Antonio J. Ricco

Point of care diagnostics: status and future.

Introduction A Why POC Diagnostics? B Time B Patient Responsibility and Compliance B Cost B Diagnostic Targets C Proteins C Metabolites and Other Small Molecules C Nucleic Acids C Human Cells D Microbes/Pathogens D Drugs and Food Safety D Current Context of POC Assays E POC Glucose Assays E Lateral Flow Assays E Limitations of “Traditional” POC Approaches F Enabling Technologies G Printing and Laminating G Microfluidic Technologies and Approaches: “Unit Operations” for POC Devices G Pumping and Valving H Mixing I Separation I Reagent Storage J Sample Preparation K Surface Chemistry and Device Substrates L Physical Adsorption L Bioaffinity Attachment L Covalent Attachment M Substrate Materials M Detection M Electrochemical Detection N Optical Detection N Magnetic Detection N Label-Free Methods O Enabling Multiplexed Assays O Recent Innovation O Lateral Flow Assay Technologies O Proteins P Antibodies P Protein Expression and Purification Q Nucleic Acids Q Aptamers R Infectious Diseases and Food/Water Safety R Blood Chemistry S Coagulation Markers S Whole Cells S Trends, Unmet Needs, Perspectives T Glucose T Global Health and the Developing World T Personalized Medicine and Home Testing U Technology Trends U Multiplexing V Author Information V Biographies V Acknowledgment W References W

Detection of Water in the LCROSS Ejecta Plume

Watering the Moon About a year ago, a spent upper stage of an Atlas rocket was deliberately crashed into a crater at the south pole of the Moon, ejecting a plume of debris, dust, and vapor. The goal of this event, the Lunar Crater Observation and Sensing Satellite (LCROSS) experiment, was to search for water and other volatiles in the soil of one of the coldest places on the Moon: the permanently shadowed region within the Cabeus crater. Using ultraviolet, visible, and near-infrared spectroscopy data from accompanying craft, Colaprete et al. (p. 463; see the news story by Kerr; see the cover) found evidence for the presence of water and other volatiles within the ejecta cloud. Schultz et al. (p. 468) monitored the different stages of the impact and the resulting plume. Gladstone et al. (p. 472), using an ultraviolet spectrograph onboard the Lunar Reconnaissance Orbiter (LRO), detected H2, CO, Ca, Hg, and Mg in the impact plume, and Hayne et al. (p. 477) measured the thermal signature of the impact and discovered that it had heated a 30 to 200 square-meter region from ∼40 kelvin to at least 950 kelvin. Paige et al. (p. 479) mapped cryogenic zones predictive of volatile entrapment, and Mitrofanov et al. (p. 483) used LRO instruments to confirm that surface temperatures in the south polar region persist even in sunlight. In all, about 155 kilograms of water vapor was emitted during the impact; meanwhile, the LRO continues to orbit the Moon, sending back a stream of data to help us understand the evolution of its complex surface structures. A controlled spacecraft impact into a crater in the lunar south pole plunged through the lunar soil, revealing water and other volatiles. Several remote observations have indicated that water ice may be presented in permanently shadowed craters of the Moon. The Lunar Crater Observation and Sensing Satellite (LCROSS) mission was designed to provide direct evidence (1). On 9 October 2009, a spent Centaur rocket struck the persistently shadowed region within the lunar south pole crater Cabeus, ejecting debris, dust, and vapor. This material was observed by a second “shepherding” spacecraft, which carried nine instruments, including cameras, spectrometers, and a radiometer. Near-infrared absorbance attributed to water vapor and ice and ultraviolet emissions attributable to hydroxyl radicals support the presence of water in the debris. The maximum total water vapor and water ice within the instrument field of view was 155 ± 12 kilograms. Given the estimated total excavated mass of regolith that reached sunlight, and hence was observable, the concentration of water ice in the regolith at the LCROSS impact site is estimated to be 5.6 ± 2.9% by mass. In addition to water, spectral bands of a number of other volatile compounds were observed, including light hydrocarbons, sulfur-bearing species, and carbon dioxide.

Characterization of SH acoustic plate mode liquid sensors

Abstract Two-port acoustic wave sensors have been fabricated, which utilize shear horizontal (SH) acoustic plate modes (APMs) to probe a solid/liquid interface. These modes, excited and detected by interdigital transducers on thinned quartz plates, propagate efficiently with liquid contacting the device and allow sensing to be performed on the side of the device opposite the transducers. A number of sensing mechanisms have been discovered, including mass loading, viscous entrainment of the contacting liquid, and acoustoelectric coupling between evanescent plate mode electric fields and ions and dipoles in solution. The mass sensitivity of the APM device enables it to function as a microbalance in a number of sensing applications. A chemical sensor capable of detecting low concentrations of Cu 2+ ions in solution has been constructed by chemically modifying the device surface with ethylenediamine ligands. The treated devices bind Cu 2+ ions in a manner that can be reversed by the addition of acid to the solution.

Surface acoustic wave gas sensor based on film conductivity changes

Abstract The first surface acoustic wave (SAW) sensor that functions via changes in conductivity of a thin surface film is reported. A lead phthalocyanine (PbPc) thin film is deposited on the acoustic propagation path of a LiNbO 3 SAW delay line, which serves as the feedback element of an oscillator circuit. Reaction with strongly oxidizing gases, in particular NO 2 , increases the conductivity of the PbPc film. Acousto-electric coupling of the traveling electric potential wave associated with the SAW to charge carriers in the PbPc film slows the acoustic wave velocity, altering the oscillation frequency of the circuit. This sensor is about 1000 times more sensitive, in terms of the number of NO 2 molecules that can be detected (10 16 molecules/cm 3 of PbPc film), than an identical SAW sensor functioning via mass loading would be. Sensitivity to a few ppm of NO 2 in N 2 has been demonstrated.

Acoustic wave viscosity sensor

An acoustic wave device utilizing plate modes having components of displacement parallel to a crystal surface has been demonstrated to be an effective sensor of liquid shear viscosity (η) over a wide viscosity range. When a liquid is present on the sensor surface, the propagation loss of the acoustic wave depends upon η in a calculable fashion. Because the device functions at 159 MHz, liquid relaxation effects occur with high viscosity liquids, causing the propagation loss to saturate. Viscosity is sampled in the 50‐nm‐thick liquid layer which couples to the acoustic wave, so that only a single drop of liquid is required for measurement.

Acoustoelectric interaction of plate modes with solutions

Acoustic plate mode (APM) devices operating in liquids have an associated electric field which extends several micrometers into the liquid and is capable of interacting with ions and dipoles in solution. Experiments have been performed using quartz APM devices which demonstrate these acoustoelectric interactions. Changes in the dielectric constant or conductivity of solutions in contact with the device were found to perturb the propagation velocity of the plate mode. An equivalent circuit is proposed to describe the interaction of the electric field with ions and dipoles. From this simple model we obtain the velocity shift and attenuation which should occur as a result of this interaction and compare the model predictions to the experimentally observed trends.

Three-Dimensional Wax Patterning of Paper Fluidic Devices

In this paper we describe a method for three-dimensional wax patterning of microfluidic paper-based analytical devices (μPADs). The method is rooted in the fundamental details of wax transport in paper and provides a simple way to fabricate complex channel architectures such as hemichannels and fully enclosed channels. We show that three-dimensional μPADs can be fabricated with half as much paper by using hemichannels rather than ordinary open channels. We also provide evidence that fully enclosed channels are efficiently isolated from the exterior environment, decreasing contamination risks, simplifying the handling of the device, and slowing evaporation of solvents.

Miniaturized capillary isoelectric focusing in plastic microfluidic devices

We report the demonstration of miniaturized capillary isoelectric focusing (CIEF) in plastic microfluidic devices. Conventional CIEF technique was adapted to the microfluidic devices to separate proteins and to detect protein‐protein interactions. Both acidic and basic proteins with isoelectric points (pI) ranging from 5.4 to 11.0 were rapidly focused, mobilized, and detected in a 1.2 cm long channel (50 νm deep×120 νm wide) with a total analysis time of 150 s. In a device with a focusing distance of 4.7 cm, the separation efficiency for a basic protein, lysozyme, was achieved as high as 1.5×105 plates, corresponding to 3.2 million plates per meter. We also experimentally confirmed that IEF resolution is essentially independent of focusing length when the applied voltage is kept the same and within a range that it does not cause Joule heating. Further, we demonstrated the use of miniaturized CIEF to study the interactions between two pairs of proteins, immunoglobulin G (IgG) with protein G and anti‐six histidine (anti‐6xHis) with 6xHis‐tagged green fluorescent protein (GFP). Using this approach, protein‐protein interactions can be detected for as little as 50 fmol of protein. We believe miniaturized CIEF is useful for studying protein‐protein interactions when there is a difference in pI between a protein‐protein complex and its constitutent proteins.

X‐ray photoelectron and Auger electron spectroscopic study of the CdTe surface resulting from various surface pretreatments: Correlation of photoelectrochemical and capacitance‐potential behavior with surface chemical composition

The surface chemistry and stoichiometry of p‐ and n‐type CdTe photoelectrodes treated with oxidizing and reducing etches have been characterized by x‐ray photoelectron and Auger electron spectroscopies. The results of surface analysis have been correlated with the photoelectrochemical and capacitance–potential behavior of the photoelectrodes. ‘‘Oxidized’’ surfaces are covered by a thin Te0/TeO2 layer (or a thicker Te0 layer, if the etching procedure is slightly altered), resulting in Fermi level pinning: a constant photovoltage is found for a wide range of redox potentials and potential‐independent space charge layer capacitance obtains. ‘‘Reduced’’ surfaces closely resemble ion sputtered CdTe in chemical state and stoichiometry, resulting in more nearly ‘‘ideal’’ behavior: the semiconductor/electrolyte interface is rectifying in the dark; capacitance–potential behavior follows the Mott–Schottky equation near flat band conditions; and photovoltage varies with redox potential, from 0 to ∼0.7 V for p‐CdTe.

Ultrahigh vacuum studies of Pd metal‐insulator‐semiconductor diode H2 sensors

Hydrogen sensitive Pd metal/insulator/semiconductor diodes provide an ambient temperature, low power electronic sensor for hydrogen as a result of hydrogen trapping at the Pd/insulator interface. Current kinetic models consider the rate limiting step to be adsorption at the Pd surface followed by rapid transport to the interface. We have obtained both steady‐state and kinetic results for diodes with clean Pd surfaces over hydrogen pressures ranging from 10−10 to 10−1 Torr. The sensitivity limit (equivalent to <1011 total H2 impacts/cm2 at the Pd surface) is set by our vacuum capabilities, and is at least seven orders of magnitude greater than that obtained for devices with contaminated surfaces. These results clearly show that the kinetic and sensitivity limitations reported for such devices are a result of surface contamination. For diodes with a clean Pd surface, analysis of the steady‐state results requires at least two binding states (9 and 6.8 kcal/mol of H relative to H2(g)) for H at the Pd/SiO2 int...