Imperial College London

DrStuartHiggins

Faculty of EngineeringDepartment of Materials

Research Associate
 
 
 
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Contact

 

stuart.higgins

 
 
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2M11Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
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21 results found

Lin Y, Penna M, Spicer CD, Higgins SG, Gelmi A, Kim N, Wang S-T, Wojciechowski JP, Pashuck ET, Yarovsky I, Stevens MMet al., 2021, High-throughput peptide derivatization toward supramolecular diversification in microtiter plates, ACS Nano, Vol: 15, Pages: 4034-4044, ISSN: 1936-0851

The evolution of life on earth eventually leads to the emergence of species with increased complexity and diversity. Similarly, evolutionary chemical space exploration in the laboratory is a key step to pursue the structural and functional diversity of supramolecular systems. Here, we present a powerful tool that enables rapid peptide diversification and employ it to expand the chemical space for supramolecular functions. Central to this strategy is the exploitation of palladium-catalyzed Suzuki-Miyaura cross-coupling reactions to direct combinatorial synthesis of peptide arrays in microtiter plates under an open atmosphere. Taking advantage of this in situ library design, our results unambiguously deliver a fertile platform for creating a set of intriguing peptide functions including green fluorescent protein-like peptide emitters with chemically encoded emission colors, hierarchical self-assembly into nano-objects, and macroscopic hydrogels. This work also offers opportunities for quickly surveying the diversified peptide arrays and thereby identifying the structural factors that modulate peptide properties.

Journal article

Belessiotis-Richards A, Higgins S, Sansom MSP, Alexander-Katz A, Stevens Met al., 2020, Coarse Grained Simulations Suggest the Epsin N-Terminal Homology Domain Can Sense Membrane Curvature Without its Terminal Amphipathic Helix, ACS Nano, Vol: 14, Pages: 16919-6928, ISSN: 1936-0851

Nanoscale membrane curvature is a common feature in cell biology required for functions such as endocytosis, exocytosis and cell migration. These processes require the cytoskeleton to exert forces on the membrane to deform it. Cytosolic proteins contain specific motifs which bind to the membrane, connecting it to the internal cytoskeletal machinery. These motifs often bind charged phosphatidylinositol phosphate lipids present in the cell membrane which play significant roles in signaling. These lipids are important for membrane deforming processes, such as endocytosis, but much remains unknown about their role in the sensing of membrane nanocurvature by protein domains. Using coarse-grained molecular dynamics simulations, we investigated the interaction of a model curvature active protein domain, the epsin N-terminal homology domain (ENTH), with curved lipid membranes. The combination of anionic lipids (phosphatidylinositol 4,5-bisphosphate and phosphatidylserine) within the membrane, protein backbone flexibility, and structural changes within the domain were found to affect the domain's ability to sense, bind, and localize with nanoscale precision at curved membrane regions. The findings suggest that the ENTH domain can sense membrane curvature without the presence of its terminal amphipathic α helix <i>via</i> another structural region we have denoted as H3, re-emphasizing the critical relationship between nanoscale membrane curvature and protein function.

Journal article

Higgins S, Lo Fiego A, Patrick I, Creamer A, Stevens Met al., 2020, Organic bioelectronics: using highly conjugated polymers to interface with biomolecules, cells and tissues in the human body, Advanced Materials Technologies, Vol: 5, Pages: 1-35, ISSN: 2365-709X

Conjugated polymers exhibit interesting material and optoelectronic properties that makethem well-suited to the development of biointerfaces. Their biologically relevant mechanicalcharacteristics, ability to be chemically modified, and mixed electronic and ionic chargetransport are captured within the diverse field of organic bioelectronics. Conjugated polymershave been used in wide range of device architectures, and cell and tissue scaffolds. Thesedevices enable biosensing of many biomolecules, such as metabolites, nucleic acids and more.Devices can be used to both stimulate and sense the behavior of cells and tissues. Similarly,tissue interfaces permit interaction with complex organs, aiding both fundamental biologicalunderstanding and providing new opportunities for stimulating regenerative behaviors andbioelectronic based therapeutics. Applications of these materials are broad, and muchcontinues to be uncovered about their fundamental properties. This report covers the currentunderstanding of the fundamentals of conjugated polymer biointerfaces and their interactionswith biomolecules, cells and tissues in the human body. An overview of current materials anddevices is presented, along with highlighted major in vivo and in vitro applications. Finally,open research questions and opportunities are discussed.

Journal article

Seong H, Higgins SG, Penders J, Armstrong JPK, Crowder SW, Moore AC, Sero JE, Becce M, Stevens MMet al., 2020, Size-tunable nanoneedle arrays for influencing stem cell morphology, gene expression and nuclear membrane curvature, ACS Nano, Vol: 14, Pages: 5371-5381, ISSN: 1936-0851

High-aspect-ratio nanostructures have emerged as versatile platforms for intracellular sensing and biomolecule delivery. Here, we present a microfabrication approach in which a combination of reactive ion etching protocols was used to produce high-aspect-ratio, nondegradable silicon nanoneedle arrays with tip diameters that can be finely tuned between 20 and 700 nm. We used these arrays to guide the long-term culture of human mesenchymal stem cells (hMSCs). Notably, we used the nanoneedle tip diameter to control the morphology, nuclear size and F-actin alignment of interfaced hMSCs, and to regulate the expression of nuclear lamina genes, Yes-associated protein (YAP) target genes and focal adhesion genes. These topography-driven changes were attributed to signaling by Rho-family GTPase pathways, differences in the effective stiffness of the nanoneedle arrays and the degree of nuclear membrane impingement, with the latter clearly visualized using focused-ion beam scanning electron microscopy (FIB-SEM). Our approach to design high-aspect-ratio nanostructures will be broadly applicable to design biomaterials and biomedical devices used for long-term cell stimulation and monitoring.

Journal article

Higgins S, Becce M, Belessiotis Richards A, Seong H, Sero J, Stevens Met al., 2020, High-aspect-ratio nanostructured surfaces as biological metamaterials, Advanced Materials, Vol: 32, Pages: 1-44, ISSN: 0935-9648

Materials patterned with high-aspect-ratio nanostructures have features on similar lengthscales to cellular components. These surfaces are an extreme topography on the cellular leveland have become useful tools for perturbing and sensing the cellular environment. Motivationcomes from the ability of high-aspect-ratio nanostructures to deliver cargoes into cells andtissues, access the intracellular environment, and control cell behavior. These structuresdirectly perturb cells’ ability to sense and respond to external forces, influencing cell fate andenabling new mechanistic studies. Through careful design of their nanoscale structure, thesesystems act as biological metamaterials, eliciting unusual biological responses. Whilepredominantly used to interface eukaryotic cells, there is growing interest in non-animal andprokaryotic cell interfacing. Both experimental and theoretical studies have attempted todevelop a mechanistic understanding for the observed behaviors, predominantly focusing onthe cell – nanostructure interface. Here, we consider how high-aspect-ratio nanostructuredsurfaces are used to both stimulate and sense biological systems and discuss remainingresearch questions.

Journal article

Higgins SG, Becce M, Seong H, Stevens MMet al., 2020, Nanoneedles and Nanostructured Surfaces for Studying Cell Interfacing, Pages: 209-212, ISSN: 1680-0737

Nanoneedles are a materials platform that facilitates intimate tissue- and cell-interfacing, and drug and nanoparticle delivery. Engineering silicon needles, with <100 nm sharpened tips, allows the response of cells to be studied when the cell membrane and nucleus is placed under extreme curvature. Different cell types respond differently, and are influenced by the geometry of the nanostructures. Topography, material mechanical properties, and surface chemistry all play important roles—with the challenge understanding the impact of each. Here, we briefly review the use of nanoneedles in multiple applications within the Stevens Group, and present the fabrication method used to create biologically relevant nanostructured surfaces. We also discuss the current challenges and future opportunities for nanoneedles.

Conference paper

Higgins SG, 2019, Understanding scientists is key for science, NATURE MATERIALS, Vol: 18, Pages: 1144-1144, ISSN: 1476-1122

Journal article

Belessiotis-Richards A, Higgins SG, Butterworth B, Stevens MM, Alexander-Katz Aet al., 2019, Single-nanometer changes in nanopore geometry influence curvature, local properties, and protein localization in membrane simulations, Nano Letters, Vol: 19, Pages: 4770-4778, ISSN: 1530-6984

Nanoporous surfaces are used in many applications in intracellular sensing and drug delivery. However, the effects of such nanostructures on cell membrane properties are still far from understood. Here, we use coarse-grained molecular dynamics simulations to show that nanoporous substrates can stimulate membrane-curvature effects and that this curvature-sensing effect is much more sensitive than previously thought. We define a series of design parameters for inducing a nanoscale membrane curvature and show that nanopore taper plays a key role in membrane deformation, elucidating a previously unexplored fabrication parameter applicable to many nanostructured biomaterials. We report significant changes in the membrane area per lipid and thickness at regions of curvature. Finally, we demonstrate that regions of the nanopore-induced membrane curvature act as local hotspots for an increased bioactivity. We show spontaneous binding and localization of the epsin N-terminal homology (ENTH) domain to the regions of curvature. Understanding this interplay between the membrane curvature and nanoporosity at the biointerface helps both explain recent biological results and suggests a pathway for developing the next generation of cell-active substrates.

Journal article

Mylonaki I, Amoli MS, Brito L, Higgins S, Moore A, Lin Y, Seong H, Becce M, Harding S, Stevens MMet al., 2019, Intracellular siRNA delivery using silicon nanoneedle arrays, British-Society-for-Gene-and-Cell-Therapy Autumn Conference, Publisher: MARY ANN LIEBERT, INC, Pages: A7-A7, ISSN: 1043-0342

Conference paper

Higgins S, 2018, Organising and running a STEM engagement stand inside a supermarket, Organising and running a STEM engagement stand inside a supermarket

Project report and evaluation for ‘Science in the Supermarket’

Report

Higgins SG, Agostinelli T, Markham S, Whiteman R, Sirringhaus Het al., 2017, Organic Diode Rectifiers Based on a High-Performance Conjugated Polymer for a Near-Field Energy-Harvesting Circuit, ADVANCED MATERIALS, Vol: 29, ISSN: 0935-9648

Journal article

Higgins SG, Stevens MM, 2017, Extracting the contents of living cells, SCIENCE, Vol: 356, Pages: 379-380, ISSN: 0036-8075

Being able to monitor cells at different times is key to tracking fundamental cellular processes such as differentiation and cellular senescence, as well as disease progression and the effectiveness of drugs. However, most approaches are destructive and involve lysing the cells. Different time points can be studied by using parallel cell cultures, but the inferred changes could also be the result of cell heterogeneity (1, 2). Techniques for extracting small quantities of the cytosol for long-term tracking of a single cell's response must manipulate picoliter-scale volumes, maintain high cell viability, and give an accurate reflection of the cell's multiple biological components, as well as avoid influencing the ongoing development of the cell (see the figure) (1, 3). Cao et al. approached this problem by culturing cells on top of a random arrangement of hollow cylinders, which they call nanostraws (2). These 150-nm-diameter alumina tubes can sample 5 to 10% of proteins, messenger RNA (mRNA), and small molecules from the cells but only reduce cell viability by ∼5%. Their approach allows intracellular sampling and characterization at multiple time points from the same cells to track changes.

Journal article

Higgins SG, Muir BVO, DellErba G, Perinot M, Caironi M, Campbell Aet al., 2016, Self-Aligned Organic Field-Effect Transistors on Plastic with Picofarad Overlap Capacitances and Megahertz Operating Frequencies, Applied Physics Letters, Vol: 108, ISSN: 0003-6951

Using a combination of nanoimprint lithography, gate-source/drain self-alignment, and gravure and inkjet printing, we fabricate organic field-effect transistors on flexible plastic substrates with gate-source and gate-drain electrode overlap capacitances of COL < 1 pF, equivalent to channel-width normalised capacitances of C*OL = 0.15–0.23 pF mm−1. We compare photopatterned and nanoimprint lithography patterned channels of L ≈ 3.8 μm and L ≈ 800 nm, respectively. The reduction in L was found on average to result in order of magnitude greater switching frequencies. Gravure printing the dielectric (versus photo-patterning) was found to yield an order of magnitude lower overlap capacitanceC*OL = 0.03 pF mm−1, at the expense of greater processing variation. Inkjet printed p- and n-type polymeric organic semiconductors were used to fabricate organic-field effect transistors with a peak cutoff frequencies of fS = 9.0 ± 0.3 MHz at VGS = 30 V, and transition frequencies of fT = 3.3 ± 0.2 MHz at VGS = 30 V.

Journal article

Higgins S, Muir B, Dell'Erba G, Perinot A, Caironi M, Campbell Aet al., 2016, Complementary Organic Logic Gates on Plastic Formed by Self-Aligned Transistors with Gravure and Inkjet Printed Dielectric and Semiconductors, Advanced Electronic Materials, Vol: 2, ISSN: 2199-160X

Complementary organic field-effect transistors, inverters, NAND and NOR logic on plastic are demonstrated using a combination of nanoimprint lithography, self-alignment, gravure, and inkjet printing. Sub-micrometer channel lengths, electrode overlaps and sub-100 nm dielectrics are compared to photolithographically patterned equivalents, as are inkjet and gravure printed semiconductors.

Journal article

Campbell AJ, Higgins SG, Muir BVO, Heeney Met al., 2015, Indacenodithiophene–benzothiadiazole organic field-effect transistorswith gravure-printed semiconductor and dielectric on plastic, MRS Communications, Vol: 5, Pages: 599-603, ISSN: 2159-6867

We demonstrate the gravure printing of a high-performance indacenodithiophene (IDT) copolymer, indacenodithiophene–benzothiadiazole (C16IDT–BT), onto self-aligned organic field-effect transistor architectures on flexible plastic substrates. We observed that the combination of a gravure-printed dielectric with gravure-printed semiconductor yielded devices with higher mean-effective mobility than devices manufactured using photolithographically patterned dielectric. Peak mobilities of μ = 0.1 cm2 V−1 s−1 were measured, and exceed previous reports for non-printed C16IDT-BT on non-flexible silicon substrates.

Journal article

Higgins SG, Muir BVO, Wade J, Chen J, Striedinger B, Gold H, Stadlober B, Caironi M, Kim JS, Steinke JHG, Campbell AJet al., 2015, Organic Transistors: Self-Aligned Megahertz Organic Transistors Solution-Processed on Plastic (Adv. Electron. Mater. 5/2015), Advanced Electronic Materials, Vol: 1

Journal article

Higgins SG, Muir BVO, Wade J, Chen J, Striedinger B, Gold H, Stadlober B, Caironi M, Kim J-S, Steinke JHG, Campbell AJet al., 2015, Self-aligned megahertz organic transistors solution-processed on plastic, Advanced Electronic Materials, Vol: 1, ISSN: 2199-160X

Journal article

Higgins SG, Boughey FL, Hills R, Steinke JHG, Muir BVO, Campbell AJet al., 2015, Quantitative Analysis and Optimization of Gravure Printed Metal Ink, Dielectric, and Organic Semiconductor Films, ACS APPLIED MATERIALS & INTERFACES, Vol: 7, Pages: 5045-5050, ISSN: 1944-8244

Journal article

Ginzel R, Higgins SG, Mrowcynski P, Northway P, Simon MC, Tawara H, Lopez-Urrutia JRC, Ullrich J, Kowarik G, Ritter R, Meissl W, Vasko C, Goesselsberger C, El-Said AS, Aumayr Fet al., 2010, A deceleration system at the Heidelberg EBIT providing very slow highly charged ions for surface nanostructuring, NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS, Vol: 268, Pages: 2972-2976, ISSN: 0168-583X

Journal article

Simon MC, Schwarz M, Epp SW, Beilmann C, Schmitt BL, Harman Z, Baumann TM, Mokler PH, Bernitt S, Ginzel R, Higgins SG, Keitel CH, Klawitter R, Kubicek K, Maeckel V, Ullrich J, Lopez-Urrutia JRCet al., 2010, Photoionization of N3+ and Ar8+ in an electron beam ion trap by synchrotron radiation, JOURNAL OF PHYSICS B-ATOMIC MOLECULAR AND OPTICAL PHYSICS, Vol: 43, ISSN: 0953-4075

Journal article

Simon MC, Schwarz M, Schmitt BL, Beilmann C, Epp SW, Baumann TM, Kubicek K, Ginzel R, Higgins SG, Klawitter R, Maeckel V, Bernitt S, Mokler PH, Ullrich J, Lopez-Urrutia JRCet al., 2009, Photoionization of ions in arbitrary charge states by synchrotron radiation in an electron beam ion trap, XXVI INTERNATIONAL CONFERENCE ON PHOTONIC, ELECTRONIC AND ATOMIC COLLISIONS, Vol: 194, ISSN: 1742-6588

Journal article

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