Development of a low cost biosensing platform for highly sensitive and specific on-site detection of pathogens and infections

A highly sensitive, specific, real time, and field-deployable surveillance tool is critical to the control of pathogens and infections, as well as ecological impact of chemicals exposure. This work investigates the development of a low cost biosensing platform that can be used for viral disease diagnosis and chemical detection. The sensing mechanism is known as AC electrokinetics (ACEK) capacitive sensing. By applying an inhomogeneous AC electric field on sensor electrodes, positive dielectrophoresis is induced to accelerate the travel of analytes. The same applied AC signal also directly measures the capture of target by the probe on sensor surface. The realized sensing platform is not only rapid but also highly sensitive and specific. Built on our initial proof-of-concept of ACEK capacitive sensing, this work studies in details the immobilization of probes on electrode surface, electrode design, the interactions between biomolecules such as nucleic acids and testing buffers, and the effect of dielectrophoresis and accompanying ACEK phenomena. Experimental comparisons are made between sensors with various probe immobilization, different electrode designs, testing buffer and detection protocols. As a result, much higher sensitivity and selectivity have been achieved. We are able to successfully detect virus particles in nasal swab samples, specific antibody in serum and whole genome nuclei acids in serum. To extend the application of this sensing method on other electrode platform, polyimide-based laser printed electrodes are also investigated and successfully demonstrated for small molecule detection. However, this type of sensor exhibits high internal resistance, making it only suitable for chemical or particle detection in highly resistive electrolyte, such as de-ionized water. With procedural and design improvements discussed in this work, it is expected that ACEK capacitive sensing will become a disruptive technology in on-site biochemical detection

Field Effect Transistor Nanosensor for Breast Cancer Diagnostics

Silicon nanochannel field effect transistor (FET) biosensors are one of the most promising technologies in the development of highly sensitive and label-free analyte detection for cancer diagnostics. With their exceptional electrical properties and small dimensions, silicon nanochannels are ideally suited for extraordinarily high sensitivity. In fact, the high surface-to-volume ratios of these systems make single molecule detection possible. Further, FET biosensors offer the benefits of high speed, low cost, and high yield manufacturing, without sacrificing the sensitivity typical for traditional optical methods in diagnostics. Top down manufacturing methods leverage advantages in Complementary Metal Oxide Semiconductor (CMOS) technologies, making richly multiplexed sensor arrays a reality. Here, we discuss the fabrication and use of silicon nanochannel FET devices as biosensors for breast cancer diagnosis and monitoring

For the Sensing of Viral DNA: An Integrated Polydimethylsiloxane Accurate CRISPR Detection (IMPACT) System

Infectious disease outbreaks have become more frequent and extreme in recent years, and as populations continue to grow and the world becomes more interconnected, they show no signs of stopping. The current COVID-19 pandemic affecting the world and grinding economies to a halt was known about months ago but could not be contained. One of the largest issues facing the containment of infectious disease is a lack of real-time, point-of-care detection devices which can accurately and effectively identify those who are infected so they can be treated and quarantined. Here, an Integrated Micropillar Polydimethylsiloxane Accurate CRISPR Detection (IMPACT) system is developed for detection of viral DNA. Single-stranded DNA reporter probes with fluorescent dyes are immobilized within the system, taking advantage of the increased surface area from the micropillar. A CRISPR-Cas12a and crRNA complex is then injected into the system, and if double-stranded target DNA is present, the CRISPR enzyme is activated and indiscriminately cleaves reporter probes, greatly increasing the fluorescent signal. The system can then be washed and the supernatant collected and measured, revealing accurate detection of the viral DNA target down to 0.1 nM concentration with no fluorescence background

Testing systems of identical components

We consider the problem of testing sequentially the components of a multi-component reliability system in order to figure out the state of the system via costly tests. In particular, systems with identical components are considered. The notion of lexicographically large binary decision trees is introduced and a heuristic algorithm based on that notion is proposed. The performance of the heuristic algorithm is demonstrated by computational results, for various classes of functions. In particular, in all 200 random cases where the underlying function is a threshold function, the proposed heuristic produces optimal solutions

Index to 1981 NASA Tech Briefs, volume 6, numbers 1-4

Short announcements of new technology derived from the R&D activities of NASA are presented. These briefs emphasize information considered likely to be transferrable across industrial, regional, or disciplinary lines and are issued to encourage commercial application. This index for 1981 Tech Briefs contains abstracts and four indexes: subject, personal author, originating center, and Tech Brief Number. The following areas are covered: electronic components and circuits, electronic systems, physical sciences, materials, life sciences, mechanics, machinery, fabrication technology, and mathematics and information sciences

A BCB Diaphragm Based Adhesive Wafer Bonded CMUT Probe for Biomedical Application

This dissertation presents the design methodology, fabrication procedure, and key experimental characterization results of a linear array of capacitive micromachined ultrasonic transducers (CMUT) for possible ophthalmic anterior segment imaging application. The design methodology involves analytical, 3-D electromechanical finite element analysis, and Verasonics Vantage 128 ultrasonic research platform based diagnostic imaging simulations to develop a technique that minimizes electrical charging and center frequency drift while improving the transduction efficiency. In the design, Bisbenzocyclobutene (BCB), a low K polymer from Dow Chemical Company, has been innovatively used for the first time to fabricate the structural layer of the CMUT diaphragm, realize the interelectrode dielectric spacer, and to act as a low temperature adhesive bonding agent. Additionally, the top CMUT electrode has been placed at the bottom of the diaphragm to affect higher capacitance change that increases sensitivity and provides additional decoupling of the electrical charging effects. Several arrays with element count ranging from 8 to 128 elements and a center frequency range of 5 MHz to 40 MHz have been designed and fabricated. Due to an unforeseen adhesion issue during wirebonding, a 32 channel 40 MHz CMUT array has been packaged manually to validate the fabrication process and CMUT operation. Extensive SEM inspections of the CMUT cross-sections show good agreement with the design specifications. Static and dynamic measurements using a Polytec laser Doppler vibrometer, impedance measurement using an Agilent vector network analyzer, and LCR measurement results are in excellent agreement with analytical and FEA analysis using IntelliSuite. The frequency analysis exhibits high electromechanical coupling coefficient of 0.66 at a low bias voltage of 20 V and high uniformity. A successful measurement of the lower drift of the center frequency 0.32% and higher coupling coefficient verifies the hypothesis that the excellent electrical, structural, and processing characteristics of BCB is a viable option to mitigate the dielectric charging and improve the transduction efficiency of CMUTs

Chronic neural probe for simultaneous recording of single-unit, multi-unit, and local field potential activity from multiple brain sites

Drug resistant focal epilepsy can be treated by resecting the epileptic focus requiring a precise focus localization using stereoelectroencephalography (SEEG) probes. As commercial SEEG probes offer only a limited spatial resolution, probes of higher channel count and design freedom enabling the incorporation of macro and microelectrodes would help increasing spatial resolution and thus open new perspectives for investigating mechanisms underlying focal epilepsy and its treatment. This work describes a new fabrication process for SEEG probes with materials and dimensions similar to clinical probes enabling recording single neuron activity at high spatial resolution. Polyimide is used as a biocompatible flexible substrate into which platinum electrodes and leads are... The resulting probe features match those of clinically approved devices. Tests in saline solution confirmed the probe stability and functionality. Probes were implanted into the brain of one monkey (Macaca mulatta), trained to perform different motor tasks. Suitable configurations including up to 128 electrode sites allow the recording of task-related neuronal signals. Probes with 32 and 64 electrode sites were implanted in the posterior parietal cortex. Local field potentials and multi-unit activity were recorded as early as one hour after implantation. Stable single-unit activity was achieved for up to 26 days after implantation of a 64-channel probe. All recorded signals showed modulation during task execution. With the novel probes it is possible to record stable biologically relevant data over a time span exceeding the usual time needed for epileptic focus localization in human patients. This is the first time that single units are recorded along cylindrical polyimide probes chronically implanted 22 mm deep into the brain of a monkey, which suggests the potential usefulness of this probe for human applications

The Boston University Photonics Center annual report 2015-2016

This repository item contains an annual report that summarizes activities of the Boston University Photonics Center in the 2015-2016 academic year. The report provides quantitative and descriptive information regarding photonics programs in education, interdisciplinary research, business innovation, and technology development. The Boston University Photonics Center (BUPC) is an interdisciplinary hub for education, research, scholarship, innovation, and technology development associated with practical uses of light.This has been a good year for the Photonics Center. In the following pages, you will see that this year the Center’s faculty received prodigious honors and awards, generated more than 100 notable scholarly publications in the leading journals in our field, and attracted $18.9M in new research grants/contracts. Faculty and staff also expanded their efforts in education and training, and cooperated in supporting National Science Foundation sponsored Sites for Research Experiences for Undergraduates and for Research Experiences for Teachers. As a community, we emphasized the theme of “Frontiers in Plasmonics as Enabling Science in Photonics and Beyond” at our annual symposium, hosted by Bjoern Reinhard. We continued to support the National Photonics Initiative, and contributed as a cooperating site in the American Institute for Manufacturing Integrated Photonics (AIM Photonics) which began this year as a new photonics-themed node in the National Network of Manufacturing Institutes. Highlights of our research achievements for the year include an ambitious new DoD-sponsored grant for Development of Less Toxic Treatment Strategies for Metastatic and Drug Resistant Breast Cancer Using Noninvasive Optical Monitoring led by Professor Darren Roblyer, continued support of our NIH-sponsored, Center for Innovation in Point of Care Technologies for the Future of Cancer Care led by Professor Cathy Klapperich, and an exciting confluence of new grant awards in the area of Neurophotonics led by Professors Christopher Gabel, Timothy Gardner, Xue Han, Jerome Mertz, Siddharth Ramachandran, Jason Ritt, and John White. Neurophotonics is fast becoming a leading area of strength of the Photonics Center. The Industry/University Collaborative Research Center, which has become the centerpiece of our translational biophotonics program, continues to focus onadvancing the health care and medical device industries, and has entered its sixth year of operation with a strong record of achievement and with the support of an enthusiastic industrial membership base

Performance of a Diaphragmed Microlens for a Packaged Microspectrometer

This paper describes the design, fabrication, packaging and testing of a microlens integrated in a multi-layered MEMS microspectrometer. The microlens was fabricated using modified PDMS molding to form a suspended lens diaphragm. Gaussian beam propagation model was used to measure the focal length and quantify M2 value of the microlens. A tunable calibration source was set up to measure the response of the packaged device. Dual wavelength separation by the packaged device was demonstrated by CCD imaging and beam profiling of the spectroscopic output. We demonstrated specific techniques to measure critical parameters of microoptics systems for future optimization of spectroscopic devices