[Show abstract][Hide abstract] ABSTRACT: Purpose
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.
The device includes a pH sensor based on differential measurement of an ISFET-REFET pair. The drawbacks associated with this type of configuration, namely short lifetime and manual fabrication, have been overcome in the prototype. An automatic one point calibration is performed when turning on the system. Two buffer solutions were utilized to determine the intra- and inter-day precision of the device. The pH of 30 fresh human urine samples was measured using a pH-meter, a dipstick and the new electronic device.
In some cases, dipstick measurements differed from those of the pH meter by more than 0.40 units, a clinically relevant discrepancy, whereas none of the measurements made with the new electronic device differed from the results of the pH-meter by more than 0.1 pH units.
This new electronic device has the possibility to be used by stone-formers to control their urinary pH at home, increasing the tools available for stone prevention and prophylaxis.
[Show abstract][Hide abstract] ABSTRACT: In this work a low-consumption, fast-response and small size, wax microvalve capable of multiple-actuation is described. This microvalve is fully integrated and electrically controlled. The response time varies from 150 ms to 400 ms. The energy consumption never exceeds 50 mJ which is orders of magnitude lower than other integrated microvalves. The present design is able to complete 10 open-close cycles with water and 20 with air working at 30 kPa and 60 kPa, respectively.
[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).
Full-text · Article · Feb 2013 · Applied Physics Letters
[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.
[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.
No preview · Article · Oct 2012 · Journal of Micromechanics and Microengineering
[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.
No preview · Article · Feb 2011 · Analytical Chemistry
[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: One of the main drawbacks of antenna integration on standard CMOS silicon substrates are the low radiation efficiency levels obtained due to the high silicon losses. This paper studies the use of micromachining techniques to remove silicon beneath the antenna as a solution to improve radiation efficiency. Several etching patterns are analyzed for different etching depths through simulations and measurements in order to find out which are the best ones for the micromachining process. Results are verified in two operating scenarios.
Preview · Article · Jan 2011 · Progress In Electromagnetics Research
[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: 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.
[Show abstract][Hide abstract] ABSTRACT: Fabrication of the array of electrodes was carried out in a microfabrication clean room using common deposition and patterning techniques. Fabrication started with the deposition of a triple layer of Ti/Ni/Au (500Å /500Å /500Å ) on a 500-μm-thick Pyrex wafer. After the metal layers were patterned with standard photolithography and wet etching of the metals, a 1-μm-thick silicon oxide passivation coating was deposited and patterned. Finally, the passivation layer was removed from the pads and from the interdigitated area with a second photolithography step and oxide dry etching. The peptide nanotubes were prepared by self-assembly from the bolaamphiphilic peptide monomer bis(Na- amidoglycylglycine)-1,7-heptane dicarboxylate and used as templates for the immobilization of antibodies as reported previously.[19,20,9] To obtain antibody nanotubes, after centrifuging 1mL of the peptide-nanotube solution at 14 000 rpm for 1 h, the resulting pellet was suspended in 100μL of phosphate buffer (PB, 1mM, pH 7) containing either anti-E. coli (goat polyclonal, 0.1mgmL-1, Abcam), anti-S. typhi (rabbit polyclonal, 0.1mgmL-1, Abcam), or IgG from rabbit serum (0.1mgmL -1, Sigma) overnight. Then, 500mL of bovine serum albumin (BSA, 10mgmL-1) were added for 1 h to block free adsorption sites on the tubes and the nanotubes were washed once with PB by centrifugation. After mixing 10μL of antibody nanotubes with 10mL of bacteria solutions in PB with different concentrations for 1 h, 1μL of the resulting nanotube- bacteria adducts were spotted on each transducer and Z0 at 316 kHz was measured with a 1260 Solartron Impedance Analyzer by applying a peak-to-peak excitation voltage of 10mV. The x axis in Figure 3 shows the number of cells in the 10mL solution. In Figure 3b, Z0 at 15-s sedimentation time of bacteria-nanotube complexes was converted into a color code by calculating the percentage variation of this parameter with respect to the maximum signal and tuning the brightness of the spot accordingly. Scanning electron microscopy (SEM) images were taken with a Zeiss Supra 55VP microscope by using an acceleration voltage of 0.5 kV after depositing the samples onto porous membranes (0.1-μm-diameter pore size, Whatman) and coating them with carbon.
[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.
[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: Das Auftragen von und die Musterbildung mit halbleitenden Oxiden bei Raumtemperatur gelingt mit der im Titel bezeichneten BCN-Methode. Sie liefert recht beständige amorphe ZnO-Tinten, die mit der Spitze eines Rasterkraftmikroskops in die Form von Nanomustern gebracht werden können. Dieser Schritt löst zudem die Kristallisation der Tinten aus. Mögliche Anwendungsgebiete für solche Halbleiternanostrukturen sind die Nanoelektronik und -optik.
No preview · Article · Feb 2010 · Angewandte Chemie International Edition
[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.
Full-text · Article · Feb 2010 · Journal of Controlled Release
[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 a broad range of dimensions, from the micron to the nanometer scale. Although most of the current research is geared towards the nanodomain, a good 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 a commercial 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 a major impact in a variety 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.
Full-text · Article · Nov 2009 · Analytical Chemistry
[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.