The comet assay is a technique used to assess the DNA damage in individual cells. The extent of the damage is indicated by the ratio between the amount of DNA in the tail of the comet and the amount in the head. This assessment is typically made by the operator manually analyzing the images. This process is inefficient and time consuming. Researchers in the past have used machine learning techniques to automate this process but it required manual feature extraction. In some cases, deep learning was applied but only for damage classification. We have successfully applied Convolutional Neural Networks(CNN) to achieve automated quantification of DNA damage from comet images. Typically deep learning techniques such as CNN require large amounts of labelled training data, which may not always be available. We demonstrate that by applying deep transfer learning, state of the art results can be obtained in the detection of DNA damage, even with a limited number of comet images.
We report on highly sensitive and flexible biosensors for noninvasive lactate and alcohol monitoring in human perspiration based on zinc oxide (ZnO) nanostructures that does not require linker layer for surface functionalization due to the high isoelectric point of ZnO. Towards fabrication of the biosensors, two-dimensional (2D) ZnO nanoflakes (NFs) were synthesized on flexible polyethylene terephthalate (PET) substrates employing single step sonochemical method after which lactate oxidase (LOx) and anti-body for ethyl glucuronide (EtG)-a metabolite of ethanol were immobilized atop without a linker layer. The cyclic voltammetry (CV) measurements in the concentration range of 10pM-10μM for lactate and 4.5 μM-0.45 M for EtG yielded minimum limit of detection of 10 pM and 4.5 μM, respectively for the electrode area of 0.5 × 0.5 cm2. Moreover, lactate sensor with ZnO NF electrodes demonstrated four times higher sensitivity compared to the ones with gold electrode that required DTSP linker layer for surface functionalization. High isoelectric point allows a direct, stable pathway for rapid electron transport without any mediator when an analyte is immobilized on NFs and improves electron transfer rate.
Extracellular vesicles (EVs) have been gaining increasing attention given their role in communicating information between cells. Composition-based isolation of EVs is particularly of high significance as the proteomic and lipidomic characterization of their cargo could provide valuable clues to the role of EVs in mediating the biology of various conditions. This has, however, proved to be challenging as EVs, despite their abundance, are very small and difficult to be differentiated from the other constituents of host media. In addition, currently available methods like ultracentrifugation and filtration are cumbersome and capable of achieving mostly size-based separations. In this work, we demonstrate the possibility of separating submicron EV-like vesicles from cancer cells using a thermally-assisted acoustophoretic device. In a system composed of MCF-7 breast cancer cells spiked with two different types of same-size vesicles, composition-based isolation of vesicles was shown to be realizable through opposite focusing of the system’s components at the node and antinodes of the overlaid ultrasonic standing wave. By proper choice of temperature in the microchannel, we were able to achieve separations with purities exceeding 93%. Furthermore, cells recovered from the channel were shown to be viable after the separation.
In this paper, we report on fabrication of a label free, highly sensitive and selective electrochemical cortisol
immunosensors using one dimensional (1D) ZnO nanorods (ZnO-NRs) and two dimensional nanoflakes (ZnO-NFs)
as immobilizing matrix. The synthesized ZnO nanostructures (NSs) were characterized using scanning electron
microscopy (SEM), selective area diffraction (SAED) and photoluminescence spectra (PL) which showed that both
ZnO-NRs and ZnO-NFs are single crystalline and oriented in  direction. Anti-cortisol antibody (Anti-Cab) are
used as primary capture antibodies to detect cortisol using electrochemical impedance spectroscopy (EIS). The
charge transfer resistance increases linearly with increase in cortisol concentration and exhibits a sensitivity of 3.078
KΩ. M-1 for ZnO-NRs and 540 Ω. M -1 for ZnO-NFs. The developed ZnO-NSs based immunosensor is capable of
detecting cortisol at 1 pM. The observed sensing parameters are in physiological range. The developed sensors can
be integrated with microfluidic system and miniaturized potentiostat to detect cortisol at point-of-care.
In a previous paper we had described a novel concept on ultra-small, ultra-compact, unattended multi-phenomenological sensor systems for rapid deployment, with integrated classification-and-decision-information extraction capability from the sensed environment. Specifically, we had proposed placing such integrated capability on a 3-D Heterogeneous System on a Chip (HSoC). This paper amplifies two key aspects of that future sensor technology. These are the creation of inter-layer vias by high aspect ratio MPS (Macro Porous Silicon) process, and the adaptation of the TESH (Tori connected mESHes) network to bind the diverse leaf nodes on multiple layers of the 3-D structure. Interesting also is the inter-relationship between these two aspects. In particular, the issue of overcoming via failures, catastrophic as well as high-resistance failures, through the existence of alternative paths in the TESH network and corresponding routing strategies is discussed. A probabilistic model for via failures is proposed and the testing of the vias between the sensor layer and the adjacent processing layer is discussed.
Miniaturization of laboratory sensors has been enabled by continued evolution of technology. Field portable systems are often desired, because they reduce sample handling, provide rapid feedback capability, and enhance convenience. Fieldable sensor systems should include a method for initiating the analysis, storing and displaying the results, while consuming minimal power and being compact and portable. Low cost will allow widespread usage of these systems. In
this paper, we discuss a reconfigurable Personal Data Assistant (PDA) based control and data collection system for use with miniature sensors. The system is based on the Handspring visor PDA and a custom designed motherboard, which connects directly to the PDA microprocessor. The PDA provides a convenient and low cost graphical user interface, moderate processing capability, and integrated battery power. The low power motherboard provides the voltage levels, data collection, and input/output (I/O) capabilities required by many MEMS and miniature sensors. These capabilities
are relayed to connectors, where an application specific daughterboard is attached. In this paper, two applications are
demonstrated. First, a handheld nucleic acid sequence-based amplification (NASBA) detection sensor consisting of a heated and optical fluorescence detection system is discussed. Second, an electrostatically actuated MEMS micro mirror controller is realized.
This paper describes a new concept for ultra-small, ultra-compact, unattended multi-phenomenological sensor systems for rapid deployment, with integrated classification-and-decision-information extraction capability from a sensed environment. We discuss a unique approach, namely a 3-D Heterogeneous System on a Chip (HSoC) in order to achieve a minimum 10X reduction in weight, volume, and power and a 10X or greater increase in capability and reliability -- over the alternative planar approaches. These gains will accrue from (a) the avoidance of long on-chip interconnects and chip-to-chip bonding wires, and (b) the cohabitation of sensors, preprocessing analog circuitry, digital logic and signal processing, and RF devices in the same compact volume. A specific scenario is discussed in detail wherein a set of four types of sensors, namely an array of acoustic and seismic sensors, an active pixel sensor array, and an uncooled IR imaging array are placed on a common sensor plane. The other planes include an analog plane consisting of transductors and A/D converters. The digital processing planes provide the necessary processing and intelligence capability. The remaining planes provide for wireless communications/networking capability. When appropriate, this processing and decision-making will be accomplished on a collaborative basis among the distributed sensor nodes through a wireless network.
This paper describes development of the modular microfluidic components and their integration, directed toward the development of an electrochemical immunoassay-based bio-chemical detection system. The entire system consists of an array of fluid reservoirs, microfluidic valves & pump, a sampling/reaction chamber with integrated electromagnetic filterless bio-separator and a detection chamber comprising of the filterless bio-separator and an immunosensor. The magnetic beads are used to capture and detect the target toxins/molecules. This paper discusses the performance of the fluidic components and presents the preliminary results and packaging aspects of the 1st generation fluidic system. The effect of component size on system performance is also discussed.
This work investigates a radical new approach for plasma display production that is potentially easier to produce and results in plasma displays that are of significantly higher resolution. Most of the current modern plasma displays operate on essentially the same principle as a cathode ray tube. Using this technique, plasma displays are capable of resolutions of 1024 by 1024 pixels on a 42-inch display . This is equivalent to 215 pixels per square cm. In this paper we propose a new application of the Coherent Porous Silicon enabled fabrication technique that can be used to develop a display that contains 250,000 discharge lamps per square centimeter. This is over three orders of magnitude better density than the current displays. The core CPS technology at the heart of this application can be used to produce substrates with over 1,000,000 pores per square centimeter, allowing development of even higher density displays. The paper discusses the fabrication technology and underlying experiments that have been successfully conducted to validate the concept and reports on the feasibility studies that have been carried out.
This paper describes our investigation of the dynamic, information rich, mOlecular structure of the ultimate smart interface — human skin - by coupling advances in biological, Microsystems, and information technology. The outer layer of human skin, the stratum comeum, is a biologically complex thin film that has unique molecular mechanisms that allow it to function simultaneously as a structural and as a perceptual interface. It is continuously "sampled" by the brain in terms of visual, tactile, and olfactory cues. It interfaces the organism with its environment and has unique micro/nano architecture from an engineering standpoint; e.g., it simultaneously retains and uses water to plasticize the membrane for flexibility. This paper focuses on the development of a sampling interface and MEMS components for a freestanding, multifunctional, multimode, microfluidics-based sensor system for real time physiological monitoring. This research will enable us to gain an insight into the functioning of the human at a fundamental level (from cellular to population) that has not been possible before.
A very simple room-temperature procedure is presented herein for formation of true three-dimensionality of microplumbing in plastic (silicone elastomer in this case), by molding the plastic to simply encapsulate a pre-formed network of sacrificial wax threads or other connected wax configurations which are ultimately to become micro channels and cavities in the plastic motherboard. When these wax sacrificial areas are etched away with acetone, precise cavities, channels, and capillaries results with direct arbitrary three- dimensionality for the first time. This method leads also to a simple and effective external interconnect scheme where ordinary fused silica tubes may be press-fitted into the surface opening to withstand high pressure. This method may be extended for connection of multiple levels of silicone motherboards together using small sections of fused silica tubing, with no loss of stacking volume because of the lack of any connector lips or bosses. An array of micro channels having circular cross sections with diameters of 100, 150 and 200 microns were molded on silicone elastomer using wax thread. The wax thread was dissolved in acetone after the silicon elastometer became components (motherboards) while being able to control the channel lengths within the stacks as desired. Mixing chambers were also molded in a single silicone elastomer layer, because true three-dimensionality is trivially possible without the complexity of multi stacked lithography.
We are currently developing a generic microfluidic system (on chip) for the detection of bio-organisms. Numerous bio/chemical compatibility issues arise in development of these chip based microfluidic systems. The resolution of bio/compatibility issues often necessitates a change in materials and, on occasion, leads to redesigning of the system itself. We have successfully decoupled the fabrication and compatibility issues that arose in the fabrication of a generic microfluidic system for chemical detection. We have successfully developed techniques for coating the offending surfaces with a TeflonTM-like amorphous fluorocarbon polymer CYTOPTM and assembling the coated components. In this paper we briefly discuss the microfluidic system being developed by us and the bio/chemical compatibility issues that need to be addressed in this system. Next we discuss the material CYTOP and its application to surfaces and devices. The bonding technique developed to bond the polymer coated structures and some of the components fabricated using this material are also discussed.
A separate-target sputtering process has been applied to fabrication of TiNi shape memory alloy (SMA) for microelectromechanical systems (MEMS). This process employs separate Ti and Ni sputtering targets and independently controllable RF power source for each target. Since RF power ratio can change the composition of the films as required, the shape memory properties can be better controlled. This process would enable efficient batch production of MEMS devices and components similarly to the LSI batch process. This process is expected to be a more appropriate method for mass production than other techniques such as machining from bulk SMA sheets or wires and deposition of SMA films from a single TiNi alloy target. The TiNi SMA films in the present study were fabricated by co-sputtering from two separate targets and vacuum-annealing for crystallization. The phase transformation behavior of the crystallized films was observed by differential scanning calorimetry (DSC) and x-ray diffractometry (XRD). DSC showed exothermic/endothermic peaks corresponding to phase transformations: martensitic transformation around at 345 K and reverse martensitic transformation around at 365 K. The transformations of crystal structure were also examined by temperature-controlled XRD analysis. The formed films were confirmed to show shape memory effect (SME) by these results.