[Show abstract][Hide abstract] ABSTRACT: Urinary pH is an important factor linked to renal stone disease and a useful marker in the treatment of urolithiasis. Although the gold standard for measuring urinary pH utilizes a glass electrode and a pH meter, at present dipstick testing is largely used to estimate urinary pH. However, the accuracy and precision of this method may be insufficient for making clinical decisions in patients with lithiasis. The aim of this study is to describe a new device for urinary pH testing.
[Show abstract][Hide abstract] ABSTRACT: In this work, non-functional radio frequency identification pad-free chips are analyzed by modulating its powering scheme and noninvasively sensing their surface infrared (IR) emission with an IR camera following lock-in strategies. This approach is justified by the chip wireless powering strategy and its pad-free design. As a result, latch-up triggering has been identified as the failure mechanism, also showing that electrical figures of merit can be extracted non-invasively (i.e., coils coupling frequency and its bandwidth).
[Show abstract][Hide abstract] ABSTRACT: An electrical readout system of protein microarrays comprising arrays of gold interdigitated electrode pairs, which enabled impedance multiplexed detection of up to 36 biological events on the same substrate, and of polydimethylsiloxane (PDMS) microwells, is reported. Similarly to fluorescent readout counterparts, regular glass slides were applied for carrying out the microarray. However, unlike them, the presented system is compact and requires a simple and inexpensive instrumentation, thus being ideally suited for deployment of bioarray detection approaches. The system was based on the use of urease-based immunoassay formats applied to the detection of boldenone steroid achieving analytical results similar to those obtained by fluorescent scanner detection approaches.
Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS & EUROSENSORS XXVII), 2013 Transducers & Eurosensors XXVII: The 17th International Conference on; 01/2013
[Show abstract][Hide abstract] ABSTRACT: A new scheme for the integration of small semiconductor transducer chips with microfluidic structures on printed circuit board (PCB) is presented. The proposed approach is based on a packaging technique that yields a large and flat area with small and shallow (∼44 µm deep) openings over the chips. The photocurable encapsulant material used, based on a diacrylate bisphenol A polymer, enables irreversible bonding of polydimethylsiloxane microfluidic structures at moderate temperatures (80 °C). This integration scheme enables the insertion of transducer chips in microfluidic systems with a lower added volume than previous schemes. Leakage tests have shown that the bonded structures withstand more than 360 kPa of pressure. A prototype microfluidic system with two detection chips, including one inter-digitated electrode (IDE) chip for conductivity and one ion selective field effect transistor (ISFET) chip for pH, has been implemented and characterized. Good electrical insulation of the chip contacts and silicon edge surfaces from the solution in the microchannels has been achieved. This integration procedure opens the door to the low-cost fabrication of complex analytical microsystems that combine the extraordinary potential of both the microfluidics and silicon microtechnology fields.
Journal of Micromechanics and Microengineering 01/2012; 22(10):105022. · 1.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this work, two types of polycrystalline silicon (polysilicon) microparticles were modified with specific ligands in order to be selectively attached to chemical residues located at the plasma membrane and thus to be applied to study individual cells in culture. Two different functionalization approaches based on adsorption and covalent attachment were assayed. A comparative study of the efficiency of the ligand immobilization and stability of the modified particle in the culture medium was carried out using the selected ligands labeled with a fluorophore. Cylindrical microparticles (nonencoded microparticles) and shape-encoded microparticles (bar codes) were used with the aim of demonstrating the nondependence of the particle size and shape on the efficiency of the immobilization protocol. Fluorescence imaging and statistical analysis of the recorded fluorescence intensity showed that the covalent attachment of the ligand to the surface of the microparticle, previously modified with an aldehyde-terminated silane, gave the best results. As a proof of concept, Vero cells in culture were labeled with the covalently modified bar codes and successfully tracked for up to 1 week without observing any alteration in the viability of the cells. Bar code numbers could be easily read by eye using a bright-field optical microscope. It is anticipated that such modified microparticles could be feasible platforms for the introduction of other analytical functions of interest in single-cell monitoring and cell sorting in automatic analysis systems.
[Show abstract][Hide abstract] ABSTRACT: A new approach for the electrical readout of microarrays prepared on regular glass slides, using an array of impedimetric transducers (interdigitated electrodes, IDEs) is presented in this work. Impedance detection relies on the use of a urease-labeled immunoassay scheme. Urease is able to produce an increase in conductivity by hydrolysis of the urea substrate, which is measured with the IDEs and directly related to the amount of target analyte. Unlike previous electrical microarrays, the assay does not take place on top of the transducers but on a regular glass slide, which may enable the development of compact multiplexed analytical systems with lower cost per assay. A droplet of solution with the enzymatic substrate is deposited on each transducer of the array, and the microarray is positioned at a short distance (300 μm) so that each droplet wets one transducer and one spot of the microarray. This procedure allows reusing the transducer array for readout of a virtually unlimited number of microarrays. A microarray based on an immunoassay for the detection of a mouse generic protein in a concentration range from 0.03 to 30 μg mL(-1) was carried out to assess the performance of the electrical readout approach. A sigmoid response with a limit of detection of 0.1 μg mL(-1) and a dynamic range of 1 order of magnitude was obtained. A comparative study was also carried out with two well established analytical procedures. First, the urease-based immunoassay was tested in a 96 well microtiter plate using phenol red pH indicator and absorbance detection. Second, the microarray was carried out using the same target protein concentration range but applying a Cy3 label and fluorescence detection. Both assays allowed for the validation of the performance of the presented electrical readout system.
[Show abstract][Hide abstract] ABSTRACT: In this paper we present some guidelines for the design of single-chip RFID sensors, focusing in the powering aspects of these wireless systems. The methodology and key aspects for the optimization of the powering coil and the integrated inductor based on finite element analysis simulations and lumped-element models, correspondingly, is described. Simulation results are shown for an example of design, and compared with measurements of a real coil fabricated with a 0.18 µm CMOS technology. Parameters obtained by simulation and by measurement are in good agreement. With this example we show that a wireless sensor in a 1.5 × 1.5 mm2 chip with a consumption of 400 µA at 1.8 V could be powered at a distance of 4.4 mm with a 1.2 cm powering coil connected to a 250 mW RF amplifier working at 13.56 MHz.
[Show abstract][Hide abstract] ABSTRACT: In remote sensors a RF wireless link can be used to transmit the collected data to a reader unit. In order to improve the sensor lifetime, an inductive link could be used to sporadically reload the sensor battery without physical access to it. However the presence of a coil integrated in the same chip together with the antenna will degrade the RF link performance. In this paper, simulated and measured results will be used to quantify this degradation as a function of the distance between both elements, which will limit the minimum chip dimensions. Index Terms— Dipole antennas, integrated antennas, CMOS technology, parasitic elements, inductive coupling.
[Show abstract][Hide abstract] ABSTRACT: Electrical detection systems of protein microarrays is an attractive alternative to optical detection ones because of their potential low limit of detection, as well as their cost and portability. In the present work the readout of regular glass slide microarrays using a microelectrode array chip and enzyme-labelled impedimetric detection is demonstrated. The detection principle has previously been validated for individual biosensors .
The novelty here is not only the array format, but also the physical separation of the recognition surface and the detection electrodes, which allows working with low-cost disposable glass slide substrates. The detection chip consists of an array of 36 pairs of gold interdigitated microelectrodes (13 20-μm wide 20-μm spaced fingers in each IDE) fabricated on glass substrates. This type of transducers allows row-column interconnection and addressing, with negligible cross-talk, which has greatly simplified the instrumentation made in-house. The measurement of all 36 IDEs takes less than 1 s.
Regarding the protein microarrays, aldehyde-modifed glass slide substrates were used for the covalent anchorage of the corresponding biomolecule. The detection principle of the readout system was based on the use of the enzyme urease. Urea substrate undergoes a catalytic hydrolysis to give carbon dioxide and ammonium. The generation of these ionic species increases the solution conductivity, which is measured with the IDEs. The developed electrical readout system was applied to the detection of a mouse immunoglobulin G (mIgG) as a model protein, using a biotinylated anti-mIgG and streptavidin-urease conjugate. Results were compared with a colorimetric ELISA in microtiter plates also using urease label and phenol red pH indicator.
 R. de la Rica, A. Baldi, C. Fernández-Sánchez, Appl. Physics Lett. 90 (2007) 074102.
13 th International Conference on Electroanalysis ESEAC 2010 Gijón; 06/2010
[Show abstract][Hide abstract] ABSTRACT: This paper presents a comparative analysis of the performance offered by classical miniaturization techniques when they are applied to Standard CMOS technology integrated antennas. Top loaded and meandered dipoles are analyzed. It will be shown as the trade off between miniaturization and efficiency levels becomes much more significant due to the high losses of the low resistivity silicon used in Standard CMOS technologies.
Antennas and Propagation (EuCAP), 2010 Proceedings of the Fourth European Conference on; 05/2010
[Show abstract][Hide abstract] ABSTRACT: We review efforts to produce microfabricated glucose sensors and closed-loop insulin delivery systems. These devices function due to the swelling and shrinking of glucose-sensitive microgels that are incorporated into silicon-based microdevices. The glucose response of the hydrogel is due to incorporated phenylboronic acid (PBA) side chains. It is shown that in the presence of glucose, these polymers alter their swelling properties, either by ionization or by formation of glucose-mediated reversible crosslinks. Swelling pressures impinge on microdevice structures, leading either to a change in resonant frequency of a microcircuit, or valving action. Potential areas for future development and improvement are described. Finally, an asymmetric nano-microporous membrane, which may be integrated with the glucose-sensitive devices, is described. This membrane, formed using photolithography and block polymer assembly techniques, can be functionalized to enhance its biocompatibility and solute size selectivity. The work described here features the interplay of design considerations at the supramolecular, nano, and micro scales.
Journal of Controlled Release 02/2010; 141(3):303-13. · 7.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report on the design and characterization of the building blocks of a single-chip wireless chemical sensor fabricated with a commercial complementary metal-oxide-silicon (CMOS) technology, which includes two types of transducers for impedimetric measurements (4-electrode array and two interdigitated electrodes), instrumentation circuits, and a metal coil and circuits for inductive power and data transfer. The electrodes have been formed with a polycrystalline silicon layer of the technology by a simple post-process that does not require additional deposition or lithography steps, but just etching steps. A linear response to both conductivity and permittivity of solutions has been obtained. Wireless communication of the sensor chip with a readout unit has been demonstrated. The design of the chip was prepared for individual block characterization and not for full system characterization. The integration of chemical transducers within monolithic wireless platforms will lead to smaller, cheaper, and more reliable chemical microsensors, and will open up the door to numerous new applications where liquid mediums that are enclosed in sealed receptacles have to be measured.
[Show abstract][Hide abstract] ABSTRACT: This chapter outlines and discusses important micro- and nanofabrication techniques. We start with the
most basic methods borrowed from the integrated circuit (IC) industry, such as thin-film deposition, lithography and etching,
and then move on to look at microelectromechanical systems (MEMS) and nanofabrication technologies. We cover abroad range
of dimensions, from the micron to the nanometer scale. Although most of the current research is geared towards the nanodomain,
agood understanding of top-down methods for fabricating micron-sized objects can aid our understanding of this research.
Due to space constraints, we focus here on the most important technologies; in the microdomain these include surface, bulk,
and high-aspect-ratio micromachining; in the nanodomain we concentrate on e-beam lithography, epitaxial growth, template manufacturing,
and self-assembly. MEMS technology is maturing rapidly, with some new technologies displacing older ones that have proven
to be unsuited to manufacture on acommercial scale. However, the jury is still out on methods used in the nanodomain, although
it appears that bottom-up methods are the most feasible, and these will have amajor impact in avariety of application areas
such as biology, medicine, environmental monitoring, and nanoelectronics.
[Show abstract][Hide abstract] ABSTRACT: While cancer is still an implacable disease, many cancers can be cured if they are diagnosed in an early stage. Recently, it was reported that the transformation from normal cells to cancer cells can change their mechanoelastic properties to become softer and more deformable. If some cancer cells are more deformable, then a progressive increase of the volume of softer cancer cells should be induced as an abrupt change in osmolarity is applied. On the basis of this hypothesis, we developed a sensor that can electronically monitor the volume increase of cancer cells under hyposmotic pressure. By this methodology, K:Molv NIH 3T3 cells, 786-O human kidney carcinoma cells, and MPSC-1 ovarian cancer cells were successfully detected within 30 min using on the order of 10 cells. These cancer cells could be detected with the same sensitivity even in the presence of a vast excess of the respective noncancerous cells [NIH 3T3 cells, human embryonic kidney (HEK) 293 cells, ovarian surface epithelial (OSE) cells]. Since the proposed impedimetric sensor could be useful for detecting cancer cells fast and reliably, it could be further implemented in the screening of large populations of tissue samples and the detection of circulating tumor cells for point-of-care applications.
[Show abstract][Hide abstract] ABSTRACT: The risk of infectious diseases has compelled some industries to establish a zero-tolerance standard for the presence of microorganisms in a given sample. Here, we address this issue with a novel reverse-phase immunoassay on impedimetric transducers for the specific detection of extremely low numbers of pathogens (less than 10 cells). After simply spotting the sample onto the electrodes, physisorbed analytes were targeted with urease-labeled antibodies, and the urease on the pathogens hydrolyzed urea to ionic species with a concomitant decrease of the resistivity of the solution. By this methodology, the limit of detection (LOD) based on the 3sigma criterion was 1 Escherichia coli cell with an assay time under 1 h. However, the precise number of cells present in highly diluted samples is uncertain, making it difficult to assess the final LOD of the sensor. We overcome this problem by using an atomic force microscope to deposit and image in situ the exact number cells on the transducer. After performing the immunoassay, a single E. coli cell was successfully detected without ambiguity in the number of cells even in the presence of a 10(4) excess of a competing microorganism, thus demonstrating the outstanding LOD and selectivity of the proposed reverse-phase immunoassay.
[Show abstract][Hide abstract] ABSTRACT: Detection of physical changes of cells is emerging as a new diagnostic approach to determine their phenotypical features. One of such changes is related to their viability; live (viable) cells are more voluminous than the dead ones, and monitoring this parameter in tissue cells becomes essential in fields such as drug discovery and hazard evaluation. In the area of pathogen detection, an analytical system capable of specifically detecting viable cells with the simple sample preparation and detection process would be highly desirable since live microorganisms can rapidly increase their numbers even at extremely low concentration and become a severe health risk. However, current sensing strategies cannot clearly determine the viability of cells, and hence they are susceptible to false-positive signals from harmless dead pathogens. Here we developed a robust electronic immunoassay that uses a pair of polycrystalline silicon interdigitated electrodes for the rapid detection of pathogens with high specificity for live cells. After bacterial cells were specifically anchored to the surface of the antibody-modified electrode, the characteristic geometry of the transducer enables the selective detection of viable cells with a limit of detection of 3 x 10(2) cfu/mL and an incubation time of only 1 h. The CMOS compatible fabrication process of the chip along with the label-free, reagent-less electronic detection and the easy electrode regeneration to recycle for another impedance measurement make this approach an excellent candidate for oncoming economical in-field viable-cell detection systems, fully integrable with sophisticated signal processing circuits.
[Show abstract][Hide abstract] ABSTRACT: A simple means for weaving a hydrogel into a microdevice is presented. A glass plate is scored on both sides with trenches of depth slightly more than half the plate thickness. Trenches on the two faces of the wafer are perpendicular to each other, and integral holes are formed at the intersections between the perpendicular trenches. This crosscut microstructure is readily loaded with a hydrogel, which interlocks with the wafer. When the hydrogel is thermoresponsive in its swelling, the hydrogel crosscut construct (HyC) can be used for thermofluidic gating of flow perpendicular to the plate surface. A simple test rig to demonstrate this principle is constructed, and response times to changes in temperature are determined. An autonomous thermofluidic oscillator, which makes use of the HyC and functions by the coupled dissipation of thermal and hydraulic pressure gradients, is demonstrated.