Nanocarbons for Biology and Medicine: Sensing, Imaging, and Drug Delivery.

Nanocarbons with different dimensions (e.g., 0D fullerenes and carbon nanodots, 1D carbon nanotubes and graphene nanoribbons, 2D graphene and graphene oxides, and 3D nanodiamonds) have attracted enormous interest for applications ranging from electronics, optoelectronics, and photovoltaics to sensing, bioimaging, and therapeutics due to their unique physical and chemical properties. Among them, nanocarbon-based theranostics (i.e., therapeutics and diagnostics) is one of the most intensively studied applications, as these nanocarbon materials serve as excellent biosensors, versatile drug/gene carriers for specific targeting in vivo, effective photothermal nanoagents for cancer therapy, and promising fluorescent nanolabels for cell and tissue imaging. This review provides a systematic overview of the latest theranostic applications of nanocarbon materials with a comprehensive comparison of the characteristics of different nanocarbon materials and their influences on theranostic applications. We first introduce the different carbon allotropes that can be used for theranostic applications with their respective preparation and surface functionalization approaches as well as their physical and chemical properties. Theranostic applications are described separately for both in vitro and in vivo systems by highlighting the protocols and the studied biosystems, followed by the toxicity and biodegradability implications. Finally, this review outlines the design considerations for nanocarbon materials as the key unifying themes that will serve as a foundational first principle for researchers to study, investigate, and generate effective, biocompatible, and nontoxic nanocarbon materials-based models for cancer theranostics applications. Finally, we summarize the review with an outlook on the challenges and novel theranostic protocols using nanocarbon materials for hard-to-treat cancers and other diseases. This review intends to present a comprehensive guideline for researchers in nanotechnology and biomedicine on the selection strategy of nanocarbon materials according to their specific requirements.

Enhanced field emission properties of carbon nanotube bundles confined in SiO2 pits.

It has been widely reported that carbon nanotubes (CNTs) exhibit superior field emission (FE) properties due to their high aspect ratios and unique structural properties. Among the various types of CNTs, random growth CNTs exhibit promising FE properties due to their reduced inter-tube screening effect. However, growing random growth CNTs on individual catalyst islands often results in spread out CNT bundles, which reduces overall field enhancement. In this study, significant improvement in FE properties in CNT bundles is demonstrated by confining them in microfabricated SiO2 pits. Growing CNT bundles in narrow (0.5 µm diameter and 2 µm height) SiO2 pits achieves FE current density of 1-1.4 A cm-2, which is much higher than for freestanding CNT bundles (76.9 mA cm-2). From the Fowler Nordheim plots, confined CNT bundles show a higher field enhancement factor. This improvement can be attributed to the reduced bundle diameter by SiO2 pit confinement, which yields bundles with higher aspect ratios. Combining the obtained outcomes, it can be conclusively summarized that confining CNTs in SiO2 pits yields higher FE current density due to the higher field enhancement of confined CNTs.

Multifunctional Hyperbolic Nanogroove Metasurface for Submolecular Detection.

Metasurface serves as a promising plasmonic sensing platform for engineering the enhanced light-matter interactions. Here, a hyperbolic metasurface with the nanogroove structure in the subwavelength scale is designed. This metasurface is able to modify the wavefront and wavelength of surface plasmon wave with the variation of the nanogroove width or periodicity. At the specific optical frequency, surface plasmon polaritons are tightly confined and propagated with a diffraction-free feature due to the epsilon-near-zero effect. Most importantly, the groove hyperbolic metasurface can enhance the plasmonic sensing with an ultrahigh phase sensitivity of 30 373 deg RIU-1 and Goos-Hänchen shift sensitivity of 10.134 mm RIU-1 . The detection resolution for refractive index change of glycerol solution is achieved as 10-8 RIU based on the phase measurement. The detection limit of bovine serum albumin (BSA) molecule is measured as low as 0.1 × 10-18 m (1 × 10-19 mol L-1 ), which corresponds to a submolecular detection level (0.13 BSA mm-2 ). As for low-weight biotin molecule, the detection limit is estimated below 1 × 10-15 m (1 × 10-15 mol L-1 , 1300 biotin mm-2 ). This enhanced plasmonic sensing performance is two orders of magnitude higher than those with current state-of-art plasmonic metamaterials and metasurfaces.

Preparation of biofunctionalized quantum dots using microfluidic chips for bioimaging.

Biofunctionalized quantum dots (QDs), especially protein-coated QDs, are known to be useful targeted fluorescent labels for cellular and deep-tissue imaging. These nanoparticles can also serve as efficient energy donors in fluorescence resonance energy transfer (FRET) binding assays for the multiplexed sensing of tumor markers. However, current preparation processes for protein-functionalized QDs are laborious and require multiple synthesis steps (e.g. preparing them in high temperature, making them dispersible in water, and functionalizing them with surface ligands) to obtain a high quality and quantity of QD formulations, significantly impeding the progress of employing QDs for clinical diagnostics use such as a QD-based immunohistofluorescence assay. Herein, we demonstrate a one-step synthesis approach for preparing protein-functionalized QDs using a microfluidic (MF) chip setup. Using bovine serum albumin (BSA) molecules as the surface ligand model, we first studied and optimized the MF reaction synthesis parameters (e.g. reaction temperature, and channel width and length) for making protein-functionalized QDs using COMSOL simulation modeling, followed by experimental verification. Moreover, in comparison with the BSA-functionalized QDs synthesized using the conventional bench-top method, BSA-QDs prepared using the MF approach exhibit a significantly higher protein-functionalization efficiency, photostability and colloidal stability. The proposed one-step MF synthesis approach provides a rapid, cost effective, and a small-scale production of nanocrystals platform for developing new QD formulations in applications ranging from cell labeling to biomolecular sensing. Most importantly, this approach will considerably reduce the amount of chemical waste generated during the trial-and-error stage of developing and perfecting the desired physical and optical properties of new QD materials.

Label-free plasmonic-based biosensing using a gold nanohole array chip coated with a wafer-scale deposited WS2 monolayer.

This paper reports the fabrication, testing and obtained performance of a plasmonic sensor employing a gold (Au) nanohole array chip coated with tungsten disulphide (WS2), which is then functionalized for the detection of protein-protein interactions. A key novelty is that the WS2 was deposited as a monoatomic layer using a wafer-scale synthesis method that successfully provided a film of both high quality and uniform thickness. The deposited WS2 film was transferred onto a Au nanohole array chip using a novel method and was subsequently functionalized with biotin. The final sensor was tested and it demonstrated efficient real-time and label-free plasmonic detection of biotin-streptavidin coupling. Specifically, compared to a standard (i.e. uncoated) Au nanohole-based sensor, our WS2-coated Au nanohole array boosted the spectral shift of the resonance wavelength by ∼190%, resulting in a 7.64-fold improvement of the limit of detection (LOD).

Development of a CMOS-Compatible Carbon Nanotube Array Transfer Method.

Carbon nanotubes (CNTs) have, over the years, been used in research as a promising material in electronics as a thermal interface material and as interconnects amongst other applications. However, there exist several issues preventing the widespread integration of CNTs onto device applications, e.g., high growth temperature and interfacial resistance. To overcome these issues, a complementary metal oxide semiconductor (CMOS)-compatible CNT array transfer method that electrically connects the CNT arrays to target device substrates was developed. The method separates the CNT growth and preparation steps from the target substrate. Utilizing an alignment tool with the capabilities of thermocompression enables a highly accurate transfer of CNT arrays onto designated areas with desired patterns. With this transfer process as a starting point, improvement pointers are also discussed in this paper to further improve the quality of the transferred CNTs.

Author Correction: Modelling of free-form conformal metasurfaces.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Modelling of free-form conformal metasurfaces.

Artificial electromagnetic surfaces, metasurfaces, control light in the desired manner through the introduction of abrupt changes of electromagnetic fields at interfaces. Current modelling of metasurfaces successfully exploits generalised sheet transition conditions (GSTCs), a set of boundary conditions that account for electric and magnetic metasurface-induced optical responses. GSTCs are powerful theoretical tools but they are not readily applicable for arbitrarily shaped metasurfaces. Accurate and computationally efficient algorithms capable of implementing artificial boundary conditions are highly desired for designing free-form photonic devices. To address this challenge, we propose a numerical method based on conformal boundary optics with a modified finite difference time-domain (FDTD) approach which accurately calculates the electromagnetic fields across conformal metasurfaces. Illustrative examples of curved meta-optics are presented, showing results in good agreement with theoretical predictions. This method can become a powerful tool for designing and predicting optical functionalities of conformal metasurfaces for new lightweight, flexible and wearable photonic devices.

Human Rett-derived neuronal progenitor cells in 3D graphene scaffold as an in vitro platform to study the effect of electrical stimulation on neuronal differentiation.

Studies of electrical stimulation therapies for the treatment of neurological disorders, such as deep brain stimulation, have almost exclusively been performed using animal-models. However, because animal-models can only approximate human brain disorders, these studies should be supplemented with an in vitro human cell-culture based model to substantiate the results of animal-based studies and further investigate therapeutic benefit in humans. This study presents a novel approach to analyze the effect of electrical stimulation on the neurogenesis of patient-induced pluripotent stem cell (iPSC) derived neural progenitor cell (NPC) lines, in vitro using a 3D graphene scaffold system. The iPSC-derived hNPCs used to demonstrate the system were collected from patients with Rett syndrome, a debilitating neurodevelopmental disorder. The graphene scaffold readily supported both the wild-type and Rett NPCs. Electrical stimulation parameters were optimized to accommodate both wild-type and Rett cells. Increased cell maturation and improvements in cell morphology of the Rett cells was observed after electrical stimulation. The results of the pilot study of electrical stimulation to enhance Rett NPCs neurogenesis were promising and support further investigation of the therapy. Overall, this system provides a valuable tool to study electrical stimulation as a potential therapy for neurological disorders using patient-specific cells.

NucleiNet: A convolutional encoder-decoder network for bio-image denoising.

Generic and scalable data analysis procedures are highly demanded by the increasing number of multi-dimensional biomedical data. However, especially for time-lapse biological data, the high level of noise prevents for automated high-throughput analysis methods. The rapid developing of machine-learning methods and particularly deep-learning methods provide new tools and methodologies that can help in the denoising of such data. Using a convolutional encoder-decoder network, one can provide a scalable bio-image platform, called NucleiNet, to automatically segment, classify and track cell nuclei. The proposed method can achieve 0.99 F-score and 0.99 pixel-wise accuracy on C. elegans dataset, which means that over 99% of nuclei can be successfully detected with no merging nuclei found.

Sensitivity Enhancement of Transition Metal Dichalcogenides/Silicon Nanostructure-based Surface Plasmon Resonance Biosensor.

In this work, we designed a sensitivity-enhanced surface plasmon resonance biosensor structure based on silicon nanosheet and two-dimensional transition metal dichalcogenides. This configuration contains six components: SF10 triangular prism, gold thin film, silicon nanosheet, two-dimensional MoS2/MoSe2/WS2/WSe2 (defined as MX2) layers, biomolecular analyte layer and sensing medium. The minimum reflectivity, sensitivity as well as the Full Width at Half Maximum of SPR curve are systematically examined by using Fresnel equations and the transfer matrix method in the visible and near infrared wavelength range (600 nm to 1024 nm). The variation of the minimum reflectivity and the change in resonance angle as the function of the number of MX2 layers are presented respectively. The results show that silicon nanosheet and MX2 layers can be served as effective light absorption medium. Under resonance conditions, the electrons in these additional dielectric layers can be transferred to the surface of gold thin film. All silicon-MX2 enhanced sensing models show much better performance than that of the conventional sensing scheme where pure Au thin film is used, the highest sensitivity can be achieved by employing 600 nm excitation light wavelength with 35 nm gold thin film and 7 nm thickness silicon nanosheet coated with monolayer WS2.

Three-Dimensional Graphene: A Biocompatible and Biodegradable Scaffold with Enhanced Oxygenation.

Owing to its high porosity, specific surface area and three-dimensional structure, three-dimensional graphene (3D-C) is a promising scaffold material for tissue engineering, regenerative medicine as well as providing a more biologically relevant platform for living organisms in vivo studies. Recently, its differentiation effects on cells growth and anti-inflammation properties have also been demonstrated. Here, we report a complete study of 3D-C as a fully adequate scaffold for tissue engineering and systematically analyze its biocompatibility and biodegradation mechanism. The metabolic activities of liver cells (HepG2 hepatocarcinoma cells) on 3D-C are studied and our findings show that cell growth on 3D-C has high cell viability (> 90%), low lactate production (reduced by 300%) and its porous structure also provides an excellent oxygenation platform. 3D-C is also biodegradable via a 2-step oxidative biodegradation process by first, disruption of domains and lift off of smaller graphitic particles from the surface of the 3D-C and subsequently, the decomposition of these graphitic flakes. In addition, the speed of the biodegradation can be tuned with pretreatment of O2 plasma.

Graphene-Gold Metasurface Architectures for Ultrasensitive Plasmonic Biosensing.

Graphene-gold metasurface architectures that can provide significant gains in plasmonic detection sensitivity for trace-amount target analytes are reported. Benefiting from extreme phase singularities of reflected light induced by strong plasmon-mediated energy confinements, the metasurface demonstrates a much-improved sensitivity to molecular bindings nearby and achieves an ultralow detection limit of 1 × 10(-18) m for 7.3 kDa 24-mer single-stranded DNA.