Publications

Khoo, BL, Chaudhuri, PK, Lim, CT & Warkiani, ME 2017, 'Advancing Techniques and Insights in Circulating Tumor Cell (CTC) Research' in Cancer Drug Discovery and Development, Springer International Publishing, pp. 71-94.
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Cancer is a major cause of mortality worldwide, with a disease burden estimated to grow over the coming decades. Circulating tumor cells (CTCs) are rare cancer cells released from the primary or metastatic tumors and transported though the peripheral circulatory system to their specific secondary locations. The presence of CTCs in the a cancer patient’s blood has been used as a prognostic biomarker, with lower CTC count correlating with greater overall survival [1]. In spite of its clinical potential, the isolation and detection of CTCs has been a challenging task due to its rare presence amongst other blood cells (as low as 1-10 CTCs per billions of blood cells) and variability in terms of both morphological and biochemical markers. Recent developments of microfluidics technology have paved the way for better isolation and characterization of CTCs due to several advantages such as lower sample volume, higher sensitivity and throughput and lesser production cost [2, 3]. In this chapter, various CTC isolation devices are classified under two major categories: microfluidics and conventional macro-scale devices, as illustrated in Fig. 1. We will be discussing both label-free methods and antibody-dependent methods for CTC isolation, and will provide discussion and future perspectives on the advantages and drawbacks of both these techniques on potential clinical applications. Advancement in these technologies for CTCs and associated components, such as exosomes, led to an unraveling of tumor variation, ranging histology, molecular, proteomic and functional heterogeneity, which will be discussed in the subsequent sections.

Pandya, HJ, Draz, MS, Warkiani, ME & Shafiee, H 2017, 'Diagnostic Devices with Microfluidics' in Piraino, F, Selimović, Š & Iniewski, K (eds), Diagnostic Devices with Microfluidics, CRC Press, pp. 145-161.
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Infectious diseases remain the primary public health challenge in many countries. Every year, infectious diseases account for more than 13 million deaths around the world, and for 30% of the total burden of disease. Developing countries are especially challenged with infectious diseases. According to world health organization (WHO), 50% of the total deaths in developing countries are attributed to various infections, including respiratory tract infections, diarrheal diseases, human immunodeficiency virus (HIV), tuberculosis, and malaria. In the healthcare system, a diagnostic cycle consists of several time-consuming steps besides sample transportation, pre-and postanalytical phases, result transmission, and batching practices augmenting the turnaround time from disease interpretation to results (Figure 7.1) [1-3]. The downside of experience-based empiric therapy management involves the choice of inappropriate antibiotherapy or late initiation of treatment often resulting in treatment failure [4-7].

Shimoni, O & Valenzuela, SM 2017, 'Nanotechnology in Biology and Medicine' in Vo-Dinh, T (ed), Nanotechnology in Biology and Medicine: Methods, Devices, and Applications, Second Edition, CRC Press, USA, pp. 47-59.
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© 2018 by Taylor & Francis Group, LLC. Gold nanoparticles (Au NPs) have a rich history of drawing the attention, at first, of alchemists followed by scientists from the fields of chemistry, physics, photonics, and, in more recent times, biology and medicine. Such wide scientific attention has arisen due to the unique physical and chemical properties of these nanoparticles, including their optical and electronic virtues dependent on size, shape, and high surface-to-volume area with facile surface chemistry. Added to these favorable physicochemical properties is their highly desirable and now increasingly accepted biocompatible profile.

Alizadeh, A, Warkiani, ME & Wang, M 2017, 'Manipulating electrokinetic conductance of nanofluidic channel by varying inlet pH of solution', Microfluidics and Nanofluidics, vol. 21, no. 3, pp. 1-15.
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© 2017, Springer-Verlag Berlin Heidelberg. The electrokinetic conductivity of micro-/nanofluidic systems, which strongly depends on the local solution properties (e.g., pH and ionic strength), has wide applications in nanosystems to control the system performance and ion rectification. Accurate and active manipulation of this parameter is proven to be very challenging since, in nanoscale, the ion transport is particularly dominated by the acquired surface charge on the solid–liquid interfaces. In this study, we propose an approach to manipulate the nanochannel electrokinetic conductivity by changing the pH value of the solution at the inlet in order to impose asymmetrical conditions inside nanochannel. The variable surface charge of walls is determined by considering the chemical adsorption on the solid–liquid interface and the electrical double layer interaction. The presented numerical model, which couples Poisson–Nernst–Planck and Navier–Stokes equations, can fully consider the electro-chemo-mechanical transport phenomena and predict the electrokinetic conductivity of nanofluidic channels with good accuracy. Modeling results show that the electrokinetic conductivity of the nanofluidic systems can be regulated by varying the solution pH at the inlet. It is revealed that the stronger electric double layers interaction can enhance the sensitivity of the nanochannel electrokinetic conductance to the inlet pH. This unique behavior of the nanochannel electrokinetic conductivity could broaden potential applications in biomedical, energy, and environmental systems using nanofluidic devices.

Asadnia, M, Khorasani, AM & Warkiani, ME 2017, 'An Accurate PSO-GA Based Neural Network to Model Growth of Carbon Nanotubes', Journal of Nanomaterials, vol. 2017, pp. 1-6.
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By combining particle swarm optimization (PSO) and genetic algorithms (GA) this paper offers an innovative algorithm to train artificial neural networks (ANNs) for the purpose of calculating the experimental growth parameters of CNTs. The paper explores experimentally obtaining data to train ANNs, as a method to reduce simulation time while ensuring the precision of formal physics models. The results are compared with conventional particle swarm optimization based neural network (CPSONN) and Levenberg–Marquardt (LM) techniques. The results show that PSOGANN can be successfully utilized for modeling the experimental parameters that are critical for the growth of CNTs.

Asadnia, M, Mousavi Ehteshami, SM, Chan, SH & Warkiani, ME 2017, 'Development of a fiber-based membraneless hydrogen peroxide fuel cell', RSC Advances, vol. 7, no. 65, pp. 40755-40760.
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Polyvinylidene fluoride (PVDF) electrospun nano-fiber is suggested as the substrate material for developing biocompatible membraneless hydrogen peroxide fuel cells.

Aya-Bonilla, CA, Marsavela, G, Freeman, JB, Lomma, C, Frank, MH, Khattak, MA, Meniawy, TM, Millward, M, Warkiani, ME, Gray, ES & Ziman, M 2017, 'Isolation and detection of circulating tumour cells from metastatic melanoma patients using a slanted spiral microfluidic device', Oncotarget, vol. 8, no. 40, pp. 67355-67368.
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Circulating Tumour Cells (CTCs) are promising cancer biomarkers. Several methods have been developed to isolate CTCs from blood samples. However, the isolation of melanoma CTCs is very challenging as a result of their extraordinary heterogeneity, which has hindered their biological and clinical study. Thus, methods that isolate CTCs based on their physical properties, rather than surface marker expression, such as microfluidic devices, are greatly needed in melanoma. Here, we assessed the ability of the slanted spiral microfluidic device to isolate melanoma CTCs via label-free enrichment. We demonstrated that this device yields recovery rates of spiked melanoma cells of over 80% and 55%, after one or two rounds of enrichment, respectively. Concurrently, a two to three log reduction of white blood cells was achieved with one or two rounds of enrichment, respectively. We characterised the isolated CTCs using multimarker flow cytometry, immunocytochemistry and gene expression. The results demonstrated that CTCs from metastatic melanoma patients were highly heterogeneous and commonly expressed stem-like markers such as PAX3 and ABCB5. The implementation of the slanted microfluidic device for melanoma CTC isolation enables further understanding of the biology of melanoma metastasis for biomarker development and to inform future treatment approaches.

Cheng, YY, Mok, E, Tan, S, Leygo, C, McLaughlin, C, George, AM & Reid, G 2017, 'SFRPTumour Suppressor Genes Are Potential Plasma-Based Epigenetic Biomarkers for Malignant Pleural Mesothelioma', Disease Markers, vol. 2017, pp. 1-10.
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Malignant pleural mesothelioma (MPM) is associated with asbestos exposure. Asbestos can induce chronic inflammation which in turn can lead to silencing of tumour suppressor genes. Wnt signaling pathway can be affected by chronic inflammation and is aberrantly activated in many cancers including colon and MPM.SFRPgenes are antagonists of Wnt pathway, andSFRPs are potential tumour suppressors in colon, gastric, breast, ovarian, and lung cancers and mesothelioma. This study investigated the expression and DNA methylation ofSFRPgenes in MPM cells lines with and without demethylation treatment. Sixty-six patient FFPE samples were analysed and have showed methylation ofSFRP2(56%) andSFRP5(70%) in MPM.SFRP2andSFRP5tumour-suppressive activity in eleven MPM lines was confirmed, and long-term asbestos exposure led to reduced expression of theSFRP1andSFRP2 genes in the mesothelium (MeT-5A) via epigenetic alterations. Finally, DNA methylation ofSFRPs is detectable in MPM patient plasma samples, with methylatedSFRP2andSFRP5showing a tendency towards greater abundance in patients. These data suggested thatSFRPgenes have tumour-suppresive activity in MPM and that methylated DNA fromSFRPgene promoters has the potential to serve as a biomarker for MPM patient plasma.

Cranfield, CG, Henriques, ST, Martinac, B, Duckworth, P, Craik, DJ & Cornell, B 2017, 'Kalata B1 and Kalata B2 Have a Surfactant-Like Activity in Phosphatidylethanolomine-Containing Lipid Membranes', Langmuir, vol. 33, no. 26, pp. 6630-6637.
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© 2017 American Chemical Society. Cyclotides are cyclic disulfide-rich peptides that are chemically and thermally stable and possess pharmaceutical and insecticidal properties. The activities reported for cyclotides correlate with their ability to target phosphatidylethanolamine (PE)-phospholipids and disrupt cell membranes. However, the mechanism by which this disruption occurs remains unclear. In the current study we examine the effect of the prototypic cyclotides, kalata B1 (kB1) and kalata B2 (kB2), on tethered lipid bilayer membranes (tBLMs) using swept frequency electrical impedance spectroscopy. We confirmed that kB1 and kB2 bind to bilayers only if they contain PE-phospholipids. We hypothesize that the increase in membrane conduction and capacitance observed upon addition of kB1 or kB2 is unlikely to result from ion channel like pores but is consistent with the formation of lipidic toroidal pores. This hypothesis is supported by the concentration dependence of effects of kB1 and kB2 being suggestive of a critical micelle concentration event rather than a progressive increase in conduction arising from increased channel insertion. Additionally, conduction behavior is readily reversible when the peptide is rinsed from the bilayer. Our results support a mechanism by which kB1 and kB2 bind to and disrupt PE-containing membranes by decreasing the overall membrane critical packing parameter, as would a surfactant, which then opens or increases the size of existing membrane defects. The cyclotides need not participate directly in the conductive pore but might exert their effect indirectly through altering membrane packing constraints and inducing purely lipidic conductive pores.

Deng, K, Li, C, Huang, S, Xing, B, Jin, D, Zeng, Q, Hou, Z & Lin, J 2017, 'Recent Progress in Near Infrared Light Triggered Photodynamic Therapy', Small, vol. 13, no. 44, pp. 1702299-1702299.
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AbstractNowadays, photodynamic therapy (PDT) is under the research spotlight as an appealing modality for various malignant tumors. Compared with conventional PDT treatment activated by ultraviolet or visible light, near infrared (NIR) light‐triggered PDT possessing deeper penetration to lesion area and lower photodamage to normal tissue holds great potential for in vivo deep‐seated tumor. In this review, recent research progress related to the exploration of NIR light responsive PDT nanosystems is summarized. To address current obstacles of PDT treatment and facilitate the effective utilization, several innovative strategies are developed and introduced into PDT nanosystems, including the conjugation with targeted moieties, O2 self‐sufficient PDT, dual photosensitizers (PSs)‐loaded PDT nanoplatform, and PDT‐involved synergistic therapy. Finally, the potential challenges as well as the prospective for further development are also discussed.

Fu, L, Morsch, M, Shi, B, Wang, G, Lee, A, Radford, R, Lu, Y, Jin, D & Chung, R 2017, 'A versatile upconversion surface evaluation platform for bio–nano surface selection for the nervous system', Nanoscale, vol. 9, no. 36, pp. 13683-13692.
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There is considerable interest in developing diagnostic nanotools for early detection and delivery of various therapeutic agents for treatment of neurodegenerative diseases.

Gerami, A, Armstrong, RT, Johnston, B, Warkiani, ME, Mosavat, N & Mostaghimi, P 2017, 'Coal-on-a-Chip: Visualizing Flow in Coal Fractures', Energy & Fuels, vol. 31, no. 10, pp. 10393-10403.
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© 2017 American Chemical Society. Geomaterial microfluidics are the next generation of tools necessary for studying fluid flows related to subsurface engineering technologies. Traditional microfluidic devices do not capture surface wettability and roughness parameters that can have a significant influence on porous media flows. This is particularly important for coal seam gas reservoirs in which methane gas is transported through a well-developed system of natural fractures that display unique wettability and roughness characteristics. A coal geomaterial microfluidic device can be generated by etching a fracture pattern on a coal surface by using three-dimensional laser micromachining; however, it is unclear if the resulting surface properties are representative of real coal. In an effort to generate a realistic coal microfluidic device, we characterize coal surface roughness properties from real coal cleats. We then compare these results to the roughness of the patterns, generated from laser etching. Roughness measurements in real coal fractures show that cleats and microfractures are mostly oriented parallel to the coal beddings rather than perpendicular to the bedding, which is important when selecting coal for fabrication of a microfluidic device since we find that the natural microfractures influence the resulting roughness of etched fractures. We also compare resulting coal/brine/gas contact angles under static and dynamics conditions. The contact angle for coal is highly heterogeneous. Surface roughness and pore pressure may influence the contact angle. With the aid of the coal geomaterial device, the effect of these parameters on coal wettability can be explored and a range of possible coal contact angles can be visualized and represented. The geomaterial fabrication, as outlined herein, provides a tool to capture more realistic coal surface properties in microfluidics experiments.

Gholami, A, Amirabad, TN & Maddahfar, M 2017, 'Investigation of photovoltaic properties of silver-doped ZnTiO3 nanoparticles', Journal of Materials Science: Materials in Electronics, vol. 28, no. 20, pp. 15327-15332.
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Guan, R, Zhang, L, Su, QP, Mickolajczyk, KJ, Chen, G-Y, Hancock, WO, Sun, Y, Zhao, Y & Chen, Z 2017, 'Crystal structure of Zen4 in the apo state reveals a missing conformation of kinesin', Nature Communications, vol. 8, no. 1.
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AbstractKinesins hydrolyse ATP to transport intracellular cargoes along microtubules. Kinesin neck linker (NL) functions as the central mechano-chemical coupling element by changing its conformation through the ATPase cycle. Here we report the crystal structure of kinesin-6 Zen4 in a nucleotide-free, apo state, with the NL initial segment (NIS) adopting a backward-docked conformation and the preceding α6 helix partially melted. Single-molecule fluorescence resonance energy transfer (smFRET) analyses indicate the NIS of kinesin-1 undergoes similar conformational changes under tension in the two-head bound (2HB) state, whereas it is largely disordered without tension. The backward-docked structure of NIS is essential for motility of the motor. Our findings reveal a key missing conformation of kinesins, which provides the structural basis of the stable 2HB state and offers a tension-based rationale for an optimal NL length to ensure processivity of the motor.

Hao, H, Su, Q, Zhao, S & Sun, Y 2017, 'Golgi Microtubules are Hyper-Acetylated and Participate in Fast Cargo Trafficking', Biophysical Journal, vol. 112, no. 3, pp. 238a-238a.
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Hernandez-Fernaud, JR, Ruengeler, E, Casazza, A, Neilson, LJ, Pulleine, E, Santi, A, Ismail, S, Lilla, S, Dhayade, S, MacPherson, IR, McNeish, I, Ennis, D, Ali, H, Kugeratski, FG, Al Khamici, H, van den Biggelaar, M, van den Berghe, PVE, Cloix, C, McDonald, L, Millan, D, Hoyle, A, Kuchnio, A, Carmeliet, P, Valenzuela, SM, Blyth, K, Yin, H, Mazzone, M, Norman, JC & Zanivan, S 2017, 'Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity', Nature Communications, vol. 8, no. 1, pp. 1-17.
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AbstractThe secretome of cancer and stromal cells generates a microenvironment that contributes to tumour cell invasion and angiogenesis. Here we compare the secretome of human mammary normal and cancer-associated fibroblasts (CAFs). We discover that the chloride intracellular channel protein 3 (CLIC3) is an abundant component of the CAF secretome. Secreted CLIC3 promotes invasive behaviour of endothelial cells to drive angiogenesis and increases invasiveness of cancer cells both in vivo and in 3D cell culture models, and this requires active transglutaminase-2 (TGM2). CLIC3 acts as a glutathione-dependent oxidoreductase that reduces TGM2 and regulates TGM2 binding to its cofactors. Finally, CLIC3 is also secreted by cancer cells, is abundant in the stromal and tumour compartments of aggressive ovarian cancers and its levels correlate with poor clinical outcome. This work reveals a previously undescribed invasive mechanism whereby the secretion of a glutathione-dependent oxidoreductase drives angiogenesis and cancer progression by promoting TGM2-dependent invasion.

Hossain, KR, Holt, SA, Le Brun, AP, Al Khamici, H & Valenzuela, SM 2017, 'X-ray and Neutron Reflectivity Study Shows That CLIC1 Undergoes Cholesterol-Dependent Structural Reorganization in Lipid Monolayers', Langmuir, vol. 33, no. 43, pp. 12497-12509.
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© 2017 American Chemical Society. CLIC1 belongs to the ubiquitous family of chloride intracellular ion channel proteins that are evolutionarily conserved across species. The CLICs are unusual in that they exist mainly as soluble proteins but possess the intriguing property of spontaneous conversion from the soluble to an integral membrane-bound form. This conversion is regulated by the membrane lipid composition, especially by cholesterol, together with external factors such as oxidation and pH. However, the precise physiological mechanism regulating CLIC1 membrane insertion is currently unknown. In this study, X-ray and neutron reflectivity experiments were performed to study the interaction of CLIC1 with different phospholipid monolayers prepared using POPC, POPE, or POPS with and without cholesterol in order to better understand the regulatory role of cholesterol in CLIC1 membrane insertion. Our findings demonstrate for the first time two different structural orientations of CLIC1 within phospholipid monolayers, dependent upon the absence or presence of cholesterol. In phospholipid monolayers devoid of cholesterol, CLIC1 was unable to insert into the lipid acyl chain region. However, in the presence of cholesterol, CLIC1 showed significant insertion within the phospholipid acyl chains occupying an area per protein molecule of 6-7 nm2 with a total CLIC1 thickness ranging from ∼50 to 56 Å across the entire monolayer. Our data strongly suggests that cholesterol not only facilitates the initial docking or binding of CLIC1 to the membrane but also promotes deeper penetration of CLIC1 into the hydrophobic tails of the lipid monolayer.

Kabakova, IV, Xiang, Y, Paterson, C & Török, P 2017, 'Fiber-integrated Brillouin microspectroscopy: Towards Brillouin endoscopy', Journal of Innovative Optical Health Sciences, vol. 10, no. 06, pp. 1742002-1742002.
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Brillouin imaging (BI) for micromechanical characterization of tissues and biomaterials is a fast-developing field of research with a strong potential for medical diagnosis of disease-modified tissues and cells. Although the principles of BI imply its compatibility with in vivo and in situ measurements, the integration of BI with a flexible catheter, capable of reaching the region of interest within the body, is yet to be reported. Here, for the first time, we experimentally investigate integration of the Brillouin spectroscope with standard optical fiber components to achieve a Brillouin endoscope. The performance of single-fiber and dual-fiber endoscopes are demonstrated and analyzed. We show that a major challenge in construction of Brillouin endoscopes is the strong backward Brillouin scattering in the optical fiber and we present a dual-fiber geometry as a possible solution. Measurements of Brillouin spectra in test liquids (water, ethanol and glycerol) are demonstrated using the dual-fiber endoscope and its performance is analyzed numerically with the help of a beam propagation model.

Kianinia, M, Bradac, C, Wang, F, Sontheimer, B, Tran, TT, Nguyen, M, Kim, S, Xu, Z-Q, Jin, D, Schell, AW, Lobo, CJ, Aharonovich, I & Toth, M 2017, 'Super-resolution imaging of quantum emitters in layered materials', Nature Communications, vol. 9, no. 1, pp. 874-874.
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Layered van der Waals materials are emerging as compelling two-dimensional(2D) platforms for studies of nanophotonics, polaritonics, valleytronics andspintronics, and have the potential to transform applications in sensing,imaging and quantum information processing. Amongst these, hexagonal boronnitride (hBN) is unique in that it hosts ultra-bright, room temperature singlephoton emitters (SPEs). However, an outstanding challenge is to locate SPEs inhBN with high precision, a task which requires breaking the optical diffractionlimit. Here, we report the imaging of SPEs in layered hBN with a spatialresolution of 63 nm using ground state depletion (GSD) nanoscopy. Furthermore,we show that SPEs in hBN possess nonlinear photophysical properties which canbe used to realize a new variant of GSD that employs a coincident pair ofdoughnut-shaped lasers to reduce the laser power that is needed to achieve agiven resolution target. Our findings expand the current understanding of thephotophysics of quantum emitters in layered hBN and demonstrate the potentialfor advanced nanophotonic and bio-imaging applications which requirelocalization of individual emitters with super-resolution accuracy.

Kulasinghe, A, Perry, C, Kenny, L, Warkiani, ME, Nelson, C & Punyadeera, C 2017, 'PD-L1 expressing circulating tumour cells in head and neck cancers', BMC Cancer, vol. 17, no. 1, pp. 1-6.
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© 2017 The Author(s). Background: Blockade of the PD-1/PD-L1 immune checkpoint pathway is emerging as a promising immunotherapeutic approach for the management and treatment of head and neck cancer patients who do not respond to 1st/2nd line therapy. However, as checkpoint inhibitors are cost intensive, identifying patients who would most likely benefit from anti PD-L1 therapy is required. Developing a non-invasive technique would be of major benefit to the patient and to the health care system. Case presentation: We report the case of a 56 year old man affected by a supraglottic squamous cell carcinoma (SCC). A CT scan showed a 20 mm right jugulodigastric node and suspicious lung lesions. The lung lesion was biopsied and confirmed to be consistent with SCC. The patient was offered palliative chemotherapy. At the time of presentation, a blood sample was taken for circulating tumour cell (CTC) analysis. The dissemination of cancer was confirmed by the detection of CTCs in the peripheral blood of the patient, measured by the CellSearch System (Janssen Diagnostics). Using marker-independent, low-shear spiral microfluidic technology combined with immunocytochemistry, CTC clusters were found in this patient at the same time point, expressing PD-L1. Conclusion: This report highlights the potential use of CTCs to identify patients which might respond to anti PD-L1 therapy.

Kulasinghe, A, Tran, THP, Blick, T, O’Byrne, K, Thompson, EW, Warkiani, ME, Nelson, C, Kenny, L & Punyadeera, C 2017, 'Enrichment of circulating head and neck tumour cells using spiral microfluidic technology', Scientific Reports, vol. 7, no. 1, pp. 1-10.
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AbstractWhilst locoregional control of head and neck cancers (HNCs) has improved over the last four decades, long-term survival has remained largely unchanged. A possible reason for this is that the rate of distant metastasis has not changed. Such disseminated disease is reflected in measurable levels of cancer cells in the blood of HNC patients, referred to as circulating tumour cells (CTCs). Numerous marker-independent techniques have been developed for CTC isolation and detection. Recently, microfluidics-based platforms have come to the fore to avoid molecular bias. In this pilot, proof of concept study, we evaluated the use of the spiral microfluidic chip for CTC enrichment and subsequent detection in HNC patients. CTCs were detected in 13/24 (54%) HNC patients, representing both early to late stages of disease. Importantly, in 7/13 CTC-positive patients, CTC clusters were observed. This is the first study to use spiral microfluidics technology for CTC enrichment in HNC.

Kwon, T, Prentice, H, Oliveira, JD, Madziva, N, Warkiani, ME, Hamel, J-FP & Han, J 2017, 'Microfluidic Cell Retention Device for Perfusion of Mammalian Suspension Culture', Scientific Reports, vol. 7, no. 1, pp. 1-11.
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AbstractContinuous production of biologics, a growing trend in the biopharmaceutical industry, requires a reliable and efficient cell retention device that also maintains cell viability. Current filtration methods, such as tangential flow filtration using hollow-fiber membranes, suffer from membrane fouling, leading to significant reliability and productivity issues such as low cell viability, product retention, and an increased contamination risk associated with filter replacement. We introduce a novel cell retention device based on inertial sorting for perfusion culture of suspended mammalian cells. The device was characterized in terms of cell retention capacity, biocompatibility, scalability, and long-term reliability. This technology was demonstrated using a high concentration (>20 million cells/mL) perfusion culture of an IgG1-producing Chinese hamster ovary (CHO) cell line for 18–25 days. The device demonstrated reliable and clog-free cell retention, high IgG1 recovery (>99%) and cell viability (>97%). Lab-scale perfusion cultures (350 mL) were used to demonstrate the technology, which can be scaled-out with parallel devices to enable larger scale operation. The new cell retention device is thus ideal for rapid perfusion process development in a biomanufacturing workflow.

Lei, L, Wu, R, Zhou, J, Zhang, S, Xiao, Z, Zhang, J & Xu, S 2017, 'The enhanced 1830nm emission in Yb/Tm:NaYF4@NaYF4 active-core/inert-shell nanocrystals', Materials Letters, vol. 189, pp. 35-37.
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The strong 1830 nm emission is realized in Yb/Tm:NaYF4@Yb:NaYF4 core/shell nanocrystals for the first time. The optimal Tm3+ concentration, shell thickness and composition respectively are 2 mol%, 6.5 nm and inert NaYF4. In comparison with Yb/Tm:NaYF4 nanocrystals, the luminescence intensity of Yb/Tm:NaYF4@NaYF4 core/shell nanocrystals enhances about 160 times.

Li, D, Yang, J, Wen, S, Shen, M, Zheng, L, Zhang, G & Shi, X 2017, 'Targeted CT/MR dual mode imaging of human hepatocellular carcinoma using lactobionic acid-modified polyethyleneimine-entrapped gold nanoparticles', Journal of Materials Chemistry B, vol. 5, no. 13, pp. 2395-2401.
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Multifunctional PEI-entrapped gold nanoparticles modified with lactobionic acid enable efficient targeted dual mode CT/MR imaging of human hepatocellular carcinoma.

Li, H, Lan, R, Chan, C-F, Bao, G, Xie, C, Chu, P-H, Tai, WCS, Zha, S, Zhang, J-X & Wong, K-L 2017, 'A luminescent lanthanide approach towards direct visualization of primary cilia in living cells', Chemical Communications, vol. 53, no. 52, pp. 7084-7087.
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A simple and direct imaging tool (HGEu001) for primary cilia based on long-lived europium luminescence is firstly presented.

Lin, G, Makarov, D & Schmidt, OG 2017, 'Magnetic sensing platform technologies for biomedical applications', Lab on a Chip, vol. 17, no. 11, pp. 1884-1912.
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A review highlighting the historical basis, routes and roadmap of the development of magnetic biosensing platform technologies.

Liu, Y, Lu, Y, Yang, X, Zheng, X, Wen, S, Wang, F, Vidal, X, Zhao, J, Liu, D, Zhou, Z, Ma, C, Zhou, J, Piper, JA, Xi, P & Jin, D 2017, 'Amplified stimulated emission in upconversion nanoparticles for super-resolution nanoscopy', Nature, vol. 543, no. 7644, pp. 229-233.
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Lanthanide-doped glasses and crystals are attractive for laser applications because the metastable energy levels of the trivalent lanthanide ions facilitate the establishment of population inversion and amplified stimulated emission at relatively low pump power. At the nanometre scale, lanthanide-doped upconversion nanoparticles (UCNPs) can now be made with precisely controlled phase, dimension and doping level. When excited in the near-infrared, these UCNPs emit stable, bright visible luminescence at a variety of selectable wavelengths, with single-nanoparticle sensitivity, which makes them suitable for advanced luminescence microscopy applications. Here we show that UCNPs doped with high concentrations of thulium ions (Tm3+), excited at a wavelength of 980 nanometres, can readily establish a population inversion on their intermediate metastable 3H4 level: The reduced inter-emitter distance at high Tm3+ doping concentration leads to intense cross-relaxation, inducing a photon-avalanche-like effect that rapidly populates the metastable 3H4 level, resulting in population inversion relative to the 3H6 ground level within a single nanoparticle. As a result, illumination by a laser at 808 nanometres, matching the upconversion band of the 3H4 - 3H6 transition, can trigger amplified stimulated emission to discharge the 3H4 intermediate level, so that the upconversion pathway to generate blue luminescence can be optically inhibited. We harness these properties to realize low-power super-resolution stimulated emission depletion (STED) microscopy and achieve nanometre-scale optical resolution (nanoscopy), imaging single UCNPs; the resolution is 28 nanometres, that is, 1/36th of the wavelength. These engineered nanocrystals offer saturation intensity two orders of magnitude lower than those of fluorescent probes currently employed in stimulated emission depletion microscopy, suggesting a new way of alleviating the square-root law that typically limits the resolut...

Ma, C, Xu, X, Wang, F, Zhou, Z, Liu, D, Zhao, J, Guan, M, Lang, CI & Jin, D 2017, 'Optimal Sensitizer Concentration in Single Upconversion Nanocrystals', Nano Letters, vol. 17, no. 5, pp. 2858-2864.
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© 2017 American Chemical Society. Each single upconversion nanocrystal (UCNC) usually contains thousands of photon sensitizers and hundreds of photon activators to up-convert near-infrared photons into visible and ultraviolet emissions. Though in principle further increasing the sensitizers’ concentration will enhance the absorption efficiency to produce brighter nanocrystals, typically 20% of Yb3+ ions has been used to avoid the so-called “concentration quenching” effect. Here we report that the concentration quenching effect does not limit the sensitizer concentration and NaYbF4 is the most bright host matrix. Surface quenching and the large size of NaYbF4 nanocrystals are the only factors limiting this optimal concentration. Therefore, we further designed sandwich nanostructures of NaYbF4 between a small template core to allow an epitaxial growth of the size-tunable NaYbF4 shell enclosed by an inert shell to minimize surface quenching. As a result, the suspension containing 25.2 nm sandwich structure UCNCs is 1.85 times brighter than the homogeneously doped ones, and the brightness of each single 25.2 nm heterogeneous UCNC is enhanced by nearly 3 times compared to the NaYF4: 20% Yb3+, 4% Tm3+ UCNCs in similar sizes. Particularly, the blue emission intensities of the UCNCs with the sandwich structure in the size of 13.6 and 25.2 nm are 1.36 times and 3.78 times higher than that of the monolithic UCNCs in the similar sizes. Maximizing the sensitizer concentration will accelerate the development of brighter and smaller UCNCs as more efficient biomolecule probes or photon energy converters.

Maqsood, M, Nawab, Y, Umar, J, Umair, M & Shaker, K 2017, 'Comparison of compression properties of stretchable knitted fabrics and bi-stretch woven fabrics for compression garments', The Journal of The Textile Institute, vol. 108, no. 4, pp. 522-527.
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Marciniak, L, Pilch, A, Arabasz, S, Jin, D & Bednarkiewicz, A 2017, 'Heterogeneously Nd³⁺ doped single nanoparticles for NIR-induced heat conversion, luminescence, and thermometry', Nanoscale, vol. 9, no. 24, pp. 8288-8297.
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© 2017 The Royal Society of Chemistry. The current frontier in nanomaterials engineering is to intentionally design and fabricate heterogeneous nanoparticles with desirable morphology and composition, and to integrate multiple functionalities through highly controlled epitaxial growth. Here we show that heterogeneous doping of Nd3+ ions following a core-shell design already allows three optical functions, namely efficient (η > 72%) light-to-heat conversion, bright NIR emission, and sensitive (SR > 0.1% K-1) localized temperature quantification, to be built within a single ca. 25 nm nanoparticle. Importantly, all these optical functions operate within the transparent biological window of the NIR spectral region (λexc ∼ 800 nm, λemi ∼ 860 nm), in which light scattering and absorption by tissues and water are minimal. We find NaNdF4 as a core is efficient in absorbing and converting 808 nm light to heat, while NaYF4:1%Nd3+ as a shell is a temperature sensor based on the ratio-metric luminescence reading but an intermediate inert spacer shell, e.g. NaYF4, is necessary to insulate the heat convertor and thermometer by preventing the possible Nd-Nd energy relaxation. Moreover, we notice that while temperature sensitivity and luminescence intensity are optically stable, increased excitation intensity to generate heat above room temperature may saturate the sensing capacity of temperature feedback. We therefore propose a dual beam photoexcitation scheme as a solution for possible light-induced hyperthermia treatment.

McNally, R, Alqudah, A, Obradovic, D & McClements, L 2017, 'Elucidating the Pathogenesis of Pre-eclampsia Using In Vitro Models of Spiral Uterine Artery Remodelling', Current Hypertension Reports, vol. 19, no. 11, pp. 93-93.
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© 2017, The Author(s). Purpose of Review: The aim of the study is to perform a critical assessment of in vitro models of pre-eclampsia using complementary human and cell line-based studies. Molecular mechanisms involved in spiral uterine artery (SUA) remodelling and trophoblast functionality will also be discussed. Recent Findings: A number of proteins and microRNAs have been implicated as key in SUA remodelling, which could be explored as early biomarkers or therapeutic targets for prevention of pre-eclampsia. Summary: Various 2D and 3D in vitro models involving trophoblast cells, endothelial cells, immune cells and placental tissue were discussed to elucidate the pathogenesis of pre-eclampsia. Nevertheless, pre-eclampsia is a multifactorial disease, and the mechanisms involved in its pathogenesis are complex and still largely unknown. Further studies are required to provide better understanding of the key processes leading to inappropriate placental development which is the root cause of pre-eclampsia. This new knowledge could identify novel biomarkers and treatment strategies.

Miao, S, He, S, Liang, M, Lin, G, Cai, B & Schmidt, OG 2017, 'Microtubular Fuel Cell with Ultrahigh Power Output per Footprint', Advanced Materials, vol. 29, no. 34, pp. 1607046-1607046.
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A novel realization of microtubular direct methanol fuel cells (µDMFC) with ultrahigh power output is reported by using “rolled‐up” nanotechnology. The microtube (Pt‐RuO2‐RUMT) is prepared by rolling up Ru2O layers coated with magnetron‐sputtered Pt nanoparticles (cat‐NPs). The µDMFC is fabricated by embedding the tube in a fluidic cell. The footprint of per tube is as small as 1.5 × 10−4 cm2. A power density of ≈257 mW cm−2 is obtained, which is three orders of magnitude higher than the present microsized DFMCs. Atomic layer deposition technique is applied to alleviate the methanol crossover as well as improve stability of the tube, sustaining electrolyte flow for days. A laminar flow driven mechanism is proposed, and the kinetics of the fuel oxidation depends on a linear‐diffusion‐controlled process. The electrocatalytic performance on anode and cathode is studied by scanning both sides of the tube wall as an ex situ working electrode, respectively. This prototype µDFMC is extremely interesting for integration with micro‐ and nanoelectronics systems.

Mostafa Hosseinpour-Mashkani, S, Maddahfar, M & Sobhani-Nasab, A 2017, 'Novel silver-doped NiTiO3: auto-combustion synthesis, characterization and photovoltaic measurements', South African Journal of Chemistry, no. 70.
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Nizalapur, S, Kimyon, O, Yee, E, Ho, K, Berry, T, Manefield, M, Cranfield, CG, Willcox, M, Black, DS & Kumar, N 2017, 'Amphipathic guanidine-embedded glyoxamide-based peptidomimetics as novel antibacterial agents and biofilm disruptors', Organic & Biomolecular Chemistry, vol. 15, no. 9, pp. 2033-2051.
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Novel antibacterial peptidomimetics that inhibit the growth of planktonic cells and reduce biofilm formation in both Gram-positive and Gram-negative bacteria.

Rafeie, M, Welleweerd, M, Hassanzadeh-Barforoushi, A, Asadnia, M, Olthuis, W & Ebrahimi Warkiani, M 2017, 'An easily fabricated three-dimensional threaded lemniscate-shaped micromixer for a wide range of flow rates', Biomicrofluidics, vol. 11, no. 1, pp. 014108-014108.
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Mixing fluid samples or reactants is a paramount function in the fields of micro total analysis system (μTAS) and microchemical processing. However, rapid and efficient fluid mixing is difficult to achieve inside microchannels because of the difficulty of diffusive mass transfer in the laminar regime of the typical microfluidic flows. It has been well recorded that the mixing efficiency can be boosted by migrating from two-dimensional (2D) to three-dimensional (3D) geometries. Although several 3D chaotic mixers have been designed, most of them offer a high mixing efficiency only in a very limited range of Reynolds numbers (Re). In this work, we developed a 3D fine-threaded lemniscate-shaped micromixer whose maximum numerical and empirical efficiency is around 97% and 93%, respectively, and maintains its high performance (i.e., >90%) over a wide range of 1 < Re < 1000 which meets the requirements of both the μTAS and microchemical process applications. The 3D micromixer was designed based on two distinct mixing strategies, namely, the inducing of chaotic advection by the presence of Dean flow and diffusive mixing through thread-like grooves around the curved body of the mixers. First, a set of numerical simulations was performed to study the physics of the flow and to determine the essential geometrical parameters of the mixers. Second, a simple and cost-effective method was exploited to fabricate the convoluted structure of the micromixers through the removal of a 3D-printed wax structure from a block of cured polydimethylsiloxane. Finally, the fabricated mixers with different threads were tested using a fluorescent microscope demonstrating a good agreement with the results of the numerical simulation. We envisage that the strategy used in this work would expand the scope of the micromixer technology by broadening the range of efficient working flow rate and providing an easy way to the fabrication of 3D convoluted microstru...

Ramalingam, N, Warkiani, ME & Gong, TH-Q 2017, 'Acetylated bovine serum albumin differentially inhibits polymerase chain reaction in microdevices', Biomicrofluidics, vol. 11, no. 3, pp. 034110-034110.
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Bovine serum albumin (BSA) is widely used as an additive in polymerase chain reaction (PCR)-based microfluidic devices to passivate reactors and alleviate nucleic-acid amplification. BSA is available commercially in two types: either acetylated or non-acetylated. A survey of literature indicates that both types of BSA are used in PCR-based microfluidic devices. Our study results reveal that the use of acetylated BSA in PCR micro-devices leads to differential inhibition of PCR, compared to non-acetylated BSA. This result is noticed for the first time, and the differential inhibition generally goes un-noticed, as compared to complete PCR inhibition.

Razmjou, A, Asadnia, M, Ghaebi, O, Yang, H-C, Ebrahimi Warkiani, M, Hou, J & Chen, V 2017, 'Preparation of Iridescent 2D Photonic Crystals by Using a Mussel-Inspired Spatial Patterning of ZIF-8 with Potential Applications in Optical Switch and Chemical Sensor', ACS Applied Materials & Interfaces, vol. 9, no. 43, pp. 38076-38080.
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© 2017 American Chemical Society. In this work, spatial patterning of a thin, dense, zeolitic imidazolate framework (ZIF-8) pattern was generated using photolithography and nanoscale (60 nm) dopamine coating. A bioinspired, unique, reversible, two-color iridescent pattern can be easily obtained for potential applications in sensing and photonics.

Rong, Y, Wang, D, Xu, C, Ji, Y, Jin, D, Wu, W, Xu, X, Kuang, T & Lou, W 2017, 'Prognostic value of histological subtype in intraductal papillary mucinous neoplasm of the pancreas', Medicine, vol. 96, no. 15, pp. e6599-e6599.
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Sadraeian, M, Guimarães, FEG, Araújo, APU, Worthylake, DK, LeCour, L & Pincus, SH 2017, 'Selective cytotoxicity of a novel immunotoxin based on pulchellin A chain for cells expressing HIV envelope', Scientific Reports, vol. 7, no. 1.
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AbstractImmunotoxins (ITs), which consist of antibodies conjugated to toxins, have been proposed as a treatment for cancer and chronic infections. To develop and improve the ITs, different toxins such as ricin, have been used, aiming for higher efficacy against target cells. The toxin pulchellin, isolated from theAbrus pulchellusplant, has similar structure and function as ricin. Here we have compared two plant toxins, recombinant A chains from ricin (RAC) and pulchellin (PAC) toxins, for their ability to kill HIV Env-expressing cells. In this study, RAC and PAC were produced inE. coli, and chromatographically purified, then chemically conjugated to two different anti-HIV monoclonal antibodies (MAbs), anti-gp120 MAb 924 or anti-gp41 MAb 7B2. These conjugates were characterized biochemically and immunologically. Cell internalization was studied by flow cytometry and confocal microscopy. Results showed that PAC can function within an effective IT. The ITs demonstrated specific binding against native antigens on persistently HIV-infected cells and recombinant antigens on Env-transfected cells. PAC cytotoxicity appears somewhat less than RAC, the standard for comparison. This is the first report that PAC may have utility for the design and construction of therapeutic ITs, highlighting the potential role for specific cell targeting.

Sengupta, D, Kottapalli, AGP, Chen, SH, Miao, JM, Kwok, CY, Triantafyllou, MS, Warkiani, ME & Asadnia, M 2017, 'Characterization of single polyvinylidene fluoride (PVDF) nanofiber for flow sensing applications', AIP Advances, vol. 7, no. 10, pp. 105205-105205.
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The use of Polyvinylidene Fluoride (PVDF) based piezoelectric nanofibers for sensing and actuation has been reported widely in the past. However, in most cases, PVDF piezoelectric nanofiber mats have been used for sensing applications. This work fundamentally characterizes a single electrospun PVDF nanofiber and demonstrates its application as a sensing element for nanoelectromechanical sensors (NEMS). PVDF nanofiber mats were spun by far field electrospinning (FFES) process and complete material characterization was conducted by means of scanning electron microscope (SEM) imaging, Raman Spectroscopy and FTIR spectroscopy. An optimized recipe was developed for spinning a single suspended nanofiber on a specially designed MEMS substrate which allows the nano-mechanical and electrical characterization of a single PVDF nanofiber. Electrical characterization is conducted using a single suspended nanofiber to determine the piezoelectric coefficient (d33) of the nanofiber to be -58.77 pm/V. Also the mechanical characterization conducted using a nanoindenter revealed a Young’s Modulus and hardness of 2.2 GPa and 0.1 GPa respectively. Finally, an application that utilizes the single PVDF nanofiber as a sensing element to form a NEMS flow sensor is demonstrated. The single nanofiber flow sensor is tested in presence of various oscillatory flow conditions.

Shakeel Syed, M, Rafeie, M, Henderson, R, Vandamme, D, Asadnia, M & Ebrahimi Warkiani, M 2017, 'A 3D-printed mini-hydrocyclone for high throughput particle separation: application to primary harvesting of microalgae', Lab on a Chip, vol. 17, no. 14, pp. 2459-2469.
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3D-printed hydrocyclones are low-cost microdevices which be part of a library of standardized active and passive microfluidic components, suitable for particle–liquid separation.

Shi, B, Zheng, M, Tao, W, Chung, R, Jin, D, Ghaffari, D & Farokhzad, OC 2017, 'Challenges in DNA Delivery and Recent Advances in Multifunctional Polymeric DNA Delivery Systems', Biomacromolecules, vol. 18, no. 8, pp. 2231-2246.
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© 2017 American Chemical Society. After more than 20 years of intensive investigations, gene therapy has become one of the most promising strategies for treating genetic diseases. However, the lack of ideal delivery systems has limited the clinical realization of gene therapy's tremendous potential, especially for DNA-based gene therapy. Over the past decade, considerable advances have been made in the application of polymer-based DNA delivery systems for gene therapy, especially through multifunctional systems. The core concept behind multifunctional polymeric DNA delivery systems is to endow one single DNA carrier, via materials engineering and surface modification, with several active functions, e.g., good cargo DNA protection, excellent colloidal stability, high cellular uptake efficiency, efficient endo/lysosome escape, effective import into the nucleus, and DNA unpacking. Such specially developed vectors would be capable of overcoming multiple barriers to the successful delivery of DNA. In this review, we first provide a comprehensive overview of the interactions between the protein corona and DNA vectors, the mechanisms and challenges of nonviral DNA vectors, and important concepts in the design of DNA carriers identified via past reports on DNA delivery systems. Finally, we highlight and discuss recent advances in multifunctional polymeric DNA delivery systems based on 'off-the-shelf' polycations including polyethylenimine (PEI), poly-l-lysine (PLL), and chitosan and offer perspectives on future developments.

Shirani, E, Razmjou, A, Tavassoli, H, Landarani-Isfahani, A, Rezaei, S, Abbasi Kajani, A, Asadnia, M, Hou, J & Ebrahimi Warkiani, M 2017, 'Strategically Designing a Pumpless Microfluidic Device on an “Inert” Polypropylene Substrate with Potential Application in Biosensing and Diagnostics', Langmuir, vol. 33, no. 22, pp. 5565-5576.
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© 2017 American Chemical Society. This study is an attempt to make a step forward to implement the very immature concept of pumpless transportation of liquid into a real miniaturized device or lab-on-chip (LOC) on a plastic substrate. 'Inert' plastic materials such as polypropylene (PP) are used in a variety of biomedical applications but their surface engineering is very challenging. Here, it was demonstrated that with a facile innovative wettability patterning route using fluorosilanized UV-independent TiO2 nanoparticle coating it is possible to create wedge-shaped open microfluidic tracks on inert solid surfaces for low-cost biomedical devices (lab-on-plastic). For the future miniaturization and integration of the tracks into a device, a variety of characterization techniques were used to not only systematically study the surface patterning chemistry and topography but also to have a clear knowledge of its biological interactions and performance. The effect of such surface architecture on the biological performance was studied in terms of static/dynamic protein (bovine serum albumin) adsorption, bacterial (Staphylococcus aureus and Staphylococcus epidermidis) adhesion, cell viability (using HeLa and MCF-7 cancer cell lines as well as noncancerous human fibroblast cells), and cell patterning (Murine embryonic fibroblasts). Strategies are discussed for incorporating such a confined track into a diagnostic device in which its sensing portion is based on protein, microorganism, or cells. Finally, for the proof-of-principle of biosensing application, the well-known high-affinity molecular couple of BSA-antiBSA as a biological model was employed.

Sobhani-Nasab, A, Zahraei, Z, Akbari, M, Maddahfar, M & Hosseinpour-Mashkani, SM 2017, 'Synthesis, characterization, and antibacterial activities of ZnLaFe 2 O 4 /NiTiO 3 nanocomposite', Journal of Molecular Structure, vol. 1139, pp. 430-435.
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Song, W, Lin, G, Ge, J, Fassbender, J & Makarov, D 2017, 'Encoding Microreactors with Droplet Chains in Microfluidics', ACS Sensors, vol. 2, no. 12, pp. 1839-1846.
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© 2017 American Chemical Society. Droplet-based high throughput biomolecular screening and combinatorial synthesis entail a viable indexing strategy to be developed for the identification of each microreactor. Here, we propose a novel indexing scheme based on the generation of droplet sequences on demand to form unique encoding droplet chains in fluidic networks. These codes are represented by multiunit and multilevel droplets packages, with each code unit possessing several distinct signal levels, potentially allowing large encoding capacity. For proof of concept, we use magnetic nanoparticles as the encoding material and a giant magnetoresistance (GMR) sensor-based active sorting system supplemented with an optical detector to generate and decode the sequence of one exemplar sample droplet reactor and a 4-unit quaternary magnetic code. The indexing capacity offered by 4-unit multilevel codes with this indexing strategy is estimated to exceed 104, which holds great promise for large-scale droplet-based screening and synthesis.

Su, QP, Du, W, Ji, Q, Xue, B, Jiang, D, Zhu, Y, Ren, H, Zhang, C, Lou, J, Yu, L & Sun, Y 2017, 'Correction: Corrigendum: Vesicle Size Regulates Nanotube Formation in the Cell', Scientific Reports, vol. 7, no. 1, p. 40108.
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Scientific Reports 6: Article number: 24002; published online: 07 April 2016; updated: 09 February 2017 He Ren and Chuanmao Zhang were omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article, as well as the Supplementary Information that now accompanies the Article.

T. Chorsi, H, Zhu, Y & Zhang, JXJ 2017, 'Patterned Plasmonic Surfaces—Theory, Fabrication, and Applications in Biosensing', Journal of Microelectromechanical Systems, vol. 26, no. 4, pp. 718-739.
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Low-profile patterned plasmonic surfaces are synergized with a broad class of silicon microstructures to greatly enhance near-field nanoscale imaging, sensing, and energy harvesting coupled with far-field free-space detection. This concept has a clear impact on several key areas of interest for the MEMS community, including but not limited to ultra-compact microsystems for sensitive detection of small number of target molecules, and 'surface' devices for optical data storage, micro-imaging and displaying. In this paper, we review the current state-of-the-art in plasmonic theory as well as derive design guidance for plasmonic integration with microsystems, fabrication techniques, and selected applications in biosensing, including refractive-index based label-free biosensing, plasmonic integrated lab-on-chip systems, plasmonic near-field scanning optical microscopy and plasmonics on-chip systems for cellular imaging. This paradigm enables low-profile conformal surfaces on microdevices, rather than bulk material or coatings, which provide clear advantages for physical, chemical and biological-related sensing, imaging, and light harvesting, in addition to easier realization, enhanced flexibility, and tunability.

Teng, B, Ma, P, Yu, C, Zhang, X, Feng, Q, Wen, L, Li, C, Cheng, Z, Jin, D & Lin, J 2017, 'Upconversion nanoparticles loaded with eIF4E siRNA and platinum(iv) prodrug to sensitize platinum based chemotherapy for laryngeal cancer and bioimaging', Journal of Materials Chemistry B, vol. 5, no. 2, pp. 307-317.
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Eukaryotic translation initiation factor (eIF) 4E is a valuable marker in cancer prognostics in many human cancers.

Wang, L, Ren, L, Mitchell, D, Casillas-Garcia, G, Ren, W, Ma, C, Xu, XX, Wen, S, Wang, F, Zhou, J, Xu, X, Hao, W, Dou, SX & Du, Y 2017, 'Enhanced energy transfer in heterogeneous nanocrystals for near infrared upconversion photocurrent generation', Nanoscale, vol. 9, no. 47, pp. 18661-18667.
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A heterogeneous NaYF₄:Yb,Tm@ZnO nanoparticle with an epitaxial interface is prepared, and it possesses an enhanced upconversion emission intensity and an excellent photocurrent response.

Wang, S, Clapper, A, Chen, P, Wang, L, Aharonovich, I, Jin, D & Li, Q 2017, 'Tuning Enhancement Efficiency of Multiple Emissive Centers in Graphene Quantum Dots by Core–Shell Plasmonic Nanoparticles', The Journal of Physical Chemistry Letters, vol. 8, no. 22, pp. 5673-5679.
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© 2017 American Chemical Society. Graphene quantum dots (GQDs) are emerging luminescent nanomaterials for energy, bioimaging, and optoelectronic applications. However, unlike conventional fluorophores, GQDs contain multiple emissive centers that result in a complex interaction with external electromagnetic fields. Here we utilize core-shell plasmonic nanoparticles to simultaneously enhance and modulate the photoluminescence (PL) intensities and spectral profiles of GQDs. By analyzing the spectral profiles, we show that the emissive centers are highly influenced by the proximity to the metal particles. Under optimal spacer thickness of 25 nm, the overall PL displays a four-fold enhancement compared with a pristine GQD. However, detailed lifetime measurements indicate the presence of midgap states that act as the bottleneck for further enhancement. Our results offer new perspectives for fundamental understanding and new design of functional luminescent materials (e.g., GQDs, graphene oxide, carbon dots) for imaging, sensing, and light harvesting.

Wen, S, Zhao, L, Zhao, Q, Li, D, Liu, C, Yu, Z, Shen, M, Majoral, J-P, Mignani, S, Zhao, J & Shi, X 2017, 'A promising dual mode SPECT/CT imaging platform based on^99mTc-labeled multifunctional dendrimer-entrapped gold nanoparticles', Journal of Materials Chemistry B, vol. 5, no. 21, pp. 3810-3815.
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Multifunctional^99mTc-labeled dendrimer-entrapped gold nanoparticles modified with different surface groups can be used for preferential SPECT/CT imaging of different organs.

Wu, G, Jiang, Y, Zhu, X, Jin, D, Han, Y, Han, J, Wu, Z & Wu, Z 2017, 'Prevalence and risk factors for complications in adult patients with short bowel syndrome receiving long-term home parenteral nutrition.', Asia Pac J Clin Nutr, vol. 26, no. 4, pp. 591-597.
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BACKGROUND AND OBJECTIVES: Short bowel syndrome (SBS) is a complicated and challenging disease where home parenteral nutrition (HPN) is widely used. The complications of long-term HPN-dependent in adult patients with SBS are poorly documented. This study was mainly aimed to assess the prevalence and risk factors of HPNassociated complications in adult patients with SBS, especially the catheter-related sepsis and HPN-associated liver/biliary disorders. METHODS AND STUDY DESIGN: 47 non-malignant adult patients with SBS who received HPN for more than 2 years in our clinical nutrition center were included. Patients were divided into two groups according to whether HPN-associated complications were present or not. Student's t-test and χ2 test were applied to compare the differences between the two groups. RESULTS: The mean frequency of catheter-related sepsis was 0.31±0.05 per catheter year of HPN. An higher incidence of catheter-related infections (p<0.001) and shorter delay between HPN onset and first infection (p<0.001) were identified as risk factors for catheter-related sepsis. A total of 25 patients (53.2%) developed HPN-associated liver/biliary diseases. The identified risk factors for HPNassociated liver/biliary disorders were higher rate of catheter-related infections (p=0.009), shorter delay between HPN onset and first infection (p=0.017), higher energy content of HPN (p=0.014), higher glucose rate of HPN (p=0.009), and lower lipid rate of HPN (p=0.022). CONCLUSION: Our study revealed that adult patients with SBS receiving long-term HPN treatment developed a low prevalence of catheter-related sepsis but a rather high prevalence of HPN-associated liver/biliary disorders. We also identified several risk factors for HPN-associated complications which should be taken notice of in clinical practice.

Wu, R, Zhou, J, Lei, L, Zhang, S, Xiao, Z, Zhang, J & Xu, S 2017, 'α-NaYF4:Yb3+-Tm3+@CaF2 nanocrystals for NIR-to-NIR temperature sensing', Chemical Physics Letters, vol. 667, pp. 206-210.
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© 2016 The approach of lanthanides doping upconversion temperature sensing exhibits high superiority in bioscience. However, most of the upconversion nanothermometers show their fluorescences temperature sensing beyond biological transparent window (650–950 nm) while suffering from the interference of surrounding environment. Here we report a nanoprobe with ultrasmall size, i.e. α-NaYF4:Yb-Tm@CaF2 nanocrystal, which has a sensitive capability to realize NIR-to-NIR temperature sensing. Temperature sensing sensitivities through 3H4 → 3H6 and 1G4 → 3H6 transitions of Tm3+ ions are evaluated in temperature region of 313–373 K. The results indicate that α-NaYF4:Yb-Tm@CaF2 nanocrystal is a promising candidate for biological temperature sensing.

Xie, J, Xie, X, Mi, C, Gao, Z, Pan, Y, Fan, Q, Su, H, Jin, D, Huang, L & Huang, W 2017, 'Controlled Synthesis, Evolution Mechanisms, and Luminescent Properties of ScF_x:Ln (x = 2.76, 3) Nanocrystals', Chemistry of Materials, vol. 29, no. 22, pp. 9758-9766.
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© 2017 American Chemical Society. Kinetic or thermodynamic control has been employed to guide the selective synthesis of conventional organic compounds, and it should be a powerful tool as well for accessing unusual inorganic nanocrystals, particularly when a series of members with similar chemical compositions and phase structures exist. Indeed, a comprehensive mapping of the energy barrier distribution of each nanocrystal in a predefined reaction system will enable not only the precise synthesis of nanocrystals with expected sizes, morphologies, phase structures, and ultimately functionalities, but also disclosure of the evolution details of nanocrystals from one structure to another. Using ScFx:Ln (x = 2.76, 3) series as a proof-of-concept, we have successfully mapped out the energy barriers that correspond to each of the ScFx:Ln nanocrystals, unraveled suitable temperatures for each type of nanocrystal formation, recorded their phase transition procedures, and also discovered the relationships of the products at each reaction stage. To testify how this approach allows one to tailor the structure-related optical properties, different lanthanide-doped ScFx nanocrystals were synthesized and a wide-range of luminescence fine-tuning was achieved, which not only showcases high quality of the nanocrystals, but also provides more candidates for various luminescence applications, especially when single-particle upconversion emission is required.

Xu, X, Clarke, C, Ma, C, Casillas, G, Das, M, Guan, M, Liu, D, Wang, L, Tadich, A, Du, Y, Ton-That, C & Jin, D 2017, 'Depth-profiling of Yb³⁺ sensitizer ions in NaYF₄ upconversion nanoparticles', Nanoscale, vol. 9, no. 23, pp. 7719-7726.
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© 2017 The Royal Society of Chemistry. Enhancing the efficiency of upconversion nanoparticles (UCNPs) and therefore their brightness is the critical goal for this emerging material to meet growing demands in many potential applications including sensing, imaging, solar energy conversion and photonics. The distribution of the photon sensitizer and activator ions that form a network of energy transfer systems within each single UCNP is vital for understanding and optimizing their optical properties. Here we employ synchrotron-based X-ray Photoelectron Spectroscopy (XPS) to characterize the depth distribution of Yb3+ sensitizer ions in host NaYF4 nanoparticles and systematically correlate the structure with the optical properties for a range of UCNPs with different sizes and doping concentrations. We find a radial gradient distribution of Yb3+ from the core to the surface of the NaYF4 nanoparticles, regardless of their size or the sensitizer's concentration. Energy dispersive X-ray Spectroscopy (EDX) was also used to further confirm the distribution of the sensitizer ions in the host matrix. These results have profound implications for the upconversion optical property variations.

Yang, Y, Zhu, Y, Zhou, J, Wang, F & Qiu, J 2017, 'Integrated Strategy for High Luminescence Intensity of Upconversion Nanocrystals', ACS Photonics, vol. 4, no. 8, pp. 1930-1936.
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© 2017 American Chemical Society. The growing applications of upconversion nanocrystals in bioimaging, therapeutics, and photonics have given rise to a demand of high quality nanocrystals with desirable luminescence intensity. Although the design of optimal nanocrystals such as core-shell nanostructures has improved the intensity, the internal links between dopant concentration balance, epitaxial growth protection, and shell thickness effect encounter a compromised situation that lacks of integrated consideration and comprehensive assessment. Here we propose an integrated strategy based on a core-shell design for the enhancement of upconversion luminescence intensity. Epitaxial protection can enable higher activator accommodation capacity in limited spatial scale, which leads to an Er3+ concentration threshold improvement in β-NaYF4 core-shell nanocrystals from 2 to 6 mol %. We further perform a comprehensive assessment of the nanocrystals with convincing performance improvement in ensemble spectroscopic intensity, upconversion quantum yield, and single nanocrystal intensity. Our findings provide improved understanding of electronic behaviors in multiphoton upconversion and opportunities for diverse applications requiring high quality upconversion nanocrystals.

Yu, TT, Nizalapur, S, Ho, KKK, Yee, E, Berry, T, Cranfield, CG, Willcox, M, Black, DS & Kumar, N 2017, 'Design, Synthesis and Biological Evaluation of N‐Sulfonylphenyl glyoxamide‐Based Antimicrobial Peptide Mimics as Novel Antimicrobial Agents', ChemistrySelect, vol. 2, no. 12, pp. 3452-3461.
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AbstractAntibiotic resistance is a major global health concern. There is an urgent need for the development of novel antimicrobials. Recently, phenylglyoxamide‐based small molecular antimicrobial peptide mimics have been identified as potential new leads to treat bacterial infections. Here, we describe the synthesis of novel phenylglyoxamide derivatives via the ring‐opening reaction of N‐sulfonylisatins with primary amines, followed by conversion into hydrochloride, quaternary ammonium iodide or gunidinium salts. The antibacterial activity of the compounds against Staphylococcus aureus was evaluated by in vitro assays. Structure‐activity relationship studies revealed that 5‐bromo‐substituent at the phenyl ring, octyl group appended to the ortho sulfonamide group or guanidine hydrochloride salt as the terminal group significantly contributed to potency. The most potent compound, the gunidinium salt 35 d, exhibited a minimum inhibitory concentration value of 12 μM and a therapeutic index of 15. It also demonstrated its potential to act as antimicrobial pore‐forming agent. Overall, the results identified 35 d as a new lead antimicrobial compound.

Zou, R, Huang, J, Shi, J, Huang, L, Zhang, X, Wong, K-L, Zhang, H, Jin, D, Wang, J & Su, Q 2017, 'Silica shell-assisted synthetic route for mono-disperse persistent nanophosphors with enhanced in vivo recharged near-infrared persistent luminescence', Nano Research, vol. 10, no. 6, pp. 2070-2082.
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© 2016, Tsinghua University Press and Springer-Verlag Berlin Heidelberg. Near-infrared (NIR) persistent-luminescence nanoparticles have emerged as a new class of background-free contrast agents that are promising for in vivo imaging. The next key roadblock is to establish a robust and controllable method for synthesizing monodisperse nanoparticles with high luminescence brightness and long persistent duration. Herein, we report a synthesis strategy involving the coating/etching of the SiO2 shell to obtain a new class of small NIR highly persistent luminescent ZnGa2O4:Cr3+,Sn4+ (ZGOCS) nanoparticles. The optimized ZGOCS nanoparticles have an excellent size distribution of ~15 nm without any agglomeration and an NIR persistent luminescence that is enhanced by a factor of 13.5, owing to the key role of the SiO2 shell in preventing nanoparticle agglomeration after annealing. The ZGOCS nanoparticles have a signal-to-noise ratio ~3 times higher than that of previously reported ZnGa2O4:Cr3+ (ZGC-1) nanoparticles as an NIR persistent-luminescence probe for in vivo bioimaging. Moreover, the persistent-luminescence signal from the ZGOCS nanoparticles can be repeatedly re-charged in situ with external excitation by a white lightemitting diode; thus, the nanoparticles are suitable for long-term in vivo imaging applications. Our study suggests an improved strategy for fabricating novel high-performance optical nanoparticles with good biocompatibility.

Alqudah, A, McNally, R, Connell, A, Lyons, T, Grieve, D, Robson, T & McClements, L 1970, 'Irish Endocrine Society 41st Annual Meeting, 13th and 14th October 2017, Grand Hotel, Malahide, Dublin', Irish Journal of Medical Science (1971 -), Irish Endocrine Society 41st Annual Meeting, Springer Science and Business Media LLC, Malahide, Dublin, pp. 343-385.
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People with diabetes show five-fold higher incidence of cardiovascular disease, the leading causes of death globally. FKBPL is a novel angiogenesisrelated protein, with a critical role in physiological and pathological angiogenesis. A first-in-class clinical FKBPL peptide mimetic, ALM201, is currently in phase I/II clinical trials for treatment of solid tumours. More recently, in FKBPL knockdown (FKBPL+/-) mice, a pro-angiogenic phenotype was observed, accompanied by vascular dysfunction and a propensity to become overweight and glucose intolerant when fed a high fat diet. We now investigate a specific role for FKBPL in myocardial angiogenesis associated with diabetes. In streptozotocin (STZ) mice, cardiac FKBPL mRNA levels were significantly downregulated at 12 weeks post STZ injection versus vehicle controls (p<0.05, n=5), in association with diastolic dysfunction (e.g. mitral valve E/A ratio). This was in concert with a reduction of FKBPL protein in hearts from STZ-induced vs. control diabetic rats (p<0.01, n=3), also at 12 weeks. Complementary in vitro studies in cultured endothelial cells (HUVEC) demonstrated two-fold reduction in FKBPL protein levels following exposure to hypoxia (1%) for 24 h (p<0.01, n=6), indicating that reduced FKBPL levels observed in vivo may be, at least in part, driven by impaired oxygenation. Indeed, in an experimental mouse model of myocardial infarction (MI), associated with severe cardiac ischaemia/hypoxia and increased angiogenesis, FKBPL mRNA (p<0.05) and protein levels (p<0.01) were downregulated versus sham controls (n≥3). In conclusion, FKBPL may be a key early regulator of cardiac angiogenesis in diabetes, and may thereby hold novel biomarker and therapeutic potential.

Alzahid, Y, Mostaghimi, P, Warkiani, ME, Armstrong, RT, Joekar-Niasar, V & Karadimitriou, N 1970, 'Alkaline Surfactant Polymer Flooding: What Happens at the Pore Scale?', Day 2 Tue, June 13, 2017, SPE Europec featured at 79th EAGE Conference and Exhibition, SPE, pp. 386-402.
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Abstract Alkaline-surfactant-polymer (ASP) flooding is a Chemical Enhanced Oil Recovery (CEOR) method whereby alkali, surfactant and polymer are injected as the same slug. It is one of the most promising world-wide focus of CEOR research and field trials, due to the unique synergy of the three chemical components. Polymers increase the viscosity of injected water, which improves macroscopic sweep efficiency by stabilizing the displacing front and counteracting heterogeneity effects. Surfactants, on the other hand, decrease the interfacial tension between the injected water and crude oil, which improves microscopic displacement efficiency by mobilizing trapped oil. Alkaline chemicals generate soap when reacting with crude oil, which reduces surfactant adsorption to grain surfaces. To fully understand the flow mechanisms in oil reservoirs and develop efficient recovery methods, it is essential to recognize the physics at the pore scale since this is the length scale at which capillary-trapped oil is mobilized. We developed an experimental micro-scale approach in which oil recovery is analyzed using microfluidics. The micromodels are fabricated based on: (1) a pore network generated via a Delaunay triangulation with an average pore size of 60 µm, (2) X-ray micro-Computed Tomography images of Bentheimer sandstone with resolution of 4.95 µm, and (3) a fractured network with a porosity of 10%. The networks are etched into silicon wafers and used to fabricate polydimethylsiloxane (PDMS) microfluidic devices. We compare not only oil recovery with ASP flooding between different porous networks but we also study displacement mechanisms and pore scale emulsion formation for ASP formulations that exhibit Winsor Type II+, II- and III behaviour. Our studies elucidate micro-scale oil recovery mechanisms for different ASP flooding scenarios. Our results provide direct visualization of the micro-scale phenomena occurring d...

Asadnia, M, Kottapalli, AGP, Warkiani, ME, Miao, JM & Triantafyllou, MS 1970, 'Engineering miniaturized hair cell sensors for auditory system', 2017 IEEE 30th International Conference on Micro Electro Mechanical Systems (MEMS), 2017 IEEE 30th International Conference on Micro Electro Mechanical Systems (MEMS), IEEE, Las Vegas, NV, pp. 1173-1176.
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© 2017 IEEE. Mechanosensory haircells are well-evolved biological sensors found in nature. In this paper, we present a novel artificial NEMS stereovilli sensor developed through novel fabrication techniques. The NEMS stereovilli sensor fabrication combines soft-polymer material synthesis methods and nanofiber generation techniques with conventional microfabrication methods to form novel flow sensors. The sensor fabrication mainly consists of three major steps which are 1) fabrication of artificial stereovilli of varying aspect ratios, 2) formation of nanofiber tip-links through electrospinning of PVDF material and 3) development of biomimetic HA-MA hydrogel cupula. These artificial sensors closely mimic stereovilli and achieve ultrahigh sensitivities through a biomimetic design. The sensors achieve a sensitivity and threshold detection limit of 300 mV/(m/s) and 8 μm/s, respectively.

Fu, LB, Shi, BY, Jin, DY & Chung, R 1970, 'Versatile upconversion surfaces evaluation platform for bio-nano surface selection for nervous system', 2017 IEEE 17th International Conference on Nanotechnology (IEEE-NANO), 2017 IEEE 17th International Conference on Nanotechnology (IEEE-NANO), IEEE, Pittsburgh, PA, USA, pp. 932-933.
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© 2017 IEEE. Neurodegenerative disorder diseases have been perplexing physicians and scientists for many years. There is considerable interest in developing diagnostic nanotools for diagnosis and therapeutic treatment strategies for the neuron diseases. However, a key challenge remains in selection of suitable surface to overcome the nano-bio interface issue as many nanoparticles indicate instability when administered into biological environments and show serious cytotoxicity to sensitive central nervous system. We have developed new-generation upconversion nanoparticles (UCNPs) which represent a promising model nanoparticle for suitable evaluation due to its superior properties in bio photonics.

Ghorbani, S, Razavi Bazaz, S, Ebrahimi Warkiani, M, Soleimani, M & Abouei Mehrizi, A 1970, 'Evaluation of Nanofiber PLA Scaffolds Using Dry-and Wet-Electro Spinning Methods', 2017 24th National and 2nd International Iranian Conference on Biomedical Engineering (ICBME), 2017 24th National and 2nd International Iranian Conference on Biomedical Engineering (ICBME), IEEE, Tehran, IRAN, pp. 89-94.
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© 2017 IEEE. Investigating the fabrication of a favorable scaffold is a continuing sconcern and an essential step within tissue engineering. An ideal scaffold should mimic the structure of extracellular matrix (ECM) which has considerable impacts on its function. To meet this demands, in this study, three-dimensional scaffolds by polylactic acid (PLA) polymer 10%, 13%, 15%, 17% and 20% (w/v) with a novel architecture produced by a wet-electrospinning process have been fabricated and compared with dry-electrospun scaffolds that have been developed for tissue engineering applications. In the wet-electrospinning method, an aqueous solution of sodium hydroxide (NaOH) (pH∼13) has been used as the coagulation bath instead of the aluminum collector which is used in the dry method. Comparing with usual nanofiber non-woven PLA fabric prepared by a conventional electrospinning method, wet-electrospun spongiform PLA nanofiber scaffolds have low apparent density and high porosity. The porosity of the scaffolds has been examined in this two methods and their mechanical properties as well as their morphology are investigated. All in all, it is shown that the novel nanofiber fabrication system would be amazingly useful for the structure control of the nanofiber fabric.

McClements, L, McNally, R, Alqudah, A, Robson, T, Watson, C & Lyons, T 1970, '53 rd EASD Annual Meeting of the European Association for the Study of Diabetes', Diabetologia, 53 rd EASD Annual Meeting of the European Association for the Study of Diabetes, Springer Science and Business Media LLC, Lisbon, Portugal, pp. 1-608.
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Background and aims: Diabetic vascular complications are closely related to irregular angiogenesis, oxidative stress and lipid peroxidation.Preeclampsia (PE) is a pregnancy condition characterised by high bloodpressure, proteinuria and multi-organ dysfunction. PE occurs in 4-6% ofpregnancies; however in women with diabetes the incidence of PE isincreased four-fold. Furthermore, PE does not only have short-term risks,but long-term is associated with cardiovascular disease and/or Type 2diabetes in both mothers and offspring. Despite research efforts in thisarea, currently there are no reliable early biomarkers, preventative ortreatment strategies for PE, other than delivery. Moreover, paucity ofmechanistic data is impeding the development of successful preventativeand curative therapies of PE, particularly in the context of diabetes. The novel angiogenesis-related protein, FKBPL, is a critical regulator of developmental and pathological angiogenesis and closely associated with nutrient-sensing protein, SIRT-1. Therefore, FKBPL may play a key role in the pathophysiology of PE associated with diabetes.Materials and methods: Three different trophoblast cells lines(HTR8.SV.neo, BeWo and Jar) were exposed to diabetic stimuli: normalvs. high glucose (5.5 vs. 10, 20, 40 mM), native vs. highly oxidised,glycated low density lipoprotein (N- vs. HOG-LDL; 25 μg protein/ml),or hypoxia (1%); then FKBPL and SIRT-1 protein expression and mRNAlevels were measured in cell lysates. FKBPL and SIRT-1 were also measured in placental extracts using western blotting.Results: FKBPL and SIRT-1 protein expression differed across the threetrophoblast cell lines, with Jar cells expressing the highest levels ofFKBPL and SIRT-1, BeWo cells expressing the lowest level of SIRT-1and HTR8.SV.neo cells expressing the lowest level of FKBPL. In BeWocells treated with high vs. normal glucose (48 h), FKBPL mRNA levelswere increased 1.3-fold (10mM; p=0.001; n=3), 1.21-fold (...

Yang, X, Ma, C, Wang, F, Jin, D & Xi, P 1970, 'Long-term ultra-low-level power STED nanoscopy', International Conference on Photonics and Imaging in Biology and Medicine, International Conference on Photonics and Imaging in Biology and Medicine, OSA.
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Through the strategic application of upconversion rare-earth nanoparticles (UCNPs), this work has reduced the intensity of the traditional super-resolution by 2-3 orders of magnitude. It reveals a new mechanism of stimulated emission caused by the photon avalanche effect. With only 30mW continuous laser, resolution down to 28nm has been attained, which is only 1/36 of the excitation wavelength.

Yang, X, Xie, H, Alonas, E, Liu, Y, Chen, X, Santangelo, PJ, Ren, Q, Xi, P & Jin, D 1970, 'Mirror enhanced STED super-resolution microscopy', 2017 Conference on Lasers and Electro-Optics, CLEO 2017 - Proceedings, Conference on Lasers and Electro-Optics, IEEE, San Jose, CA, USA, pp. 1-2.
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Through reflective interference, the axial thickness of confocal point spread function can be easily improved to 100 nm. Six-fold of axial resolution and two-fold of lateral resolution can be obtained for STED nanoscopy.

Bray, K, Cheung, L, Aharonovich, I, Valenzuela, SM & Shimoni, O 2017, 'Versatile Multicolor Nanodiamond Probes for Intracellular Imaging and Targeted Labeling', Cold Spring Harbor Laboratory.
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AbstractDiamond nanoparticles that host bright luminescent centers are attracting attention for applications in bio-labeling and bio-sensing. Beyond their unsurpassed photostability, diamond can host multiple color centers, from the blue to the near infra-red spectral range. While nanodiamonds hosting nitrogen vacancy defects have been widely employed as bio-imaging probes, production and fabrication of nanodiamonds with other color centers is a challenge. In this work, a large scale production of fluorescent nanodiamonds (FNDs) containing a near infrared (NIR) color center – namely the silicon vacancy (SiV) defect, is reported. More importantly, a concept of application of different color centers for multi-color bio-imaging to investigate intercellular processes is demonstrated. Furthermore, two types of FNDs within cells can be easily resolved by their specific spectral properties, where data shows that SiV FNDs initially dispersed throughout the cell interior while NV FNDs localized in a close proximity to nucleus. The reported results are the first demonstration of multi-color labeling with FNDs that can pave the way for the wide-ranging use of FNDs in applications, including bio-sensing, bio-imaging and drug delivery applications.

Duong, H, Chen, Y, Tawfik, SA, Wen, S, Parviz, M, Ford, MJ, Shimoni, O & Jin, D 2017, 'Systematic Investigation of Functional Ligands for Colloidal Stable Upconversion Nanoparticles', American Chemical Society (ACS).
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Despite intense efforts on surface functionalization to generate hydrophilic upconversion nanoparticles (UCNPs), long-term colloidal stability in physiological buffers remains a major concern. Here we quantitatively investigate the competitive adsorption of phosphate, carboxylic acid and sulphonic acid onto the surface of UCNPs and study their binding strength to identify the best conjugation strategy. To achieve this, we designed and synthesized three di-block copolymers composed of poly(ethylene glycol) methyl ether acrylate and a polymer block bearing phosphate, carboxylic or sulphonic acid anchoring groups prepared by an advanced polymerization technique, Reversible Addition Fragmentation Chain Transfer (RAFT). Analytical tools provide the evidence that phosphate ligands completely replaced all the oleic acid capping molecules on the surface of the UCNPs compared with incomplete ligand exchange by carboxylic and sulphonic acid groups. In the meanwhile, simulated quantitative adsorption energy measurements confirmed that among three functional groups, calculated adsorption strength for phosphate anchoring ligands is higher which is in good agreement with experimental results regarding the best colloidal stability especially in phosphate buffer solution. The finding suggests that polymers with multiple anchoring negatively charged phosphate moieties provide excellent colloidal stability for lanthanide ion-doped luminescent nanoparticles for various potential applications.

Wu, P-J, Kabakova, I, Ruberti, J, Sherwood, JM, Dunlop, IE, Paterson, C, Török, P & Overby, DR 2017, 'Brillouin microscopy, what is it really measuring?'.
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Brillouin microscopy measures compressibility, but is being increasingly usedto assess stiffness of cells and tissues. Using hydrogels with tunableproperties, we demonstrate that Brillouin microscopy is insensitive tostiffness of hydrated materials, but depends strongly on water content,consistent with a theoretical model of biphasic compressibility. Empiricalcorrelations between Brillouin measurements and stiffness arise due to theirmutual dependence on water content, but correlations vanish once hydration iscontrolled.