A microfluidics-integrated impedance/surface acoustic resonance tandem sensor

We demonstrate a dual sensor concept for lab-on-a-chip in-liquid sensing through integration of surface acoustic wave resonance (SAR) sensing with electrochemical impedance spectroscopy (EIS) in a single device. In this concept, the EIS is integrated within the building blocks of the SAR sensor, but features a separate electrical port. The two-port sensor was designed, fabricated, and embedded in a soft polymer microfluidic delivery system, and subsequently characterized. The SAR-EIS tandem sensor features low cross-talk between SAR and EIS ports, thus promoting non-interfering gravimetric and impedimetric measurements. The EIS was characterized by means of the modified Randle\u27s cell lumped element model. Four sensitive parameters could be established from the tandem sensor readout, and subsequently employed in a proof of principle study of liposome layers and their interaction with Ca2+ ions, leading to transformation into molecular film structures. The associated shift of the sensing quantities is analysed and discussed. The combination of impedimetric and gravimetric sensing quantities provides a unique and detailed description of physicochemical surface phenomena as compared to a single mode sensing routine

Generation of interconnected vesicles in a liposomal cell model

We introduce an experimental method based upon a glass micropipette microinjection technique for generating a multitude of interconnected vesicles (IVs) in the interior of a single giant unilamellar phospholipid vesicle (GUV) serving as a cell model system. The GUV membrane, consisting of a mixture of soybean polar lipid extract and anionic phosphatidylserine, is adhered to a multilamellar lipid vesicle that functions as a lipid reservoir. Continuous IV formation was achieved by bringing a micropipette in direct contact with the outer GUV surface and subjecting it to a localized stream of a Ca2+ solution from the micropipette tip. IVs are rapidly and sequentially generated and inserted into the GUV interior and encapsulate portions of the micropipette fluid content. The IVs remain connected to the GUV membrane and are interlinked by short lipid nanotubes and resemble beads on a string. The vesicle chain-growth from the GUV membrane is maintained for as long as there is the supply of membrane material and Ca2+ solution, and the size of the individual IVs is controlled by the diameter of the micropipette tip. We also demonstrate that the IVs can be co-loaded with high concentrations of neurotransmitter and protein molecules and displaying a steep calcium ion concentration gradient across the membrane. These characteristics are analogous to native secretory vesicles and could, therefore, serve as a model system for studying secretory mechanisms in biological systems

A high-performance lab-on-a-chip liquid sensor employing surface acoustic wave resonance: part II

We recently introduced an in-liquid sensing concept based on surface acoustic resonance (SAR) in a lab-on-a-chip resonant device with one electrical port. The 185 MHz one-port SAR sensor has a sensitivity comparable to other surface acoustic wave (SAW) in-liquid sensors, while offering a high quality factor (Q) in water, low impedance, and fairly low susceptibility to viscous damping. In this work, we present significant design and performance enhancements of the original sensor presented in part I. A novel \u27lateral energy confinement\u27 (LEC) design is introduced, where the spatially varying reflectivity of the SAW reflectors enables strong SAW localization inside the sensing domain at resonance. An improvement in mass-sensitivity greater than 100% at resonance is achieved, while the measurement noise stays below 0.5 ppm. Sensing performance was evaluated through real-time measurements of the binding of 40 nm neutravidin-coated SiO2nanoparticles to a biotin-labeled lipid bilayer. Two complementary sensing parameters are studied, the shift of resonance frequency and the shift of conductance magnitude at resonance

Integration of Surface Acoustic Wave and Microfluidic Technologies for Liquid-Phase Sensing Applications

This thesis discusses a new concept for construction of a novel SAW in-liquid sensor employing surface acoustic wave resonance (SAR) in a one-port configuration. In this concept, the reflective gratings of a one-port SAW resonator are employed as mass loading-sensing elements, while the SAW transducer is protected from the measurement environment, reducing power losses significantly.Microfluidic technologies have developed during the last decades into versatile platforms for miniaturized analytical devices. The devices are small, low cost, capable of multi-step automation resulting in fast turnaround, and allow reducing the amount of reagent and sample consumption, while maintaining a precise control over the environment. In this context, small, cheap and efficient sensors capable of in-liquid operation within microfluidic devices are in a great demand. The introduction of acoustic wave technology onto lab-on-a-chip platforms provides sensing capability that meets these criteria, and allows for an extended set of functions to be implemented, e.g., fast fluidic actuation, contact-free particle manipulation, sorting, and others. A resonant SAW sensor topology embedded in a polydimethylsiloxane (PDMS) microfluidic analyte delivery system was fabricated and characterized. Designs with the best performance were identified, and initial measurements in a liquid environment are discussed. In comparison to a delay-line topology, the proposed one-port resonant configuration features improved sensitivity, while offering better electrical performance and smaller size, which allows for wafer-scale fabrication and facilitates integration. Following optimization, sensing performance was evaluated by means of different assays, and multiparametric sensing was demonstrated by sharing of sensor components for simultaneous SAR sensing and electrochemical impedance spectroscopy in different frequency bands.This technological advancement may open pathways to new analytical instrumentation. The small sensor footprint, low energy consumption, and simple two-wire readout facilitate the integration in hand-held “lab on a chip” assay devices, the construction of sensing arrays for parallel sample processing, and the implementation of wireless data transfer schemes

A Four Parameter Microfluidic Tandem SAW-IS Bio-Sensor

Surface Acoustic Resonance (SAR) biosensing has recently been proposed as a highly compact and robust alternative to the conventional SAW delay-line based biosensing. The device can also be presented as a one-port high frequency alternative to the QCM, employing SAW resonance. It enables simple one-port measurements at low powers, while offering robust integration with microfluidics and implementation in integrated sensor arrays. Here we discuss the SAR approach as a key enabling and demonstrate its integration with the impedance spectroscopy (IS) concept in a single microfluidic device. The IS is integrated within a SAW reflector formed as interdigitated electrode (IDE) capacitor. A test fixture with SAW and IS ports is designed and fabricated. Four sensitive parameters are deduced from the tandem sensor readout and employed in a proof of principle study of liposome layers and their interaction with Ca2+ ions

Design and characterization of surface acoustic wave resonance (SAR) system for in-liquid sensing

Sensors capable of in-liquid operation are of primary importance not only for biosensors applications, but also for liquid monitoring. Surface acoustic waves (SAW) have been employed for long time in various in-liquid sensors at relatively high frequencies. Unlike their QCM counterparts, SAW in-liquid sensors employ delay-line topology. Here, for the first time, we discuss a new concept for building a SAW in-liquid sensor employing surface acoustic wave resonance (SAR) in a one-port configuration. To demonstrate its utility, a SAR technological platform embedded in a polydimethylsiloxane (PDMS) microfluidic device was fabricated and characterized. Designs with suppressed spurious content were identified. Initial measurements in a liquid environment are performed. In comparison to a delay-line topology, the SAR concept features comparable sensitivity, while offering better electrical performance and smaller size

A one-port SAW in-liquid sensor platform: Design and fabrication

SH-SAW In-liquid sensors have been explored extensively in recent decades. They propose an ability to work at higher frequencies, than the well-known QCM, with the aim to reduce the size and ease the integration in sensor arrays. So far SH-SAW liquid phase sensors are designed in two-port delay line configurations because of the need to protect the IDT from the conductive and dielectric loads from the liquid. A compact one-port resonant SH-SAW liquid sensor is yet to be developed as an alternative of QCM at high frequencies

A high-performance lab-on-a-chip liquid sensor employing surface acoustic wave resonance

We demonstrate herein a new concept for lab-on-a-chip in-liquid sensing, through integration of surface acoustic wave resonance (SAR) in a one-port configuration with a soft polymer microfluidic delivery system. In this concept, the reflective gratings of a one-port surface acoustic wave (SAW) resonator are employed as mass loading-sensing elements, while the SAW transducer is protected from the measurement environment. We describe the design, fabrication, implementation, and characterization using liquid medium. The sensor operates at a frequency of 185 MHz and has demonstrated a comparable sensitivity to other SAW in-liquid sensors, while offering quality factor (Q) value in water of about 250, low impedance and fairly low susceptibility to viscous damping. For proof of principle, sensing performance was evaluated by means of binding 40 nm neutravidin-coated SiO2 nanoparticles to a biotin-labeled lipid bilayer deposited over the reflectors. Frequency shifts were determined for every step of the affinity assay. Demonstration of this integrated technology highlights the potential of SAR technology for in-liquid sensing

Molecular Lipid Films on Microengineering Materials

In this study, we have systematically investigated the formation of molecular phospholipid films on a variety of solid substrates fabricated from typical surface engineering materials and the fluidic properties of the lipid membranes formed on these substrates. The surface materials comprise of borosilicate glass, mica, SiO2, Al (native oxide), Al2O3, TiO2, ITO, SiC, Au, Teflon AF, SU-8, and graphene. We deposited the lipid films from small unilamellar vesicles (SUVs) by means of an open-space microfluidic device, observed the formation and development of the films by laser scanning confocal microscopy, and evaluated the mode and degree of coverage, fluidity, and integrity. In addition to previously established mechanisms of lipid membrane–surface interaction upon bulk addition of SUVs on solid supports, we observed nontrivial lipid adhesion phenomena, including reverse rolling of spreading bilayers, spontaneous nucleation and growth of multilamellar vesicles, and the formation of intact circular patches of double lipid bilayer membranes. Our findings allow for accurate prediction of membrane–surface interactions in microfabricated devices and experimental environments where model membranes are used as functional biomimetic coatings