Ping Lab | Nano-Bio Interface & Application Lab


DNA Nano-Tweezers and Graphene Transistor Enable Label-Free Genotyping

Electronic DNA-biosensor with a single nucleotide resolution capability is highly desirable for personalized medicine. We used DNA-tweezers with graphene FET for SNP detection and transmitted data for analysis by wireless. Picomolar sensitivity of quantitative SNP detection was achieved by observing changes in Dirac point shift and resistance change. The use of DNA-tweezers probe with high quality graphene FET significantly improves analytical characteristics of SNP detection by enhancing the sensitivity more than 1,000-fold in comparison to published work of the same type. The electrical signal resulting from resistance changes triggered by DNA strand-displacement and related changes in the DNA geometry was recorded and transmitted remotely to personal electronics. Practical implementation of this enabling technology will provide cheaper, faster and portable point-of-care molecular health status monitoring and diagnostic devices.

The paper was accepted by Advanced Materials and highlited on Advanced Science News.

Detection of Sub-fM DNA with on-Chip Target Recycling and Self-Assembly Amplification

For sensors based on DNA-functionalized graphene field-effect transistors (GFETs), the sensitivity is limited by the binding affinity of the target oligonucleotide, in the nM range for 20 mer targets. We report a ∼20 000× improvement in sensitivity through the use of engineered hairpin probe DNA that allows for target recycling and hybridization chain reaction. This enables detection of 21 mer target DNA at sub-fM concentration and provides superior specificity against single-base mismatched oligomers. The work is based on a scalable fabrication process for biosensor arrays that is suitable for multiplexed detection. This approach overcomes the binding-affinity-dependent sensitivity of nucleic acid biosensors and offers a pathway toward multiplexed and label-free nucleic acid testing with high accuracy and selectivity.

The paper was published in Nano Letters.

All-Electronic Quantification of Neuropeptide-Receptor Interaction Using a Bias-Free Functionalized Graphene Microelectrode

Opioid neuropeptides play a significant role in pain perception, appetite regulation, sleep, memory, and learning. Advances in understanding of opioid peptide physiology are held back by the lack of methodologies for real-time quantification of affinities and kinetics of the opioid neuropeptide-receptor interaction at levels typical of endogenous secretion (~pM) in biosolutions with physiological ionic strength. To address this challenge, we developed all-electronic opioid-neuropeptide biosensors based on graphene microelectrodes functionalized with a computationally redesigned water-soluble μ-opioid receptor. We used the functionalized microelectrode in a bias-free charge measurement configuration to measure the binding kinetics and equilibrium binding properties of the engineered receptor with [D-Ala2, N-MePhe4, Gly-ol]-enkephalin and β-endorphin at pM-level in real time.

The paper was published in ACS Nano.

Growth of Bilayer Graphene with High Scalability and Crystallinity

Previously reported approaches for growth of bi-layer graphene (BLG) include flat growth substrates of Cu and Ni–Cu uniform alloys and "copper pocket" structures, which suffers from either growth of multicrystalline BLG byproduct and low scalability respectively. We used a Ni–Cu gradient alloy to graphene with both high scalability and crystallinity. The BLG layer stacking was almost exclusively Bernal or twisted with an angle of 30°, consistent with first-principles calculations.

The paper was published in ACS Nano.


Graphene-Based Sensor Rapidly Detects HIV Drug in Nanoscale Concentrations

Typical medical tests for biomarkers and drugs rely on liquid chromatography-mass spectrometry (LC-MS), an expensive, slow technique that often requires external lab analysis, making it not suitable for point-of-care use. We developed rapid (~ min), inexpenisve (< $2/test) apatsensors based on graphene field-effect transistors to detect anti-HIV drug, whic paves the way for new methods of measuring these markers with high efficency in cost and time.

The paper was published as a featured article in AIP advances, as well as highlighted by Scilight.

An Aptamer-biosensor for Azole Class Antifungal Drugs

DNA-based aptamers hold great promise to serve as the recgonizer of biosensors. We developed a methodlogy for scallable production of biosensors based on graphene-aptamer hybrids, paving the way for point-of-use theraputic drug detection.

The paper was published in mSphere.

Structural-Functional Analysis of Engineered Protein-Nanoparticle Assemblies Using Graphene Microelectrodes

Nanoparticle-driven current is measured with a graphene electrode to quantify the pore-size of the ferritin enclosing the nanoparticle. It was found that for open-pore ferritin, the size and shape of the pore is very likely to be retained when a gold nanoparticle is enclosed in the cage. This research first characterized the structure and function of protein-nanoparticle assemblies in solution and implies the potential of using graphene-based charge measurement technology to develop low-cost high-sensitivity disease diagnostic systems.

The paper was published in Chemical Science and selected as one of the two HOT articles in Chemical Science Blog. It was also highlighted by myScience, Medium, TrendinTech, Penn News, etc.

Bias-free Quantifying Human Serum pH Using Graphene Microelectrode

Intrinsic Faradaic charge follows into flexible graphene microelectrode in the absence of any bias. The characteristic current responds sensitively and rapidly to pH variation of complex biofluids. The results shed light on the polarity of the electrical double layer above graphene and pave the way for early cancer diagnosis via extracelluar pH monitoring.

The paper was published in Small.


DNA Biosensors with Record-Breaking Sensitivity

I developed a methodology for scalable production of graphene-based DNA biosensor array with record-braking sensitivity 1 fM. That is, ~60,000 DNA molecules in a 1 mL drop of solution, or, one grain of salt (1g) dissolve into 6,800,000 international standard swimming pool.

The paper was published in ACS Nano.

Scalable Production of Nanohybrid Biosensors

We developed a scallable production method for four-probe transistor arrays with a novel configuration that comprises nano-bio hybrids of DNA, monodisperse gold nanoparticles (AuNPs), and graphene.

The paper was published in ACS Applied Materials and Interfaces.

Scalable Preparation of MoTe2 Monolayers in 1T'-Phase

MoTe2 monolayers with size ~102 were prepared with chemical vapor depostion. The synthesized 1T'-phase MoTe2 monolayers demonstrate clear weak anti-localization effects that are associated with spin-orbit coupling of topological insulators.

The paper can be found in Nano Letters.

Measuring Spontaneous Faradaic Charge Transfer with Graphene Microelectrodes

Pico-Ampere-level of Fradaic current from ionic solution to graphene was measured at room temperature through a feedback capacitor. In the absence of bias, this spontaneous Faradaic current was driven at the graphene-solution interface. This technique paves the way for non-perturbative probing aquoues bio-systems.

The paper was picked by the Editors of Applied Physics Letters.

Detection of Breast Cancer Biomarker, HER3

Nanohybrid of graphene and platinum nanoparticle was used as conducting channels in field-effect transistors. Functionalized with genetically engineered antibody, the transistors demonstrated high sensibility (300 fg mL-1) for detection of HER3, the breast cancer biomarker.

The paper was picked by the Editors of Advanced Materials Interfaces.

Prior to 2016

Accurate Protein Detection with Graphene Transistors

Liquid-based applications of biomolecule-decorated field-effect transistors (FETs) range from biosensors to in vivo implants. A critical scientific challenge is to develop a quantitative understanding of the gating effect of charged biomolecules in ionic solution and how this influences the readout of the FETs. To address this issue, we fabricated protein-decorated graphene FETs and measured their electrical properties, specifically the shift in Dirac voltage, in solutions of varying ionic strength. We found excellent quantitative agreement with a model that accounts for both the graphene polarization charge and ionic screening of ions adsorbed on the graphene as well as charged amino acids associated with the immobilized protein. The technique and analysis presented here directly couple the charging status of bound biomolecules to readout of liquid-phase FETs fabricated with graphene or other two-dimensional materials.

The paper can be found in Biosensors and Bioelectronics.

Seeded Growth of MoS2 at Designed Positions

By using a seeded growth technique, semiconducting MoS2 monolayers with mobility ~10 cm2V-1s-1 were deposited at desired positions on SiO2 substrate—a needed enabling step for scalable production of devices based on discontinuous two-dimensional materials.

The paper can be found in Nature Communications.

Disorder-Induced Quadratic Magnetoresistance in Two-Dimensional Systems

Quadratic magnetoresistance is often constrained only to systems with more than one electron band. I demonstrated that for single-band two-dimensional electron systems, quadraltic magnetoresistance can be induced by disorder of the systems.

The paper was highlighted in Editor's Suggestion of Physics Review Letters and Highlights in Nanotechnology.

As-grown Nanocrystalline Impurities under Graphene

I discovered as-grown impurities with graphene synthesized on platinum via chemical vapor deposition, which are nanocrystalline graphene uncoverred by electron diffraction. I also proved that these impurites are grown UNDER a monolayer graphene.

The paper can be found in Journal of Applied Physics or downloaded here.

Counting Stacking Order of Graphene by TEM

I developed a methodlogy using the diffraction and dark-field technique of transmission electron microscopy (TEM) to measure the layer-number and stacking-order of graphene up to seven(7) layers.

The paper is one of the 20 most download papers of the month in Nano Letters.