Jonghyun Go

Silicon nanowires with high-k hafnium oxide dielectrics for sensitive detection of small nucleic acid oligomers.

Nanobiosensors based on silicon nanowire field effect transistors offer advantages of low cost, label-free detection, and potential for massive parallelization. As a result, these sensors have often been suggested as an attractive option for applications in point-of-care (POC) medical diagnostics. Unfortunately, a number of performance issues, such as gate leakage and current instability due to fluid contact, have prevented widespread adoption of the technology for routine use. High-k dielectrics, such as hafnium oxide (HfO(2)), have the known ability to address these challenges by passivating the exposed surfaces against destabilizing concerns of ion transport. With these fundamental stability issues addressed, a promising target for POC diagnostics and SiNWFETs has been small oligonucleotides, more specifically, microRNA (miRNA). MicroRNAs are small RNA oligonucleotides which bind to mRNAs, causing translational repression of proteins, gene silencing, and expressions are typically altered in several forms of cancer. In this paper, we describe a process for fabricating stable HfO(2) dielectric-based silicon nanowires for biosensing applications. Here we demonstrate sensing of single-stranded DNA analogues to their microRNA cousins using miR-10b and miR-21 as templates, both known to be upregulated in breast cancer. We characterize the effect of surface functionalization on device performance using the miR-10b DNA analogue as the target sequence and different molecular weight poly-l-lysine as the functionalization layer. By optimizing the surface functionalization and fabrication protocol, we were able to achieve <100 fM detection levels of the miR-10b DNA analogue, with a theoretical limit of detection of 1 fM. Moreover, the noncomplementary DNA target strand, based on miR-21, showed very little response, indicating a highly sensitive and highly selective biosensing platform.

Coupled heterogeneous nanowire-nanoplate planar transistor sensors for giant (>10 V/pH) nernst response

We offer a comprehensive theory of pH response of a coupled ISFET sensor to show that the maximum achievable response is given by ΔV/ΔpH = 59 mV/pH × α, where 59 mV/pH is the intrinsic Nernst response and α an amplification factor that depends on the geometrical and electrical properties of the sensor and transducer nodes. While the intrinsic Nernst response of an electrolyte/site-binding interface is fundamental and immutable, we show that by using channels of different materials, areas, and bias conditions, the extrinsic sensor response can be increased dramatically beyond the Nernst limit. We validate the theory by measuring the pH response of a Si nanowire-nanoplate transistor pair that achieves >10 V/pH response and show the potential of the scheme to achieve (asymptotically) the theoretical lower limit of signal-to-noise ratio for a given configuration. We suggest the possibility of an even larger pH response based on recent trends in heterogeneous integration on the Si platform.

Statistical interpretation of “femtomolar” detection

We calculate the statistics of diffusion-limited arrival-time distribution by a Monte Carlo method to suggest a simple statistical resolution of the enduring puzzle of nanobiosensors: a persistent gap between reports of analyte detection at approximately femtomolar concentration and theory suggesting the impossibility of approximately subpicomolar detection at the corresponding incubation time. The incubation time used in the theory is actually the mean incubation time, while experimental conditions suggest that device stability limited the minimum incubation time. The difference in incubation times-both described by characteristic power laws-provides an intuitive explanation of different detection limits anticipated by theory and experiments.

Beating the Nernst limit of 59mV/pH with double-gated nano-scale field-effect transistors and its applications to ultra-sensitive DNA biosensors

Electronic sensing of biomolecules is an area of immerse interest for semiconductor industry. Here we utilize the remarkable sensitivity of double-gated field-effect transistors above the fundamental Nernst limit (59mV/pH) in pH sensing to improve the sensitivity of biomolecule detection in electrolyte screening limited conditions. Our simulation results and compact models are broadly supported by various experiments and will have important implications for the design and optimization of low cost, large throughput, semiconductor based biosensors.

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.

The future scalability of pH-based genome sequencers: A theoretical perspective

Sequencing of human genome is an essential prerequisite for personalized medicine and early prognosis of various genetic diseases. The state-of-art, high-throughput genome sequencing technologies provide improved sequencing; however, their reliance on relatively expensive optical detection schemes has prevented wide-spread adoption of the technology in routine care. In contrast, the recently announced pH-based electronic genome sequencers achieve fast sequencing at low cost because of the compatibility with the current microelectronics technology. While the progress in technology development has been rapid, the physics of the sequencing chips and the potential for future scaling (and therefore, cost reduction) remain unexplored. In this article, we develop a theoretical framework and a scaling theory to explain the principle of operation of the pH-based sequencing chips and use the framework to explore various perceived scaling limits of the technology related to signal to noise ratio, well-to-well crosst...

A novel model for (percolating) nanonet chemical sensors for microarray-based E-nose applications

Our numerical simulations for percolating multi-nanowire (NW) chemical sensors demonstrate the fundamental role of potential barriers at NW-to-NW junctions in dictating sensor response and how the sensor response changes with NW density. Based on this model, we explain the counterintuitive enhancement of detection limit at a high-density NW network sensor.

Effect of Fluid Gate on the Electrostatics of ISFET-Based pH Sensors

We demonstrate that the role of fluid gate or reference electrode in ISFET system is critical in dictating the operation mode of the ISFET and the local pH at the electrolyte-oxide interface as well.

Physics and scaling prospects of pH-based genome sequencers

Fig. 2 shows the temporal distribution of proton inside the well and the polymer layer (the diffusion coefficient of protons in electrolyte and polymer is D_free = 9.31×10^-5 and D_poly = 4×10^-8 cm²/s, respectively). The calculated voltage shift (ΔV) in MOSFET successfully explains the experiment data with two different sizes of wells and beads, as shown in Fig. 3. As we scale the microwells by a factor of k, the sensitivity remains constant: this is because the number of protons released from bead is proportional to the bead area (~k^-2) and the sensor surface area is also scaled by a factor of k^-2. Since the surface group charge on the oxide surface changes linearly with proton density while the amount excess protons is much smaller than that in the well, the voltage signal remains constant.