Browsing by Author "Elbüken, Çağlar"

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Open Access
Assessment of stored red blood cells through lab-on-a-chip technologies for precision transfusion medicine
(National Academy of Sciences, 2023-07-26) Isiksacan, Z.; D’Alessandro, A.; Wolf, S. M.; McKenna, D. H.; Tessier, S. N.; Kucukal, E.; Gokaltun, A. A.; William, N.; Sandlin, R. D.; Bischof, J.; Mohandas, N.; Busch, M. P.; Elbüken, Çağlar; Gurkan, U. A.; Toner, M.; Acker, J. P.; Yarmush, M. L.; Usta, O. B.
Transfusion of red blood cells (RBCs) is one of the most valuable and widespread treatments in modern medicine. Lifesaving RBC transfusions are facilitated by the cold storage of RBC units in blood banks worldwide. Currently, RBC storage and subsequent transfusion practices are performed using simplistic workflows. More specifically, most blood banks follow the “first-in-first-out” principle to avoid wastage, whereas most healthcare providers prefer the “last-in-first-out” approach simply favoring chronologically younger RBCs. Neither approach addresses recent advances through -omics showing that stored RBC quality is highly variable depending on donor-, time-, and processing-specific factors. Thus, it is time to rethink our workflows in transfusion medicine taking advantage of novel technologies to perform RBC quality assessment. We imagine a future where lab-on-a-chip technologies utilize novel predictive markers of RBC quality identified by -omics and machine learning to usher in a new era of safer and precise transfusion medicine.
Open Access
Contactless pulsed and continuous microdroplet release using photothermal liquid crystals
(Wiley-VCH Verlag GmbH & Co. KGaA, 2022-10-24) Beyazkilic, P.; Akçimen, Samet; Elbüken, Çağlar; Ortaç, Bülent; Cai, S.; Bukusoglu, E.
Targeted, on-demand delivery has been of interest using materials responsive to environmental stimuli. A delivery technique based on precise release of aqueous microdroplets from a liquid crystal (LC) medium with contactless stimulation is presented. A nematic LC is doped with a photothermal dye that produces heat under near IR light exposure. The heat is used to overcome the elastic strains in the LC phase, promoting the release of initially entrapped water droplets to the neighboring aqueous solution. Designing the geometry of LC-based emulsions and tuning the light intensity and position allows for manipulation of the release in two distinct modes defined as pulsated and continuous. In the pulsated mode, water droplets are released transiently from the casted water-in-LC emulsion layer based on sweeping by the moving isotropic-nematic phase boundary controlled by light. In the continuous mode, water droplets are ejected continuously from a droplet-shaped water-in-LC emulsion, due to a heating-induced internal flow controlled by light. The droplet release by contactless stimulation is used for the on-demand dosing of dopamine and its oxidizing reagent from isolated reservoirs to obtain an in situ reaction signal for a hydrogen peroxide assay. A new dual-mode release system developed with photothermal LCs holds potential in drug release, controlled mixing, and photothermal therapy
Open Access
Damping hydrodynamic fluctuations in microfluidic systems
(Elsevier, 2018) Kalantarifard, Ali; Haghighi, Elnaz Alizadeh; Elbüken, Çağlar
In this article, we report a method to damp microfluidic hydrodynamic fluctuations caused by flow sources. We demonstrate that compliance of elastomeric off-chip tubings can be used to damp fluctuations and lead to steady flow rates. We analyze the whole microfluidic system using electrical circuit analogies, and demonstrate that off-chip compliances are significant, especially for displacement pump driven systems. We apply this hydrodynamic damping method to microfluidic droplet generation. Our results show that highly monodisperse microdroplets can be obtained by syringe pump driven systems utilizing this damping effect. We reached a coefficient of variation of 0.39% for the microdroplet area using a standard T-junction geometry. Additionally, we demonstrated that pressure pumps inherently use this effect, and have so far led the high performances reported in the literature in terms of droplet monodispersity. The presented off-chip hydrodynamic damping method is not only low-cost and practical, but can also be used in elastomeric and rigid microchannels without need to introduce additional components to the fluidic circuit.
Open Access
Eco-friendly fabrication of plasmonically active substrates based on end-grafted poly(ethylene glycol) layers
(American Chemical Society, 2019) Karabel Öcal, S.; Pekdemir, S.; Serhatlıoğlu, Murat; İpekçi, H. H.; Şahmetlioğlu, E.; Narin, İ.; Duman, F.; Elbüken, Çağlar; Demirel, G.; Önses, Mustafa Serdar
We report completely sustainable processes and materials for inexpensive and scalable fabrication of plasmonically active solid substrates, which are critical for emerging applications in sensing, catalysis, and metasurfaces. Our approach involves grafting of poly(ethylene glycol) (PEG) onto silicon oxide terminated solid substrates using all-water based processing leading to an ultrathin (12 nm) and smooth (roughness of ∼1 nm) functional layer. The resulting surfaces facilitate robust and effective immobilization of gold nanoparticles (NPs) with a density that is superior to the organic solvent based processing. This new process achieves size dependent assembly of the citrate-stabilized gold NPs resulting in high plasmonic activity in surface-enhanced Raman scattering (SERS). The use of leaf extracts derived from Quercus pubescens as a reducing and stabilizing agent allowed for green synthesis of gold NPs with an average diameter of 25.6 ± 11.1 nm. The assembly of the green synthesized gold NPs on all-water processed PEG grafted layers enabled a fully sustainable route for fabrication of plasmonically active solid substrates. The resulting substrates exhibited high SERS response over the entire (∼1 cm2) substrate surface with an analytical enhancement factor of 9.48 × 104 for the probe molecule rhodamine 6G under 532 nm laser excitation. A microfluidic device was also constructed on the fabricated platform for SERS mediated simultaneous detection of two nonsteroidal anti-inflammatory drugs, dexketoprofen and ibuprofen, which are widely used in human medicine and present as contaminants in wastewater. The biocompatibility of PEG together with all-water based processing overcome the need for waste management and ventilation of the working place enabling cost and energy efficient, environmentally benign fabrication of plasmonic devices.
Open Access
Electro-viscoelastic migration under simultaneously applied microfluidic pressure-driven flow and electric field
(American Chemical Society, 2020-04) Serhatlıoğlu, Murat; Işıksaçan, Ziya; Özkan, Melis; Tuncel, Dönüş; Elbüken, Çağlar
Under the simultaneous use of pressure-driven flow and DC electric field, migration of particles inside microfluidic channels exhibits intricate focusing dynamics. Available experimental and analytical studies fall short in giving a thorough explanation to particle equilibrium states. Also, the understanding is so far limited to the results based on Newtonian and neutral viscoelastic carrier fluids. Hence, a holistic approach is taken in this study to elaborate the interplay of governing electrophoretic and slip-induced/elastic/shear gradient lift forces. First, we carried out experimental studies on particle migration in Newtonian, neutral viscoelastic, and polyelectrolyte viscoelastic media to provide a comprehensive understanding of particle migration. The experiments with the viscoelastic media led to contradictory results with the existing explanations. Then, we introduced the Electro-Viscoelastic Migration (EVM) theory to give a unifying explanation to particle migration in Newtonian and viscoelastic solutions. Confocal imaging with fluorescent-labeled polymer solutions was used to explore the underlying migration behavior. A surprising outcome of our results is the formation of cross-sectionally nonuniform viscoelasticity that may have unique applications in microfluidic particle focusing.
Open Access
Focusing-free impedimetric differentiation of red blood cells and leukemia cells: a system optimization
(Elsevier, 2020) Bilican, İ.; Güler, M. T.; Serhatlıoğlu, Murat; Kırındı, T.; Elbüken, Çağlar
A focusing-free microfluidic impedimetric cell detection system is developed. The effect of the channel dimensions, solution conductivity, excitation voltage, and particle size on impedimetric signal outputs were optimized to increase the sensitivity of the system. Conventional microfabrication techniques were adapted to obtain low height, resealable microchannels. The geometry optimization was performed by a combination of analytical, numerical and experimental approaches. The results demonstrate that reliable impedimetric particle differentiation can be achieved without any labeling or particle focusing. The system parameters were studied and rule-of-thumb design criteria were provided. Finally, using the developed system, red blood cells and leukemia cells were experimentally detected and differentiated. Thanks to its simplicity, the focusing-free cell differentiation system may find applications in several cellular diagnostic uses.
Open Access
From bio-waste to biomaterials: The eggshells of Chinese oak silkworm as templates for SERS-active surfaces
(Elsevier BV, 2021-12-15) Zang, Lian-Sheng; Chen, Yong-Ming; Bilican, Behlül Koç; Bilican, İsmail; Sakir, Menekşe; Wait, James; Çolak, Arzu; Karaduman, Tuğçe; Ceylan, Ahmet; Ali, Asad; Elbüken, Çağlar; Onses, M. Serdar; Kaya, Murat
Although over 80% of the world’s existing animal species are insects, with each of these species having unique eggshell morphologies, limited information is available regarding the use of their eggshells in material science applications. The present research discusses using discarded eggshells of the Chinese oak silkworm (Antheraea pernyi) as a technological material. The 3-dimensional aspects of the insect’s eggshell were examined in detail, demonstrating the complexity of their novel surface morphology. The outer surface of the eggshell was comprised of a hexagonal structure, whereas the inner surface consists of a mostly smooth surface. Distinctive layers of the eggshell were observed when cross sections of the surface were analyzed. The elastic modulus of the inner part of the eggshell is substantially greater than that of the outer part. The physicochemical properties of the eggshell were characterized and no toxic properties were found. The hexagonal structures found on the outer surface of the eggshell provide a highly suitable template for silver nanostructure deposition. The resulting silver decorated surfaces can be used to detect molecules via surface-enhanced Raman scattering (SERS) effects. The deposition of silver renders the surface antimicrobial, whereas the original surface was microbial. Collectively, the insights gained in this study will be key in developing advanced engineering applications of the insect eggshells.
Open Access
A handheld microfluidic device for whole blood coagulation measurement using erythrocyte aggregation
(Chemical and Biological Microsystems Society, 2020) Işıksaçan, Ziya; Erel, O; Elbüken, Çağlar
We present a portable platform that enables coagulation time measurement from a drop of whole blood at the point-of-care by optical investigation of erythrocyte aggregation. The assay was demonstrated for the evaluation of both intrinsic and extrinsic pathways of the coagulation cascade.
Open Access
In vitro analysis of multiple blood flow determinants using red blood cell dynamics under oscillatory flow
(Royal Society of Chemistry, 2020-06) Işıksaçan, Ziya; Serhatlıoğlu, Murat; Elbüken, Çağlar
The flow behavior of blood is determined mainly by red blood cell (RBC) deformation and aggregation as well as blood viscoelasticity. These intricately interdependent parameters should be monitored by healthcare providers to understand all aspects of circulatory flow dynamics under numerous cases including cardiovascular and infectious diseases. Current medical instruments and microfluidic systems lack the ability to quantify these parameters all at once and in physiologically relevant flow conditions. This work presents a handheld platform and a measurement method for quantitative analysis of multiple of these parameters from 50 μl undiluted blood inside a miniaturized channel. The assay is based on an optical transmission analysis of collective RBC deformation and aggregation under near-infrared illumination during a 1 s damped oscillatory flow and at stasis, respectively. Measurements with blood of different hemo-rheological properties demonstrate that the presented approach holds a potential for initiating simultaneous and routine on-chip blood flow analysis even in resource-poor settings.
Open Access
An integrated microfluidic device for the sorting of yeast cells using image processing
(Nature Publishing Group, 2018) Yu, B. Y.; Elbüken, Çağlar; Shen, C.; Huissoon, J. P.; Ren, C. L.
The process of detection and separation of yeast cells based on their morphological characteristics is critical to the understanding of cell division cycles, which is of vital importance to the understanding of some diseases such as cancer. The traditional process of manual detection is usually tedious and inconsistent. This paper presents a microfluidic device integrated with microvalves for fluid control for the sorting of yeast cells using image processing algorithms and confirmation based on their fluorescent tag. The proposed device is completely automated, low cost and easy to implement in an academic research setting. Design details of the integrated microfluidic system are highlighted in this paper, along with experimental validation. Real time cell sorting was demonstrated with a cell detection rate of 12 cells per minute.
Open Access
Integration of glass micropipettes with a 3D printed aligner for microfluidic flow cytometer
(Elsevier B.V., 2018) Bayram, A.; Serhatlıoğlu, Murat; Ortaç, Bülend; Demic, S.; Elbüken, Çağlar; Sen, M.; Solmaz, M. E.
In this study, a facile strategy for fabricating a microfluidic flow cytometer using two glass micropipettes with different sizes and a 3D printed millifluidic aligner was presented. Particle confinement was achieved by hydrodynamic focusing using a single sample and sheath flow. Device performance was extracted using the forward and side-scattered optical signals obtained using fiber-coupled laser and photodetectors. The 3-D printing assisted glass capillary microfluidic device is ultra-low-cost, not labor-intensive and takes less than 10 min to fabricate. The present device offers a great alternative to conventional benchtop flow cytometers in terms of optofluidic configuration.
Open Access
Lab-on-a-chip platforms for disease detection and diagnosis
(Wiley Blackwell, 2018) Işıksaçan, Ziya.; Güler, M. T.; Kalantarifard, Ali; Asghari, Mohammad; Elbüken, Çağlar; Altıntaş, Z.
The adaptation of silicon electronics microfabrication technologies to other materials led to the birth of microfluidic systems. These systems allow investigation and control of fluids at micrometer scale. Due to the wide variety of applications of microfluidics, several research groups have been involved in the development of basic microfluidic components. After the development of fundamental fluid handling components, these technologies have been integrated for numerous applications one of which is disease detection and diagnostics. This chapter summarizes the microfluidic platforms that are mature enough for adaptation towards disease detection. The microfluidic platforms were discussed under six categories: continuous flow, paper‐based, microdroplets, digital microfluidics, compact disk‐based, and wearable platforms. Seminal works and recent developments in each category have been presented together with successful commercial examples. It is worth noting that some studies straddle more than one category, therefore, this classification is strictly for the ease of the reader. Each section discusses the benefits of a specific microfluidic platform. Engineering of microfluidic systems lead to lab‐on‐a‐chip (LOC) systems that can be used for diagnostics whether at point‐of‐care as portable systems or at clinical settings as advanced detection systems. The increasing awareness on personalized treatments proves the importance of such democratizing technologies. The increasing market share of microfluidic platforms in nearly all sectors is also an indication of the bright future of microfluidics and lab‐on‐a‐chip systems. The chapter is ended with a future outlook.
Open Access
A microfluidic droplet system for ultra-monodisperse droplet generation: A universal approach
(Elsevier Ltd, 2022-07-22) Kalantarifard, Ali; Alizadeh-Haghighi, Elnaz; Elbüken, Çağlar
Despite the importance of droplet monodispersity, a universal methodology for high monodispersity droplet generation does not exist yet. We have recently demonstrated that unlike the conventional method of droplet generation, applying an identical pressure from a single source makes the microfluidic droplet system immune to the external fluctuations that originate from the imperfection of the flow source. In this work, we show that our method is universal and applicable to other common microfluidic devices and flow sources. We applied this method to flow-focusing and coflow devices that are commonly used for high-frequency microdroplet generation. In addition to the pressure pump, we used a syringe pump to show that our method is applicable to flow rate controllable systems as well. We compared the monodispersity of droplets formed by the conventional methods and the novel method explained in this work. © 2022 The Authors
Open Access
An optofluidic point-of-care device for quantitative investigation of erythrocyte aggregation during coagulation
(Elsevier B.V., 2018) Işıksaçan, Ziya; Hastar, Nurcan; Erel, Ö.; Elbüken, Çağlar
Coagulation, the process leading to clot formation with the interplay of blood constituents, is a self-regulating mechanism, requiring attentive and periodic monitoring for numerous clinical cases. Erythrocyte aggregation (EA) is a characteristic behaviour of erythrocytes forming reversible clumps especially in vitro at low shear rates. The effect of EA during coagulation is overlooked in whole blood (WB) clotting assays, and the relationship between the two mechanisms is not well understood. We present an optofluidic point-of-care device enabling quantitative investigation of EA from 50 μl WB during the coagulation process. Not only did we explain the coagulation mechanism considering EA, but we also demonstrated coagulation time measurement from optical EA analysis. The device consists of a disposable cartridge and a handheld analyzer containing a pinch valve for fluid motion and optics for transmitted light measurement. Following the sample introduction and cessation of the valve operation, the optical signal is the lowest due to shear-induced cell disaggregation. Then, the signal increases due to EA until reaching a peak, indicating blood clotting. The working principle was proven through clinical tests for prothrombin time measurement. In addition to revealing the relation between coagulation and aggregation, this device is promising for rapid WB coagulation time measurement.
Open Access
Reaction kinetic studies by compliance-induced ultra monodisperse microdroplets
(Chemical and Biological Microsystems Society, 2020) Kalantalifard, A.; Saateh, A.; Beyazkılıç, Pınar; Elbüken, Çağlar
Open Access
Real-time image-based droplet measurement
(Chemical and Biological Microsystems Society, 2020) Elahi, Sepehr; Kalantarifard, Ali; Kalantarifard, Fatemeh; Elbüken, Çağlar
The ability to measure physical properties of droplets in real-time is required to design precise operations on droplet-based systems. In this study, we implemented a real-time droplet tracker that tracks the positions of droplets and measures droplet generation frequency as well as droplets' physical properties, such as size, size distribution, shape, velocity, circularity. Furthermore, using the droplet length, we use curve fitting to determine the dispersed phase viscosity. Our droplet tracker is implemented in Python, using the OpenCV library and can be run on a routine PC.
Open Access
Real-time impedimetric droplet measurement (iDM)
(Royal Society of Chemistry, 2019) Saateh, Abtin; Kalantarifard, Ali; Çelik, Oğuz Tolga; Asghari, Mohammad; Serhatlıoğlu, Murat; Elbüken, Çağlar
Droplet-based microfluidic systems require a precise control of droplet physical properties; hence, measuring the morphological properties of droplets is critical to obtain high sensitivity analysis. The ability to perform such measurements in real-time is another demand which has not been addressed yet. In this study, we used coplanar electrodes configured in the differential measurement mode for impedimetric measurement of size and velocity. To obtain the size of the droplets, detailed 3D finite element simulations of the system were performed. The interaction of the non-uniform electric field and the droplet was investigated. Electrode geometry optimization steps were described and design guideline rules were laid out. User-friendly software was developed for real-time observation of droplet length and velocity together with in situ statistical analysis results. A comparison between impedimetric and optical measurement tools is given. Finally, to illustrate the benefit of having real-time analysis, iDM was used to synthesize particles with a predefined monodispersity limit and to study the response times of syringe pump and pressure pump driven droplet generation devices. This analysis allows one to evaluate the ‘warm-up’ time for a droplet generator system, after which droplets reach the desired steady-state size required by the application of interest.
Open Access
Real-Time In Vivo Control of Neural Membrane Potential by Electro-Ionic Modulation
(Elsevier, 2019) Soybas, Z.; Şimşek, S.; Erol, F. M. B.; Erdogan, U. Ç.; Şimşek, E. N.; Şahin, B.; Marçalı, M.; Aydogdu, B.; Elbüken, Çağlar; Melik, R.
Theoretically, by controlling neural membrane potential (Vm) in vivo, motion, sensation, and behavior can be controlled. Until now, there was no available technique that can increase or decrease ion concentration in vivo in real time to change neural membrane potential. We introduce a method that we coin electro-ionic modulation (EIM), wherein ionic concentration around a nerve can be controlled in real time and in vivo. We used an interface to regulate the Ca2+ ion concentration around the sciatic nerve of a frog and thus achieved stimulation and blocking with higher resolution and lower current compared with electrical stimulation. As EIM achieves higher controllability of Vm, it has potential to replace conventional methods used for the treatment of neurological disorders and may bring a new perspective to neuromodulation techniques.
Open Access
Reversible decryption of covert nanometer-thick patterns in modular metamaterials
(OSA - The Optical Society, 2019) Bakan, Gökhan; Ayas, Sencer; Serhatlıoğlu, Murat; Dana, Aykutlu; Elbüken, Çağlar
Continuous development of security features is mandatory for the fight against forgery of valuable documents and products, the most notable example being banknotes. Such features demonstrate specific properties under certain stimuli such as fluorescent patterns glowing under ultraviolet light. These security features should also be hard to copy by unlicensed people and be interrogated by anyone using easily accessible tools. To this end, this Letter demonstrates the development of an ideal security feature enabled by the realization of modular metamaterials based on metal–dielectric–metal cavities that consist of two separate parts: metal nanoparticles on an elastomeric substrate and a bottom mirror coated with a thin dielectric. Patterns generated by creating nanometer-thick changes in the dielectric layer are invisible (encrypted) and can only be detected (decrypted) by sticking the elastomeric patch on. The observed optical effects such as visibility and colors can only be produced with the correct combination of materials and film thicknesses, making the proposed structures a strong alternative to compromised security features.
Open Access
Rose petal topography mimicked poly(dimethylsiloxane) substrates for enhanced corneal endothelial cell behavior
(Elsevier, 2021-04-30) Öztürk-Öncel, M. Ö.; Erkoc-Biradli, F. Z.; Rasier, R.; Marçalı, Merve; Elbüken, Çağlar; Garipcan, B.
Low proliferation capacity of corneal endothelial cells (CECs) and worldwide limitations in transplantable donor tissues reveal the critical need of a robust approach for in vitro CEC growth. However, preservation of CEC-specific phenotype with increased proliferation has been a great challenge. Here we offer a biomimetic cell substrate design, by optimizing mechanical, topographical and biochemical characteristics of materials with CEC microenvironment. We showed the surprising similarity between topographical features of white rose petals and corneal endothelium due to hexagonal cell shapes and physiologically relevant cell density (≈ 2000 cells/mm2). Polydimethylsiloxane (PDMS) substrates with replica of white rose petal topography and cornea-friendly Young's modulus (211.85 ± 74.9 kPa) were functionalized with two of the important corneal extracellular matrix (ECM) components, collagen IV (COL 4) and hyaluronic acid (HA). White rose petal patterned and COL 4 modified PDMS with optimized stiffness provided enhanced bovine CEC response with higher density monolayers and increased phenotypic marker expression. This biomimetic approach demonstrates a successful platform to improve in vitro cell substrate properties of PDMS for corneal applications, suggesting an alternative environment for CEC-based therapies, drug toxicity investigations, microfluidics and organ-on-chip applications.