Microfluidics for High Pressure: Integration on GaAs Acoustic Biosensors with a Leakage-Free PDMS Based on Bonding Technology.

Microfluidics integration of acoustic biosensors is an actively developing field. Despite significant progress in "passive" microfluidic technology, integration with microacoustic devices is still in its research state. The major challenge is bonding polymers with monocrystalline piezoelectrics to seal microfluidic biosensors. In this contribution, we specifically address the challenge of microfluidics integration on gallium arsenide (GaAs) acoustic biosensors. We have developed a robust plasma-assisted bonding technology, allowing strong connections between PDMS microfluidic chip and GaAs/SiO2 at low temperatures (70 °C). Mechanical and fluidic performances of fabricated device were studied. The bonding surfaces were characterized by water contact angle measurement and ATR-FTIR, AFM, and SEM analysis. The bonding strength was characterized using a tensile machine and pressure/leakage tests. The study showed that the sealed chips were able to achieve a limit of high bonding strength of 2.01 MPa. The adhesion of PDMS to GaAs was significantly improved by use of SiO2 intermediate layer, permitting the bonded chip to withstand at least 8.5 bar of burst pressure. The developed bonding approach can be a valuable solution for microfluidics integration in several types of MEMS devices.

Label-Free Physical Techniques and Methodologies for Proteins Detection in Microfluidic Biosensor Structures.

Proteins in biological fluids (blood, urine, cerebrospinal fluid) are important biomarkers of various pathological conditions. Protein biomarkers detection and quantification have been proven to be an indispensable diagnostic tool in clinical practice. There is a growing tendency towards using portable diagnostic biosensor devices for point-of-care (POC) analysis based on microfluidic technology as an alternative to conventional laboratory protein assays. In contrast to universally accepted analytical methods involving protein labeling, label-free approaches often allow the development of biosensors with minimal requirements for sample preparation by omitting expensive labelling reagents. The aim of the present work is to review the variety of physical label-free techniques of protein detection and characterization which are suitable for application in micro-fluidic structures and analyze the technological and material aspects of label-free biosensors that implement these methods. The most widely used optical and impedance spectroscopy techniques: absorption, fluorescence, surface plasmon resonance, Raman scattering, and interferometry, as well as new trends in photonics are reviewed. The challenges of materials selection, surfaces tailoring in microfluidic structures, and enhancement of the sensitivity and miniaturization of biosensor systems are discussed. The review provides an overview for current advances and future trends in microfluidics integrated technologies for label-free protein biomarkers detection and discusses existing challenges and a way towards novel solutions.

Label-Free Protein Detection by Micro-Acoustic Biosensor Coupled with Electrical Field Sorting. Theoretical Study in Urine Models.

Diagnostic devices for point-of-care (POC) urine analysis (urinalysis) based on microfluidic technology have been actively developing for several decades as an alternative to laboratory based biochemical assays. Urine proteins (albumin, immunoglobulins, uromodulin, haemoglobin etc.) are important biomarkers of various pathological conditions and should be selectively detected by urinalysis sensors. The challenge is a determination of different oligomeric forms of the same protein, e.g., uromodulin, which have similar bio-chemical affinity but different physical properties. For the selective detection of different types of proteins, we propose to use a shear bulk acoustic resonator sensor with an additional electrode on the upper part of the bioliquid-filled channel for protein electric field manipulation. It causes modulation of the protein concentration over time in the near-surface region of the acoustic sensor, that allows to distinguish proteins based on their differences in diffusion coefficients (or sizes) and zeta-potentials. Moreover, in order to improve the sensitivity to density, we propose to use structured sensor interface. A numerical study of this approach for the detection of proteins was carried out using the example of albumin, immunoglobulin, and oligomeric forms of uromodulin in model urine solutions. In this contribution we prove the proposed concept with numerical studies for the detection of albumin, immunoglobulin, and oligomeric forms of uromodulin in urine models.

Assessment of Shear-Dependent Kinetics of Primary Haemostasis With a Microfluidic Acoustic Biosensor.

Primary haemostasis is a complex dynamic process, which involves in-flow interactions between platelets and sub-endothelial matrix at the area of the damaged vessel wall. It results in a first haemostatic plug, which stops bleeding, before coagulation ensues and consolidates it. The diagnosis of primary haemostasis defect would benefit from evaluation of the whole sequence of mechanisms involved in platelet plug formation in flow. This work proposes a new approach that is based on characterization of the shear-dependent kinetics that enables the evaluation of the early stages of primary haemostasis. We used a label-free method with a quartz crystal microbalance (QCM) biosensor to measure the platelet deposits over time onto covalently immobilized type I fibrillar collagen. We defined three metrics: total frequency shift, lag time, and growth rate. The measurement was completed at four predefined shear rates prevailing in small vessels (500, 770, 1000 and 1500 s-1) during five minutes of perfusion with anticoagulated normal whole blood. The rate of the frequency shift over the first five minutes was strongly influenced by shear rate conditions, presenting a maximum around 770 s-1, and varying by a factor larger than three in the studied shear rate range. To validate the biosensor signal, the total frequency shift was compared to results obtained by atomic force microscopy (AFM) on final platelet deposits. The results show that shear-dependent kinetic assays are promising as an advanced method for screening of primary haemostasis.

Topology Challenge for the Assessment of Living Cell Deposits with Shear Bulk Acoustic Biosensor.

Shear bulk acoustic type of resonant biosensors, such as the quartz crystal microbalance (QCM), give access to label-free in-liquid analysis of surface interactions. The general understanding of the sensing principles was inherited from past developments in biofilms measurements and applied to cells while keeping the same basic assumptions. Thus, the biosensor readouts are still quite often described using 'mass' related terminology. This contribution aims to show that assessment of cell deposits with acoustic biosensors requires a deep understanding of the sensor transduction mechanism. More specifically, the cell deposits should be considered as a structured viscoelastic load and the sensor response depends on both material and topological parameters of the deposits. This shifts the paradigm of acoustic biosensor away from the classical mass loading perspective. As a proof of the concept, we recorded QCM frequency shifts caused by blood platelet deposits on a collagen surface under different rheological conditions and observed the final deposit shape with atomic force microscopy (AFM). The results vividly demonstrate that the frequency shift is highly impacted by the platelet topology on the bio-interface. We support our findings with numerical simulations of viscoelastic unstructured and structured loads in liquid. Both experimental and theoretical studies underline the complexity behind the frequency shift interpretation when acoustic biosensing is used with cell deposits.

Narrow Band Solid-Liquid Composite Arrangements: Alternative Solutions for Phononic Crystal-Based Liquid Sensors.

Periodic elastic composite structures attract great attention. They offer the ability to design artificial properties to advance the control over the propagation of elastic/acoustic waves. In previous work, we drew attention to composite periodic structures comprising liquids. It was shown that the transmission spectrum of the structure, specifically a well-isolated peak, follows the material properties of liquid constituent in a distinct manner. This idea was realized in several liquid sensor concepts that launched the field of phononic crystal liquid sensors. In this work we introduce a novel concept-narrow band solid-liquid composite arrangements. We demonstrate two different concepts to design narrow band structures, and show the results of theoretical studies and results of experimental investigations that confirm the theoretical predictions. This work extends prior studies in the field of phononic crystal liquid sensors with novel concepts and results that have a high potential in a field of volumetric liquid properties evaluation.

Heat-Resistant Ferroelectric-Polymer Nanocomposite with High Dielectric Constant.

The high dielectric constant ferroelectric-polymer nanocomposite was developed for producing the heat-resistant and chemical stable planar layers. According to the composite coatings formation conditions, the following value ranges of dielectric constant and loss factor were received: 30⁻400 for dielectric constant and 0.04⁻0.1 for loss tangent, accordingly. Unlike of composite components, the obtained composite material is characterized by thermo-stability of electrical parameters up to 250 °C. The dielectric frequency spectra of the composite exhibit two clearly visible peaks in contrast to the spectra of the polymer and ferroelectric ceramics. The developed composite material can be used as a built-in film capacitors material in microelectronic devices.

Hybrid structures based on gold nanoparticles and semiconductor quantum dots for biosensor applications.

BACKGROUND: The luminescence amplification of semiconductor quantum dots (QD) in the presence of self-assembled gold nanoparticles (Au NPs) is one of way for creating biosensors with highly efficient transduction. AIMS: The objective of this study was to fabricate the hybrid structures based on semiconductor CdSe/ZnS QDs and Au NP arrays and to use them as biosensors of protein. METHODS: In this paper, the hybrid structures based on CdSe/ZnS QDs and Au NP arrays were fabricated using spin coating processes. Au NP arrays deposited on a glass wafer were investigated by optical microscopy and absorption spectroscopy depending on numbers of spin coating layers and their baking temperature. Bovine serum albumin (BSA) was used as the target protein analyte in a phosphate buffer. A confocal laser scanning microscope was used to study the luminescent properties of Au NP/QD hybrid structures and to test BSA. RESULTS: The dimensions of Au NP aggregates increased and the space between them decreased with increasing processing temperature. At the same time, a blue shift of the plasmon resonance peak in the absorption spectra of Au NP arrays was observed. The deposition of CdSe/ZnS QDs with a core diameter of 5 nm on the surface of the Au NP arrays caused an increase in absorption and a red shift of the plasmon peak in the spectra. The exciton-plasmon enhancement of the QDs' photoluminescence intensity has been obtained at room temperature for hybrid structures with Au NPs array pretreated at temperatures of 100°C and 150°C. It has been found that an increase in the weight content of BSA increases the photoluminescence intensity of such hybrid structures. CONCLUSION: The ability of the qualitative and quantitative determination of protein content in solution using the Au NP/QD structures as an optical biosensor has been shown experimentally.

SAW-Based Phononic Crystal Microfluidic Sensor-Microscale Realization of Velocimetry Approaches for Integrated Analytical Platform Applications.

The current work demonstrates a novel surface acoustic wave (SAW) based phononic crystal sensor approach that allows the integration of a velocimetry-based sensor concept into single chip integrated solutions, such as Lab-on-a-Chip devices. The introduced sensor platform merges advantages of ultrasonic velocimetry analytic systems and a microacoustic sensor approach. It is based on the analysis of structural resonances in a periodic composite arrangement of microfluidic channels confined within a liquid analyte. Completed theoretical and experimental investigations show the ability to utilize periodic structure localized modes for the detection of volumetric properties of liquids and prove the efficacy of the proposed sensor concept.

Phoxonic crystals--a new platform for chemical and biochemical sensors.

A new sensor platform is based on so-called phoxonic crystals. Phoxonic crystals are structures designed for simultaneous control of photon and phonon propagation and interaction. They are characterized by a periodic spatial modulation of the dielectric constant as well as elastic properties on a common wavelength scale. Multiple scattering of photons and phonons results in a band gap where propagation of both waves is prohibited. The existence of photonic and phononic band gaps opens up opportunities for novel devices and functional materials. The usage of defect modes is an advantageous concept for measurement. The defect also acts as point of measurement. We show theoretically that the properties of the defect mode can be tailored to provide very high sensitivity to optical and acoustic properties of matter confined within a defect cavity or surrounding the defect or being adsorbed at the cavity surface. In this paper, we introduce the sensor platform and analyze the key features of the sensor transduction scheme. Experimental investigations using a macroscopic device support the theoretical findings.