Piyush Dak

Two-dimensional Layered MoS2 Biosensors Enable Highly Sensitive Detection of Biomolecules

We present a MoS2 biosensor to electrically detect prostate specific antigen (PSA) in a highly sensitive and label-free manner. Unlike previous MoS2-FET-based biosensors, the device configuration of our biosensors does not require a dielectric layer such as HfO2 due to the hydrophobicity of MoS2. Such an oxide-free operation improves sensitivity and simplifies sensor design. For a quantitative and selective detection of PSA antigen, anti-PSA antibody was immobilized on the sensor surface. Then, introduction of PSA antigen, into the anti-PSA immobilized sensor surface resulted in a lable-free immunoassary format. Measured off-state current of the device showed a significant decrease as the applied PSA concentration was increased. The minimum detectable concentration of PSA is 1 pg/mL, which is several orders of magnitude below the clinical cut-off level of ~4 ng/mL. In addition, we also provide a systematic theoretical analysis of the sensor platform – including the charge state of protein at the specific pH level, and self-consistent channel transport. Taken together, the experimental demonstration and the theoretical framework provide a comprehensive description of the performance potential of dielectric-free MoS2-based biosensor technology.

High‐Mobility Transistors Based on Large‐Area and Highly Crystalline CVD‐Grown MoSe2 Films on Insulating Substrates

Large-area and highly crystalline CVD-grown multilayer MoSe2 films exhibit a well-defined crystal structure (2H phase) and large grains reaching several hundred micrometers. Multilayer MoSe2 transistors exhibit high mobility up to 121 cm(2) V(-1) s(-1) and excellent mechanical stability. These results suggest that high mobility materials will be indispensable for various future applications such as high-resolution displays and human-centric soft electronics.

Ultralocalized thermal reactions in subnanoliter droplets-in-air

Miniaturized laboratory-on-chip systems promise rapid, sensitive, and multiplexed detection of biological samples for medical diagnostics, drug discovery, and high-throughput screening. Within miniaturized laboratory-on-chips, static and dynamic droplets of fluids in different immiscible media have been used as individual vessels to perform biochemical reactions and confine the products. Approaches to perform localized heating of these individual subnanoliter droplets can allow for new applications that require parallel, time-, and space-multiplex reactions on a single integrated circuit. Our method positions droplets on an array of individual silicon microwave heaters on chip to precisely control the temperature of droplets-in-air, allowing us to perform biochemical reactions, including DNA melting and detection of single base mismatches. We also demonstrate that ssDNA probe molecules can be placed on heaters in solution, dried, and then rehydrated by ssDNA target molecules in droplets for hybridization and detection. This platform enables many applications in droplets including hybridization of low copy number DNA molecules, lysing of single cells, interrogation of ligand–receptor interactions, and rapid temperature cycling for amplification of DNA molecules.

Droplet-based Biosensing for Lab-on-a-Chip, Open Microfluidics Platforms.

Low cost, portable sensors can transform health care by bringing easily available diagnostic devices to low and middle income population, particularly in developing countries. Sample preparation, analyte handling and labeling are primary cost concerns for traditional lab-based diagnostic systems. Lab-on-a-chip (LoC) platforms based on droplet-based microfluidics promise to integrate and automate these complex and expensive laboratory procedures onto a single chip; the cost will be further reduced if label-free biosensors could be integrated onto the LoC platforms. Here, we review some recent developments of label-free, droplet-based biosensors, compatible with “open” digital microfluidic systems. These low-cost droplet-based biosensors overcome some of the fundamental limitations of the classical sensors, enabling timely diagnosis. We identify the key challenges that must be addressed to make these sensors commercially viable and summarize a number of promising research directions.

Extended-gate biosensors achieve fluid stability with no loss in charge sensitivity

The detection of toxic chemicals/biomolecules is of paramount importance for medical applications, environmental monitoring, food and pharmaceutical industries. Among the sensors available, FET based chemical/biosensors promise highly-sensitive, label-free detection for point-of-care applications. Further, compatibility with CMOS technology reduces costs and allows functional integration. Unfortunately, very poor reliability/stability of these sensors in the fluidic environment has been a key roadblock to the commercialization of technology. Fig. 1(a) shows the schematic of a conventional ISFET [1]: The gate oxide of the transistor is directly exposed to the ionic solution. Ions from the solution can penetrate into the gate oxide, causing voltage-dependent hysteresis [2] in the measured IV characteristics. Since, the sensing mechanism relies on the induced change in conductance/threshold voltage; this hysteresis can lead to false positives. Extended-gate FETs (Figs. 1(b) and 1(c)) promise to improve reliability by isolating the sensor (Asensor) from the transducer (Aox), connecting the two by an interconnect (Aint) [3][4]. The theory of pH-sensitivity (AISFET) for a classical ISFET is known from 1970s, however, a theoretical understanding of how the decoupling of sensor-transducer changes the sensitivity of an EGFET (SEGFET) remains unknown. In this paper, we use detailed numerical simulations, compact modeling, and experimental results to conclude that regardless of the interconnect penalty, SEGFET → AISFET with Asensor ≫ Aox.

Electronic desalting for controlling the ionic environment in droplet-based biosensing platforms

The ability to control the ionic environment in saline waters and aqueous electrolytes is useful for desalination as well as electronic biosensing. We demonstrate a method of electronic desalting at micro-scale through on-chip micro electrodes. We show that, while desalting is limited in bulk solutions with unlimited availability of salts, significant desalting of ≥1 mM solutions can be achieved in sub-nanoliter volume droplets with diameters of ∼250 μm. Within these droplets, by using platinum-black microelectrodes and electrochemical surface treatments, we can enhance the electrode surface area to achieve >99% and 41% salt removal in 1 mM and 10 mM salt concentrations, respectively. Through self-consistent simulations and experimental measurements, we demonstrate that conventional double-layer theory over-predicts the desalting capacity and, hence, cannot be used to model systems that are mass limited or undergoing significant salt removal from the bulk. Our results will provide a better understanding of capacitive desalination, as well as a method for salt manipulation in high-throughput droplet-based microfluidic sensing platforms.

Numerical and Analytical Modeling to Determine Performance Tradeoffs in Hydrogel-Based pH Sensors

Hydrogel-based pH sensors are promising candidates for implantable sensors due to their low cost and biocompatibility. Despite their commercial potential and numerous theoretical/experimental reports, the tradeoffs between different performance parameters are not well understood and explicitly stated. In this work, we develop a numerical and analytical framework to show that there is a fundamental tradeoff between the performance parameters, i.e., sensitivity/ dynamic range versus response-time/response-asymmetry in hydrogel sensors under constrained swelling conditions. Specifically, we consider the effect of the gel parameters, such as the ionizable group density (Nf) and its dissociation constant (Ka), on the sensor performance. We show that improvement in sensitivity/dynamic range leads to degradation in response time/symmetry and, therefore, a compromise must be made to optimize device performance.

Transistors: High‐Mobility Transistors Based on Large‐Area and Highly Crystalline CVD‐Grown MoSe2 Films on Insulating Substrates (Adv. Mater. 12/2016)

On page 2316, M. A. Alam, S. K. Kim, and co-workers describe a 2D layered semiconductor used to fabricate a mechanically flexible, high-mobility thin-film transistor based on large-area and highly crystalline MoSe2 films grown by chemical vapor deposition (CVD). It is thought that such high-mobility materials will be indispensable for various future applications, such as high-resolution displays and human-centric soft electronics.

Predictive model for hydrogel based wireless implantable bio-chemical sensors

The model suggests improvement in sensitivity of the hydrogel based glucose and pH sensors by fine tuning of several critical process and environmental parameters. This should lead to development of more sensitive non-enzymatic biocompatible sensors for continuous monitoring of vital health parameters.

Electrostatic desalting of micro-droplets to enable novel chemical/biosensing applications

Motivation/Background: Salt-based electrolyte plays a fundamentally important role in many chemical/biochemical processes. For example, sodium is found in extracellular fluid and controls the blood pressure. Similarly, magnesium is required for optimization of polymerase-chain reaction (PCR) which is important for genome sequencing. Further, ions have recently also found broad applications in flexible and transparent electronics. Indeed, precise control of electrolyte concentration at micro-scale is essential for many lab-on-chip technologies. In this paper, we provide a novel scheme to electrostatically control the spatial distribution of ions within a miniaturized droplet. Specifically, an applied bias helps accumulate ions near the electrode-surface, thereby depleting the bulk salt concentration of a small droplet. We demonstrate that the bulk desalting of droplet may potentially enable a broad range of novel applications, namely: improvement of detection limit of biosensor necessary for early-disease detection, modulation of pH profile for isoelectric protein separation, electrostatic denaturation of DNA for sensor reusability by modification of its melting temperature.