KEYWORDS: Biological detection systems, Nanosensors, Cell phones, Error analysis, Light sources and illumination, Video processing, Medical diagnostics, Opacity, Data processing, Video
Urinalysis dipsticks were designed to revolutionize urine-based medical diagnosis. They are cheap, extremely portable, and have multiple assays patterned on a single platform. They were also meant to be incredibly easy to use. Unfortunately, there are many aspects in both the preparation and the analysis of the dipsticks that are plagued by user error. This high error is one reason that dipsticks have failed to flourish in both the at-home market and in low-resource settings. Sources of error include: inaccurate volume deposition, varying lighting conditions, inconsistent timing measurements, and misinterpreted color comparisons. We introduce a novel manifold and companion software for dipstick urinalysis that eliminates the aforementioned error sources. A micro-volume slipping manifold ensures precise sample delivery, an opaque acrylic box guarantees consistent lighting conditions, a simple sticker-based timing mechanism maintains accurate timing, and custom software that processes video data captured by a mobile phone ensures proper color comparisons. We show that the results obtained with the proposed device are as accurate and consistent as a properly executed dip-and-wipe method, the industry gold-standard, suggesting the potential for this strategy to enable confident urinalysis testing. Furthermore, the proposed all-acrylic slipping manifold is reusable and low in cost, making it a potential solution for at-home users and low-resource settings.
In this manuscript we describe an electronic label-free method for detection of target cells, which has potential
applications ranging from pathogen detection for food safety all the way to detection of circulating tumor cells for cancer
diagnosis. The nanoelectronic platform consists of a stack of electrodes separated by a 30nm thick insulating layer. Cells
binding to the tip of the sensor result in a decrease in the impedance at the sensing tip due to an increase in the fringing
capacitance between the electrodes. As a proof of concept we demonstrate the ability to detect Saccharomyces Cerevisae
cells with high specificity using a sensor functionalized with Concanavalin A. Ultimately we envision using this sensor
in conjunction with a technology for pre-concentration of target cells to develop a fully integrated micro total analysis
system.
Diagnosis of Phenylketonuria (PKU) in newborns is important because it can potentially help prevent mental retardation since it is treatable by dietary means. PKU results in phenylketonurics having phenylalanine levels as high as 2 mM whereas the normal upper limit in healthy newborns is 120 uM. To this end, we are developing a microfluidic platform integrated with a SERS substrate for detection of high levels of phenylalanine. We have successfully demonstrated SERS detection of phenylalanine using various SERS substrates fabricated using nanosphere lithography, which exhibit high levels of field enhancement. We show detection of SERS at clinically relevant levels.
This paper introduces a label-free, electronic biomolecular sensing platform for the detection and
characterization of trace amounts of biological toxins within a complex background matrix. The mechanism
for signal transduction is the electrostatic coupling of molecule bond vibrations to charge transport across an
insulated electrode-electrolyte interface. The current resulting from the interface charge flow has long been
regarded as an experimental artifact of little interest in the development of traditional charge based biosensors
like the ISFET, and has been referred to in the literature as a "leakage current". However, we demonstrate by
experimental measurements and theoretical modeling that this current has a component that arises from the
rate-limiting transition of a quantum mechanical electronic relaxation event, wherein the electronic tunneling
process between a hydrated proton in the electrolyte and the metallic electrode is closely coupled to the bond
vibrations of molecular species in the electrolyte. Different strategies to minimize the effect of quantum
decoherence in the quantized exchange of energy between the molecular vibrations and electron energy will
be discussed, as well as the experimental implications of such strategies. Since the mechanism for the
transduction of chemical information is purely electronic and does not require labels or tags or optical
transduction, the proposed platform is scalable. Furthermore, it can achieve the chemical specificity typically
associated with traditional micro-array or mass spectrometry-based platforms that are used currently to
analyze complex biological fluids for trace levels of toxins or pathogen markers.
Pathogenic bacterial cell detection is currently performed using techniques such as culture enrichment and various plating methods, which are expensive and can take up to several days. In this study, we describe the design, fabrication, and testing of a rapid and inexpensive sensor for detection of target cells electrically in
real-time. The sensor operates with the use of microelectrodes integrated in a micro-channel. As a proof of principle, we have successfully demonstrated real-time detection of target yeast cells with a concentration of 107 cells/ml. We have also demonstrated the selectivity of our sensors in responding to target cells while remaining irresponsive to non-target cells. We also perform theoretical modeling in order to determine the ultimate detection limit of the sensor. Based on our modeling results, proper optimization of the sensor can yield detection limits approaching the single cell level.
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