Rapid, multiparameter profiling of cellular secretion using silicon photonic microring resonator arrays

We have developed a silicon photonic biosensing chip capable of multiplexed protein measurements in a biomolecularly complex cell culture matrix. Using this multiplexed platform combined with fast one-step sandwich immunoassays, we perform a variety of T cell cytokine secretion studies with excellent time-to-result. Using 32-element arrays of silicon photonic microring resonators, the cytokines interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5), and tumor necrosis factor alpha (TNFα) were simultaneously quantified with high accuracy in serum-containing cell media. Utilizing this cytokine panel, secretion profiles were obtained for primary human Th0, Th1, and Th2 subsets differentiated from na?ve CD4+ T cells, and we show the ability to discriminate between lineage commitments at early stages of culture differentiation. We also utilize this approach to probe the temporal secretion patterns of each T cell type using real-time binding analyses for direct cytokine quantitation down to ～100 pM with just a 5 min-analysis.     

Colorimetric sensor arrays for molecular recognition

The development of colorimetric sensor arrays for the detection of volatile organic compounds is reported. Using an array of chemo-responsive dyes, enormous discriminatory power is created in a simple device that can imaged easily with an ordinary flat-bed scanner. High sensitivities (ppb) have been demonstrated for the detection of biologically important analytes, including amines, carboxylic acids, and thiols. By the proper choice of dyes and substrate, the array can be made essentially non-responsive to changes in humidity.     

Sequential polymer lithography for chemical sensor arrays

A simple process for the deposition of up to six different polymers in selected areas to be used as sensitive layers in chemical sensor arrays is presented. The process is based on photolithographic processes and takes advantage of the balance between UV exposure dose, material tone and developers used. The sensing properties of the deposited films in the array were characterized by the in situ monitoring of volume expansion upon exposure to analytes using white light reflectance sspectroscopy. The swelling properties of processed films are compared to the unprocessed ones for the purpose of examining the variation induced by the processing steps (exposure and development circles). Additionally, the repeatability of the processes as well as the effect of analyte sequence is examined. This process offers good control of the lateral dimensions and the thickness of the polymeric films and allows for the parallel fabrication of sensors based on different transduction mechanisms including mass sensitive and stress induced bending chemical sensors.     

Supramolecular optical sensor arrays for on-site analytical devices

Supramolecular optical chemosensors are useful tools in analytical chemistry for the visualization of molecular recognition information. One advantage is that they can be utilized for array systems to detect multiple analytes. However, chemosensor arrays have been evaluated mainly in the solution phase, which limits a wide range of practical applications. Thus, appropriate solid support materials such as polymer gels and papers are required to broaden the scope of the application of chemosensors as on-site analytical tools. In this review, we summarize the actual approaches for the fabrication of solid-state chemosensor arrays combined with powerful data processing techniques and portable digital recorders for real-world applications.     

Molecularly imprinted polymer sensor arrays

An eight channel molecularly imprinted polymer sensor array was prepared that was able to differentiate six different aryl amine analytes, including diastereomers with 94% accuracy.     

Prion protein detection in serum using micromechanical resonator arrays

Prion proteins that have transformed from their normal cellular counterparts (PrP^c) into infectious form (PrP^res) are responsible for causing progressive neurodegenerative diseases in numerous species, such as bovine spongiform encephalopathy (BSE) in cattle (also known as mad cow disease), scrapie in sheep, and Creutzfeldt-Jakob disease (CJD) in humans. Due to a possible link between BSE and CJD it is highly desirable to develop non-invasive and ante mortem tests for the detection of prion proteins in bovine samples. Such ante mortem tests of all cows prior to slaughter will help to prevent the introduction of PrP^res into the human food supply. Furthermore, detection of PrP^res in donated blood will also help to prevent the transmission of CJD among humans through blood transfusion. In this study, we have continued development of a micromechanical resonator array that is capable of detecting PrP^c in bovine blood serum. The sensitivity of the resonators for the detection of PrP^c is further enhanced by the use of secondary mass labels. A pair of antibodies is used in a sandwich immunoassay format to immobilize PrP^c on the surface of resonators and attach nanoparticles as secondary mass labels to PrP^c. Secondary mass labeling is optimized in terms of incubation time to maximize the frequency shifts that correspond to the presence of PrP^c on the surface of resonators. Our results show that a minimum of 200 pg mL⁻¹ of PrP^c in blood serum can be detected using micromechanical resonator arrays.     

Optical colorimetric sensor arrays for chemical and biological analysis

In recent years, the sensor array has attracted much attention in the field of complex system analysis on the basis of its good selectivity and easy operation. Many optical colorimetric sensor arrays are designed to analyze multi-target analytes due to the good sensitivity of optical signal. In this review, we introduce the targeting analytes, sensing mechanisms and data processing methods of the optical colorimetric sensor array based on optical probes (including organic molecular probes, polymer materials and nanomaterials). The research progress in the detection of metal ions, anions, toxic gases, organic compounds, biomolecules and living organisms (such as DNA, amino acids, proteins, microbes and cells) and actual sample mixtures are summarized here. The review illustrates the types, application advantages and development prospects of the optical colorimetric sensor array to help broad readers to understand the research progress in the application of chemical sensor array.     

Multiplexed evaluation of capture agent binding kinetics using arrays of silicon photonic microring resonators

High affinity capture agents recognizing biomolecular targets are essential in the performance of many proteomic detection methods. Herein, we report the application of a label-free silicon photonic biomolecular analysis platform for simultaneously determining kinetic association and dissociation constants for two representative protein capture agents: a thrombin-binding DNA aptamer and an anti-thrombin monoclonal antibody. The scalability and inherent multiplexing capability of the technology make it an attractive platform for simultaneously evaluating the binding characteristics of multiple capture agents recognizing the same target antigen, and thus a tool complementary to emerging high-throughput capture agent generation strategies.     

SU-8 as a structural material for labs-on-chips and microelectromechanical systems

Since its introduction in the nineties, the negative resist SU-8 has been increasingly used in micro- and nanotechnologies. SU-8 has made the fabrication of high-aspect ratio structures accessible to labs with no high-end facilities such as X-ray lithography systems or deep reactive ion etching systems. These low-cost techniques have been applied not only in the fabrication of metallic parts or molds, but also in numerous other micromachining processes. Its ease of use has made SU-8 to be used in many applications, even when high-aspect ratios are not required. Beyond these pattern transfer applications, SU-8 has been used directly as a structural material for microelectromechanical systems and microfluidics due to its properties such as its excellent chemical resistance or the low Young modulus. In contrast to conventional resists, which are used temporally, SU-8 has been used as a permanent building material to fabricate microcomponents such as cantilevers, membranes, and microchannels. SU-8-based techniques have led to new low-temperature processes suitable for the fabrication of a wide range of objects, from the single component to the complete lab-on-chip. First, this article aims to review the different techniques and provides guidelines to the use of SU-8 as a structural material. Second, practical examples from our respective labs are presented.     

Theory and application of a quartz resonator as a sensor for viscous liquids

A comprehensive analysis of the interaction between an AT-cut quartz crystal resonator and a viscous fluid is presented. The analysis, which includes peizoelectric effects, assumes a liquid of finite extent and therefore could also be used to study thin film of viscous liquids. A novel continuous flow cell system was designed and fabricated to monitor viscosity using an 11-MHz quartz crystal resonator. Measured data for frequency shifts of aqueous solutions of alcohols and sugars are in excellent agreement with theory.     

Orthogonal gas sensor arrays by chemoresistive material design

Gas sensor arrays often lack discrimination power to different analytes and robustness to interferants, limiting their success outside of research laboratories. This is primarily due to the widely sensitive (thus weakly-selective) nature of the constituent sensors. Here, the effect of orthogonality on array accuracy and precision by selective sensor design is investigated. Therefore, arrays of (2–5) selective and non-selective sensors are formed by systematically altering array size and composition. Their performance is evaluated with 60 random combinations of ammonia, acetone and ethanol at ppb to low ppm concentrations. Best analyte predictions with high coefficients of determination (R²) of 0.96 for ammonia, 0.99 for acetone and 0.88 for ethanol are obtained with an array featuring high degree of orthogonality. This is achieved by using distinctly selective sensors (Si:MoO₃ for ammonia and Si:WO₃ for acetone together with Si:SnO₂) that improve discrimination power and stability of the regression coefficients. On the other hand, arrays with collinear sensors (Pd:SnO₂, Pt:SnO₂ and Si:SnO₂) hardly improve gas predictions having R² of 0.01, 0.86 and 0.28 for ammonia, acetone and ethanol, respectively. Sometimes they even exhibited lower coefficient of determination than single sensors as a Si:MoO₃ sensor alone predicts ammonia better with a R² of 0.68.

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Graphical abstract Conventional arrays (red) with weakly-selective sensors span a significantly smaller volume in the analyte space than arrays containing distinctly-selective sensors (orthogonal array, green). Orthogonal arrays feature better accuracy and precision than conventional arrays in mixtures of ammonia, acetone and ethanol.

     

Automatic decoding of sensor types within randomly ordered,high-density optical sensor arrays

In this paper automatic sensor identification of sensor classes within a high-density randomized array, without a priori knowledge of sensor locations, is demonstrated. Two different fluorescence-based sensor types, with hundreds of replicates each, were randomly distributed into an optical imaging fiber array platform. The sensor element types were vapor-sensitive microspheres with the environmentally-sensitive fluorescent dye Nile Red adsorbed on their surface. Nile Red undergoes spectral changes when exposed to different microenvironmental polarity conditions, e.g. microsphere surface polarity or odor exposure. These reproducible sensor spectral changes, or sensor-response profiles, enable sensors within a randomized array to be grouped into categories by optical decoding methods. Two computational decoding methods (supervised and unsupervised) are introduced; equal classification rates were achieved for both. By comparing sensor responses from a randomized array with those obtained from known (control) arrays, 587 sensors were correctly classified with 99.32% accuracy. Although both methods were equally effective, the unsupervised method, which uses sensor response changes to odor exposure, is a better decoding model for the vapor-sensitive arrays studied, because it relies only on the odor-response profiles. Another decoding technique employed the emission spectra of the sensors and is more applicable to other types of multiplexed fluorescence-based arrays and assays. The sensor-decoding techniques are compared to demonstrate that sensors within high-density optical chemosensor arrays can be positionally-registered, or decoded, with no additional overhead in time or expense other than collecting the sensor-response profiles.     

A sulpha-drug sensitive sensor based on ion-pair complex modified PQC resonator

The construction and general performance characteristics of the piezoelectric sensors responsive to sulpha-drug are described here. The proposed sensing method is based on the use of the ion-pair complex of sulphadiazine-cetyltrioctylammonium. The complex, together with cholestyramine was embedded in PVC matrix. This sensor exhibited reasonable selectivity and a sensitive mass response to sulpha-drugs. The response range of the sensor was between 1.0x10(-7) and 1.0x10(-5) M with a detection limit of 8x10(-8) M at pH 8.63. The influencing factors were investigated in detail and optimized.     

Charge transfer from metallic single-walled carbon nanotube sensor arrays

This paper explores the possibility of using arrays of metallic carbon nanotubes as sensors. Unlike their semiconducting counterparts, single-walled carbon nanotube arrays or networks that are dominated by metallic conduction pathways have not been investigated for their environmental sensitivity. In this work, we demonstrate transduction of molecular adsorption via charge transfer through predominantly metallic single-walled carbon nanotubes. Raman spectroscopy and electric field dependent transport confirm that signal transduction takes place through primarily large diameter metallic nanotubes. This unique signal transduction mechanism might have implications for novel sensors. The scaling of the signal with array impedance is well described using an irreversible binding model developed previously. The arrays have several advantages including a simple, two-electrode fabrication, rapid regeneration, and a responsivity that scales predictably and linearly with the number of adsorption sites. An array-assisted hydrolysis of reactive analytes is found to regenerate the nanotube surface from hydrolyzable species which include important organophosphate nerve agents.     

Study of ionic liquid immobilization on polyvinyl ferrocene substrates for gas sensor arrays

In this report, the effects of conductive polymer oxidation states and structures on the design and development of ionic liquid (IL)/conductive polymer (CP) composite films for gas sensing are systematically characterized. Four different polyvinyl ferrocene (PVF) films synthesized by varying the conditioning potential (0.7 vs 0.0 V) and the electrolyte are tested for their gas-sensing properties (e.g., sensitivity, selectivity, response time, linearity, and dynamic range against various gas analytes such as dichloromethane, ethanol, natural gas, methane, formaldehyde (37%), and benzene) utilizing the quartz crystal microbalance (QCM) and ATR-FT-IR. The best available film is further studied as a substrate for the immobilization of various ILs that enhanced both the sensitivity and selectivity. Finally, two arrays, each comprising four sensors with the following scheme are developed and characterized for their ability to classify the four target analytes by using linear discriminant analysis: (1) the highest sensitivity PVF film immobilized with four different ILs and (2) the highest sensitivity IL immobilized in four different PVF films. Array 2 is proven to be much better than array 1 in discriminating the analytes, which is very significant in establishing the fact that a diverse set of PVF redox states allow the rational development of a PVF/IL composite-based sensor array in order to analyze complex mixtures utilizing structural differences and the extent of intermolecular interactions.     

Design strategies for multielectrode arrays applicable for high-throughput impedance spectroscopy on novel gas sensor materials

This paper reports the first design and fabrication of a 64 multielectrode array for high-throughput impedance spectroscopy. The purpose of this work is the development of a measurement system for the discovery and improvement of sensor materials using combinatorial methods. An array of interdigital capacitors (IDC) screen-printed onto a high-temperature-resistant Al(2)O(3) substrate is determined to be the optimal test plate. The electrode layout, and therefore also the idle capacity, is determined by specific requirements. Calculation of the idle capacity of the IDC as a function of the electrode width and distance allows adjustment and thus optimization of the array. Parasitic effects caused by the leads and contacts are compensated by a software-aided calibration. Apart from the use of the substrates for discovery of new sensor materials, the presented electrode array is also suitable for electrocatalytic applications as well as impedance spectroscopic studies of semiconductors and dielectrics.     

Transdermal microneedle sensor arrays based on palladium: Polymer composites

The solvent based casting of metal particle-polymer mixtures has been investigated as a rapid means through which to produce a 10 × 10 array of pyramidal (200 × 200 × 350 μm) microneedles for electroanalytical sensing applications. The incorporation of nanoparticulate palladium powder within either a polycarbonate or polystyrene binder is shown to result in mechanically robust microneedles. The electrochemical properties of the resulting structures have been investigated and their application for transdermal sensing applications has been demonstrated through the use of epidermal/skin mimic.