure even if some of these modes cannot be detected conventionally.
Open Access
Leveraging the elastic deformability of polydimethylsiloxane microfluidic channels for efficient intracellular delivery
(Royal Society of Chemistry, 2022-11-25) Alhmoud, Hashim; Alkhaled, Mohammed; Kaynak, Batuhan E.; Hanay, M. Selim
With the rapid development of microfluidic based cell therapeutics systems, the need arises for compact, modular, and microfluidics-compatible intracellular delivery platforms with small footprints and minimal operational requirements. Physical deformation of cells passing through a constriction in a microfluidic channel has been shown to create transient membrane perturbations that allow passive diffusion of materials from the outside to the interior of the cell. This mechanical approach to intracellular delivery is simple to implement and fits the criteria outlined above. However, available microfluidic platforms that operate through this mechanism are traditionally constructed from rigid channels with fixed dimensions that suffer from irreversible clogging and incompatibility with larger size distributions of cells. Here we report a flexible and elastically deformable microfluidic channel, and we leverage this elasticity to dynamically generate temporary constrictions with any given size within the channel width parameters. Additionally, clogging is prevented by increasing the size of the constriction momentarily to allow clogs to pass. By tuning the size of the constriction appropriately, we show the successful delivery of GFP-coding plasmids to the interior of three mammalian cell lines and fluorescent gold nanoparticles to HEK293 FT cells all the while maintaining a high cell viability rate. We also demonstrate the device capabilities by systematically identifying the optimum constriction size that maximizes the intracellular delivery efficiency of FITC-dextran for three different cell lines. This development will no doubt lead to miniaturized intracellular delivery microfluidic components that can be easily integrated into larger lab-on-a-chip systems for future cell modification devices.
Open Access
Measurement and characterization of nano-electro-mechanical systems using laser interferometry
(IEEE, 2020) Bello, V.; Ari, A. B.; Hanay, M. Selim; Ekinci, K. L.
In this work, we describe a method to measure and characterize the mechanical properties of nano-electromechanical systems (NEMS) based on laser interferometry. The resonant mechanical modes of doubly-clamped nanomechanical beam resonators were first characterized using their thermal fluctuations in air. Afterwards, the NEMS devices were electrothermally actuated, and their frequency responses were measured, also in air. The main novelty in this work is the simultaneous use of two electro-thermal actuators integrated on opposite ends of the NEMS, which could selectively actuate higher order modes based on the relative phase difference (of 0°, 45° or 90°) applied between the two actuators. All the measurements were carried out in a homodyne Michelson interferometer, allowing for ultrasensitive non-contact, noninvasive, remote, and non-destructive analysis.
Open Access
Microfluidics-integrated microwave sensors for single cells size discrimination
(Institute of Electrical and Electronics Engineers, 2021-04-01) Seçme, Arda; Pisheh, Hadi Sedaghat; Uslu, H. Dilara; Akbulut, Özge; Erdoğan, R. Tufan; Hanay, M. Selim
The size of a cell is one of the most fundamental biophysical parameters it possesses. Traditionally size measurements are done by using optical microscopy and quantitative phase imaging. However, a sensor with higher resolution, high throughput and lower cost is still needed. Here, a novel microfluidics-integrated microwave sensor is demonstrated to characterize single cells in real-time without labelling. Coplanar waveguide resonator is designed with a bowtie-shaped sensing electrodes separated by 50 μm. Cells are transported to sensing region by microfluidic channels and their sizes are measured simultaneously by the microwave sensors and optical microscopy. To enhance the microwave resolution, the microwave resonator is equipped with external heterodyne measurement circuitry detecting each and every cell passing through the sensing region. By comparing quantitative microscopic image analysis with frequency shifts, we show that microwave sensors can effectively measure cellular size. Our results indicate that microfluidics-integrated microwave sensors (MIMS) can be used for detecting.
Open Access
On-chip liquid and gas flow rate sensing via membrane deformation and bistability probed by microwave resonators
(Springer, 2022-11-15) Seçme, Arda; Pisheh, Hadi Sedaghat; Uslu, H. Dilara; Tefek, Uzay; Küçükoğlu, Berk; Alataş, Ceren; Kelleci, Mehmet; Hanay, M. Selim
Abstract Precise monitoring of fluid flow rates constitutes an integral problem in various lab-on-a-chip applications. While off-chip flow sensors are commonly used, new sensing mechanisms are being investigated to address the needs of increasingly complex lab-on-a-chip platforms which require local and non-intrusive flow rate sensing. In this regard, the deformability of microfluidic components has recently attracted attention as an on-chip sensing mechanism. To develop an on-chip flow rate sensor, here we utilized the mechanical deformations of a 220 nm thick Silicon Nitride membrane integrated with the microfluidic channel. Fluid flow induces deformations on the membrane, which is electronically probed by the changes in the capacitance and resonance frequency of an overlapping microwave resonator. By tracking the resonance frequency, both liquid and gas flows were probed with the same device architecture. For liquid flow experiments, a secondary sensing mechanism emerged when it was observed that steady liquid flow induces periodic deformations on the membrane. Here, the period of membrane deformation depends on the flow rate and can again be measured electronically by the microwave sensor. Flow rate measurements based on the deformation and instability of thin membranes demonstrate the transduction potential of microwave resonators for fluid-structure interactions at micro and nanoscales.
Open Access
Piezoresistive silicon nanowire resonators as embedded building blocks in thick SOI
(Institute of Physics Publishing, 2018) Esfahani, M. N.; Kılınç, Y.; Karakan, M. Çağatay; Orhan, Ezgi; Hanay, M. Selim; Leblebici, Y.; Alaca, B. E.
The use of silicon nanowire resonators in nanoelectromechanical systems for new-generation sensing and communication devices faces integration challenges with higher-order structures. Monolithic and deterministic integration of such nanowires with the surrounding microscale architecture within the same thick crystal is a critical aspect for the improvement of throughput, reliability and device functionality. A monolithic and IC-compatible technology based on a tuned combination of etching and protection processes was recently introduced yielding silicon nanowires within a 10 μm-thick device layer. Motivated by its success, the implications of the technology regarding the electromechanical resonance are studied within a particular setting, where the resonator is co-fabricated with all terminals and tuning electrodes. Frequency response is measured via piezoresistive readout with frequency down-mixing. Measurements indicate mechanical resonance with frequencies as high as 100 MHz exhibiting a Lorentzian behavior with proper transition to nonlinearity, while Allan deviation on the order of 3-8 ppm is achieved. Enabling the fabrication of silicon nanowires in thick silicon crystals using conventional semiconductor manufacturing, the present study thus demonstrates an alternative pathway to bottom-up and thin silicon-on-insulator approaches for silicon nanowire resonators.
Open Access
Towards microwave imaging of cells
(Royal Society of Chemistry, 2018) Kelleci, Mehmet; Aydoğmuş, Hande; Aslanbaş, Levent; Erbil, Selçuk Oğuz; Hanay, M. Selim
Integrated detection techniques that can characterize the morphological properties of cells are needed for the widespread use of lab-on-a-chip technology. Herein, we establish a theoretical and experimental framework to use resonant microwave sensors in their higher order modes so that the morphological properties of analytes inside a microfluidic channel can be obtained electronically. We built a phase-locked loop system that can track the first two modes of a microstrip line resonator to detect the size and location of microdroplets and cells passing through embedded microfluidic channels. The attained resolution, expressed in terms of Allan deviation at the response time, is as small as 2 × 10-8 for both modes. Additionally, simulations were performed to show that sensing with higher order modes can yield the geometrical volume, effective permittivity, two-dimensional extent, and the orientation of analytes. The framework presented here makes it possible to develop a novel type of microscope that operates at the microwave band, i.e., a radar for cells.
Open Access
Vapor sensing of colorectal cancer biomarkers in isolation by bare and functionalized nanoelectromechanical sensors
(Institute of Electrical and Electronics Engineers, 2023-08-04) Karakan, M. C.; Ari, Atakan B.; Kelleci, M.; Yanik, C.; Kaya, I. I.; Tastan, O.; Hanay, M. Selim
Small dimensions and high resonance frequencies render nanoelectromechanical systems (NEMS) sensitive mass detectors. Mass detection capability can be used to sense chemicals in the gas phase by functionalizing the device, usually with a polymeric film. The performance of NEMS-based gas detectors in breath analysis applications depends crucially on the selectivity between selected functionalization layers and targeted biomarkers. Here, we report the detection of four colorectal cancer biomarkers at parts-per-million concentration levels, when introduced in isolation to the sensor system within a dry nitrogen stream. The biomarkers, 3-methylpentane, cyclohexane, nonanal, and decanal, were then discriminated from each other by using the combined response of three NEMS devices: one bare device, and two devices coated with either poly(ethyleneoxide) or poly(caprolactone). Our results indicate that bare NEMS are more responsive to high molar mass biomarkers, whereas functionalized sensors are more responsive toward more volatile biomarkers. Considering the inherently fast response times and minuscule limits of detection of NEMS devices, the combined response of differentially coated sensors can be used as the main sensing element to identify and distinguish cancer biomarkers in human breath.