Browsing by Author "Alkhaled, Mohammed"

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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
Atmospheric-pressure mass spectrometry by single-mode nanoelectromechanical systems
(American Chemical Society, 2023-09-08) Kaynak, Batuhan Emre; Alkhaled, Mohammed; Kartal, Enise; Yanık, Cenk; Hanay, Mehmet Selim
Weighing particles above the megadalton mass range has been a persistent challenge in commercial mass spectrometry. Recently, nanoelectromechanical systems-based mass spectrometry (NEMS-MS) has shown remarkable performance in this mass range, especially with the advance of performing mass spectrometry under entirely atmospheric conditions. This advance reduces the overall complexity and cost while increasing the limit of detection. However, this technique required the tracking of two mechanical modes and the accurate knowledge of mode shapes that may deviate from their ideal values, especially due to air damping. Here, we used a NEMS architecture with a central platform, which enables the calculation of mass by single-mode measurements. Experiments were conducted using polystyrene and gold nanoparticles to demonstrate the successful acquisition of mass spectra using a single mode with an improved areal capture efficiency. This advance represents a step forward in NEMS-MS, bringing it closer to becoming a practical application for the mass sensing of nanoparticles. © 2023 The Authors. Published by American Chemical Society.
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.
Embargo
Nanomechanical and microwave resonance sensing for characterization of individual virions and nanoparticles in atmospheric conditions
(2023-09) Alkhaled, Mohammed
This dissertation focuses on Nanoelectromechanical-based Mass Spectrometry (NEMS-MS), an innovative technique for characterizing nanoparticles and biomolecules weighing above the working limit of commercial mass spectrometry tools. It suggests performing NEMS-MS under atmospheric conditions and enhancing its capabilities with a built-in focusing lens. Amid the COVID-19 pandemic, the study addresses urgent virus detection needs, proposing a label-free method using NEMS-MS for individual virus detection and characterization. Notably, the study achieves mass spectrometry measurement of the SARS-CoV-2 virus using a NEMS-MS system operating entirely under atmospheric pressure. As the first to pioneer NEMS-MS in air, the study examines challenges tied to this, particularly how NEMS response in dissipative environments, known as Mode Shape Attenuation. Mathematical models and experiments dissect factors contributing to this attenuation, resulting in improved mass spectra and contributing toward the utilization of NEMS-MS for real-world application. Taking innovation a step further, the study introduces a microwave-based sensor for inferring electrical properties of nanoparticles. This sensor works in the electro-magnetic domain, determining properties like dielectric constant and expanding the sensing possibilities. Overall, this dissertation propels NEMS-based sensing and characterization by combining mass spectrometry, microwave sensing, and atmospheric pressure operation. Addressing challenges and introducing innovative solutions, it advances NEMS-MS technology and offers a cost-effective tool for characterizing nanoparticles and biomolecules across various applications.