Field-effect transistor (FET)-based biosensors allow label-free detection of biomolecules by measuring their intrinsic charges. The detection limit of these sensors is determined by the Debye screening of the charges from counter ions in solutions. Here, we use FETs with a deformed monolayer graphene channel for the detection of nucleic acids. These devices with even millimeter scale channels show an ultra-high sensitivity detection in buffer and human serum sample down to 600 zM and 20 aM, respectively, which are ∼18 and ∼600 nucleic acid molecules. Computational simulations reveal that the nanoscale deformations can form 'electrical hot spots' in the sensing channel which reduce the charge screening at the concave regions. Moreover, the deformed graphene could exhibit a band-gap, allowing an exponential change in the source-drain current from small numbers of charges. Collectively, these phenomena allow for ultrasensitive electronic biomolecular detection in millimeter scale structures.
Universal platforms for biomolecular analysis using label‐free sensing modalities can address important diagnostic challenges. Electrical field effect‐sensors are an important class of devices that can enable point‐of‐care sensing by probing the charge in the biological entities. Use of crumpled graphene for this application is especially promising. It is previously reported that the limit of detection (LoD) on electrical field effect‐based sensors using DNA molecules on the crumpled graphene FET (field‐effect transistor) platform. Here, the crumpled graphene FET‐based biosensing of important biomarkers including small molecules and proteins is reported. The performance of devices is systematically evaluated and optimized by studying the effect of the crumpling ratio on electrical double layer (EDL) formation and bandgap opening on the graphene. It is also shown that a small and electroneutral molecule dopamine can be captured by an aptamer and its conformation change induced electrical signal changes. Three kinds of proteins were captured with specific antibodies including interleukin‐6 (IL‐6) and two viral proteins. All tested biomarkers are detectable with the highest sensitivity reported on the electrical platform. Significantly, two COVID‐19 related proteins, nucleocapsid (N‐) and spike (S‐) proteins antigens are successfully detected with extremely low LoDs. This electrical antigen tests can contribute to the challenge of rapid, point‐of‐care diagnostics.
Enzymatic DNA amplification-based approaches involving intercalating DNA-binding fluorescent dyes and expensive optical detectors are the gold standard for nucleic acid detection. As components of a simplified and miniaturized system, conventional silicon-based Ion sensitive field effect transistors (ISFETs) that measure decrease in pH due to generation of pyrophosphates during DNA amplification have been previously reported. In this paper, we use Bst polymerase in a Loop Mediated Isothermal Amplification (LAMP) reaction combined with target specific primers and crumpled graphene field effect transistors (gFET) to electrically detect the amplification by sensing the reduction in primers. Graphene is known to adsorb single stranded DNA due to noncovalent π-π bonds, but not double stranded DNA. Our approach does not require any surface functionalization and allows the detection of primer concentrations at the endpoint of reactions. We chose crumpled gFET over the conventional flat gFET sensors due to their superior sensitivity as recently demonstrated. We were able to detect the endpoint of amplification reaction with starting concentrations down to 8 zeptomolar in 90 minutes including the time of amplification and detection. With its high sensitivity and small footprint, our platform will help bring complex lab based diagnostic and genotyping amplification assays to the point-of-care.
Existing three-dimensional (3D) culture techniques are limited by trade-offs between throughput, capacity for high-resolution imaging in living state, and geometric control. Here, we introduce a modular microscale hanging drop culture where simple design elements allow high replicates for drug screening, direct on-chip real-time or high-resolution confocal microscopy, and geometric control in 3D. Thousands of spheroids can be formed on our microchip in a single step and without any selective pressure from specific matrices. Microchip cultures from human LN229 glioblastoma and patient-derived mouse xenograft cells retained genomic alterations of originating tumors based on mate pair sequencing. We measured response to drugs over time with real-time microscopy on-chip. Last, by engineering droplets to form predetermined geometric shapes, we were able to manipulate the geometry of cultured cell masses. These outcomes can enable broad applications in advancing personalized medicine for cancer and drug discovery, tissue engineering, and stem cell research.
We propose novel nano-plasmonic-based structures for rapid sequencing of DNA molecules. The optical properties of DNA nucleotides have notable differences in the ultraviolet (UV) region of light. Using nanopore, bowtie, and bowtie-nanopore compound structures, probable application of the surface plasmon resonance (SPR) in DNA sequencing is investigated by employing the discrete dipole approximation method. The effects of different materials like chromium (Cr), aluminum (Al), rhodium (Rh), and graphene (Gr) are studied. We show that for Cr/Al/Gr/Rh, the nucleotide presented shifts the SPR spectra for the nanopore 1/29/5/34 to 14/39/15/67 nm, bowtie 8/2/49/38 to 31/20/79/55 nm, and bowtie-nanopore compound 25/77/5/16 to 80/80/22/39 nm. The Cr-based compound structure shows excellent sensitivity and selectivity which can make it a promising methodology for DNA sequencing.
We propose a new DNA sensing mechanism based on optical properties of graphene oxide (GO) and molybdenum disulphide ( MoS 2 ) nanopores. In this method, GO and MoS 2 is utilized as quantum dot (QD) nanopore and DNA molecule translocate through the nanopore. A recently-developed hybrid quantum/classical method (HQCM) is employed which uses time-dependent density functional theory and quasi-static finite difference time domain approach. Due to good biocompatibility, stability and excitation wavelength dependent emission behavior of GO and MoS 2 we use them as nanopore materials. The absorption and emission peaks wavelengths of GO and MoS 2 nanopores are investigated in the presence of DNA nucleobases. The maximum sensitivity of the proposed method to DNA is achieved for the 2-nm GO nanopore. Results show that insertion of DNA nucleobases in the nanopore shifts the wavelength of the emitted light from GO or MoS 2 nanopore up to 130 nm. The maximum value of the relative shift between two different nucleobases is achieved by the shift between cytosine (C) and thymine (T) nucleobases, ~111 nm for 2-nm GO nanopore. Results show that the proposed mechanism has a superior capability to be used in future DNA sequencers.
The reversible insulating-to-conducting phase transition (ICPT) of vanadium dioxide (VO2) makes it a versatile candidate for the implementation of integrated optical devices. In this paper, a bi-functional in-line optical device based on a four-layer stack of PMMA/graphene/VO2/graphene deposited on a side-polished fiber (SPF) is proposed. The structure can be employed as an ultra-compact TE modulator or a TM-pass polarizer, operating at 1.55 μm. We show that the ICPT characteristic can be used for polarization-selective mode shaping (PSMS) to manipulate orthogonal modes separately. On the one hand, as an optical modulator, the PSMS is used to modify mode profiles so that the TE mode attenuation is maximized in the off-state (and IL is minimized in the on-state), while the power carried by the TM mode remains unchanged. As a result, a TE modulator with an ultrahigh extinction ratio (ER) of about ER = 165 dB/mm and a very low insertion loss (IL) of IL = 2.3 dB/mm is achieved. On the other hand, the structure can act as a TM-pass polarizer featuring an extremely high polarization extinction ratio (PER) of about PER = 164 dB/mm and a low TM insertion of IL = 3.86 dB/mm. The three-dimensional heat transfer calculation for the ICPT process reveals that the response time of the modulator is in the order of few nanoseconds. Moreover, the required bias voltage of the proposed device is calculated to be as low as 1.1 V. The presented results are promising a key step towards the realization of an integrated high-performance in-line modulator/polarizer.
We propose surface plasmon resonance biosensors based on crumpled graphene and molybdenum disulphide (MoS2) flakes supported on stretchable polydimethylsiloxane (PDMS) or silicon substrates. Accumulation of specific biomarkers resulting in measurable shifts in the resonance wavelength of the plasmon modes of two-dimensional (2D) material structures, with crumpled structures demonstrating large refractive index shifts. Using theoretical calculations based on the semiclassical Drude model, combined with the finite element method, we demonstrate that the interaction between the surface plasmons of crumpled graphene/MoS2 layers and the surrounding analyte results in high sensitivity to biomarker driven refractive index shifts, up to 7499 nm/RIU for structures supported on silicon substrates. We can achieve a high figure of merit (FOM), defined as the ratio of the refractive index sensitivity to the full width at half maximum of the resonant peak, of approximately 62.5 RIU-1. Furthermore, the sensing properties of the device can be tuned by varying crumple period and aspect ratio through simple stretching and integrating material interlayers. By stacking multiple 2D materials in heterostructures supported on the PDMS layer, we produced hybrid plasmon resonances detuned from the PDMS absorbance region allowing higher sensitivity and FOM compared to pure crumpled graphene structures on the PDMS substrates. The high sensitivity and broad mechanical tunability of these crumpled 2D material biosensors considerable advantages over traditional refractive index sensors, providing a new platform for ultrasensitive biosensing.
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