Publications

Kulasinghe, A, Warkiani, ME & Punyadeera, C 2019, 'The Isolation and Characterization of Circulating Tumor Cells from Head and Neck Cancer Patient Blood Samples Using Spiral Microfluidic Technology' in Methods in Molecular Biology, Springer New York, pp. 129-136.
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Metastasis is responsible for 90% of cancer-related deaths. The study of circulating tumor cells (CTCs) enables the study of the units of disease responsible for the process of metastasis. While the biology of the primary tissue is relatively known, little is understood about the cells en route to distant sites. Here we describe the isolation of CTCs using the spiral microfluidic technology for the efficient sorting of CTCs from head and neck cancer (HNC) patient blood samples. Furthermore, the molecular characterization of CTCs can aid in stratifying patients for targeted therapy such as immunotherapy, which is having a profound impact in the treatment of metastatic HNC.

Abbasi, QH, Kiourti, A, Heidari, H, He, Y, Warkiani, M & Alomainy, A 2019, 'IEEE Access Special Section Editorial: Wearable and Implantable Devices and Systems', IEEE Access, vol. 7, pp. 139512-139517.
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© 2013 IEEE. Circuit techniques, sensors, antennas and communications systems are envisioned to help build new technologies over the next several years. Advances in the development and implementation of such technologies have already shown us their unique potential in realizing next-generation sensing systems. Applications include wearable consumer electronics, healthcare monitoring systems, and soft robotics, as well as wireless implants. There have been some interesting developments in the areas of circuits and systems, involving studies related to low-power electronics, wireless sensor networks, wearable circuit behaviour, security, real-time monitoring, connectivity of sensors, and Internet of Things (IoT). The direction for the current technology is electronics systems on large area electronics, integrated implantable systems and wearable sensors. So far, the research in the field has focused on materials, new processing techniques and one-off devices, such as diodes and transistors. However, current technology is not sufficient for future electronics to be useful in new applications; a great demand exists to scale up the research towards circuits and systems. Recent developments indicate that, in addition to fabrication technology, special attention should also be given to design, simulation and modeling of electronics, while keeping sensing system integration, power management, and sensors network under consideration.

Alghalayini, A, Garcia, A, Berry, T & Cranfield, C 2019, 'The Use of Tethered Bilayer Lipid Membranes to Identify the Mechanisms of Antimicrobial Peptide Interactions with Lipid Bilayers', Antibiotics, vol. 8, no. 1, pp. 12-12.
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This review identifies the ways in which tethered bilayer lipid membranes (tBLMs) can be used for the identification of the actions of antimicrobials against lipid bilayers. Much of the new research in this area has originated, or included researchers from, the southern hemisphere, Australia and New Zealand in particular. More and more, tBLMs are replacing liposome release assays, black lipid membranes and patch-clamp electrophysiological techniques because they use fewer reagents, are able to obtain results far more quickly and can provide a uniformity of responses with fewer artefacts. In this work, we describe how tBLM technology can and has been used to identify the actions of numerous antimicrobial agents.

Alqudah, A, McMullan, P, Todd, A, O’Doherty, C, McVey, A, McConnell, M, O’Donoghue, J, Gallagher, J, Watson, CJ & McClements, L 2019, 'Service evaluation of diabetes management during pregnancy in a regional maternity hospital: potential scope for increased self-management and remote patient monitoring through mHealth solutions', BMC Health Services Research, vol. 19, no. 1.
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Abstract Background Pre-gestational and gestational diabetes mellitus are common complications in pregnancy affecting one in six pregnancies. The maternity services are under significant strain managing the increasing number of complex pregnancies. This has an impact on patients’ experience of antenatal care. Therefore, there is a clear need to address pregnancy care. One possible solution is to use home-based digital technology to reduce clinic visits and improve clinical monitoring. Methods The aim of this study was to evaluate the antenatal services provided to pregnant women with diabetes who were monitored at the joint metabolic and obstetric clinic at the Southern Health and Social Care Trust in Northern Ireland. Results The questionnaires were completed by sixty-three women, most of whom had gestational diabetes mellitus. Most of the participants were between 25 and 35 years of age (69.8%), had one or more children (65.1%) and spent over 2 h attending the clinics (63.9%); 78% of women indicated that their travel time to and from the clinic appointment was over 15 min. Over 70% of women used smartphones for health-related purposes. However, only 8.8% used smartphones to manage their health or diabetes. Less than 25% of the women surveyed expressed concerns about using digital technology from home to monitor various aspects of their health in pregnancy. Conclusions Overall, pregnant women who had or developed diabetes in pregnancy experience frequent hospital visits a...

Andrejic, OM, Vucic, RM, Pavlovic, M, McClements, L, Stokanovic, D, Jevtovic–Stoimenov, T & Nikolic, VN 2019, 'Association between Galectin-3 levels within central and peripheral venous blood, and adverse left ventricular remodelling after first acute myocardial infarction', Scientific Reports, vol. 9, no. 1, p. 13145.
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AbstractOur study investigates association between Galectin-3 levels and adverse left ventricular remodelling (LVR) at six months. Fifty-seven patients following first acute myocardial infarction (AMI) were enrolled in this study and blood samples collected on day 1 from the femoral vein and artery, the right atrium near the coronary sinus and the aortic root, and on day 30, from the cubital vein. Patients with LVESV ≥20% at six months, were included in the LVR group. On day 1, Galectin-3 plasma levels in the femoral vein (10.34 ng/ml ± 3.81 vs 8.22 ng/ml ± 2.34, p = 0.01), and near coronary sinus (10.7 ng/ml ± 3.97 vs 8.41 ng/ml ± 2.56, p = 0.007) were higher in the LVR group. Positive correlations between Galectin-3 levels from aortic root and coronary sinus, aortic root and femoral vein, and coronary sinus and femoral vein, were observed in both groups. On day 30, Galectin-3 concentration in the cubital vein was an independent risk factor of LVR six months post-AMI, demonstrating 1.5-fold increased risk. Day-30 Galectin-3 also showed positive correlations with echocardiography parameters indicative of diastolic and systolic dysfunction. Determining Galectin-3 plasma concentration on day 30 following AMI could have beneficial prognostic value in predicting LVR.

Ashtari, K, Nazari, H, Ko, H, Tebon, P, Akhshik, M, Akbari, M, Alhosseini, SN, Mozafari, M, Mehravi, B, Soleimani, M, Ardehali, R, Ebrahimi Warkiani, M, Ahadian, S & Khademhosseini, A 2019, 'Electrically conductive nanomaterials for cardiac tissue engineering', Advanced Drug Delivery Reviews, vol. 144, pp. 162-179.
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© 2019 Elsevier B.V. Patient deaths resulting from cardiovascular diseases are increasing across the globe, posing the greatest risk to patients in developed countries. Myocardial infarction, as a result of inadequate blood flow to the myocardium, results in irreversible loss of cardiomyocytes which can lead to heart failure. A sequela of myocardial infarction is scar formation that can alter the normal myocardial architecture and result in arrhythmias. Over the past decade, a myriad of tissue engineering approaches has been developed to fabricate engineered scaffolds for repairing cardiac tissue. This paper highlights the recent application of electrically conductive nanomaterials (carbon and gold-based nanomaterials, and electroactive polymers) to the development of scaffolds for cardiac tissue engineering. Moreover, this work summarizes the effects of these nanomaterials on cardiac cell behavior such as proliferation and migration, as well as cardiomyogenic differentiation in stem cells.

Azadi, S, Aboulkheyr Es, H, Razavi Bazaz, S, Thiery, JP, Asadnia, M & Ebrahimi Warkiani, M 2019, 'Upregulation of PD-L1 expression in breast cancer cells through the formation of 3D multicellular cancer aggregates under different chemical and mechanical conditions', Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, vol. 1866, no. 12, pp. 118526-118526.
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© 2019 Elsevier B.V. Expression of programmed death-ligand 1 (PD-L1) in cancer cells plays an important role in cancer-immune cell interaction. The emerging evidence suggests regulation of PD-L1 expression by several tumor microenvironmental cues. However, the association of PD-L1 expression with chemical and mechanical features of the tumor microenvironment, specifically epidermal growth factor receptor (EGFR) signaling and matrix stiffness, remains elusive. Herein, we determine whether EGFR targeting and substrate stiffness affect the regulation of PD-L1 expression. Breast carcinoma cell lines, MCF7 and MDA-MB-231, were cultured under different conditions targeting EGFR and exposing cells to distinct substrate stiffness to evaluate PD-L1 expression. Furthermore, the ability to form aggregates in short-term culture of breast carcinoma cells and its effect on expression level of PD-L1 was probed. Our results indicated that PD-L1 expression was altered in response to both EGFR inhibition and substrate stiffness. Additionally, a positive association between the formation of multicellular aggregates and PD-L1 expression was observed. MDA-MB-231 cells expressed the highest PD-L1 level on a stiff substrate, while inhibition of EGFR reduced expression of PD-L1. The results suggested that both physical and chemical features of tumor microenvironment regulate PD-L1 expression through alteration of tumor aggregate formation potential. In line with these results, the in-silico study highlighted a positive correlation between PD-L1 expression, EGFR signaling, epithelial to mesenchymal transition related transcription factors (EMT-TFs) and stemness markers in metastatic breast cancer. These findings improve our understanding of regulation of PD-L1 expression by tumor microenvironment leading to evasion of tumor cells from the immune system.

Azadi, S, Tafazzoli‐Shadpour, M, Soleimani, M & Warkiani, ME 2019, 'Modulating cancer cell mechanics and actin cytoskeleton structure by chemical and mechanical stimulations', Journal of Biomedical Materials Research Part A, vol. 107, no. 8, pp. 1569-1581.
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AbstractTo date, a myriad of strategies has been suggested for targeting the chemical signaling of cancer cells. Also, biomechanical features are gaining much more attention. These features can be used as biomarkers which influence cancer progression. Current approaches on cancer treatment are mainly focused on changing the biochemical signaling of cancer cells, whereas less attention was devoted to their biomechanical properties. Herein, we propose targeting of cancer cell mechanics through the microenvironmental mechanical and chemical cues. As such, we examined the role of substrate stiffness as well as the effect of epidermal growth factor receptor (EGFR) blockade in the cell mechanics. As a mechanical stimulus, stiff and soft polydimethylsiloxane substrates were utilized, while as a chemical stimulus, EGFR blockade was considered. Thus, breast cancer cell lines, MCF7 and MDA‐MB‐231, were cultured among chemical and mechanical groups. The local elasticity of cancer cells was assessed by atomic force microscopy nanoindentation method. Furthermore, we evaluated the effect of mentioned mechanical and chemical treatments on the morphology, actin cytoskeleton structures, and cancer cell migration abilities. The stiffness and migration ability of cancer cells increased by substrate stiffening while Cetuximab treatment demonstrated an elevation in the elastic modulus of cells followed by a reduction in the migration ability. These findings indicate that cancer cell mechanics is modulated not only by the mechanical cues but also by the chemical ones through EGFR signaling pathway. Overall, our results illustrate that manipulation of cell mechanics allows for the possible modulation of tumor cell migration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1569–1581, 2019.

Bao, G & Jin, D 2019, 'Nanoparticles give mice infrared vision', Nature Photonics, vol. 13, no. 5, pp. 304-305.
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© 2019, Springer Nature Limited. The injection of rare-earth-doped upconversion nanoparticles into the eyes of mice allows them to visualize near-infrared light with a wavelength of ~1 μm.

Bao, G, Liu, Z, Luo, Y, Wong, K-L & Tanner, PA 2019, 'Effects of europium spectral probe interchange in Ln-dyads with cyclen and phen moieties', Dalton Transactions, vol. 48, no. 13, pp. 4314-4323.
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Antenna-lanthanide energy transfer is investigated via a bimetallic complex with one silent and one probe lanthanide ion, when their positions are interchanged in the complex.

Bao, G, Wong, K & Tanner, PA 2019, 'A Reversible Rhodamine B Based pH Probe with Large Pseudo‐Stokes Shift', ChemPlusChem, vol. 84, no. 7, pp. 816-820.
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AbstractA reversible and sensitive pH probe DPE−Rh operates by Förster resonance energy transfer from 1,2‐diphenylethyne (DPE) to Rhodamine B (Rh). In the presence of H+, the spirolactam ring of the Rhodamine B unit was opened and this resulted in ca. 1000‐fold enhancement of fluorescence intensity with linear change over the pH range of 2.0 to 5.5. The Förster resonance energy transfer offered this probe an effective excitation–emission wavelength shift of around 240 nm with about 100 % quenching of the donor emission. The response of the sensor is tolerant towards a wide range of metal ions and the sensing mechanism was deduced by 1H NMR spectrometry. This FRET‐based molecule not only provides a sensitive pH probe, but also suggests an effective strategy to eliminate the interference of excitation light.

Biglari, S, Le, TYL, Tan, RP, Wise, SG, Zambon, A, Codolo, G, De Bernard, M, Warkiani, M, Schindeler, A, Naficy, S, Valtchev, P, Khademhosseini, A & Dehghani, F 2019, 'Simulating Inflammation in a Wound Microenvironment Using a Dermal Wound‐on‐a‐Chip Model', Advanced Healthcare Materials, vol. 8, no. 1, pp. 1801307-1801307.
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AbstractConsiderable progress has been made in the field of microfluidics to develop complex systems for modeling human skin and dermal wound healing processes. While microfluidic models have attempted to integrate multiple cell types and/or 3D culture systems, to date they have lacked some elements needed to fully represent dermal wound healing. This paper describes a cost‐effective, multicellular microfluidic system that mimics the paracrine component of early inflammation close to normal wound healing. Collagen and Matrigel are tested as materials for coating and adhesion of dermal fibroblasts and human umbilical vein endothelial cells (HUVECs). The wound‐on‐chip model consists of three interconnecting channels and is able to simulate wound inflammation by adding tumor necrosis factor alpha (TNF‐α) or by triculturing with macrophages. Both the approaches significantly increase IL‐1β, IL‐6, IL‐8 in the supernatant (p < 0.05), and increases in cytokine levels are attenuated by cotreatment with an anti‐inflammatory agent, Dexamethasone. Incorporation of M1 and M2 macrophages cocultured with fibroblasts and HUVECs leads to a stimulation of cytokine production as well as vascular structure formation, particularly with M2 macrophages. In summary, this wound‐on‐chip system can be used to model the paracrine component of the early inflammatory phase of wound healing and has the potential for the screening of anti‐inflammatory compounds.

Chang, L, Ni, J, Zhu, Y, Pang, B, Graham, P, Zhang, H & Li, Y 2019, 'Liquid biopsy in ovarian cancer: recent advances in circulating extracellular vesicle detection for early diagnosis and monitoring progression', Theranostics, vol. 9, no. 14, pp. 4130-4140.
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The current biomarkers available in the clinic are not enough for early diagnosis or for monitoring disease progression of ovarian cancer. Liquid biopsy is a minimally invasive test and has the advantage of early diagnosis and real-time monitoring of treatment response. Although significant progress has been made in the usage of circulating tumor cells and cell-free DNA for ovarian cancer diagnosis, their potential for early detection or monitoring progression remains elusive. Extracellular vesicles (EVs) are a heterogeneous group of lipid membranous particles released from almost all cell types. EVs contain proteins, mRNA, DNA fragments, non-coding RNAs, and lipids and play a critical role in intercellular communication. Emerging evidence suggests that EVs have crucial roles in cancer development and metastasis, thus holding promise for liquid biopsy-based biomarker discovery for ovarian cancer diagnosis. In this review, we discuss the advantages of EV-based liquid biopsy, summarize the protein biomarkers identified from EVs in ovarian cancer, and highlight the utility of new technologies recently developed for EV detection with an emphasis on their use for diagnosing ovarian cancer, monitoring cancer progression, and developing personalized medicine.

Chen, C, liu, Z & Jin, D 2019, 'Bypassing the limit in volumetric imaging of mesoscale specimens', Advanced Photonics, vol. 1, no. 02, pp. 1-1.
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Chen, T, Liu, AB, Sun, S, Ajami, NJ, Ross, MC, Wang, H, Zhang, L, Reuhl, K, Kobayashi, K, Onishi, JC, Zhao, L & Yang, CS 2019, 'Green Tea Polyphenols Modify the Gut Microbiome in db/db Mice as Co‐Abundance Groups Correlating with the Blood Glucose Lowering Effect', Molecular Nutrition & Food Research, vol. 63, no. 8, pp. e1801064-1801064.
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ScopeThe effects of green tea polyphenols, Polyphenon E (PPE), and black tea polyphenols, theaflavins (TFs), on gut microbiota and development of diabetes in db/db mice are investigated and compared.Methods and resultsSupplementation of PPE (0.1%) in the diet of female db/db mice for 7 weeks decreases fasting blood glucose levels and mesenteric fat while increasing the serum level of insulin, possibly through protection against β‐cell damage. However, TFs are less or not effective. Microbiome analysis through 16S rRNA gene sequencing shows that PPE and TFs treatments significantly alter the bacterial community structure in the cecum and colon, but not in the ileum. The key bacterial phylotypes responding to the treatments are then clustered into 11 co‐abundance groups (CAGs). CAGs 6 and 7, significantly increased by PPE but not by TFs, are negatively associated with blood glucose levels. The operational taxonomic units in these CAGs are from two different phyla, Firmicutes and Bacteroidetes. CAG 10, decreased by PPE and TFs, is positively associated with blood glucose levels.ConclusionGut microbiota respond to tea polyphenol treatments as CAGs instead of taxa. Some of the CAGs associated with the blood glucose lowering effect are enriched by PPE, but not TFs.

Chen, Y, Ju, LA, Zhou, F, Liao, J, Xue, L, Su, QP, Jin, D, Yuan, Y, Lu, H, Jackson, SP & Zhu, C 2019, 'An integrin αIIbβ3 intermediate affinity state mediates biomechanical platelet aggregation', Nature Materials, vol. 18, no. 7, pp. 760-769.
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© 2019, The Author(s), under exclusive licence to Springer Nature Limited. Integrins are membrane receptors that mediate cell adhesion and mechanosensing. The structure–function relationship of integrins remains incompletely understood, despite the extensive studies carried out because of its importance to basic cell biology and translational medicine. Using a fluorescence dual biomembrane force probe, microfluidics and cone-and-plate rheometry, we applied precisely controlled mechanical stimulations to platelets and identified an intermediate state of integrin αIIbβ3 that is characterized by an ectodomain conformation, ligand affinity and bond lifetimes that are all intermediate between the well-known inactive and active states. This intermediate state is induced by ligand engagement of glycoprotein (GP) Ibα via a mechanosignalling pathway and potentiates the outside-in mechanosignalling of αIIbβ3 for further transition to the active state during integrin mechanical affinity maturation. Our work reveals distinct αIIbβ3 state transitions in response to biomechanical and biochemical stimuli, and identifies a role for the αIIbβ3 intermediate state in promoting biomechanical platelet aggregation.

Chen, Y, Su, QP & Yu, L 2019, 'Studying Autophagic Lysosome Reformation in Cells and by an In Vitro Reconstitution System', vol. 1880, pp. 163-172.
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Autophagic lysosome reformation (ALR) is the terminal step of autophagy. ALR functions to recycle lysosomal membranes and maintain lysosome homeostasis. Maintaining a functional lysosome pool is critical for generating autolysosomes, in which cellular components are degraded and turned over during autophagy. This unit describes methods to visualize ALR in cells. In addition, this unit provides detailed protocols to establish in vitro systems which can be used to reconstitute ALR as well as to reconstitute mitochondrial tubulation/network formation, another process that is driven by motor proteins.

Condina, MR, Dilmetz, BA, Razavi Bazaz, S, Meneses, J, Ebrahimi Warkiani, M & Hoffmann, P 2019, 'Rapid separation and identification of beer spoilage bacteria by inertial microfluidics and MALDI-TOF mass spectrometry', Lab on a Chip, vol. 19, no. 11, pp. 1961-1970.
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Microfluidics and MALDI-TOF MS is a rapid, high-throughput, and accurate method for the identification of beer spoilage bacteria.

Cranfield, CG 2019, 'ABA/ASB Membrane Biophysics session II 2018', Biophysical Reviews, vol. 11, no. 3, pp. 281-282.
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Deplazes, E, White, J, Murphy, C, Cranfield, CG & Garcia, A 2019, 'Competing for the same space: protons and alkali ions at the interface of phospholipid bilayers', Biophysical Reviews, vol. 11, no. 3, pp. 483-490.
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© 2019, International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature. Maintaining gradients of solvated protons and alkali metal ions such as Na+ and K+ across membranes is critical for cellular function. Over the last few decades, both the interactions of protons and alkali metal ions with phospholipid membranes have been studied extensively and the reported interactions of these ions with phospholipid headgroups are very similar, yet few studies have investigated the potential interdependence between proton and alkali metal ion binding at the water–lipid interface. In this short review, we discuss the similarities between the proton–membrane and alkali ion–membrane interactions. Such interactions include cation attraction to the phosphate and carbonyl oxygens of the phospholipid headgroups that form strong lipid–ion and lipid–ion–water complexes. We also propose potential mechanisms that may modulate the affinities of these cationic species to the water–phospholipid interfacial oxygen moieties. This review aims to highlight the potential interdependence between protons and alkali metal ions at the membrane surface and encourage a more nuanced understanding of the complex nature of these biologically relevant processes.

Derakhshani, M, Abbaszadeh, H, Movassaghpour, AA, Mehdizadeh, A, Ebrahimi-Warkiani, M & Yousefi, M 2019, 'Strategies for elevating hematopoietic stem cells expansion and engraftment capacity', Life Sciences, vol. 232, pp. 116598-116598.
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© 2019 Elsevier Inc. Hematopoietic stem cells (HSCs) are a rare cell population in adult bone marrow, mobilized peripheral blood, and umbilical cord blood possessing self-renewal and differentiation capability into a full spectrum of blood cells. Bone marrow HSC transplantation has been considered as an ideal option for certain disorders treatment including hematologic diseases, leukemia, immunodeficiency, bone marrow failure syndrome, genetic defects such as thalassemia, sickle cell anemia, autoimmune disease, and certain solid cancers. Ex vivo proliferation of these cells prior to transplantation has been proposed as a potential solution against limited number of stem cells. In such culture process, MSCs have also been shown to exhibit high capacity for secretion of soluble mediators contributing to the principle biological and therapeutic activities of HSCs. In addition, endothelial cells have been introduced to bridge the blood and sub tissues in the bone marrow, as well as, HSCs regeneration induction and survival. Cell culture in the laboratory environment requires cell growth strict control to protect against contamination, symmetrical cell division and optimal conditions for maximum yield. In this regard, microfluidic systems provide culture and analysis capabilities in micro volume scales. Moreover, two-dimensional cultures cannot fully demonstrate extracellular matrix found in different tissues and organs as an abstract representation of three dimensional cell structure. Microfluidic systems can also strongly describe the effects of physical factors such as temperature and pressure on cell behavior.

Ding, B, Shao, S, Jiang, F, Dang, P, Sun, C, Huang, S, Ma, P, Jin, D, Kheraif, AAA & Lin, J 2019, 'MnO₂-Disguised Upconversion Hybrid Nanocomposite: An Ideal Architecture for Tumor Microenvironment-Triggered UCL/MR Bioimaging and Enhanced Chemodynamic Therapy', Chemistry of Materials, vol. 31, no. 7, pp. 2651-2660.
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Copyright © 2019 American Chemical Society. Upconversion nanoparticles (UCNPs) and MnO 2 hybrid theranostic nanoplatform (UCMn) is highly desired; however, the rational design of such UCMn hybrid nanomaterials is still a great challenge. Herein, a simple and versatile strategy for the in situ growth of MnO 2 on the surfaces of UCNPs was reported using a sacrificial template method to construct an ideal MnO 2 -disguised and tumor microenvironment-triggered architecture. Such sophisticated architecture not only achieves activatable magnetic resonance imaging and restorable upconversion luminescence (UCL) imaging with over 100-fold enhancement of UCL in vivo but also significantly improves the efficiency of chemodynamic therapy (CDT) by glutathione depletion- and cisplatin-activation-enhanced • OH generation simultaneously. Additionally, the synergetic effect of CDT and chemotherapy presents excellent therapeutic effect in vivo as compared to either CDT or chemotherapy alone. We believe that the ideal design of the MnO 2 -disguised upconversion hybrid nanocomposite will provide more revelations on the future research on nanoscale theranostic systems.

Du, W & Su, QP 2019, 'Single-molecule in vitro reconstitution assay for kinesin-1-driven membrane dynamics', Biophysical Reviews, vol. 11, no. 3, pp. 319-325.
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© 2019, International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature. Intracellular membrane dynamics, especially the nano-tube formation, plays important roles in vesicle transportation and organelle biogenesis. Regarding the regulation mechanisms, it is well known that during the nano-tube formation, motor proteins act as the driven force moving along the cytoskeleton, lipid composition and its associated proteins serve as the linkers and key mediators, and the vesicle sizes play as one of the important regulators. In this review, we summarized the in vitro reconstitution assay method, which has been applied to reconstitute the nano-tube dynamics during autophagic lysosomal regeneration (ALR) and the morphology dynamics during mitochondria network formation (MNF) in a mimic and pure in vitro system. Combined with the single-molecule microscopy, the advantage of the in vitro reconstitution system is to study the key questions at a single-molecule or single-vesicle level with precisely tuned parameters and conditions, such as the motor mutation, ion concentration, lipid component, ATP/GTP concentration, and even in vitro protein knockout, which cannot easily be achieved by in vivo or intracellular studies.

Ejeian, F, Azadi, S, Razmjou, A, Orooji, Y, Kottapalli, A, Ebrahimi Warkiani, M & Asadnia, M 2019, 'Design and applications of MEMS flow sensors: A review', Sensors and Actuators A: Physical, vol. 295, pp. 483-502.
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© 2019 Elsevier B.V. There is an indispensable need for fluid flow rate and direction sensors in various medical, industrial and environmental applications. Besides the critical demands on sensing range of flow parameters (such as rate, velocity, direction and temperature), the properties of different target gases or liquids to be sensed pose challenges to the development of reliable, inexpensive and low powered sensors. This paper presents an overview of the work done on design and development of Microelectromechanical system (MEMS)-based flow sensors in recent years. In spite of using some similar principles, diverse production methods, analysis strategies, and different sensing materials, MEMS flow sensors can be broadly categorized into three main types, namely thermal sensors, piezoresistive sensors and piezoelectric sensors. Additionally, some key challenges and future prospects for the use of the MEMS flow sensors are discussed briefly.

Facey, JA, Steele, JR, Violi, JP, Mitrovic, SM & Cranfield, C 2019, 'An examination of microcystin-LR accumulation and toxicity using tethered bilayer lipid membranes (tBLMs)', Toxicon, vol. 158, pp. 51-56.
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Microcystin-LR (MC-LR) is a potent cyanobacterial toxin responsible for animal and human poisonings worldwide. MC-LR is found in organisms throughout the foodweb, however there is conjecture regarding whether it biomagnifies. Few studies have investigated how MC-LR interacts with lipid membranes, a determinant of biomagnification potential. We tested whether 1 μM MC-LR irreversibly associates with lipid bilayers or causes the creation of pore defects upon short and long-term exposure. Using tethered bilayer lipid membranes (tBLMs), we observed an increase in membrane conduction in tBLMs, representing an interaction of microcystin-LR with the lipid bilayer and a change in membrane packing properties. However, there were minimal changes in membrane capacitance upon short and long-term exposure, and MC-LR exhibited a rapid off-rate. Upon 24 h exposure to the toxin, no lipophilic multimeric complexes were detected capable of altering the toxin's off-rate. There was no evidence of the creation of new pores. This study demonstrates that MC-LR does not irreversibly imbed itself into lipids membranes after short or long-term exposure and suggests MC-LR does not biomagnify through the food web via lipid storage.

Fang, G, Lu, H, Law, A, Gallego-Ortega, D, Jin, D & Lin, G 2019, 'Gradient-sized control of tumor spheroids on a single chip', Lab on a Chip, vol. 19, no. 24, pp. 4093-4103.
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Gradient-sized spheroids can be simultaneously generated on a single chip using a liquid-dome method assisted by the surface tension. The facile method can be used for investigation of the size-dependent behaviors of spheroids in biomedical research.

Feng, X, Bai, X, Ni, J, Wasinger, VC, Beretov, J, Zhu, Y, Graham, P & Li, Y 2019, 'CHTOP in Chemoresistant Epithelial Ovarian Cancer: A Novel and Potential Therapeutic Target', Frontiers in Oncology, vol. 9, no. JUN, pp. 1-13.
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Objective: Chemoresistance is a major challenge in epithelial ovarian cancer (EOC) treatment. Chromatin target of protein arginine methyltransferase (CHTOP) was identified as a potential biomarker in chemoresistant EOC cell lines using label-free LC-MS/MS quantitative proteomics. Thus, the aim of this study is to investigate the role of CHTOP in chemoresistant EOC and the underlying mechanism. Methods: The expression of CHTOP in human ovarian cancer cells and tissues was detected using immunofluorescence (IF), western blot (WB), and immunohistochemistry (IHC), respectively. Flow cytometry and TUNEL assay were employed to detect the effect of CHTOP knockdown (KD) in chemoresistant EOC cell apoptosis, while colony and sphere formation assays were used to evaluate its effect on cell stemness. The association of CHTOP with cell metastasis was determined using Matrigel invasion and wound-healing assays. Results: The higher level expression of CHTOP protein was found in chemoresistant EOC cells as compared to their sensitive parental cells or normal epithelial ovarian cells. Results from IHC and bioinformatic analysis showed CHTOP was highly expressed in human ovarian cancer tissues and associated with a poor progression-free survival in patients. In addition, CHTOP KD significantly enhanced cisplatin-induced apoptosis, reduced the stemness of chemoresistant EOC cells, and decreased their metastatic potential. Conclusion: Our findings suggest that CHTOP is associated with apoptosis, stemness, and metastasis in chemoresistant EOC cells and might be a promising target to overcome chemoresistance in EOC treatment.

Fergie, N, Todd, N, McClements, L, McAuley, D, O'Kane, C & Krasnodembskaya, A 2019, 'Hypercapnic acidosis induces mitochondrial dysfunction and impairs the ability of mesenchymal stem cells to promote distal lung epithelial repair', The FASEB Journal, vol. 33, no. 4, pp. 5585-5598.
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© The Author(s) Acute respiratory distress syndrome (ARDS) is a devastating disorder characterized by diffuse inflammation and edema formation. The main management strategy, low tidal volume ventilation, can be associated with the development of hypercapnic acidosis (HCA). Mesenchymal stem cells (MSCs) are a promising therapeutic candidate currently in early-phase clinical trials. The effects of HCA on the alveolar epithelium and capillary endothelium are not well established. The therapeutic efficacy of MSCs has never been reported in HCA. In the present study, we evaluated the effects of HCA on inflammatory response and reparative potential of the primary human small airway epithelial and lung microvasculature endothelial cells as well as on the capacity of bone marrow2derived MSCs to promote wound healing in vitro. We demonstrate that HCA attenuates the inflammatory response and reparative potential of primary human small airway epithelium and capillary endothelium and induces mitochondrial dysfunction. It was found that MSCs promote lung epithelial wound repair via the transfer of functional mitochondria; however, this proreparative effect of MSCs was lost in the setting of HCA. Therefore, HCA may adversely impact recovery from ARDS at the cellular level, whereas MSCs may not be therapeutically beneficial in patients with ARDS who develop HCA.

Gerami, A, Alzahid, Y, Mostaghimi, P, Kashaninejad, N, Kazemifar, F, Amirian, T, Mosavat, N, Ebrahimi Warkiani, M & Armstrong, RT 2019, 'Microfluidics for Porous Systems: Fabrication, Microscopy and Applications', Transport in Porous Media, vol. 130, no. 1, pp. 277-304.
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© 2018, Springer Nature B.V. No matter how sophisticated the structures are and on what length scale the pore sizes are, fluid displacement in porous media can be visualized, captured, mimicked and optimized using microfluidics. Visualizing transport processes is fundamental to our understanding of complex hydrogeological systems, petroleum production, medical science applications and other engineering applications. Microfluidics is an ideal tool for visual observation of flow at high temporal and spatial resolution. Experiments are typically fast, as sample volume is substantially low with the use of miniaturized devices. This review first discusses the fabrication techniques for generating microfluidics devices, experimental setups and new advances in microfluidic fabrication using three-dimensional printing, geomaterials and biomaterials. We then address multiphase transport in subsurface porous media, with an emphasis on hydrology and petroleum engineering applications in the past few decades. We also cover the application of microfluidics to study membrane systems in biomedical science and particle sorting. Lastly, we explore how synergies across different disciplines can lead to innovations in this field. A number of problems that have been resolved, topics that are under investigation and cutting-edge applications that are emerging are highlighted.

Ghorbani, F, Abbaszadeh, H, Mehdizadeh, A, Ebrahimi-Warkiani, M, Rashidi, M-R & Yousefi, M 2019, 'Biosensors and nanobiosensors for rapid detection of autoimmune diseases: a review', Microchimica Acta, vol. 186, no. 12.
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© 2019, Springer-Verlag GmbH Austria, part of Springer Nature. This review (with 77 refs.) describes the progress that has been made in biosensors for the detection of autoimmune diseases, mainly via detection of autoantibodies. In addition, specific proteins, cytokines and ions have also been introduced as promising diagnostic biomarkers. Following an introduction into the various kinds of autoimmune diseases, we first discuss the state of the art in respective electrochemical biosensors and nanobiosensors (with subsections on amperometric, impedimetric, voltammetric and photoelectrochemical methods). The next large chapter covers optical methods (with subsections on electrochemiluminescence, fluorescence and surface plasmon resonance). We then make a critical comparison between commercially available kits used for detection of autoimmune diseases with the established biosensors. Several Tables are also presented that give an overview on the wealth of methods and nanomaterials. Finally, in the conclusion part, we summarize the current status, addresse present issues, and give an outlook on potential future opportunities. [Figure not available: see fulltext.].

Ghorbani, S, Eyni, H, Khosrowpour, Z, Salari Asl, L, Shabani, R, Nazari, H, Mehdizadeh, M, Ebrahimi Warkiani, M & Amjadi, F 2019, 'Spermatogenesis induction of spermatogonial stem cells using nanofibrous poly(l‐lactic acid)/multi‐walled carbon nanotube scaffolds and naringenin', Polymers for Advanced Technologies, vol. 30, no. 12, pp. 3011-3025.
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Spermatogenesis is a process in which animals generate spermatozoa from spermatogonial stem cells (SSCs). Successful in vitro differentiation of SSCs towards spermatids holds a significant promise for regeneration of impaired spermatogenesis. The present study aims to evaluate the efficiency of a 3D culture containing naringenin on proliferation and differentiation potentials of mouse SSCs. In this study, multi‐walled carbon nanotubes (MWCNTs) were incorporated into poly(l‐lactic acid) (PLLA) fibers via electrospinning technique. The fibrous PLLA/MWCNTs were studied by Fourier‐transform infrared spectroscopy (FTIR), transmission electron microscope (TEM), water contact angle measurements, electrical conductivity, and mechanical properties. Next, the SSCs were seeded into the PLLA/MWCNTs scaffolds and exhibited preferable survival and differentiation efficiency to subsequent cell lines. To shed more light on this matter, the immunocytochemistry, reverse‐transcription polymerase chain reaction (RT‐PCR), and qRT‐PCR results showed that the aforementioned cells on the 3D fabrics overexpressed the C‐kit and SYCP3 proteins. In addition, the reactive oxygen species (ROS) measurement data demonstrated that naringenin, an effective antioxidant, plays an important role in in vitro spermatogenesis. Taken together, the results of this study revealed the synergistic effects of 3D scaffolds and naringenin for efficient spermatogenesis in laboratories.

Gu, Y, Guo, Z, Yuan, W, Kong, M, Liu, Y, Liu, Y, Gao, Y, Feng, W, Wang, F, Zhou, J, Jin, D & Li, F 2019, 'High-sensitivity imaging of time-domain near-infrared light transducer', Nature Photonics, vol. 13, no. 8, pp. 525-531.
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© 2019, The Author(s), under exclusive licence to Springer Nature Limited. The optically transparent biological window in the near-infrared (NIR) spectral range allows deep-tissue excitation and the detection of fluorescence signals1,2. Spectrum-domain discrimination of NIR contrast agents via an upconversion or downshifting scheme requires sufficient (anti-) Stokes shift to separate excitation and fluorescence emission. Here, we report a time-domain (τ) scheme in which about 5,000 ytterbium signal transducers are condensed within an optically inert and biocompatible CaF2 shell (2.3 nm), which forms a 14.5 nm τ-dot. Because of the long-lived and spectrally narrowly defined excited state of pure ytterbium ions, the NIR τ-dot can convert the NIR pulsed excitation into long-decaying luminescence with an efficiency approaching 100%. Within a safe injection dosage of 13 μg g−1, an excitation power density of 1.1 mW cm−2 was sufficient to image organs with a signal-to-noise ratio of >9. The high brightness of τ-dots further allows long-term in vivo passive targeting and dynamic tracking in a tumour-bearing mouse model.

Gu, Y, Guo, Z, Yuan, W, Kong, M, Liu, Y, Liu, Y, Gao, Y, Feng, W, Wang, F, Zhou, J, Jin, D & Li, F 2019, 'Publisher Correction: High-sensitivity imaging of time-domain near-infrared light transducer', Nature Photonics, vol. 13, no. 8, pp. 580-580.
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Gulzar, A, Xu, J, Wang, C, He, F, Yang, D, Gai, S, Yang, P, Lin, J, Jin, D & Xing, B 2019, 'Tumour microenvironment responsive nanoconstructs for cancer theranostic', Nano Today, vol. 26, pp. 16-56.
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© 2019 Elsevier Ltd The tumour mass is made up of not only of a heterogeneous population of cancer cells nonetheless also a mixture of resident as well as the infiltrating host cells, secreted factors besides extracellular matrix proteins, together recognized as the tumour microenvironment (TME). Tumour development is overwhelmingly affected through the dealings of cancer cells with their environment which eventually conclude whether the primary tumour is eliminated, metastasizes or creates dormant micro metastases. The TME may perhaps shape therapeutic responses as well as resistance. Some inimitable features of TME, for example vascular abnormalities, hypoxia, acidic pH and glutathione (GSH) are comparative to normal tissue. Several types of cells, together with tumour cells, macrophages, immune and fibroblast cells are nourished by flawed blood vessels in the solid tumour. To dispense anticancer agents to tumour sites nanovehicles can be competent carts. For augmented therapeutic efficacy, TME is the key for designing of nanoparticles (NPs). In this review, we will discuss the TME and summarize the current advancement in several nano-formulations for cancer therapy, with an extraordinary stress on TME-responsive ones. Scheme 1 highlights several TME modulation tactics with positive cancer therapeutic competence. The design of nanoconstructs and future challenges, consideration and opportunities are also discussed in detail. We have confidence in that these modulation approaches of TME tender a reliable opportunity for the practical translation of nanoparticle formulas into clinic.

Guo, Z, Yang, C, Maritz, MF, Wu, H, Wilson, P, Warkiani, ME, Chien, C, Kempson, I, Aref, AR & Thierry, B 2019, 'Validation of a Vasculogenesis Microfluidic Model for Radiobiological Studies of the Human Microvasculature', Advanced Materials Technologies, vol. 4, no. 4, pp. 1800726-1800726.
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AbstractThe therapeutic ratio of radiotherapy is limited by acute or chronic side effects with often severe consequences to patients. The microvasculature is a central player involved in both tumor responses and healthy tissue/organ radiological injuries. However, current preclinical vascular models based on 2D culture offer only limited radiobiological insight due to their failure in recapitulating the 3D nature experienced by endothelial cells within the human microvasculature. To address this issue, the use of a 3D microvasculature‐on‐a‐chip microfluidic technology is demonstrated in radiobiological studies. Within this vasculogenesis model a perfusable network that structurally mimics the human microvasculature is formed and the biological response to ionizing radiation including cellular apoptosis, vessel tight adherens junction breakage, DNA double strand break, and repair is systematically investigated. In comparison to cells grown in a 2D environment, human umbilical vein endothelial cells in the 3D microvasculature‐on‐a‐chip displays significant differences in biological responses, especially at high X‐ray dose. This data confirms the feasibility of using microvascular‐on‐a‐chip models for radiobiological studies. Such vasculogenesis models have strong potential to yield more accurate prediction of healthy tissue responses to ionizing radiation as well as to guide the development of risk‐reducing strategies to prevent radiation‐induced acute and long‐term side‐effects.

Hossain, KR, Turkewitz, DR, Holt, SA, Herson, L, Brown, LJ, Cornell, BA, Curmi, PMG & Valenzuela, SM 2019, 'A conserved GXXXG motif in the transmembrane domain of CLIC proteins is essential for their cholesterol-dependant membrane interaction', Biochimica et Biophysica Acta (BBA) - General Subjects, vol. 1863, no. 8, pp. 1243-1253.
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© 2019 Elsevier B.V. Background: Sterols have been reported to modulate conformation and hence the function of several membrane proteins. One such group is the Chloride Intracellular Ion Channel (CLIC)family of proteins. The CLIC protein family consists of six evolutionarily conserved protein members in vertebrates. These proteins exist as both monomeric soluble proteins and as membrane bound proteins. To date, the structure of their membrane-bound form remains unknown. In addition to several studies indicating cellular redox environment and pH as facilitators of CLIC1 insertion into membranes, we have also demonstrated that the spontaneous membrane insertion of CLIC1 is regulated by membrane cholesterol. Method: We have performed Langmuir-film, Impedance Spectroscopy and Molecular Docking Simulations to study the role of this GXXXG motif in CLIC1 interaction with cholesterol. Results: Unlike CLIC1-wild-type protein, the G18A and G22A mutants, that form part of the GXXXG motif, showed much slower initial kinetics and lower ion channel activity compared to the native protein. This difference can be attributed to the significantly reduced membrane interaction and insertion rate of the mutant proteins and/or slower formation of the final membrane configuration of the mutant proteins once in the membrane. Conclusion: In this study, our findings uncover the identification of a GXXXG motif in CLIC1, which likely serves as the cholesterol-binding domain, that facilitates the protein's membrane interaction and insertion. Furthermore, we were able to postulate a model by which CLIC1 can autonomously insert into membranes to form functional ion channels. General significance: Members of the CLIC family of proteins demonstrate unusual structural and dual functional properties – as ion channels and enzymes. Elucidating how the CLIC proteins' interact with membranes, thus allowing them to switch between their soluble and membrane form, will provide key information a...

Huston, WM, Cranfield, CG, Forbes, SL & Leigh, A 2019, 'A sponsorship action plan for increasing diversity in STEMM', Ecology and Evolution, vol. 9, no. 5, pp. 2340-2345.
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AbstractThere are numerous structural and cultural barriers to the progression of women and marginalized groups to leadership in academia, especially in Science, Technology, Engineering, Mathematics and Medicine (STEMM). A range of interventions have been described to address this inequity, with varying success. Here, we suggest that sponsorship could be one effective intervention and propose an institutional action plan to implement a sponsorship program in academia. We outline why sponsorship could be an effective strategy, especially if implemented through a deliberate program by an institution. We then detail the three components of an action plan to be considered in implementation: the elements of the program, the activities that sponsorship in academia likely encompasses, and the selection of sponsors and protégés. The plan could also be enacted by academic leadership in the absence of an institutional program and could serve as a guide to individuals in academia aspiring to address diversity and inclusion in STEMM.

Jerotic, D, Matic, M, Suvakov, S, Vucicevic, K, Damjanovic, T, Savic-Radojevic, A, Pljesa-Ercegovac, M, Coric, V, Stefanovic, A, Ivanisevic, J, Jelic-Ivanovic, Z, McClements, L, Dimkovic, N & Simic, T 2019, 'Association of Nrf2, SOD2 and GPX1 Polymorphisms with Biomarkers of Oxidative Distress and Survival in End-Stage Renal Disease Patients', Toxins, vol. 11, no. 7, pp. 431-431.
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The oxidative stress response via Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) interlinks inflammation- and metabolism-related pathways in chronic kidney disease. We assessed the association between polymorphisms in Nrf2, superoxide dismutase (SOD2), glutathione peroxidase (GPX1), and the risk of end-stage renal disease (ESRD). The modifying effect of these polymorphisms on both oxidative phenotype and ESRD prognosis, both independently and/or in combination with the glutathione S-transferase M1 (GSTM1) deletion polymorphism, was further analyzed. Polymorphisms in Nrf2 (rs6721961), SOD2 (rs4880), GPX1 (rs1050450), and GSTM1 were determined by PCR in 256 ESRD patients undergoing hemodialysis and 374 controls. Byproducts of oxidative stress were analyzed spectrophotometically or by ELISA. Time-to-event modeling was performed to evaluate overall survival and cardiovascular survival. The SOD2 Val/Val genotype increased ESRD risk (OR = 2.01, p = 0.002), which was even higher in combination with the GPX1 Leu/Leu genotype (OR = 3.27, p = 0.019). Polymorphism in SOD2 also showed an effect on oxidative phenotypes. Overall survival in ESRD patients was dependent on a combination of the Nrf2 (C/C) and GPX1 (Leu/Leu) genotypes in addition to a patients’ age and GSTM1 polymorphism. Similarly, the GPX1 (Leu/Leu) genotype contributed to longer cardiovascular survival. Conclusions: Our results show that SOD2, GPX1, and Nrf2 polymorphisms are associated with ESRD development and can predict survival.

Ji, D, Wen, Q, Cao, L, Kang, Q, Lin, S, Zhang, X, Jiang, L & Guo, W 2019, 'Electrokinetically Controlled Asymmetric Ion Transport through 1D/2D Nanofluidic Heterojunctions', Advanced Materials Technologies, vol. 4, no. 7.
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AbstractSupported 2D layered materials are widely used in gas separation, water treatment, energy conversion, etc. In conventional viewpoint, the atop 2D membrane functions as an active layer for mass or charge separation in vapor or liquid phase, while the substrate membrane, containing aligned or tortuous 1D micro or nanoscaled fluidic channels, functions as a mechanical support. However, asymmetric transport property induced by the mixed‐dimensional composite structure is an equally very important, yet long‐overlooked element that endows new features to the membrane‐scale nanofluidic systems and contributes to the promotion of overall performance. Here, reported are asymmetric ion transport properties through 1D/2D nanofluidic heterojunction membrane (NFHM) under three different types of electrokinetic driving force. The 1D/2D NFHM comprises of self‐assembled graphene oxide multi‐layers (2DM, negatively charged) supported on a polydopamine‐coated 1D nanopore array (1DM, ampholytic). Intriguingly, it is found that the preferential direction for electric‐field‐driven ionic transport is from the 2DM to the 1DM, while under the concentration difference or the hydraulic flow, the preferred direction for diffusion or streaming ionic current goes in the reversed direction, from the 1DM to the 2DM. A theoretical model based on coupled Poisson–Nernst–Planck and Navier–Stokes equations is employed to explain the asymmetric ion transport phenomena.

Jia, P, Wen, Q, Liu, D, Zhou, M, Jin, X, Ding, L, Dong, H, Lu, D, Jiang, L & Guo, W 2019, 'Highly Efficient Ionic Photocurrent Generation through WS₂‐Based 2D Nanofluidic Channels', Small, vol. 15, no. 50, p. e1905355.
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AbstractThe unique feature of nacre‐like 2D layered materials provides a facile, yet highly efficient way to modulate the transmembrane ion transport from two orthogonal transport directions, either vertical or horizontal. Recently, light‐driven active transport of ionic species in synthetic nanofluidic systems attracts broad research interest. Herein, taking advantage of the photoelectric semiconducting properties of 2D transition metal dichalcogenides, the generation of a directional and greatly enhanced cationic flow through WS2‐based 2D nanofluidic membranes upon asymmetric visible light illumination is reported. Compared with graphene‐based materials, the magnitude of the ionic photocurrent can be enhanced by tens of times, and its photo‐responsiveness can be 2–3.5 times faster. This enhancement is explained by the coexistence of semiconducting and metallic WS2 nanosheets in the hybrid membrane that facilitates the asymmetric diffusion of photoexcited charge carriers on the channel wall, and the high ionic conductance due to the neat membrane structure. To further demonstrate its application, photonic ion switches, photonic ion diodes, and photonic ion transistors as the fundamental elements for light‐controlled nanofluidic circuits are further developed. Exploring new possibilities in the family of liquid processable colloidal 2D materials provides a way toward high‐performance light‐harvesting nanofluidic systems for artificial photosynthesis and sunlight‐driven desalination.

Kulasinghe, A, Kapeleris, J, Cooper, C, Warkiani, ME, O’Byrne, K & Punyadeera, C 2019, 'Phenotypic Characterization of Circulating Lung Cancer Cells for Clinically Actionable Targets', Cancers, vol. 11, no. 3, pp. 380-380.
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Objectives: In non-small cell lung cancers (NSCLC), tumour biopsy can often be an invasive procedure. The development of a non-invasive methodology to study genetic changes via circulating tumour cells (CTCs) is an appealing concept. Whilst CTCs typically remain as rare cells, improvements in epitope-independent CTC isolation techniques has given rise to a greater capture of CTCs. In this cross sectional study, we demonstrate the capture and characterization of NSCLC CTCs for the clinically actionable markers epidermal growth factor receptor (EGFR) alterations, anaplastic lymphoma kinase (ALK) rearrangements and programmed death ligand-1 (PD-L1) expression. The study identified CTCs/CTC clusters in 26/35 Stage IV NSCLC patients, and subsequently characterized the CTCs for EGFR mutation, ALK status and PD-L1 status. This pilot study demonstrates the potential of a non-invasive fluid biopsy to determine clinically relevant biomarkers in NSCLC.

Li, H, Xiao, F, Hong, G, Su, J, Li, N, Cao, L, Wen, Q & Guo, W 2019, 'On the Role of Heterogeneous Nanopore Junction in Osmotic Power Generation', Chinese Journal of Chemistry, vol. 37, no. 5, pp. 469-473.
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Summary of main observation and conclusionOsmotic power generated by mixing ionic solutions of different concentration is an underutilized clean energy resource that satisfy potentially the ever‐growing energy demand. For decades, substantial efforts are made to enhance the power density. Toward this goal, we once developed a heterogeneous nanoporous membrane comprising of heterojunctions between negatively charged mesoporous carbon and positively charged macroporous alumina to harvest electric power from salinity difference and achieved outstanding performance (J. Am. Chem. Soc. 2014, 136, 12265). The heterogeneous nanopore junction effectively suppresses ion concentration polarization (ICP) at low concentration end, and consequently promotes the overall power density. However, to date, a systematic understanding of the role of the heterogeneous nanopore junction in osmotic energy conversion remains urgent and largely unexplored. Herein, we provide an in‐depth theoretical investigation on this issue with special emphasis on several influential factors, such as the ionic concentration, the surface charge density, and the geometry of heterogeneous part. To balance the suppression of ICP and maintenance of charge selectivity, we find that these influential factors in the heterogeneous part should be restricted to a specific range. These findings provide direct guidance for design and optimization of high‐performance nanofluidic power sources.

Liu, X, Liu, L, Ji, Y, Li, C, Wei, T, Yang, X, Zhang, Y, Cai, X, Gao, Y, Xu, W, Rao, S, Jin, D, Lou, W, Qiu, Z & Wang, X 2019, 'Enrichment of short mutant cell-free DNA fragments enhanced detection of pancreatic cancer', EBioMedicine, vol. 41, pp. 345-356.
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López-Campos, G, Bonner, E & McClements, L 2019, 'An Integrative Biomedical Informatics Approach to Elucidate the Similarities Between Pre-Eclampsia and Hypertension.', MedInfo, vol. 264, pp. 988-992.
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© 2019 International Medical Informatics Association (IMIA) and IOS Press. Pre-eclampsia is a pregnancy condition affecting 5-10% of pregnancies, and it is the leading cause of death in pregnancy associated with increased risk of cardiovascular disease later in life. Despite research, the pathogenesis of pre-eclampsia is still poorly understood. In this paper, we investigate the overlapping pathogenic mechanisms between pre-eclampsia and adult hypertension using an integrative biomedical informatics strategy that combined text mining techniques to identify genes and proteins, with geneset analyses, generating knowledge on the pathways and mechanisms involved in these conditions. We identified several overlapping pathogenic pathways/systems including metabolic pathways, developmental biology pathways, immune system, haemostasis, tyrosine kinase pathways, extracellular matrix and oxidative stress pathways. This bioinformatics approach could be applied for investigating mechanistic pathways of other disorders.

Ma, K, Liu, G-J, Yan, L, Wen, S, Xu, B, Tian, W, Goldys, EM & Liu, G 2019, 'AIEgen based poly(L-lactic-co-glycolic acid) magnetic nanoparticles to localize cytokine VEGF for early cancer diagnosis and photothermal therapy', Nanomedicine, vol. 14, no. 9, pp. 1191-1201.
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Aim: We demonstrated a novel theranostic system for simultaneous photothermal therapy and magnetic resonance imaging applicable to early diagnostics and treatment of cancer cells. Materials & methods: Oleic acid-Fe3O4 and triphenylamine-divinylanthracene-dicyano were loaded to the poly(L-lactic-co-glycolic acid) nanoparticles (NPs) on which anti-VEGF antibodies were modified to form anti-VEGF/OA-Fe3O4/triphenylamine-divinylanthracene-dicyano@poly(L-lactic-co-glycolic acid) NPs. The 1H nuclear magnetic resonance (NMR), mass spectra, fluorescence, UV absorption, dynamic light scattering, transmission electron microscope and inductively coupled plasma mass spectrometry tests were used to characterize the NPs, and the bioimaging was illustrated by confocal laser scanning microscope (CLSM) and in vivo MRI animal experiment. Results: This system was capable to recognize the overexpressed VEGF-A as low as 68 pg/ml in different cell lines with good selectivity and photothermal therapy effect. Conclusion: These ultrasensitive theranostic NPs were able to identify tumor cells by fluorescence imaging and MRI, and destroy tumors under near infrared illumination.

Mahmoodi, Z, Mohammadnejad, J, Razavi Bazaz, S, Abouei Mehrizi, A, Ghiass, MA, Saidijam, M, Dinarvand, R, Ebrahimi Warkiani, M & Soleimani, M 2019, 'A simple coating method of PDMS microchip with PTFE for synthesis of dexamethasone-encapsulated PLGA nanoparticles', Drug Delivery and Translational Research, vol. 9, no. 3, pp. 707-720.
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© 2019, Controlled Release Society. Dexamethasone is a widely used drug in medical and biological applications. Since the systematic and controllable release of this drug is of significant importance, encapsulation of this anti-inflammatory drug in poly(lactic-co-glycolic acid) (PLGA) nanoparticles can minimize uncontrolled issues. As dexamethasone-encapsulated PLGA nanoparticles are synthesized in the presence of organic solvents, poly(dimethylsiloxane) (PDMS)-based microchannels collapse due to the swelling problem. In present study, PTFE nanoparticles were used for the surface modification of the microchannels to prevent absorption and adhesion of solvents into the microchannels’ wall. The contact angle analysis of microchips after coating showed that the surface of microchannels bear the superhydrophobicity feature (140.30°) and SEM images revealed that PTFE covered the surface of PDMS, favorably. Then, the prepared microchip was tested for the synthesis of dexamethasone-loaded nanoparticles. SEM and atomic force microscopy (AFM) images of the synthesized nanoparticles represented that there was not any evidence of adhesion or absorption of nanoparticles. Furthermore, the monodispersity of nanoparticles was discernible. As AFM results revealed, the average diameters of 47, 63, and 82 nm were achieved for flow ratios of 0.01, 0.05, and 0.1, respectively. To evaluate the drug efficiency, cumulative release and encapsulation efficiency were analyzed which showed much more efficiency than the synthesized nanoparticles in the bulk mode. In addition, MTT test revealed that nanoparticles could be considered as a non-toxic material. Since the synthesis of drug-loaded nanoparticles is ubiquitous in laboratory experiments, the approach presented in this study can render more versatility in this regard.

McClements, L, Annett, S, Yakkundi, A, O’Rourke, M, Valentine, A, Moustafa, N, Alqudah, A, Simões, BM, Furlong, F, Short, A, McIntosh, SA, McCarthy, HO, Clarke, RB & Robson, T 2019, 'FKBPL and its peptide derivatives inhibit endocrine therapy resistant cancer stem cells and breast cancer metastasis by downregulating DLL4 and Notch4', BMC Cancer, vol. 19, no. 1, p. 351.
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© 2019 The Author(s). Background: Optimising breast cancer treatment remains a challenge. Resistance to therapy is a major problem in both ER- and ER+ breast cancer. Tumour recurrence after chemotherapy and/or targeted therapy leads to more aggressive tumours with enhanced metastatic ability. Self-renewing cancer stem cells (CSCs) have been implicated in treatment resistance, recurrence and the development of metastatic disease. Methods: In this study, we utilised in vitro, in vivo and ex vivo breast cancer models using ER+ MCF-7 and ER- MDA-MB-231 cells, as well as solid and metastatic breast cancer patient samples, to interrogate the effects of FKBPL and its peptide therapeutics on metastasis, endocrine therapy resistant CSCs and DLL4 and Notch4 expression. The effects of FKBPL overexpression or peptide treatment were assessed using a t-test or one-way ANOVA with Dunnett's multiple comparison test. Results: We demonstrated that FKBPL overexpression or treatment with FKBPL-based therapeutics (AD-01, pre-clinical peptide /ALM201, clinical peptide) inhibit i) CSCs in both ER+ and ER- breast cancer, ii) cancer metastasis in a triple negative breast cancer metastasis model and iii) endocrine therapy resistant CSCs in ER+ breast cancer, via modulation of the DLL4 and Notch4 protein and/or mRNA expression. AD-01 was effective at reducing triple negative MDA-MB-231 breast cancer cell migration (n ≥ 3, p < 0.05) and invasion (n ≥ 3, p < 0.001) and this was translated in vivo where AD-01 inhibited breast cancer metastasis in MDA-MB-231-lucD3H1 in vivo model (p < 0.05). In ER+ MCF-7 cells and primary breast tumour samples, we demonstrated that ALM201 inhibits endocrine therapy resistant mammospheres, representative of CSC content (n ≥ 3, p < 0.05). Whilst an in vivo limiting dilution assay, using SCID mice, demonstrated that ALM201 alone or in combination with tamoxifen was very effective at delaying tumour recurrence by 12 (p < 0.05) or 21 days (p < 0.001), res...

Mi, C, Zhou, J, Wang, F & Jin, D 2019, 'Thermally enhanced NIR–NIR anti-Stokes emission in rare earth doped nanocrystals', Nanoscale, vol. 11, no. 26, pp. 12547-12552.
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Surface phonons enhancing the one-photon anti-Stokes fluorescence has been demonstrated in rare earth doped nanocrystals.

Mi, C, Zhou, J, Wang, F, Lin, G & Jin, D 2019, 'Ultrasensitive Ratiometric Nanothermometer with Large Dynamic Range and Photostability', Chemistry of Materials, vol. 31, no. 22, pp. 9480-9487.
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Copyright © 2019 American Chemical Society. Thermally responsive fluorescent nanoparticles can be constructed to allow robust, rapid, and noninvasive temperature measurements. Furthermore, due to their tiny size, they can be used to detect temperature changes at the nanoscale. In this way, such sensors are ideally suited to emerging applications including intracellular temperature sensing and microelectronics failure diagnostics. Despite their potential, current nanothermometers still suffer from limited sensitivity, dynamic range, and stability. By introducing thermal enhanced anti-Stokes emission from a pair of lanthanide ions, ytterbium and neodymium, we show an increase of more than 1 order of magnitude in both the sensitivity and the dynamic range when compared to conventional ytterbium and erbium-codoped nanothermometers. Here, we report heterogeneous temperature-responsive nanoparticles with a new record of sensitivity (9.6%/K at room temperature and above 2.3%/K at elevated temperatures up to 413 K) that can be used for ratiometric thermometry. The heterogeneous nanostructure design shows that the thermal responses can be fine-tuned by the controlled growth of nanoparticles. The stability of the ultrasensitive nanothermometers has enabled long-term noncontact monitoring of local heat dissipation of a microelectronic device.

Moloudi, R, Oh, S, Yang, C, Teo, KL, Lam, AT, Ebrahimi Warkiani, M & Win Naing, M 2019, 'Scaled‐Up Inertial Microfluidics: Retention System for Microcarrier‐Based Suspension Cultures', Biotechnology Journal, vol. 14, no. 5, pp. 1800674-1800674.
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Recently, particle concentration and filtration using inertial microfluidics have drawn attention as an alternative to membrane and centrifugal technologies for industrial applications, where the target particle size varies between 1 µm and 500 µm. Inevitably, the bigger particle size (>50 µm) mandates scaling up the channel cross‐section or hydraulic diameter (DH > 0.5 mm). The Dean‐coupled inertial focusing dynamics in spiral microchannels is studied broadly; however, the impacts of secondary flow on particle migration in a scaled‐up spiral channel is not fully elucidated. The mechanism of particle focusing inside scaled‐up rectangular and trapezoidal spiral channels (i.e., 5–10× bigger than conventional microchannels) with an aim to develop a continuous and clog‐free microfiltration system for bioprocessing is studied in detail. Herein, a unique focusing based on inflection point without the aid of sheath flow is reported. This new focusing mechanism, observed in the scaled‐up channels, out‐performs the conventional focusing scenarios in the previously reported trapezoidal and rectangular channels. Finally, as a proof‐of‐concept, the utility of this device is showcased for the first time as a retention system for a cell–microcarrier (MC) suspension culture.

Nasiri, N, Jin, D & Tricoli, A 2019, 'Nanoarchitechtonics of Visible‐Blind Ultraviolet Photodetector Materials: Critical Features and Nano‐Microfabrication', Advanced Optical Materials, vol. 7, no. 2, pp. 1800580-1800580.
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AbstractAccurate measurement of ultraviolet radiation is key to many technologies including wearable devices for skin cancer prevention, optical communication systems, and missile launch detection. Nanostructuring of wide bandgap semiconductors, such as GaN, ZnO, and SiC, promises some benefits over established commercial solutions relying on n–p type Si‐homojunction technology. In the past decade, a variety of carefully nanostructured architectures have been demonstrated as efficient designs for visible‐blind UV photodetectors featuring superior detectivity, thermal stability, robust radiation hardness, and very low operation bias and power consumption. Here, a comprehensive review of the latest achievements on ultraviolet photodetector materials is presented, with focus on the multiscale engineering of composition and nano‐microscale morphology. The review concludes with a critical assessment and comparison of state‐of‐the‐art devices aiming to provide guidelines and research directions for the next generation of UV photodetector materials.

Nguyen, T, Li, GE, Chen, H, Cranfield, CG, McGrath, KC & Gorrie, CA 2019, 'Neurological Effects in the Offspring After Switching From Tobacco Cigarettes to E-Cigarettes During Pregnancy in a Mouse Model', Toxicological Sciences, vol. 172, no. 1, pp. 191-200.
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Abstract Maternal smoking is currently a public health concern and has been associated with a number of complications in the offspring. E-cigarettes are gaining popularity as a “safer” alternative to tobacco cigarettes during pregnancy, however, there are a limited number of studies to suggest that it is actually “safe.” Balb/C female mice were exposed to ambient air (n = 8; Sham), or tobacco cigarette smoke (n = 8; SE) before gestation, during gestation and lactation. A third group was exposed to cigarette smoke before gestation followed by e-cigarette aerosols during gestation and lactation (n = 8; Switch). Male offspring (12-week old, n = 10–14/group) underwent behavioral assessments to investigate short-term memory, anxiety, and activity using the novel object recognition and elevated plus maze tests. Brains were collected at postnatal day (P)1, P20, and Week 13 for global DNA methylation, epigenetic gene expression, and neuronal cell counts. The offspring from mothers switching to e-cigarettes exhibited no change in exploration/activity but showed a decrease in global DNA methylation, Aurora Kinase (Aurk) A and AurkB gene expression and a reduction in neuronal cell numbers in the cornu ammonis 1 region of the dorsal hippocampus compared with the SE group. Continuous tobacco cigarette smoke exposure during pregnancy resulted in marked neurological deficits in the offspring. Switching to e-cigarettes during pregnancy reduced these neurological deficits compared with cigarette smoke exposure. However, neurological changes were still observed, so we therefore conclude that e-cigarette use during pregnancy is not advised.

Piya, R, Zhu, Y, Soeriyadi, AH, Silva, SM, Reece, PJ & Gooding, JJ 2019, 'Micropatterning of porous silicon Bragg reflectors with poly(ethylene glycol) to fabricate cell microarrays: Towards single cell sensing', Biosensors and Bioelectronics, vol. 127, pp. 229-235.
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The work presented here describes the development of an optical label-free biosensor based on a porous silicon (PSi) Bragg reflector to study heterogeneity in single cells. Photolithographic patterning of a poly(ethylene glycol) (PEG) hydrogel with a photoinitiator was employed on RGD peptide-modified PSi to create micropatterns with cell adhesive and cell repellent areas. Macrophage J774 cells were incubated to form cell microarrays and single cell arrays. Moreover, cells on the microarrays were lysed osmotically with Milli-Q™ water and the infiltration of cell lysate into the porous matrix was monitored by measuring the red shift in the reflectivity. On average, the magnitude of red shift increased with the increase in the number of cells on the micropatterns. The red shift from the spots with single cells varied from spot to spot emphasizing the heterogeneous nature of the individual cells.

Previdi, R, Levchenko, I, Arnold, M, Gali, M, Bazaka, K, Xu, S, Ostrikov, KK, Bray, K, Jin, D & Fang, J 2019, 'Plasmonic platform based on nanoporous alumina membranes: order control via self-assembly', Journal of Materials Chemistry A, vol. 7, no. 16, pp. 9565-9577.
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A novel approach to significantly enhance and comprehensively assess the level of nanochannel ordering in self-assembled nanoporous membranes is proposed and tested.

Pu, N, Gao, S, Yin, H, Li, J-A, Wu, W, Fang, Y, Zhang, L, Rong, Y, Xu, X, Wang, D, Kuang, T, Jin, D, Yu, J & Lou, W 2019, 'Cell-intrinsic PD-1 promotes proliferation in pancreatic cancer by targeting CYR61/CTGF via the hippo pathway', Cancer Letters, vol. 460, pp. 42-53.
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Pu, N, Yin, H, Zhao, G, Nuerxiati, A, Wang, D, Xu, X, Kuang, T, Jin, D, Lou, W & Wu, W 2019, 'Independent effect of postoperative neutrophil-to-lymphocyte ratio on the survival of pancreatic ductal adenocarcinoma with open distal pancreatosplenectomy and its nomogram-based prediction', Journal of Cancer, vol. 10, no. 24, pp. 5935-5943.
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Rafeie, M, Hosseinzadeh, S, Huang, J, Mihandoust, A, Warkiani, ME & Taylor, RA 2019, 'New insights into the physics of inertial microfluidics in curved microchannels. II. Adding an additive rule to understand complex cross-sections', Biomicrofluidics, vol. 13, no. 3, pp. 034118-034118.
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Curved microchannels allow controllable microparticle focusing, but a full understanding of particle behavior has been limited—even for simple rectangular and trapezoidal shapes. At present, most microfluidic particle separation literature is dedicated to adding “internal” complexity (via sheath flow or obstructions) to relatively simple cross-sectional channel shapes. We propose that, with sufficient understanding of particle behavior, an equally viable pathway for microparticle focusing could utilize complex “external” cross-sectional shapes. By investigating three novel, complex spiral microchannels, we have found that it is possible to passively focus (6, 10, and 13 μm) microparticles in the middle of a convex channel. Also, we found that in concave and jagged channel designs, it is possible to create multiple, tight focusing bands. In addition to these performance benefits, we report an “additive rule” herein, which states that complex channels can be considered as multiple, independent, simple cross-sectional shapes. We show with experimental and numerical analysis that this new additive rule can accurately predict particle behavior in complex cross-sectional shaped channels and that it can help to extract general inertial focusing tendencies for suspended particles in curved channels. Overall, this work provides simple, yet reliable, guidelines for the design of advanced curved microchannel cross sections.

Rafeie, M, Hosseinzadeh, S, Taylor, RA & Warkiani, ME 2019, 'New insights into the physics of inertial microfluidics in curved microchannels. I. Relaxing the fixed inflection point assumption', Biomicrofluidics, vol. 13, no. 3, pp. 034117-034117.
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Inertial microfluidics represents a powerful new tool for accurately positioning cells and microparticles within fluids for a variety of biomedical, clinical, and industrial applications. In spite of enormous advancements in the science and design of these devices, particularly in curved microfluidic channels, contradictory experimental results have confounded researchers and limited progress. Thus, at present, a complete theory which describes the underlying physics is lacking. We propose that this bottleneck is due to one simple mistaken assumption—the locations of inflection points of the Dean velocity profile in curved microchannels are not fixed, but can actually shift with the flow rate. Herein, we propose that the dynamic distance (δ) between the real equilibrium positions and their nearest inflection points can clearly explain several (previously) unexplained phenomena in inertial microfluidic systems. More interestingly, we found that this parameter, δ, is a function of several geometric and operational parameters, all of which are investigated (in detail) here with a series of experiments and simulations of different spiral microchannels. This key piece of understanding is expected to open the door for researchers to develop new and more effective inertial microfluidic designs.

Raoufi, MA, Mashhadian, A, Niazmand, H, Asadnia, M, Razmjou, A & Warkiani, ME 2019, 'Experimental and numerical study of elasto-inertial focusing in straight channels', Biomicrofluidics, vol. 13, no. 3, pp. 034103-034103.
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Elasto-inertial microfluidics has drawn significant attention in recent years due to its enhanced capabilities compared to pure inertial systems in control of small microparticles. Previous investigations have focused mainly on the applications of elasto-inertial sorting, rather than studying its fundamentals. This is because of the complexity of simulation and analysis, due to the presence of viscoelastic force. There have been some investigative efforts on the mechanisms of elasto-inertial focusing in straight channels; however, these studies were limited to simple rectangular channels and neglected the effects of geometry and flow rates on focusing positions. Herein, for the first time, we experimentally and numerically explore the effects of elasticity accompanying channel cross-sectional geometry and sample flow rates on the focusing phenomenon in elasto-inertial systems. The results reveal that increasing the aspect ratio weakens the elastic force more than inertial force, causing a transition from one focusing position to two. In addition, they show that increasing the angle of a channel corner causes the elastic force to push the particles more efficiently toward the center over a larger area of the channel cross section. Following on from this, we proposed a new complex straight channel which demonstrates a tighter focusing band compared to other channel geometries. Finally, we focused Saccharomyces cerevisiae cells (3–5 μm) in the complex channel to showcase its capability in focusing small-size particles. We believe that this research work improves the understanding of focusing mechanisms in viscoelastic solutions and provides useful insights into the design of elasto-inertial microfluidic devices.

Raoufi, MA, Moshizi, SA, Razmjou, A, Wu, S, Ebrahimi Warkiani, M & Asadnia, M 2019, 'Development of a Biomimetic Semicircular Canal With MEMS Sensors to Restore Balance', IEEE Sensors Journal, vol. 19, no. 23, pp. 11675-11686.
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© 2001-2012 IEEE. A third of adults over the age of 50 suffer from chronic impairment of balance, posture, and/or gaze stability due to partial or complete impairment of the sensory cells in the inner ear responsible for these functions. The consequences of impaired balance organ can be dizziness, social withdrawal, and acceleration of the further functional decline. Despite the significant progress in biomedical sensing technologies, current artificial vestibular systems fail to function in practical situations and in very low frequencies. Herein, we introduced a novel biomechanical device that closely mimics the human vestibular system. A microelectromechanical systems (MEMS) flow sensor was first developed to mimic the vestibular haircell sensors. The sensor was then embedded into a three-dimensional (3D) printed semicircular canal and tested at various angular accelerations in the frequency range from 0.5Hz to 1.5Hz. The miniaturized device embedded into a 3D printed model will respond to mechanical deflections and essentially restore the sense of balance in patients with vestibular dysfunctions. The experimental and simulation studies of semicircular canal presented in this work will pave the way for the development of balance sensory system, which could lead to the design of a low-cost and commercially viable medical device with significant health benefits and economic potential.

Razavi Bazaz, S, Kashaninejad, N, Azadi, S, Patel, K, Asadnia, M, Jin, D & Ebrahimi Warkiani, M 2019, 'Microfluidics: Rapid Softlithography Using 3D‐Printed Molds (Adv. Mater. Technol. 10/2019)', Advanced Materials Technologies, vol. 4, no. 10, pp. 1970056-1970056.
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Razavi Bazaz, S, Kashaninejad, N, Azadi, S, Patel, K, Asadnia, M, Jin, D & Ebrahimi Warkiani, M 2019, 'Rapid Softlithography Using 3D‐Printed Molds', Advanced Materials Technologies, vol. 4, no. 10, pp. 1900425-1900425.
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AbstractPolydimethylsiloxane (PDMS) is a long‐standing material of significant interest in microfluidics due to its unique features. As such, rapid prototyping of PDMS‐based microchannels is of great interest. The most prevalent and conventional method for fabrication of PDMS‐based microchips relies on softlithography, the main drawback of which is the preparation of a master mold, which is costly and time‐consuming. To prevent the attachment of PDMS to the master mold, silanization is necessary, which can be detrimental for cellular studies. Additionally, using coating the mold with a cell‐compatible surfactant adds extra preprocessing time. Recent advances in 3D printing have shown great promise in expediting microfabrication. Nevertheless, current 3D printing techniques are sub‐optimal for PDMS softlithography. The feasibility of producing master molds suitable for rapid softlithography is demonstrated using a newly developed 3D‐printing resin. Moreover, the utility of this technique is showcased for a number of widely used applications, such as concentration gradient generation, particle separation, cell culture (to show biocompatibility of the process), and fluid mixing. This can open new opportunities for biologists and scientists with minimum knowledge of microfabrication to build functional microfluidic devices for their basic and applied research.

Rezaei, M, Winter, M, Zander-Fox, D, Whitehead, C, Liebelt, J, Warkiani, ME, Hardy, T & Thierry, B 2019, 'A Reappraisal of Circulating Fetal Cell Noninvasive Prenatal Testing', Trends in Biotechnology, vol. 37, no. 6, pp. 632-644.
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© 2018 Elsevier Ltd New tools for higher-resolution fetal genome analysis including microarray and next-generation sequencing have revolutionized prenatal screening. This article provides commentary on this rapidly advancing field and a future perspective emphasizing circulating fetal cell (CFC) utility. Despite the tremendous technological challenges associated with their reliable and cost-effective isolation from maternal blood, CFCs have a strong potential to bridge the gap between the diagnostic sensitivity of invasive procedures and the desirable noninvasive nature of cell-free fetal DNA (cffDNA). Considering the rapid advances in both rare cell isolation and low-input DNA analysis, we argue here that CFC-based noninvasive prenatal testing is poised to be implemented clinically in the near future.

Shrestha, J, Ghadiri, M, Shanmugavel, M, Razavi Bazaz, S, Vasilescu, S, Ding, L & Ebrahimi Warkiani, M 2019, 'A rapidly prototyped lung-on-a-chip model using 3D-printed molds', Organs-on-a-Chip, vol. 1, pp. 100001-100001.
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Suvakov, S, Jerotic, D, Damjanovic, T, Milic, N, Pekmezovic, T, Djukic, T, Jelic-Ivanovic, Z, Savic Radojevic, A, Pljesa-Ercegovac, M, Matic, M, McClements, L, Dimkovic, N, Garovic, VD, Albright, RC & Simic, T 2019, 'Markers of Oxidative Stress and Endothelial Dysfunction Predict Haemodialysis Patients Survival', American Journal of Nephrology, vol. 50, no. 2, pp. 115-125.
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<b><i>Introduction:</i></b> Overall survival of patients with end-stage renal disease (ESRD) remains poor. Oxidative stress is one of the major risk factors associated with mortality in this patient group. As glutathione S-transferases (GST) are well-established antioxidants, we hypothesized that a model including GST gene polymorphisms, oxidative damage byproducts and cell adhesion markers has a prognostic role in ESRD patient survival. <b><i>Methods:</i></b> A prospective study of 199 patients with ESRD on haemodialysis was conducted. GST genotype, oxidative stress byproducts and cell adhesion molecules were measured in plasma. Multivariate Cox regression and Kaplan-Meier survival analyses were performed to test the predictive ability of these parameters in the 8-year follow-up period. <b><i>Results:</i></b> GSTM1-null genotype was associated with significantly shorter overall (HR 1.6, <i>p</i> = 0.018) and cardiovascular-specific (HR 2.1, <i>p</i> = 0.010) survival. Oxidative stress byproducts (advanced oxidation protein products [AOPP], prooxidant-antioxidant balance [PAB], malondialdehyde [MDA]) and cell adhesion molecules (soluble vascular cell adhesion molecule-1 [sVCAM-1] and soluble intercellular adhesion molecule-1 [sICAM-1]) demonstrated a significant predictive role in terms of overall and cardiovascular survival. When 6 biomarkers (GSTM1 genotype, high AOPP/PAB/MDA/­sVCAM-1/sICAM-1) were combined into a scoring model, a significantly shorter overall and cardiovascular survival was observed for patients with the highest score (<i>p</i> &#x3c; 0.001). <b><i>Conclusion:</i></b> We identified a novel panel of biomarkers that can be utilized in predicting survival in ESRD patients. This biomarker signature could enable better monitoring of patients and stratification into appropriate treatment groups.

Wang, L, Cui, D, Ren, L, Zhou, J, Wang, F, Casillas, G, Xu, X, Peleckis, G, Hao, W, Ye, J, Dou, SX, Jin, D & Du, Y 2019, 'Boosting NIR-driven photocatalytic water splitting by constructing 2D/3D epitaxial heterostructures', Journal of Materials Chemistry A, vol. 7, no. 22, pp. 13629-13634.
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YF₃:Yb, Tm@BiOCl possesses epitaxial heterostructure, which can quantitatively activate multiple energy transfer channels including excited-state energy transfer and fluorescence reabsorption, and then promote the NIR-driven photocatalytic properties.

Wang, L, Wen, Q, Jia, P, Jia, M, Lu, D, Sun, X, Jiang, L & Guo, W 2019, 'Light‐Driven Active Proton Transport through Photoacid‐ and Photobase‐Doped Janus Graphene Oxide Membranes', Advanced Materials, vol. 31, no. 36, p. e1903029.
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AbstractBiological electrogenic systems use protein‐based ionic pumps to move salt ions uphill across a cell membrane to accumulate an ion concentration gradient from the equilibrium physiological environment. Toward high‐performance and robust artificial electric organs, attaining an antigradient ion transport mode by fully abiotic materials remains a great challenge. Herein, a light‐driven proton pump transport phenomenon through a Janus graphene oxide membrane (JGOM) is reported. The JGOM is fabricated by sequential deposition of graphene oxide (GO) nanosheets modified with photobase (BOH) and photoacid (HA) molecules. Upon ultraviolet light illumination, the generation of a net protonic photocurrent through the JGOM, from the HA‐GO to the BOH‐GO side, is observed. The directional proton flow can thus establish a transmembrane proton concentration gradient of up to 0.8 pH units mm−2 membrane area at a proton transport rate of 3.0 mol h−1 m−2. Against a concentration gradient, antigradient proton transport can be achieved. The working principle is explained in terms of asymmetric surface charge polarization on HA‐GO and BOH‐GO multilayers triggered by photoisomerization reactions, and the consequent intramembrane proton concentration gradient. The implementation of membrane‐scale light‐harvesting 2D nanofluidic system that mimics the charge process of the bioelectric organs makes a straightforward step toward artificial electrogenic and photosynthetic applications.

Wei, Y, Xing, G, Liu, K, Li, G, Dang, P, Liang, S, Liu, M, Cheng, Z, Jin, D & Lin, J 2019, 'New strategy for designing orangish-red-emitting phosphor via oxygen-vacancy-induced electronic localization', Light: Science & Applications, vol. 8, no. 1.
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AbstractPhosphor-converted white-light-emitting diodes (pc-WLED) have been extensively employed as solid-state lighting sources, which have a very important role in people’s daily lives. However, due to the scarcity of the red component, it is difficult to realize warm white light efficiently. Hence, red-emitting phosphors are urgently required for improving the illumination quality. In this work, we develop a novel orangish-red La4GeO8:Bi3+ phosphor, the emission peak of which is located at 600 nm under near-ultraviolet (n-UV) light excitation. The full width at half maximum (fwhm) is 103 nm, the internal quantum efficiency (IQE) exceeds 88%, and the external quantum efficiency (EQE) is 69%. According to Rietveld refinement analysis and density functional theory (DFT) calculations, Bi3+ ions randomly occupy all La sites in orthorhombic La4GeO8. Importantly, the oxygen-vacancy-induced electronic localization around the Bi3+ ions is the main reason for the highly efficient orangish-red luminescence. These results provide a new perspective and insight from the local electron structure for designing inorganic phosphor materials that realize the unique luminescence performance of Bi3+ ions.

Wen, S, Zhou, J, Schuck, PJ, Suh, YD, Schmidt, TW & Jin, D 2019, 'Future and challenges for hybrid upconversion nanosystems', Nature Photonics, vol. 13, no. 12, pp. 828-838.
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© 2019, Springer Nature Limited. To improve the efficiency of photon upconversion, a hybrid approach of combining organic dyes and inorganic nanoparticles is proving successful, especially in the form of dye-sensitized lanthanide-doped upconversion nanoparticles, nanoparticle-sensitized molecular triplet–triplet annihilation systems and metal–organic-framework nanoparticles. In this Review, we survey the latest advances and examine the key factors affecting upconversion performance, such as spectral overlap, core–shell design and the management of triplet excitons and quenchers at the interface between materials. Although issues such as stability, triplet-state quenching, concentration quenching and reabsorption must still be overcome, smart designs of hybrid nanosystems offer exciting opportunities for applications such as solar photovoltaic devices, deep-tissue biomedical imaging, optogenetics and nanomedicine among others.

Winter, M, Cai, Z, Winkler, K, Georgiou, K, Inglis, D, Lavranos, T, Rezaei, M, Warkiani, M & Thierry, B 2019, 'Circulating tumour cell RNA characterisation from colorectal cancer patient blood after inertial microfluidic enrichment', MethodsX, vol. 6, pp. 1512-1520.
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© 2019 The Authors The detection and molecular analysis of circulating tumour cells (CTCs) potentially provides a significant insight to the characterisation of disease, stage of progression and therapeutic options for cancer patients. Following on from the protocol by Warkiani et al. 2016, which describes a method of enriching CTCs from cancer patient blood with inertial microfluidics, we describe a method to measure the CTC RNA expression in the enriched fraction using droplet digital PCR and compare transcript detection with and without RNA pre-amplification. • Inertial microfluidics combined with droplet digital PCR is advantageous as it allows for CTC enrichment and subsequent RNA analysis from patient blood. This allows for patient tumour analysis with increased sensitivity and precision compared to quantitative Real Time PCR and enables the direct quantification of nucleic acids without the need for tumour biopsy. • This method demonstrates an efficient approach providing important insights into the analysis of colorectal cancer patients’ CTCs using a specific gene subset or biomarkers, an approach that may be tailored to tumour type or expanded to larger panels.

Xu, J, Gulzar, A, Yang, P, Bi, H, Yang, D, Gai, S, He, F, Lin, J, Xing, B & Jin, D 2019, 'Recent advances in near-infrared emitting lanthanide-doped nanoconstructs: Mechanism, design and application for bioimaging', Coordination Chemistry Reviews, vol. 381, pp. 104-134.
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© 2018 Elsevier B.V. Lanthanide-doped nanoconstructs (LDNCs) have been widely studied in the biomedical field. Especially, LDNCs with near-infrared (NIR) fluorescence show great promise in biological imaging. The fluorescence in the NIR window (700–1700 nm) affords increased tissue penetration due to the reduced light absorption, photon scattering and autofluorescence. Actually, LDNCs with various lanthanide-dopings can emit ultraviolet (UV), visible (VIS) and NIR photons through upconversion (UC) and downconversion (DC) processes. Moreover, there are review papers introducing different aspects of bioimaging based on LDNCs. Nevertheless, there has not been a review that systematically summarizes NIR fluorescent LDNCs. Herein, we summarize the recent progress made on NIR fluorescence imaging by highlighting the increasingly developing trend of NIR emitting LDNCs. The NIR emission mechanism of LDNCs activated by different lanthanide ions was discussed in detail, and their advantages as NIR fluorescent probes will be systematically introduced. From the aspect of realizing multimodal imaging, the advances made by combining magnetic resonance imaging (MRI), computed tomography (CT) and so on with NIR optical imaging were summarized. Finally, we discuss the superiority of NIR-II (1000–1700 nm) emitting LDNCs when applied in biomedical imaging, with an emphasis on how to use them to realize imaging guided cancer therapy.

Xu, X, Zhou, Z, Liu, Y, Wen, S, Guo, Z, Gao, L & Wang, F 2019, 'Optimising passivation shell thickness of single upconversion nanoparticles using a time-resolved spectrometer', APL Photonics, vol. 4, no. 2, pp. 026104-026104.
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© 2019 Author(s). Lanthanide-doped upconversion nanoparticles (UCNPs) are the most efficient multi-photon probe that can be used for deep tissue bio-imaging, fluorescence microscopy, and single molecule sensing applications. Passivating UCNPs with inert shell has been demonstrated to be an effective method to significantly enhance their brightness. However, this method also increases the overall size of the nanoparticles, which limited their cellular applications. Current reports to optimise the thickness of the shell are based on the spectrum measurement of ensembles of UCNPs, which are less quantitative. The characterisation of single UCNPs would be desirable, but is limited by the sensitivity of conventional spectrometers. We developed an optical filter-based spectrometer coupled to a laser scanning microscopy system and achieved a high degree of sensitivity - seven times more than the traditional amount. Through highly controlled syntheses of a range Yb 3+ and Tm 3+ doped UCNPs with different shell thickness, quantitative characterization of the emission intensity and lifetime on single UCNPs were comprehensively studied using a home-made optical system. We found that the optimal shell thickness was 6.3 nm. We further demonstrated that the system was sensitive enough to measure the time-resolved spectrum from a single UCNP, which is significantly useful for a comprehensive study of the energy transfer process of UCNPs.

Yang, J, Hu, X, Kong, X, Jia, P, Ji, D, Quan, D, Wang, L, Wen, Q, Lu, D, Wu, J, Jiang, L & Guo, W 2019, 'Photo-induced ultrafast active ion transport through graphene oxide membranes', Nature Communications, vol. 10, no. 1, p. 1171.
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AbstractLayered graphene oxide membranes (GOM) with densely packed sub-nanometer-wide lamellar channels show exceptional ionic and molecular transport properties. Mass and charge transport in existing materials follows their concentration gradient, whereas attaining anti-gradient transport, also called active transport, remains a great challenge. Here, we demonstrate a coupled photon-electron-ion transport phenomenon through the GOM. Upon asymmetric light illumination, cations are able to move thermodynamically uphill over a broad range of concentrations, at rates much faster than that via simple diffusion. We propose, as a plausible mechanism, that light irradiation reduces the local electric potential on the GOM following a carrier diffusion mechanism. When the illumination is applied to an off-center position, an electric potential difference is built that can drive the transport of ionic species. We further develop photonic ion switches, photonic ion diodes, and photonic ion transistors as the fundamental elements for active ion sieving and artificial photosynthesis on synthetic nanofluidic circuits.

Zhang, X, Wen, Q, Wang, L, Ding, L, Yang, J, Ji, D, Zhang, Y, Jiang, L & Guo, W 2019, 'Asymmetric Electrokinetic Proton Transport through 2D Nanofluidic Heterojunctions', ACS Nano, vol. 13, no. 4, pp. 4238-4245.
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Nanofluidic ion transport in nacre-like 2D layered materials attracts broad research interest due to subnanometer confined space and versatile surface chemistry for precisely ionic sieving and ultrafast water permeation. Currently, most of the 2D-material-based nanofluidic systems are homogeneous, and the investigations of proton conduction therein are restricted to symmetric transport behaviors. It remains a great challenge to endow the 2D nanofluidic systems with asymmetric proton transport characteristics and adaptive responsibilities. Herein, we report the asymmetric proton transport phenomena through a 2D nanofluidic heterojunction membrane under three different types of electrokinetic driving force, that is, the external electric field, the transmembrane concentration gradient, and the hydraulic pressure difference. The heterogeneous 2D nanofluidic membrane comprises of sequentially stacked negatively and positively charged graphene oxide (n-GO and p-GO) multilayers. We find that the preferential direction for proton transport is opposite under the three types of electrokinetic driving force. The preferential direction for electric-field-driven proton transport is from the n-GO multilayers to the p-GO multilayers, showing rectified behaviors. Intriguingly, when the transmembrane concentration difference and the hydraulic flow are used as the driving force, a preferred diffusive and streaming proton current is found in the reverse direction, from the p-GO to the n-GO multilayers. The asymmetric proton transport phenomena are explained in terms of asymmetric proton concentration polarization and difference in proton selectivity. The membrane-scale heterogeneous 2D nanofluidic devices with electrokinetically controlled asymmetric proton flow provide a facile and general strategy for potential applications in biomimetic energy conversion and chemical sensing.

Zhanghao, K, Chen, X, Liu, W, Li, M, Liu, Y, Wang, Y, Luo, S, Wang, X, Shan, C, Xie, H, Gao, J, Chen, X, Jin, D, Li, X, Zhang, Y, Dai, Q & Xi, P 2019, 'Super-resolution imaging of fluorescent dipoles via polarized structured illumination microscopy', Nature Communications, vol. 10, no. 1, p. 4694.
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AbstractFluorescence polarization microscopy images both the intensity and orientation of fluorescent dipoles and plays a vital role in studying molecular structures and dynamics of bio-complexes. However, current techniques remain difficult to resolve the dipole assemblies on subcellular structures and their dynamics in living cells at super-resolution level. Here we report polarized structured illumination microscopy (pSIM), which achieves super-resolution imaging of dipoles by interpreting the dipoles in spatio-angular hyperspace. We demonstrate the application of pSIM on a series of biological filamentous systems, such as cytoskeleton networks and λ-DNA, and report the dynamics of short actin sliding across a myosin-coated surface. Further, pSIM reveals the side-by-side organization of the actin ring structures in the membrane-associated periodic skeleton of hippocampal neurons and images the dipole dynamics of green fluorescent protein-labeled microtubules in live U2OS cells. pSIM applies directly to a large variety of commercial and home-built SIM systems with various imaging modality.

Zhou, J, Huang, B, Yan, Z & Bünzli, J-CG 2019, 'Emerging role of machine learning in light-matter interaction', Light: Science & Applications, vol. 8, no. 1, p. 84.
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AbstractMachine learning has provided a huge wave of innovation in multiple fields, including computer vision, medical diagnosis, life sciences, molecular design, and instrumental development. This perspective focuses on the implementation of machine learning in dealing with light-matter interaction, which governs those fields involving materials discovery, optical characterizations, and photonics technologies. We highlight the role of machine learning in accelerating technology development and boosting scientific innovation in the aforementioned aspects. We provide future directions for advanced computing techniques via multidisciplinary efforts that can help to transform optical materials into imaging probes, information carriers and photonics devices.

Zhou, W, Jin, W, Wang, D, Lu, C, Xu, X, Zhang, R, Kuang, T, Zhou, Y, Wu, W, Jin, D, Mou, Y & Lou, W 2019, 'Laparoscopic versus open pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a propensity score matching analysis', Cancer Communications, vol. 39, no. 1, pp. 1-11.
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AbstractBackgroundA growing body of evidence supports the use of laparoscopic pancreaticoduodenectomy (LPD) as an efficient and feasible surgical technique. However, few studies have investigated its applicability in pancreatic ductal adenocarcinoma (PDAC), and the long‐term efficacy of LPD on PDAC remains unclear. This study aimed to compare the short‐ and long‐term outcomes between LPD and open pancreaticoduodenectomy (OPD) for PDAC.MethodsThe data of patients who had OPD or LPD for PDAC between January 2013 and September 2017 were retrieved. Their postoperative outcomes and survival were compared after propensity score matching.ResultsA total of 309 patients were included. After a 2:1 matching, 93 cases in the OPD group and 55 in the LPD group were identified. Delayed gastric emptying (DGE), particularly grade B/C DGE, occurred less frequently in the LPD group than in the OPD group (1.8% vs. 36.6%, P < 0.001; 1.8% vs. 22.6%, P = 0.001). The overall complication rates were significantly lower in the LPD group than in the OPD group (49.1% vs. 71.0%, P = 0.008), whereas the rates of major complications were similar (10.9% vs. 14.0%, P = 0.590). In addition, the median overall survival was comparable between the two groups (20.0 vs. 18.7 months, P = 0.293).ConclusionLPD was found to be technically feasible with efficacy similar to OPD for patients with PDAC.

Zhou, Y, Chen, Y, He, H, Liao, J, Duong, HTT, Parviz, M & Jin, D 2019, 'A homogeneous DNA assay by recovering inhibited emission of rare earth ions-doped upconversion nanoparticles', Journal of Rare Earths, vol. 37, no. 1, pp. 11-18.
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© 2018 Chinese Society of Rare Earths Robust and easy-to-use kits specific for a particular DNA sequence are desirable for early detection of diseases. However, the major challenge with these tests is often the background fluorescence artifacts arising from biological species due to employing UV and visible range of light. Here, we have reported a near-infrared (NIR) fluorescence “turn-on” kit based on rare earth ions doped nanoparticles, upconversion nanoparticles (UCNPs), and gold nanoparticles (AuNPs), which forms a fluorescence-quencher pair, brought together by a hairpin structure through the formation of double-stranded DNA (dsDNA), with quenched upconversion luminescence. In the presence of analytes, the molecular beacon opens to push AuNPs away from UCNPs, with a distance longer than the efficient quenching distance, so that the inhibited upconversion emission will be restored. We demonstrated that this assay provides a homogeneous, facile, simple and highly selective HIV-1 based DNA detection system with restore efficiency up to 85%, and the detection limit of 5 nm.

Bai, X, Feng, X, Ni, J, Beretov, J, Deng, J, Zhu, Y, Graham, P & Li, Y 1970, 'Abstract 4754: CHTOP is a novel therapeutic target for chemoresistant epithelial ovarian cancer therapy', Experimental and Molecular Therapeutics, Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA, American Association for Cancer Research.
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Büttner, TFS, Hudson, DD, Kabakova, IV & Eggleton, BJ 1970, 'Phase-locked, multiwavelength, distributed feedback brillouin laser', Proceedings 2015 European Conference on Lasers and Electro-Optics - European Quantum Electronics Conference, CLEO/Europe-EQEC 2015, European Conference on Lasers and Electro-Optics, OSA, Munich Germany.
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Phase-locked, multiwavelength laser sources with gigahertz line spacing are important for a variety of applications including arbitrary optical waveform generation and advanced telecommunications. Recently, it was demonstrated that the interplay of cascaded stimulated Brillouin scattering (SBS) and Kerr-nonlinear four-wave mixing (FWM) in Fabry-Perot resonators can generate phase-locked, equally spaced frequency components, i.e. frequency combs [1, 2]. Instead of Fabry-Perot resonances, Bragg grating resonances offer a flexible and tunable in-fiber approach that can also lower the threshold power SBS. This has recently been used to demonstrate a distributed feedback (DFB) Brillouin laser [3] based on a uniform Bragg grating with a π- phase shift manifesting in a single resonance.

Chen, C, Wang, F, Wen, S, Liu, Y, Shan, X & Jin, D 1970, 'Upconversion nanoparticles assisted multi-photon fluorescence saturation microscopy', Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications XVI, Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications XVI, SPIE, San Francisco, CA.
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© 2019 SPIE. Bright and photo-stable luminescent nanoparticles held great potential for bioimaging, long-term molecular tracking. Rare-earth-doped upconversion nanoparticles (UCNPs) have been recently discovered with unique properties for Stimulated Emission Depletion (STED) super-resolution microscopy imaging. However, this system strictly requires optical alignment of concentric excitation and depletion beams, resulting in cost, stability, and complicity of the system. Taking the advantage of intermediate state saturation in UCNPs, emission saturation nanoscopy has been developed as a simplified modality by using a single doughnut excitation beam. In this work, we report that the emission saturation curve of fluorescence probes can modulate the performance of multi-photon emission saturation nanoscopy. With the precise synthesis of UCNPs, we demonstrate the resolution of this new imaging approach can be improved with five parameters, including emission band, activator doping, excitation power, sensitizer doping, core-shell. This approach opens a new strategy to a simple solution for super-resolution imaging and single molecule tracking at low cost, suggesting a large scope for materials science community to improve the performance of emission saturation nanoscopy.

Chen, Y, Ju, L, Zhou, F, Liao, J, Xue, L, Su, Q, Jin, D, Yuan, Y, Lu, H, Jackson, S & Zhu, C 1970, 'An Integrin alibr33Intermediate Affinity State Mediates Biomechanical Platelet Aggregation', ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, Annual Scientific Meeting and Scientific Sessions of the American-Heart-Association on Vascular Discovery - From Genes to Medicine, LIPPINCOTT WILLIAMS & WILKINS, MA, Boston.

Ding, L, Fardjahromi, MA, Bazaz, SR, Asadnia, M, Vesey, G & Warkiani, ME 1970, 'A 3D printed modular microfluidic device for large scale cell harvesting from bioreactors', 23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019, pp. 604-605.
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Mesenchymal stem cell (MSC) therapy is a research hotspot nowadays due to its multiple therapeutic effects and novel application in diseases treatments. However, the current industrial technologies for their culture and harvesting are labour-intensive, time-consuming and very expensive. Herein, we presented a 3D printed modular microfluidic system consisting of micromixers and spiral channel units for cell harvesting which will greatly reduce the time and cost needed for cell harvesting, washing and cultivation. At the meantime, this system is automatic, making it compatible to the current Good Manufacturing Practice (cGMP).

Khan, J, Seppidar, S, Paull, B & Innis, PC 1970, 'Development of textile-based microfluidic devices for electrophoretic separation', 10th Australia and New Zealand Nano and Microfluidics Symposium, University of Wollongong, Australia.

Kianinia, M, Bradac, C, Sontheimer, B, Wang, F, Tran, TT, Nguyen, M, Kim, S, Xu, Z-Q, Jin, D, Schell, AW, Lobo, C, Aharanovich, I & Toth, M 1970, 'Enhanced Super-Resolution Imaging of Quantum Emitters in Hexagonal Boron Nitride', 2019 Compound Semiconductor Week (CSW), 2019 Compound Semiconductor Week (CSW), IEEE, Nara, Japan.
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Layered van der Waals materials are emerging as compelling two-dimensional platforms for nanophotonics, polaritonics, valleytronics and spintronics, and have the potential to transform applications in sensing, imaging and quantum information processing. Amongst these, hexagonal boron nitride (hBN) is known to host ultra-bright, room-temperature quantum emitters, whose nature is yet to be fully understood. Here, we present a set of measurements which give unique insight into the photophysical properties and level structure of hBN quantum emitters. Specifically, we report the existence of a class of hBN quantum emitters with a fast-decaying intermediate and a long-lived metastable state accessible from the first excited electronic state. Furthermore, by means of a two-laser repumping scheme, we show an enhanced photoluminescence and emission intensity which can be utilized to realize a new modality of far-field super-resolution imaging. Our findings expand current understanding of quantum emitters in hBN and show new potential ways of harnessing their nonlinear optical properties in sub-diffraction nanoscopy.

Kulasinghe, A, Kapeleris, J, Kenny, L, Warkiani, M, Vela, I, Thiery, J-P, O'Byrne, K & Punyadeera, C 1970, 'Abstract 1333: Isolation, characterization and expansion of circulating tumor cells in solid cancers', Cancer Research, American Association for Cancer Research (AACR), pp. 1333-1333.
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Abstract Metastasis in cancer patients is reflected by measurable levels of circulating tumor cells (CTCs) in the blood of cancer patients. CTCs represent cancer cells from the primary and metastatic sites, thereby providing a comprehensive representation of the tumor burden of an individual patient. Recent advancements have shown that PD-1/PD-L1 immune checkpoint therapies have durable responses in a number of solid tumor types. Our study was designed to use multiple CTC enrichment platforms for the capture of CTCs and novel culture formulations for the ex vivo expansion of CTCs. Head and Neck cancer (n=300) and lung cancer (n=80) patients were recruited to investigate the prognostic role of CTCs. We evaluated multiple CTC isolation technologies (CellSearch, filtration, CD45 depletion, inertial microfluidics) using matched patient samples which showed that epitope-independent CTC isolation captured a greater proportion of CTCs. Molecular alterations present in the primary tissue were confirmed in the CTCs by 3D-DNA FISH (EGFR-amplification, ALK-translocations). In HNC, the presence of CTC clusters associated with the development of distant metastatic disease (P=0.0313). HNC CTC-positive patients had shorter progression free survival (PFS) (Hazard ratio [HR]: 4.946; 95% confidence internal [CI]:1.571-15.57; P=0.0063) and PD-L1-positive CTCs were found to be significantly associated with worse outcome ([HR]:5.159; 95% [CI]:1.011-26.33; P=0.0485). In a proof of principle study, we were able to demonstrate for the first time, short-term patient derived CTC cultures outside the patient’s body from 7/18 HNC samples (4/7 HPV-positive). Recently, we have preliminary data that suggests that PD-L1 is frequently expressed on CTCs in HNC and lung cancer and an immunoscore may be able to identify patients likely to benefit ...

Mao, W, Lv, Y, Zhang, L, Chen, W, Wang, H, Han, X, Jin, D, Wu, W, Wang, D, Kaung, T, Lou, W & Xu, X 1970, 'For endoscopically unresectable well-differentiated rectal neuroendocrine neoplasms: Is 2 cm the best cutoff value for choosing operation ?', JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, WILEY, pp. 551-551.

Warkiani, ME 1970, 'Label-free Cell Sorting Using Inertial Microfluidics', 2019 13TH IEEE INTERNATIONAL CONFERENCE ON NANO/MOLECULAR MEDICINE & ENGINEERING (IEEE-NANOMED 2019), 13th IEEE International Conference on Nano/Molecular Medicine and Engineering (IEEE NANOMED), IEEE, SOUTH KOREA, Gwangju, pp. 52-53.

Warkiani, ME, Moloudi, R, Oh, S & Naing, MW 1970, 'Inertial-based Microcarrier-cell retention in bioprocessing', Cytotherapy, Elsevier BV, Australia, pp. e4-e5.
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Su, QP, Zhao, ZW, Meng, L, Ding, M, Zhang, W, Li, Y, Liu, M, Li, R, Gao, Y-Q, Xie, XS & Sun, Y 2019, 'CTCF-mediated Chromatin Structures Dictate the Spatio-temporal Propagation of Replication Foci', Cold Spring Harbor Laboratory.
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Zhang, X, Niu, J, Li, G, Dai, Q, Jin, D, Gao, J & Zhang, MQ 2019, 'Imaging chromatin interactions at sub-kilobase resolution Via Tn5-FISH', Cold Spring Harbor Laboratory.
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