Xuexin Duan

Quantification of the affinities and kinetics of protein interactions using silicon nanowire biosensors.

Monitoring the binding affinities and kinetics of protein interactions is important in clinical diagnostics and drug development because such information is used to identify new therapeutic candidates. Surface plasmon resonance is at present the standard method used for such analysis, but this is limited by low sensitivity and low-throughput analysis. Here, we show that silicon nanowire field-effect transistors can be used as biosensors to measure protein-ligand binding affinities and kinetics with sensitivities down to femtomolar concentrations. Based on this sensing mechanism, we develop an analytical model to calibrate the sensor response and quantify the molecular binding affinities of two representative protein-ligand binding pairs. The rate constant of the association and dissociation of the protein-ligand pair is determined by monitoring the reaction kinetics, demonstrating that silicon nanowire field-effect transistors can be readily used as high-throughput biosensors to quantify protein interactions.

Mechanical and Electrical Anisotropy of Few-Layer Black Phosphorus

We combined reflection difference microscopy, electron transport measurements, and atomic force microscopy to characterize the mechanical and electrical anisotropy of few-layer black phosphorus. We were able to identify the lattice orientations of the two-dimensional material and construct suspended structures aligned with specific crystal axes. The approach allowed us to probe the anisotropic mechanical and electrical properties along each lattice axis in separate measurements. We measured the Youngs modulus of few-layer black phosphorus to be 58.6 ± 11.7 and 27.2 ± 4.1 GPa in zigzag and armchair directions. The breaking stress scaled almost linearly with the Youngs modulus and was measured to be 4.79 ± 1.43 and 2.31 ± 0.71 GPa in the two directions. We have also observed highly anisotropic transport behavior in black phosphorus and derived the conductance anisotropy to be 63.7%. The test results agreed well with theoretical predictions. Our work provided very valuable experimental data and suggested an effective characterization means for future studies on black phosphorus and anisotropic two-dimensional nanomaterials in general.

Microcontact printing of dendrimers, proteins, and nanoparticles by porous stamps.

Porous stamps fabricated by one-step phase separation micromolding were used for microcontact printing of polar inks, in particular aqueous solutions of dendrimers, proteins, and nanoparticles. Permanent hydrophilicity was achieved without any additional treatment by tailored choice of the polymer components. Pores with several hundred nanometers to micrometers were obtained during the phase separation process. These pores can act as ink reservoirs. The porous stamps were thoroughly characterized by SEM, NMR, and contact angle measurement. The versatility of the porous stamps was shown in three printing schemes. First, positive microcontact printing was achieved by printing a polar thioether-modified dendrimer as the ink, followed by backfilling and wet etching. Second, the porous stamps were used for multiple printing of fluorescent proteins without reinking. Third, nanoparticles of about 60 nm in diameter, which cannot be directly transferred by oxidized PDMS stamps, were successfully printed onto substrates by using these porous stamps.

Highly specific and sensitive non-enzymatic determination of uric acid in serum and urine by extended gate field effect transistor sensors

A potentiometric non-enzymatic sensor using off-chip extended-gate field effect transistor (EGFET) with a ferrocenyl-alkanethiol modified gold electrode is demonstrated for determining the uric acid concentration in human serum and urine. Hexacyanoferrate (II) and (III) ions are used as redox reagent. This potentiometric sensor measures the interface potential on the ferrocene immobilized gold electrode, which is modulated by the redox reaction between uric acid and hexacyanoferrate ions. The device shows a near Nernstian response to uric acid and is highly specific. The interference that comes from glucose, bilirubin, ascorbic acid and hemoglobin is negligible in normal concentration range of these interferents. The sensor also exhibits excellent long term reliability. This extended gate field effect transistor based sensors can be used as a point of care UA testing tool, due to the small size, low cost, and low sample volume consumption.

Detection of Volatile Organic Compounds Using Microfabricated Resonator Array Functionalized with Supramolecular Monolayers

This paper describes the detection of volatile organic compounds (VOCs) using an e-nose type integrated microfabricated sensor array, in which each resonator is coated with different supramolecular monolayers: p-tert-butyl calix[8]arene (Calix[8]arene), 2,3,7,8,12,13,17,18-octaethyl-21H,23H-porphine (Porphyrin), β-cyclodextrin (β-CD), and cucurbit[8]uril (CB[8]). Supramolecular monolayers fabricated by Langmuir-Blodgett techniques work as specific sensing interface for different VOCs recognition which increase the sensor selectivity. Microfabricated ultrahigh working frequency film bulk acoustic resonator (FBAR) transducers (4.4 GHz) enable their high sensitivity toward monolayer gas sensing which facilitate the analyses of VOCs adsorption isotherms and kinetics. Two affinity constants (K1, K2) are obtained for each VOC, which indicate the gas molecule adsorption happen inside and outside of the supramolecular cavities. Additional kinetic information on adsorption and desorption rate constants (ka, kd) are obtained as well from exponential fitting results. The five parameters, one from the conventional frequency shift signals of mass transducers and the other four from the indirect analyses of monolayer adsorption behaviors, thus enrich the sensing matrix (Δf, K1, K2, ka, kd) which can be used as multiparameter fingerprint patterns for highly selective detection and discrimination of VOCs.

Regenerative Electronic Biosensors Using Supramolecular Approaches

A supramolecular interface for Si nanowire FETs has been developed with the aim of creating regenerative electronic biosensors. The key to the approach is Si-NWs functionalized with β-cyclodextrin (β-CD), to which receptor moieties can be attached with an orthogonal supramolecular linker. Here we demonstrate full recycling using the strongest biomolecular system known, streptavidin (SAv)-biotin. The bound SAv and the linkers can be selectively removed from the surface through competitive desorption with concentrated β-CD, regenerating the sensor for repeated use. An added advantage of β-CD is the possibility of stereoselective sensors, and we demonstrate here the ability to quantify the enantiomeric composition of chiral targets.

Silicon Nanowire Field-Effect Transistors—A Versatile Class of Potentiometric Nanobiosensors

Silicon nanowire field-effect transistors (Si-NW FETs) have been demonstrated as a versatile class of potentiometric nanobiosensors for real time, label-free, and highly sensitive detection of a wide range of biomolecules. In this review, we summarize the principles of such devices and recent developments in device fabrication, fluid integration, surface functionalization, and biosensing applications. The main focus of this review is on CMOS compatible Si-NW FET nanobiosensors.

Performance limitations for nanowire/nanoribbon biosensors

Field-effect transistor-based biosensors (bioFETs) have shown great promise in the field of fast, ultra-sensitive, label-free detection of biomolecules. Reliability and accuracy, when trying to measure small concentrations, is of paramount importance for the translation of these research devices into the clinical setting. Our knowledge and experience with these sensors has reached a stage where we are able to identify three main aspects of bioFET sensing that currently limit their applications. By considering the intrinsic device noise as a limitation to the smallest measurable signal, we show how various parameters, processing steps and surface modifications, affect the limit of detection. We also introduce the signal-to-noise ratio of bioFETs as a universal performance metric, which allows us to gain better insight into the design of more sensitive devices. Another aspect that places a limit on the performance of bioFETs is screening by the electrolyte environment, which reduces the signal that could be potentially measured. Alternative functionalization and detection schemes that could enable the use of these charge-based sensors in physiological conditions are highlighted. Finally, the binding kinetics of the receptor-analyte system are considered, both in the context of extracting information about molecular interactions using the bioFET sensor platform and as a fundamental limitation to the number of molecules that bind to the sensor surface at steady-state conditions and to the signal that is generated. Some strategies to overcome these limitations are also proposed. Taken together, these performance-limiting issues, if solved, would bring bioFET sensors closer to clinical applications.

Limit of detection of field effect transistor biosensors: Effects of surface modification and size dependence

Field-effect transistor biosensors have shown great promise in the detection of biomolecules. However, a quantitative understanding of what limits the smallest measurable concentration of analyte (limit of detection or LOD) is still missing. By considering the signal-to-noise ratio (SNR), extracted from a combination of noise and I-V characterization, we are able to accurately predict and experimentally confirm a LOD of 0.01 pH. Our results also show that devices with larger area and with amine functionalized surfaces have larger SNR. We are able to extract the associated oxide trap densities and, thus, quantify the improvements in LOD.

Chemically Directed Immobilization of Nanoparticles onto Gold Substrates for Orthogonal Assembly Using Dithiocarbamate Bond Formation

Dithiocarbamate-mediated bond formation combined with soft lithography was used for the selective immobilization of amine-functionalized silica nanoparticles on gold substrates. The available amine groups on the upper surface of the immobilized silica nanoparticles were further utilized for postdeposition of additional materials including particles, dyes, and biomolecules. The robustness of dithiocarbamate-mediated immobilization enables orthogonal assembly on surfaces via selective removal of the masking thiol ligands using iodine vapor etching followed by further functionalization.