Yibo Zhu

An aptameric graphene nanosensor for label-free detection of small-molecule biomarkers.

This paper presents an aptameric graphene nanosensor for detection of small-molecule biomarkers. To address difficulties in direct detection of small molecules associated with their low molecular weight and electrical charge, we incorporate an aptamer-based competitive affinity assay in a graphene field effect transistor (FET), and demonstrate the utility of the nanosensor with dehydroepiandrosterone sulfate (DHEA-S), a small-molecule steroid hormone, as the target analyte. In the competitive affinity assay, DHEA-S specifically binds to aptamer molecules pre-hybridized to their complementary DNA anchor molecules immobilized on the graphene surface. This results in the competitive release of the strongly charged aptamer from the DNA anchor and hence a change in electrical properties of the graphene, which can be measured to achieve the detection of DHEA-S. We present experimental data on the label-free, specific and quantitative detection of DHEA-S at clinically appropriate concentrations with an estimated detection limit of 44.7 nM, and analyze the trend observed in the experiments using molecular binding kinetics theory. These results demonstrate the potential of our nanosensor in the detection of DHEA-S and other small molecules in biomedical applications.

A solid dielectric gated graphene nanosensor in electrolyte solutions

This letter presents a graphene field effect transistor (GFET) nanosensor that, with a solid gate provided by a high-κ dielectric, allows analyte detection in liquid media at low gate voltages. The gate is embedded within the sensor and thus is isolated from a sample solution, offering a high level of integration and miniaturization and eliminating errors caused by the liquid disturbance, desirable for both in vitro and in vivo applications. We demonstrate that the GFET nanosensor can be used to measure pH changes in a range of 5.3-9.3. Based on the experimental observations and quantitative analysis, the charging of an electrical double layer capacitor is found to be the major mechanism of pH sensing.

Fully integrated graphene electronic biosensor for label-free detection of lead (II) ion based on G-quadruplex structure-switching

This work presents a fully integrated graphene field-effect transistor (GFET) biosensor for the label-free detection of lead ions (Pb2+) in aqueous-media, which first implements the G-quadruplex structure-switching biosensing principle in graphene nanoelectronics. We experimentally illustrate the biomolecular interplay that G-rich DNA single-strands with one-end confined on graphene surface can specifically interact with Pb2+ ions and switch into G-quadruplex structures. Since the structure-switching of electrically charged DNA strands can disrupt the charge distribution in the vicinity of graphene surface, the carrier equilibrium in graphene sheet might be altered, and manifested by the conductivity variation of GFET. The experimental data and theoretical analysis show that our devices are capable of the label-free and specific quantification of Pb2+ with a detection limit down to 163.7ng/L. These results first verify the signaling principle competency of G-quadruplex structure-switching in graphene electronic biosensors. Combining with the advantages of the compact device structure and convenient electrical signal, a label-free GFET biosensor for Pb2+ monitoring is enabled with promising application potential.

Real-Time Monitoring of Insulin Using a Graphene Field-Effect Transistor Aptameric Nanosensor

This paper presents an approach to the real-time, label-free, specific, and sensitive monitoring of insulin using a graphene aptameric nanosensor. The nanosensor is configured as a field-effect transistor, whose graphene-based conducting channel is functionalized with a guanine-rich IGA3 aptamer. The negatively charged aptamer folds into a compact and stable antiparallel or parallel G-quadruplex conformation upon binding with insulin, resulting in a change in the carrier density, and hence the electrical conductance, of the graphene. The change in the electrical conductance is then measured to enable the real-time monitoring of insulin levels. Testing has shown that the nanosensor offers an estimated limit of detection down to 35 pM and is functional in Krebs-Ringer bicarbonate buffer, a standard pancreatic islet perfusion medium. These results demonstrate the potential utility of this approach in label-free monitoring of insulin and in timely prediction of accurate insulin dosage in clinical diagnostics.

A solid-gated graphene fet sensor for PH measurements

This paper presents a graphene field effect transistor (GFET) nanosensor that, with a solid gate provided by a high-κ dielectric, allows analyte detection in liquid media at low gate voltages. The gate is embedded within the sensor and thus is isolated from a sample solution, offering a high level of integration and miniaturization and eliminating errors caused by the liquid disturbance, desirable for both in vitro and in vivo applications. We demonstrate that the GFET nanosensor can be used to measure pH changes in a range of 5.3-9.3. Based on the experimental observations and quantitative analysis, the charging of an electrical double layer capacitor is found to be the major mechanism of pH sensing.

Measurement of cytokine biomarkers using an aptamer-based affinity graphene nanosensor on a flexible substrate toward wearable applications

We present an approach for the label-free detection of cytokine biomarkers using an aptamer-functionalized, graphene-based field effect transistor (GFET) nanosensor on a flexible, SiO2-coated substrate of the polymer polyethylene naphthalate (PEN). The nanosensor conforms to the underlying nonplanar surface and performs GFET-based rapid transduction of the aptamer-biomarker binding, thereby potentially allowing the detection of cytokine biomarkers that are sampled reliably from human bodily fluids (e.g., sweat) in wearable sensing applications. In characterizing the suitability of the nanosensor for wearable applications, we investigate the effects of substrate bending on the equilibrium dissociation constant between the aptamer and the biomarker as well as the graphene transconductance. The utility of the nanosensor is demonstrated by the detection of tumor necrosis factor-α (TNF-α), an inflammatory cytokine biomarker. Experimental results show that the flexible nanosensor can specifically respond to changes in the TNF-α concentration within 5 minutes with a limit of detection as low as 26 pM in a repeatable manner.

Optical conductivity-based ultrasensitive mid-infrared biosensing on a hybrid metasurface

Optical devices are highly attractive for biosensing as they can not only enable quantitative measurements of analytes but also provide information on molecular structures. Unfortunately, typical refractive index-based optical sensors do not have sufficient sensitivity to probe the binding of low-molecular-weight analytes. Non-optical devices such as field-effect transistors can be more sensitive but do not offer some of the significant features of optical devices, particularly molecular fingerprinting. We present optical conductivity-based mid-infrared (mid-IR) biosensors that allow for sensitive and quantitative measurements of low-molecular-weight analytes as well as the enhancement of spectral fingerprints. The sensors employ a hybrid metasurface consisting of monolayer graphene and metallic nano-antennas and combine individual advantages of plasmonic, electronic and spectroscopic approaches. First, the hybrid metasurface sensors can optically detect target molecule-induced carrier doping to graphene, allowing highly sensitive detection of low-molecular-weight analytes despite their small sizes. Second, the resonance shifts caused by changes in graphene optical conductivity is a well-defined function of graphene carrier density, thereby allowing for quantification of the binding of molecules. Third, the sensor performance is highly stable and consistent thanks to its insensitivity to graphene carrier mobility degradation. Finally, the sensors can also act as substrates for surface-enhanced infrared spectroscopy. We demonstrated the measurement of monolayers of sub-nanometer-sized molecules or particles and affinity binding-based quantitative detection of glucose down to 200 pM (36 pg/mL). We also demonstrated enhanced fingerprinting of minute quantities of glucose and polymer molecules.Metasurfaces: mid-infrared biosensorsA highly sensitive glucose sensor has been constructed from a functionalized graphene-metallic hybrid metasurface. Pioneered by a US-Chinese collaboration from Columbia University, University of South Carolina, Brookhaven National Laboratory and Nanjing University the device by detecting the changes in graphene optical conductivity, enables ultrasensitive detection of glucose concentrations as small as 200 pM via a small shift in its plasmonic resonant wavelength which is then measured. Importantly, the new sensing principle overcomes the detection limit defined by the molecular weight or the changes in local refractive index, which for a long time has impeded the development of more sensitive optical biosensors. The device consists of a monolayer of graphene covering an array of gold nanorods, atop a platinum-silicon dioxide-platinum sandwich that serves as an optical cavity. When the graphene is functionalized with boronic acid which serves as a glucose binding agent, the device’s wavelength response was seen to clearly red shift with increasingly glucose concentration. Experiments indicate a dynamic range of measurement of over 6 orders of magnitude from 2nM to 10mM.

Selective Detection of Water Pollutants Using a Differential Aptamer-Based Graphene Biosensor

Graphene field-effect transistor (GFET) sensors are an attractive analytical tool for the detection of water pollutants. Unfortunately, this application has been hindered by the sensitivity of such sensors to nonspecific disturbances caused by variations of environmental conditions. Incorporation of differential designs is a logical choice to address this issue, but this has been difficult for GFET sensors due to the impact of fabrication processes and material properties. This paper presents a differential GFET affinity sensor for the selective detection of water pollutants in the presence of nonspecific disturbances. This differential design allows for minimization of the effects of variations of environmental conditions on the measurement accuracy. In addition, to mitigate the impact of the fabrication process and material property variations, we introduce a compensation scheme for the individual sensing units of the sensor, so that such variations are accounted for in the compensation-based differential sensing method. We test the use of this differential sensor for the selective detection of the water pollutant 17β-estradiol in buffer and tap water. Consistent detection results can be obtained with and without interferences of pH variations, and in tap water where unknown interferences are present. These results demonstrate that the differential graphene affinity sensor is capable of effectively mitigating the effects of nonspecific interferences to enable selective water pollutant detection for water quality monitoring.

Tunable mid-infrared biosensors based on graphene metasurfaces

This paper presents actively tunable mid-infrared plasmonic biosensors that allow for detection of both concentrations and fingerprints of biomolecules. Human immunoglobulin G (IgG) concentrations down to 30 pM was resolved from the plasmonic resonance shift, corroborated by the increase in the intensities of protein amide I and amide II bands. Thanks to the enhancement of the interactions between microscale infrared light and nanoscale molecules, vibrational fingerprints of protein molecules (amide I and II) were achieved at the level of monolayer protein. By employing the graphene-metallic hybrid structure, variation of the graphene optical conductivity by a bias voltage actively tuned the plasmonic resonance toward the protein vibrational resonance frequency. This further improved the enhancement factor of amide I from 13 to 20, at a rate of ∼0.07/cm−1, exceeding most of reported tunable biosensors at the mid-infrared range.

An aptameric graphene nanosensor for analyte detection in serum

We present an aptameric graphene field-effect transistor (GFET) nanosensor for sensitive and label-free detection of biomarkers in serum. The graphene nanosensor is serially functionalized with a polyethylene glycol (PEG) nanolayer and an aptamer for specific detection of a target analyte and effective rejection of background molecules in human serum. The analyte binds to the surface-immobilized aptamer, changing the carrier concentration in the graphene. The resulting changes in the conductance of the graphene is measured to determine the analyte concentration. Experimental results show that the device is capable of detecting immunoglobulin E (IgE) in serum in a clinically relevant range of 50 pM to 35 nM.