nan Kenry

Emerging flexible and wearable physical sensing platforms for healthcare and biomedical applications

There are now numerous emerging flexible and wearable sensing technologies that can perform a myriad of physical and physiological measurements. Rapid advances in developing and implementing such sensors in the last several years have demonstrated the growing significance and potential utility of this unique class of sensing platforms. Applications include wearable consumer electronics, soft robotics, medical prosthetics, electronic skin, and health monitoring. In this review, we provide a state-of-the-art overview of the emerging flexible and wearable sensing platforms for healthcare and biomedical applications. We first introduce the selection of flexible and stretchable materials and the fabrication of sensors based on these materials. We then compare the different solid-state and liquid-state physical sensing platforms and examine the mechanical deformation-based working mechanisms of these sensors. We also highlight some of the exciting applications of flexible and wearable physical sensors in emerging healthcare and biomedical applications, in particular for artificial electronic skins, physiological health monitoring and assessment, and therapeutic and drug delivery. Finally, we conclude this review by offering some insight into the challenges and opportunities facing this field.

Cell‐Assembled Graphene Biocomposite for Enhanced Chondrogenic Differentiation

Graphene-based nanomaterials are increasingly being explored for use as biomaterials for drug delivery and tissue engineering applications due to their exceptional physicochemical and mechanical properties. However, the two-dimensional nature of graphene makes it difficult to extend its applications beyond planar tissue culture. Here, graphene-cell biocomposites are used to pre-concentrate growth factors for chondrogenic differentiation. Bone marrow-derived mesenchymal stem cells (MSCs) are assembled with graphene flakes in the solution to form graphene-cell biocomposites. Increasing concentrations of graphene (G) and porous graphene oxide (pGO) are found to correlate positively with the extent of differentiation. However, beyond a certain concentration, especially in the case of graphene oxide, it will lead to decreased chondrogenesis due to increased diffusional barrier and cytotoxic effects. Nevertheless, these findings indicate that both G and pGO could serve as effective pre-concentration platforms for the construction of tissue-engineered cartilage and suspension-based cultures in vitro.

Highly Flexible Graphene Oxide Nanosuspension Liquid-Based Microfluidic Tactile Sensor

A novel graphene oxide (GO) nanosuspension liquid-based microfluidic tactile sensor is developed. It comprises a UV ozone-bonded Ecoflex-polydimethylsiloxane microfluidic assembly filled with GO nanosuspension, which serves as the working fluid of the tactile sensor. This device is highly flexible and able to withstand numerous modes of deformation as well as distinguish various user-applied mechanical forces it is subjected to, including pressing, stretching, and bending. This tactile sensor is also highly deformable and wearable, and capable of recognizing and differentiating distinct hand muscle-induced motions, such as finger flexing and fist clenching. Moreover, subtle differences in the handgrip strength derived from the first clenching gesture can be identified based on the electrical response of our device. This work highlights the potential application of the GO nanosuspension liquid-based flexible microfluidic tactile sensing platform as a wearable diagnostic and prognostic device for real-time health monitoring. Also importantly, this work can further facilitate the exploration and potential realization of a functional liquid-state device technology with superior mechanical flexibility and conformability.

Highly sensitive reduced graphene oxide microelectrode array sensor.

Reduced graphene oxide (rGO) has been fabricated into a microelectrode array (MEA) using a modified nanoimprint lithography (NIL) technique. Through a modified NIL process, the rGO MEA was fabricated by a self-alignment of conducting Indium Tin Oxide (ITO) and rGO layer without etching of the rGO layer. The rGO MEA consists of an array of 10μm circular disks and microelectrode signature has been found at a pitch spacing of 60μm. The rGO MEA shows a sensitivity of 1.91nAμm(-1) to dopamine (DA) without the use of mediators or functionalization of the reduced graphene oxide (rGO) active layer. The performance of rGO MEA remains stable when tested under highly resistive media using a continuous flow set up, as well as when subjecting it to mechanical stress. The successful demonstration of NIL for fabricating rGO microelectrodes on flexible substrate presents a route for the large scale fabrication of highly sensitive, flexible and thin biosensing platform.

Selective Accelerated Proliferation of Malignant Breast Cancer Cells on Planar Graphene Oxide Films

Graphene nanomaterials have been actively investigated for biomedical and biological applications, including that of cancer. Despite progress made, most of such studies are conducted on dispersed graphene nanosheets in solution. Consequently, the use of planar graphene films, especially in cancer research, has not been fully explored. Here, we investigate the cellular interactions between the graphene material films and breast cancer cell lines, specifically the effects these films have on cellular proliferation, spreading area, and cytotoxicity. We demonstrate that the graphene oxide (GO) film selectively accelerates the proliferation of both metastatic (MDA-MB-231) and nonmetastatic (MCF-7) breast cancer cells, but not that of noncancer breast epithelial cells (MCF-10A). Contrastingly, this accelerated proliferation is not observed with the use of graphene (G) film. Moreover, GO induces negligible cytotoxicity on these cells. We suggest that the observed phenomena originate from the synergistic effect resulted from the high loading capacity and conformational change of cellular attachment proteins on the GO film, and the high amount of oxygenated groups present in the material. We anticipate that our findings can further shed light on the graphene-cancer cellular interactions and provide better understanding for the future design and application of graphene-based nanomaterials in cancer research.

Emergence of microfluidic wearable technologies

There has been an intense interest in the development of wearable technologies, arising from increasing demands in the areas of fitness and healthcare. While still at an early stage, incorporating microfluidics in wearable technologies has enormous potential, especially in healthcare applications. For example, current microfluidic fabrication techniques can be innovatively modified to fabricate microstructures and incorporate electrically conductive elements on soft, flexible and stretchable materials. In fact, by leverarging on such microfabrication and liquid manipulation techniques, the developed flexible microfluidic wearable technologies have enabled several biosensing applications, including in situ sweat metabolites analysis, vital signs monitoring, and gait analysis. As such, we anticipate further significant breakthroughs and potential uses of wearable microfluidics in active drug delivery patches, soft robotics sensing and control, and even implantable artificial organs in the near future.

Molecular Hemocompatibility of Graphene Oxide and Its Implication for Antithrombotic Applications

Surface-induced blood clotting is one of the major problems associated with the long-term use of blood-contacting biomedical devices. Central to this obstructive blood clotting is the adsorption of plasma proteins following the interactions between blood and material surface. Of all proteins circulating in the blood plasma, albumin and fibrinogen are the two important proteins regulating the blood-material interaction. As such, the adsorption of plasma proteins has been used as an indicator for the assessment of the blood compatibility of the biomedical devices. Numerous nanomaterials have been developed for antithrombotic surface coating applications, including the 2D graphene and its derivatives. Here, the antithrombotic property of albumin-functionalized graphene oxide (albumin-GO) and its potential for antithrombotic coating application under flow are investigated. The loading capacities, conformational changes, and adsorptions of albumin and fibrinogen on GO are probed. It is observed that GO possesses a high loading capacity for both proteins and simultaneously, it does not disrupt the overall secondary structure and conformational stability of albumin. Both albumin and fibrinogen adsorb well on the surface of GO. Subsequently, it is demonstrated that the albumin-functionalized GO possesses enhanced antithrombotic effect and may potentially be used as an antithrombotic coating material of blood-contacting devices under dynamic flow.

When stem cells meet graphene: Opportunities and challenges in regenerative medicine

Recent advances in stem cell research and nanotechnology have significantly influenced the landscape of tissue engineering and regenerative medicine. Precise and reproducible control of the fate of stem cells and their lineage specification have, therefore, become more crucial than ever for the success of stem cell-based technologies. Extensive research has been geared towards developing materials that are capable of mimicking the physiological microenvironment of stem cells and at the same time, controlling their eventual fate. An interesting example of these materials is two-dimensional graphene and its related derivatives. A high specific surface area coupled with superior chemical stability, biocompatibility, and flexibility in functionalization render graphene-based nanomaterials one of the most exciting platforms for tissue engineering and regenerative medicine applications, especially for stem cell growth, proliferation, and differentiation. In this review, we discuss the love-hate relationship between stem cells and graphene-based nanomaterials in tissue engineering and regenerative medicine. We first discuss the role and importance of stem cells in tissue engineering and regenerative medicine. We then highlight the use of nanomaterials for stem cell control, the interaction between stem cells and graphene nanomaterials as well as their biocompatibility, biodistribution, and biodegradability considerations. We also offer our perspectives on the various challenges and opportunities facing the use of graphene and its derivatives for stem cell growth and differentiation.

Metal–Organic-Framework-Assisted In Vivo Bacterial Metabolic Labeling and Precise Antibacterial Therapy

Bacterial infection is one of the most serious physiological conditions threatening human health. There is an increasing demand for more effective bacterial diagnosis and treatment through noninvasive theranostic approaches. Herein, a new strategy is reported to achieve in vivo metabolic labeling of bacteria through the use of MIL-100 (Fe) nanoparticles (NPs) as the nanocarrier for precise delivery of 3-azido-d-alanine (d-AzAla). After intravenous injection, MIL-100 (Fe) NPs can accumulate preferentially and degrade rapidly within the high H2 O2 inflammatory environment, releasing d-AzAla in the process. d-AzAla is selectively integrated into the cell walls of bacteria, which is confirmed by fluorescence signals from clickable DBCO-Cy5. Ultrasmall photosensitizer NPs with aggregation-induced emission characteristics are subsequently designed to react with the modified bacteria through in vivo click chemistry. Through photodynamic therapy, the amount of bacteria on the infected tissue can be significantly reduced. Overall, this study demonstrates the advantages of metal-organic-framework-assisted bacteria metabolic labeling strategy for precise bacterial detection and therapy guided by fluorescence imaging.

Selective concentration-dependent manipulation of intrinsic fluorescence of plasma proteins by graphene oxide nanosheets

We investigate the molecular interactions between graphene oxide (GO) and blood plasma proteins, in particular, the influence of GO on the intrinsic fluorescence of these proteins. We observe that GO acts as an efficient quencher of the intrinsic fluorescence of albumin, globulin, and fibrinogen. Interestingly, we also note for the first time that, in addition to the robust fluorescence quenching, GO is capable of selectively amplifying the fluorescence emission of fibrinogen up to approximately 30% or 1.3 fold under certain concentrations but not those of albumin and globulin. We suggest that GO may possibly play a dual role in controlling the intrinsic fluorescence emission of the plasma proteins. Furthermore, this role switching may be influenced by the competition between the aggregation and encapsulation effects. We propose that the GO-induced intrinsic fluorescence quenching is driven by the physical encapsulation of the plasma proteins by GO nanosheets. Contrastingly, the GO-mediated fluorescence amplification is promoted by an aggregation of fibrinogen.