Bulletin of the American Physical Society
APS March Meeting 2018
Volume 63, Number 1
Monday–Friday, March 5–9, 2018; Los Angeles, California
Session H01: Biosensing Techniques with Advanced Materials |
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Sponsoring Units: FIAP Chair: N. Aluru, University of Illinois at Urbana–Champaign Room: LACC 150A |
Tuesday, March 6, 2018 2:30PM - 2:42PM |
H01.00001: Protein Identification Using a Single-Layer MoS2 Nanopore: Towards Machine Learning-Based Predictive Models Mohammad Heiranian, Amir Barati Farimani, N. Aluru Protein identification can enable breakthrough advances in early diagnosis of diseases and the health status of the humans. Nanopore sequencing can be used as a label-free, single base and fast reading platform to identify amino acids of a protein. The current challenge with the nanopore technology is the noise in ionic current measurements. Here, we show that with a nanopore drilled in a single-layer molybdenum disulfide (MoS2), we can detect each single amino acid in a polypeptide chain with high distinguishability. Using extensive molecular dynamics (MD) simulations (with a total aggregate simulation time of 65 µs) and machine learning (ML) techniques, we characterize and cluster the ionic current and residence time of the 20 human amino acids. Using the split test training, logistic regression and nearest neighbor classifiers, the sensor read is predicted with an accuracy of up to 99.6%. In addition, using ML classification techniques, over 2.5 million hypothetical sensor reads’ amino acid types are predicted. |
Tuesday, March 6, 2018 2:42PM - 2:54PM |
H01.00002: A Two-pore Device to Reduce DNA Speed through a Nanopore Xu Liu, Brett Gyarfas, Roland Nagel, William Dunbar Researchers use nanopore devices to study polymers such as double-stranded DNA (dsDNA). Typically, a 48 kb λ dsDNA takes a few milliseconds to translocate a single solid-state nanopore. Reducing the speed of dsDNA through a nanopore could permit detecting features that are not otherwise observable. Currently, methods that appreciably reduce the dsDNA speed (e.g., at least 100X) require immobilization to a laser-controlled bead that uses complex instrumentation. We demonstrate a two-pore device and control logic that grabs the DNA at different regions simultaneously and pulls it in opposite directions. The voltages across the two individual pores are tuned to reduce the DNA speed. We show the total translocation time is maximized as the two pores pull the DNA at balanced force. We also illustrated the DNA will exit either pore depending on the difference forces of the two pores. In addition, the two-pore device detects mono-streptavidin “speed bumps” in the signal that decorate the DNA at site specific locations. By contrast, single nanopore events produced by the same molecules do not display such features. Electrical signals and optical image videos are used to demonstrate the control logic functions and speed reduction performance. |
(Author Not Attending)
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H01.00003: Scalable Flexible Patterned Graphene Gate TMD Biosensors Ram Surya Gona, Carl Naylor, Alan Johnson Two-dimensional transition metal dichalcogenides, such as MoS2 and WS2, have been shown to be promising materials for use in bio-sensing due to favorable electrical and mechanical properties. I will present our work on the fabrication of scalable flexible MoS2 field effect transistor with patterned graphene back-gate. Flexible devices were fabricated on a Kapton substrate and incorporating graphene as the back-gate material due to its biocompatibility and its favorable physical properties. Monolayer MoS2 single-crystal flakes were grown over a large area by chemical vapor deposition and then transferred onto a pre-patterned electrode array, resulting in a device yield > 70%, an average mobility of 10 cm2V-1s-1 and very low hysteresis. Flexibility tests confirm the flexible nature of the device when bent several hundred times. To create nano-biosensors, the surface of the MoS2 was functionalized via a re-engineered mu-opioid receptor and the devices were tested against opioid solutions of various concentrations. This work provides a pathway for the integration of MoS2 and other TMDs onto flexible/wearable/implantable devices used for trace detection of opioids or other chemicals. |
Tuesday, March 6, 2018 3:06PM - 3:18PM |
H01.00004: Attaining Attomolar Detection and Long Target Capture of Single Strand DNA with Graphene Biosensors Ramya Vishnubhotla, Jinglei Ping, Olivia Dickens, Adithya Sriram, Srinivas Mandyam, Alan Johnson Nucleic acids often behave as biomarkers for various ailments, such as cancer, where a particular strand will upregulate as an indication of the presence of the disease. The need to develop a process for detection of nucleic acids in low concentrations is pressing for the purpose of early cancer screening. Furthermore, detecting a long nucleic acid with a short nucleic acid probe also serves as a step towards early cancer diagnostics, as nucleic acids in human plasma are thousands of nucleotides in length. Here, we describe the approach for fabricating scalable graphene field effect transistors (GFETs) for detection of ssDNA down to attomolar concentrations in addition to detecting a long target with a shorter probe. Graphene was grown via chemical vapor deposition in-lab and transferred through an electrolysis bubbling technique with Raman spectroscopy to determine the quality of the graphene and atomic force microscopy to verify the presence of linker and probe molecule attachment. Data was collected via an all-electronic readout method by characterizing the shift in the Dirac voltage of the GFETs, which exhibits Hill-Langmuir behavior for varying concentrations of the target. Our results show potential for eventual early disease diagnostics in complex fluids. |
Tuesday, March 6, 2018 3:18PM - 3:30PM |
H01.00005: Exploring the Relationship Between Alpha-synuclein Concentration and Parkinson's Disease Progression with Graphene Aptasensors Olivia Dickens, Adithya Sriram, Ramya Vishnubhotla, Samantha Decker, Kelvin Luk, Alan Johnson Parkinson’s disease is a neurodegenerative disorder with no standard method of diagnosis. Studies have shown that the concentration of α-synuclein (α-syn) in the cerebral spinal fluid (CSF) is lower in Parkinson’s patients than in healthy patients, making this protein a viable biomarker for disease progression. Aptamers, or nucleic acid oligomers selected to bind a specific molecular target, can be used in conjunction with graphene field effect transistor (GFET) arrays to create biosensors capable of detecting a variety of targets. Here, we have utilized aptamer-functionalized GFET sensor arrays to detect the presence of α-syn. We show that our functionalized GFET arrays have a α-syn detection limit of 1 nM in deionized water. GFET arrays were fabricated using traditional photolithography with graphene grown via chemical vapor deposition. Functionalization of the GFET array was characterized structurally using atomic force microscopy and electronically through measurements of the current- gate voltage characteristics. In the future, we will move towards detecting α-synuclein in more complex solutions, leading to the detection of α-syn in cerebral spinal fluid samples from patients with varying levels of Parkinson’s progression. |
Tuesday, March 6, 2018 3:30PM - 3:42PM |
H01.00006: Highly Sensitive and Wearable In2O3 Nanoribbon Transistor Biosensors with Integrated On-chip Side Gate for Glucose Monitoring in Body Fluids Qingzhou Liu, Chongwu Zhou Nanoribbon and nanowire based field-effect transistor (FET) biosensors have stimulated a lot of interests. However, most of FET biosensors were achieved by using bulky Ag/AgCl electrodes or metal wire gate, which have prevented the biosensors from becoming truly wearable. Here, we demonstrate highly sensitive and conformal In2O3 nanoribbon FET biosensors with fully integrated on-chip gold side gate, which have been laminated onto various surfaces, such as artificial arms and watches, and have enabled glucose detection in various body fluids, such as sweat and saliva. The shadow-mask fabricated devices show good electrical performance with gate voltage applied using gold side gate electrode and through aqueous electrolyte. The resulted transistors show mobilities ~ 22 cm2V-1s-1 in 0.1 x phosphate-buffered saline, high on-off ratio (105), and good mechanical robustness. With the electrodes functionalized with glucose oxidase, chitosan, and single-walled carbon nanotubes, the glucose sensors show very wide detection range spanning at least 5 orders of magnitude and detection limit down to 10 nM. Therefore, our high-performance In2O3 nanoribbon sensing platform has great potential to work as indispensable components for wearable healthcare electronics. |
Tuesday, March 6, 2018 3:42PM - 3:54PM |
H01.00007: Applicability Comparison of 800 nm and 980 nm Excitable Upconversion Nanoparticles to Single Biological Molecule Study Kory Green, YING ZHOU, Shuang Fang Lim For many years upconversion nanoparticles based on rare earth doping of inorganic crystal matrices have been proposed as a useful instrument for single molecule biological experimentation. Recently the nanoscale temperature sensing capabilities of Erbium sensitized upconversion nanoparticles has come into strong focus indicating yet another advantage over conventional fluorescent dyes for single molecule study. However, the fluences necessary for two photon upconversion must be compatible with the biological molecules of study in aqueous environments. This has led to many investigations of the ability of Neodymium doping to improve the efficiency of upconversion nanoparticles at 800 nm excitation thus improving their compatibility to biological experimentation. In this work, a comparison of the photophysics and nanothermal sensing ability of 800 nm and 980 nm excitation in Erbium activated upconversion nanoparticles is presented. Further, Ytterbium only sensitization is contrasted with dual sensitization with Ytterbium and a Neodymium doped shell. In addition, the compatibility of DNA molecules in tightrope scenarios with fluences necessary for efficient upconversion is examined. |
Tuesday, March 6, 2018 3:54PM - 4:06PM |
H01.00008: High-Throughput Block Optical DNA Sequence Identification Lee Korshoj, D. M. Sagar, Katrina Hanson, Partha Chowdhury, Peter Otoupal, Anushree Chatterjee, Prashant Nagpal The goal of developing a label-free optical DNA sequencing technique will require nanoscale focusing of light to single molecules and high-throughput, multiplexed analysis. We use surface-enhanced Raman spectroscopy to demonstrate label-free identification of DNA nucleobases from multiplexed three-dimensional plasmonic nanofocusing and characterization of molecular vibrations within the fingerprinting region of ~400-1400 cm-1. While nanometer-scale mode volumes prevent resolution of single nucleobases, our block optical technique can identify relative A, T, G, and C content in DNA k-mers (where k ~10 nucleotides for a volume of ~100 nm3). We show that the content of k-mer blocks can be used as a unique and high-throughput method for identifying sequences, genes, and other biomarkers as an alternative to single letter sequencing. Additionally, we show that coupling two complementary vibrational spectroscopy techniques (infrared and Raman) can improve block characterization [1]. The results pave the way for a novel, high-throughput block optical sequencing (BOS) method with lossy genomic data compression using k-mer identification from multiplexed optical data acquisition. |
Tuesday, March 6, 2018 4:06PM - 4:18PM |
H01.00009: Discrimination of Umami Tastants Using Floating Electrode-Based Bioelectronic Tongue Mimicking Insect Taste System Minju Lee, Je Won Jung, Daesan Kim, Young-Joon Ahn, Seunghun Hong, Hyung Wook Kwon An umami taste represents the taste sense of amino acids such as glutamate. L-monosodium glutamate (MSG) is known to elicit the umami taste via umami receptors, and understanding its mechanism is important for basic research and practical applications. Thus, many researchers have tried to detect MSG through various sensors. However, these methods can be only employed to detect glutamate-based tastants, and they have limitations to characterize a synergism that is the hallmark of umami. Herein, we developed a floating electrode-based bioelectronic tongue mimicking an insect taste system for the discrimination of umami tastants. In this strategy, nanovesicles containing honeybee umami taste receptors, gustatory receptor 10 of Apis mellifera, were immobilized on the floating electrodes of a carbon nanotube field-effect transistor. This strategy allows us to discriminate between MSG and non-umami tastants. It also allows us to detect MSG in real foods. Furthermore, we quantitatively demonstrated the synergism between MSG and disodium 5’-inosinate by utilizing bioelectronic tongues. The floating electrode-based bioelectronic tongue could provide an important insight regarding the insect taste system, and it can be a powerful platform for various applications like food screening. |
Tuesday, March 6, 2018 4:18PM - 4:30PM |
H01.00010: “Bio-switch Chip” Based on Nanostructured Conducting Polymer and Entrapped Enzyme JUNGHYUN SHIN, Daesan Kim, Haneul Yoo, Jae Yeol Park, Seunghun Hong We report a switchable biochip method where enzymes were entrapped in conducting polymer layers and the enzymatic reaction of the entrapped enzymes was controlled in real-time via electrical stimuli on the polymer layers. This structure is named here as a “bio-switch chip” (BSC). As a proof of concepts, we fabricated BSC structures using polypyrrole (Ppy) with entrapped glucose oxidase (GOx) and demonstrated the switching of glucose oxidation reaction in real-time. We found that the application of a negative bias voltage on the BSC structure resulted in the enhanced glucose oxidation reaction by more than 20 times than that without a bias voltage. Moreover, because the BSC structures could be fabricated on specific regions on solid substrates, we could control the enzymatic reaction only on the regions. Since enzymes enable very useful and versatile biochemical reactions, the ability to control the enzymatic reactions via conventional electrical signals could open up various applications in the area of biochips and other biochemical industries. |
Tuesday, March 6, 2018 4:30PM - 4:42PM |
H01.00011: Magnetically-Refreshable Receptor Platform Structures for Reusable Nano-biosensor Chips Haneul Yoo, Dong Jun Lee, Dong-guk Cho, Juhun Park, Kiwan Nam, Young tak Cho, Jae Yeol Park, Xing Chen, Seunghun Hong We developed a magnetically-refreshable receptor platform structure which can be integrated with quite versatile nano-biosensor structures to build reusable nano-biosensor chips. This structure allowed us to remove used receptor molecules easily from a biosensor surface and to reuse the biosensor for repeated sensing operations. Using this structure, we demonstrated reusable immunofluorescence biosensors. Significantly, since our method can be used to place receptor molecules very close to a nano-biosensor surface, it can be utilized to build reusable carbon nanotube transistor-based biosensors which require receptor molecules within a Debye length from the sensor surface. Furthermore, we also show that a single sensor chip can be utilized to detect two different target molecules simply by replacing receptor molecules using our method. Since this method does not rely on any chemical reaction to refresh sensor chips, it can be utilized for versatile biosensor structures and virtually-general receptor molecular species. |
Tuesday, March 6, 2018 4:42PM - 4:54PM |
H01.00012: A novel enzyme-free and In-vivo glucose detection method utilizing ferric oxide modified zinc oxide nanorods and immobilized with a nafion membrane Mohammed Marie, Omar Manasreh An enzyme-free, reproducible, and sensitive glucose sensor was fabricated using ZnO NRs modified with ferric oxide Fe2O3 and immobilized with a nafion membrane. A controllable and a cost effective hydrothermal growth method was utilized to grow well-allied and high dense ZnO NRs on a FTO/glass substrate. Due to the higher isoelectric point of ZnO NRs IEP ~ 9.4 comparing with ferric oxide, the entire electroactive area of the working electrode of the sensor was successfully and effectively modified resulting in a wide linear response of the sensor to changes in D-glucose concentrations. The fabricated sensor exhibited a linear amperometric response to changes in glucose concentrations from 1-22 mmol/L, which is within the physiological interest of glucose level for diabetic patients. Because of the high surface to volume ratio provided by the ZnO NRs, the high electrocatalyst ability of Fe2O3, and the high affinity between ZnO NRs and Fe2O3, the sensor showed a high sensitivity in the order of 0.052 µA cm-2 (mg/dL)-1, a lower detection limit as 0.027 mM, and a fast and a sharp repose time ~1 s. The sensor was proved to be reproducible with a degradation rate around 10% after one month. The enzyme-free glucose sensor can be used clinically for In-vivo glucose detection. |
Tuesday, March 6, 2018 4:54PM - 5:06PM |
H01.00013: On-chip 3D Microscopy of Optically Cleared Tissue Yibo Zhang, Yoonjung Shin, Kevin Sung, Sam Yang, Harrison Chen, Hongda Wang, Da Teng, Yair Rivenson, Rajan Kulkarni, Aydogan Ozcan Low-cost tissue clearing techniques, such as the simplified CLARITY method (SCM), can be used to eliminate the need for precise micro-sectioning of tissue samples and increase the imaging throughput by chemically rendering the tissue transparent while still maintaining the tissue microstructure. However, the mainstream imaging modality for cleared tissue involves fluorescence microscopy, which suffers from limited field of view (FOV), photobleaching and signal fading related drawbacks. Here we present a cost-effective lens-free on-chip microscope for the 3D holographic imaging of tissue samples cleared using SCM and labeled with a colorimetric dye (DAB). We optimized this system by tuning the illumination wavelength, tissue thickness, staining solution, and the number of holograms used for phase retrieval, in order to maintain a high contrast-to-noise ratio while minimizing the amount of acquired data. As a proof of concept, 200 µm-thick mouse brain tissue was successfully imaged over an FOV of 20.5 mm2, revealing the 3D distributions of the neurons, which agreed well with a 20X 0.75NA scanning bright-field microscope. The lens-free holographic imaging system also achieved an order of magnitude better data efficiency compared to its lens-based counterpart. |
Tuesday, March 6, 2018 5:06PM - 5:18PM |
H01.00014: Abstract Withdrawn
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Tuesday, March 6, 2018 5:18PM - 5:30PM |
H01.00015: UV/VIS Fluorescence and Reflectance Measurements using Delta-Doped Silicon Arrays for Medical and Bio Applications Samuel Cheng, Dana Budzyn, Shouleh Nikzad Imaging in the ultraviolet (UV), visible, and near infrared (NIR) provided a wealth of information that enabled significant progress in astrophysics, planetary studies, heliophysics, commercial applications and medical diagnostics. Although several components make up the imaging system, the detector performance contributes significantly to the overall system performance metrics. JPL-developed sensor technology originally developed for space science applications, uses 2D-doping and custom coatings offer high performance across the UV, visible, and NIR region of the spectrum. Using JPL high efficiency imaging arrays, faint fluorescence signatures could be detected with small amount of stimulation, while avoiding damage to the specimen under inspection. An emergent diagnostic tool coupled with JPL high efficiency imaging arrays to detect endogenous and induced fluorescence signatures in medical and bio applications could bring the added advantage of precise faint signature detection and quantification. We present results of phantom samples calibration images for medical and bio applications. |
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