Fei Liu’s research while affiliated with Houston Methodist Hospital and other places

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Publications (4)


Nanoplasmonic Quantification of Tumor-derived Extracellular Vesicles in Plasma Microsamples for Diagnosis and Treatment Monitoring
  • Article

February 2017

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788 Reads

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319 Citations

Nature Biomedical Engineering

Kai Liang

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Fei Liu

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Jia Fan

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[...]

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Tumour-derived extracellular vesicles (EVs) are of increasing interest as a resource of diagnostic biomarkers. However, most EV assays require large samples and are time-consuming, low-throughput and costly, and thus impractical for clinical use. Here, we describe a rapid, ultrasensitive and inexpensive nanoplasmon-enhanced scattering (nPES) assay that directly quantifies tumour-derived EVs from as little as 1 μl of plasma. The assay uses the binding of antibody-conjugated gold nanospheres and nanorods to EVs captured by EV-specific antibodies on a sensor chip to produce a local plasmon effect that enhances tumour-derived EV detection sensitivity and specificity. We identified a pancreatic cancer EV biomarker, ephrin type-A receptor 2 (EphA2), and demonstrate that an nPES assay for EphA2-EVs distinguishes pancreatic cancer patients from pancreatitis patients and healthy subjects. EphA2-EVs were also informative in staging tumour progression and in detecting early responses to neoadjuvant therapy, with better performance than a conventional enzyme-linked immunosorbent assay. The nPES assay can be easily refined for clinical use, and readily adapted for diagnosis and monitoring of other conditions with disease-specific EV biomarkers.



Supplementary Information
  • Data
  • File available

May 2016

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11 Reads

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Demonstration of the pulse-sequence-adjustable electrochemical memory effect in a GFET during 20 s of wet ethanol treatment. (a) The H2O/O2 residues adsorbed on the graphene are readily soluble in ethanol, and because the charge traps are removed after the ethanol is dried, the IDS–VGS curve shows an n-type shift (the recovery of the initially p-doped GFET). (b) With the application of a positive gate-voltage pulse sequence, the dipole moments of the ethanol molecules, which point in the direction of the air region, are gradually enhanced and the capacitive electrostatic gating effect draws electrons from the metal contacts to move to and accumulate on the graphene surface. Combined with the effect in (a), the overall n-type shift of Vcnp is larger after ethanol (wet) recovery with positive-voltage pulses. (c) With the application of a negative gate-voltage pulse sequence, the dipole moments of the ethanol molecules are reversed, pushing electrons away from the graphene layer. Now, the capacitive gating effect leaves a large number of holes accumulated on the graphene, resulting in a very strong p-type shift of Vcnp.
Application example of sparsely sampled monitoring of wet chemical treatment. (a) Memory effect controlled by an electrical pulse (gate-voltage) sequence (for example, reset of the delay time) during ambient air exposure. (b) A short wet treatment (with ethanol or water) event can be monitored based on the modulation output at any sample point during the air exposure phase. The application potential of the device as a sparsely sampling nanomaterial monitor with a memory effect is clearly demonstrated: any data read during air exposure contains information regarding the previous wet treatment.
Principle of mixed modulation via the chemical gating of graphene. (a) The circuit diagram; the inset shows a microscopic image of a GFET and the Raman spectrum of the CVD graphene channel. (b) Mechanism of mixed AM/FM GFET modulation; gray: if Vcnp is zero, then the output consists only of a strong harmonic tone; blue: when Vcnp shifts away from 0 V, a large fundamental tone is present and the harmonic tone decreases; red: when Vcnp shifts higher, both the fundamental tone and the harmonic tone decrease, but the harmonic tone decreases more rapidly. (c) Physics-based modeling result (assuming electron-hole symmetry) for the two-dimensional modulation output (in terms of a normalized output voltage) depending on the Vcnp shift; a region is outlined in which both the fundamental and harmonic tones monotonically decrease, which can be used as the operation region for a demonstration of chemical modulation.
Realization of a mixed AM/FM modulation cycle of alternating phases of air exposure and wet treatment using a chemically gated GFET with a single-tone back-gate input carrier signal at 25 kHz. (a) Initially, when Vcnp is approximately 3 V, the output vector is SNR, with a noise level of −80 dBV. (b) Vcnp shifts to a higher voltage after 2 min of exposure, and the output drops to SNR. (c) Continued air exposure for a further 2 min results in an even higher Vcnp and an output of SNR. (d) The operation conditions can be reversed by means of ethanol-based wet treatment. At the moment when an ethanol droplet is applied, the intermediate output is SNR. After 20 s of treatment, the ethanol is blown dry for 5 s, after which the device is reset to the original state of SNR. SNR, signal to noise ratio.
Demonstration of the pulse-sequence-adjustable electrochemical memory effect in a GFET during 10 min of air exposure. (a) The H2O/O2 redox system adsorbed from the air serves to form charge traps that attract electrons transferred from the graphene, resulting in a p-type shift of Vcnp. (b) With the application of a positive-gate-voltage pulse sequence, electrons are temporarily pumped into the graphene channel from the source metal contact and the electric field on the graphene surface points toward the air region, accelerating the electron charge transfer from the graphene to the H2O/O2 charge traps during a positive-voltage pulse. Because a large population of electrons has been transferred to charge traps, more holes are accumulated on the graphene layer when the pulse ends, resulting in a stronger p-type shift of Vcnp than in the case without a positive-voltage pulse. (c) With the application of a negative gate-voltage pulse sequence, holes are temporarily pumped into the graphene channel and the electric field points toward the substrate, decelerating the charge transfer from the graphene to the H2O/O2 charge traps and resulting in a weaker p-type shift of Vcnp.

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Chemical-sensitive graphene modulator with a memory effect for internet-of-things applications

May 2016

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440 Reads

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42 Citations

Microsystems & Nanoengineering

Modern internet of things (IoTs) and ubiquitous sensor networks could potentially take advantage of chemically sensitive nanomaterials and nanostructures. However, their heterogeneous integration with other electronic modules on a networked sensor node, such as silicon-based modulators and memories, is inherently challenging because of compatibility and integration issues. Here we report a novel paradigm for sensing modulators: a graphene field-effect transistor device that directly modulates a radio frequency (RF) electrical carrier signal when exposed to chemical agents, with a memory effect in its electrochemical history. We demonstrated the concept and implementation of this graphene-based sensing modulator through a frequency-modulation (FM) experiment conducted in a modulation cycle consisting of alternating phases of air exposure and ethanol or water treatment. In addition, we observed an analog memory effect in terms of the charge neutrality point of the graphene, V cnp, which strongly influences the FM results, and developed a calibration method using electrochemical gate-voltage pulse sequences. This graphene-based multifunctional device shows great potential for use in a simple, low-cost, and ultracompact nanomaterial-based nodal architecture to enable continuous, real-time event-based monitoring in pervasive healthcare IoTs, ubiquitous security systems, and other chemical/molecular/gas monitoring applications.

Citations (2)


... Liang et al. performed a nanoplasmon-enhanced scattering (nPES) assay using antibody-conjugated gold nanospheres and nanorods to target EVs captured by EV-specific antibodies on a sensor chip, generating a local plasmon effect that enhanced sensitivity and specificity when detecting tumor-derived EVs. The gold nanospheres were 50 nm in diameter, while the gold nanorods had dimensions of 25 × 60 nm [36]. Gold nanoparticles scatter light at specific wavelengths determined by their size and shape. ...

Reference:

Recent Advancements in Imaging Techniques for Individual Extracellular Vesicles
Nanoplasmonic Quantification of Tumor-derived Extracellular Vesicles in Plasma Microsamples for Diagnosis and Treatment Monitoring
  • Citing Article
  • February 2017

Nature Biomedical Engineering

... Among these choices, graphene has emerged as a promising sensing material for nitrate detection when integrated with ISFETs 25,26 . Graphene offers several advantages, including an unprecedented charge carrier mobility of 7,000 cm²V -¹s -¹, rapid response time, ease of functionalization, high chemical stability, and high mechanical flexibility 27 . Although graphene-based ISFETs for nitrate sensing [28][29][30] have shown improved detection limits and linear ranges as summarized in Table S1, the achievement of ultra-low detection of nitrate is still not well realized. ...

Chemical-sensitive graphene modulator with a memory effect for internet-of-things applications

Microsystems & Nanoengineering