Dr Fatima Labeed

Senior Lecturer in Human Biology

Qualifications: BSc (Lond), MSc, PhD (Surrey)

Email:
Phone: Work: 01483 68 4536
Room no: 17 AA 02

Further information

Biography

Dr Fatima H. Labeed earned her first degree in Biochemistry from University of London, followed by a Masters in Clinical Biochemistry with Molecular Biology and a PhD, both from the University of Surrey. She has also worked in industry at Pfizer’s Parke-Davis Research Centre in Cambridge, and holds visiting positions at both the University of Bergen and the University of California Irvine. She has received research income from NIHR, EPSRC, industry (e.g. Pfizer, Smiths Industries, Smith and Nephew, Labtech) and technology transfer bodies. She has given invited seminars at Stanford University, University of Bergen and UCI and is currently co-editing a book for the Royal Society of Chemistry on microengineered detection methods, and acts as Journal Administrator for IEEE Transactions on Nanobioscience. She is a member of the British and American Associations for Cancer Research and the Biophysical Society.

Research Interests

Dr Labeed principally leads research on the applications of dielectrophoresis (cell motion induced by non-uniform electric fields) to cell biology. One such application is the use of dielectrophoresis to detect oral cancer. This project, developed in conjunction with the Eastman Dental Institute over many years, uses dielectrophoresis to discriminate between normal and cancerous epithelial cells taken from a brush biopsy of suspicious sites. The detection mechanism has already shown a statistical significance between the two cell types when taken from patients presenting at the EDI, and the project has now received ca. £200k from NIHR for a clinical trial at two more hospitals in order to quantify sensitivity and specificity, as well as identify ways of discriminating confounding factors such as ulcers.

The second research line in applications is that of stem cells. Working with international collaborators in the universities of California Irvine and Bergen, Dr Labeed has work on discriminating neural-progenitor from astrocyte-progenitor neural stem cells (with the UCI group), and between different mesenchymal cell lines to form the basis of potential cell selection (with the University of Southampton), and observing differentiation in cancer-generating stem cells with the University of Bergen and the Queen Mary University of London in order to better understand the biology of tumour stem cells.

Finally, a third line of research has been the development of drug assays using DEP to monitor electrophysiological changes more rapidly or more accurately by other means. These include very rapid apoptosis measurement, effect of ion channel blockers on cytoplasm composition, drug resistance in cancer cells and antibiotic resistance in bacteria. This has involved working closely with a major, multinational pharmaceutical company. Current applications being explored include the measurement of cytoplasmic resistance in cardiac myocyes for cardiac action potential studies, which has shown that DEP is as accurate as tissue-strip measurement, and more accurate than other methods of suspended cell measurements.

Research Collaborations

At the University of Surrey: Mike P. Hughes (Biomedical Engineering), Rita Jabr (Biochemistry and Physiology), Chris Fry (Biochemistry and Physiology), Malcolm von Schantz (Biochemistry and Physiology), Helen Coley (Toxicology), John Watts (Mechanical Engineering Sciences), Marie-Laure Abel (Mechanical Engineering Sciences), Constantina Lekakou (Mechanical Engineering Sciences), Joe Keddie (Physics).

National and International: Stefano Fedele and Stephen Porter (at Eastman Dental Institute, UCL), Mark Lewis (Loughborough University), Ian McKenzie (Queen Mary University of London), Lisa Flanagan (University of California at Irvine), Richard Oreffo (Southampton University), Daniela Costea and Ann Johanssen (University of Bergen).

Publications

Highlights

  • Lamprou D, Zhdan P, Labeed F, Lekakou C. (2011) 'Gelatine and gelatine/elastin nanocomposites for vascular grafts: processing and characterization.'. J Biomater Appl, England: 26 (2), pp. 209-226.

    Abstract

    This study involves the preparation, microstructural, physical, mechanical, and biological characterization of novel gelatine and gelatine/elastin gels for their use in the tissue engineering of vascular grafts. Gelatine and gelatine/elastin nanocomposite gels were prepared via a sol-gel process, using soluble gelatine. Gelatine was subsequently cross-linked by leaving the gels in 1% glutaraldehyde. The cross-linking time was optimized by assessing the mass loss of the cross-linked gels in water and examining their mechanical properties in dynamic mechanical tests. Atomic force microscopy (AFM) studies revealed elastin nanodomains, homogeneously distributed and embedded in a bed of gelatine nanofibrils in the 30/70 elastin/gelatine gel. It was concluded that the manufactured nanocomposite gels resembled natural arteries in terms of microstructure and stiffness. The biological characterization involved the culture of rat smooth muscle cells (SMCs) on tubular gelatine and gelatine/ elastin nanocomposite gels, and measurements of the scaffold diameter and the cell density as a function of time.

  • Bushnak IA, Labeed FH, Sear RP, Keddie JL. (2010) 'Adhesion of microorganisms to bovine submaxillary mucin coatings: effect of coating deposition conditions'. BIOFOULING, 26 (4), pp. 387-397.
  • Jaber FT, Labeed FH, Hughes MP. (2009) 'Action potential recording from dielectrophoretically positioned neurons inside micro-wells of a planar microelectrode array'. JOURNAL OF NEUROSCIENCE METHODS, 182 (2), pp. 225-235.
  • Duncan L, Shelmerdine H, Hughes MP, Coley HM, Huebner Y, Labeed FH. (2008) 'Dielectrophoretic analysis of changes in cytoplasmic ion levels due to ion channel blocker action reveals underlying differences between drug-sensitive and multidrug-resistant leukaemic cells'. PHYSICS IN MEDICINE AND BIOLOGY, 53 (2), pp. N1-N7.

Journal articles

  • Salifu A, Lekakou C , Labeed F . (2017) 'Electrospun oriented gelatin-hydroxyapatite fibre scaffolds for bone tissue engineering'. Journal of Biomedical Materials Research Part A, 105 (7), pp. pp. 1911-1926.

    Abstract

    Tissue engineering of human foetal osteoblast (hFOB) cells was investigated on gelatin-hydroxyapatite (HA), crosslinked, electrospun oriented fibre scaffolds at the different hydroxyapatite concentrations of 0, 10, 20 and 25 wt% in the dry fibres and different fibre diameter, pore size and porosity of scaffolds. Rheological tests and proton NMR spectroscopy were conducted for all solutions used for electrospinning. It was found that 25 wt% HA-gelatin scaffolds electrospun at 20 kV led to the greatest cell attachment, cell proliferation and extracellular matrix (ECM) production while fibre orientation improved the mechanical properties, where crosslinked electrospun 25 wt% HA-gelatin fibre scaffolds yielded a Young’s modulus in the range of 0.5 to 0.9 GPa and a tensile strength in the range of 4 to 10 MPa in the fibre direction for an applied voltage of 20 to 30 kV, respectively, in the electrospinning of scaffolds. Biological characterisation of cell seeded scaffolds yielded the rate of cell growth and ECM (collagen and calcium) production by the cells as a function of time; it included cell seeding efficiency tests, alamar blue cell proliferation assay, alkaline phosphate (ALP) assay, collagen assay, calcium colorimetric assay, fluorescence microscopy for live and dead cells, and scanning electron microscopy (SEM) for cell culture from 1 to 18 days. After 18 days, cells seeded and grown on the 25 wt% HA-gelatin scaffold, electrospun at 20 kV, reached production of collagen at 370 g/L and calcium production at 0.8 mM.

  • Faraghat S, Hoettges K , Steinbach M, Van Der Veen DR, Brackenbury W, Henslee E , Labeed F , Hughes MP. (2017) 'High-Throughput, Low-Loss, Low-Cost and Label-Free Cell Separation using Electrophysiology Activated Cell Enrichment (EPACE)'. Proceedings of the National Academy of Sciences, 114 (8), pp. pp. 4591-4596.

    Abstract

    Currently, cell separation occurs almost exclusively by density gradient methods and by fluorescence- and magnetic-activated cell sorting (FACS/MACS). These variously suffer from lack of specificity, high cell loss, use of labels, and high capital/operating cost. We present a dielectrophoresis (DEP)-based cell separation method, using 3D electrodes on a low-cost disposable chip; one cell type is allowed to pass through the chip whilst the other is retained and subsequently recovered. The method advances usability and throughput of DEP separation by orders of magnitude in throughput, efficiency, purity, recovery (cells arriving in the correct output fraction), cell losses (those which are unaccounted for at the end of the separation) and cost. The system was evaluated using three example separations; live and dead yeast; human cancer cells/red blood cells; and rodent fibroblasts/red blood cells. A single-pass protocol can enrich cells with cell recovery of up to 91.3% at over 300,000 cells/second with >3% cell loss. A two-pass protocol can process 300,000,000 cells in under 30 minutes, with cell recovery of up to 96.4% and cell losses below 5%, an effective processing rate >160,000 cells/second. A three-step protocol is shown to be effective for removal of 99.1% of RBCs spiked with 1% cancer cells, whilst maintaining a processing rate of ~170,000 cells/second. Furthermore, the self-contained and low-cost nature of the separator device means that it has potential application in low-contamination applications such as cell therapies, where GMP compatibility is of paramount importance. Significance statement. Cell separation is a fundamental process in biomedicine, but is presently complicated, cumbersome and expensive. We present a technique that can sort cells at a rate equivalent to or faster than gold-standard techniques such as FACS and MACs, but can do label-free and with very low cell loss. The system uses dielectrophoresis (DEP) to sort cells electrostatically, using a novel electrode chip that eschews microfabrication in favour of a laminate drilled with 397 electrode-bearing wells. This high level of parallelisation makes the system immune to the bubbles that limit labs-on-chip, whilst also increasing capacity and throughput to unprecedented levels, whilst the chip is cheap enough to be disposable, preventing inter-separation contamination.

  • Salifu A, Lekakou C , Labeed F . (2016) 'Multilayer cellular stacks of gelatin-hydroxyapatite fiber scaffolds for bone tissue engineering'. Journal of Biomedical Materials Research: Part A, 105 (3), pp. pp. 779-789.

    Abstract

    Multilayer cellular stacks of crosslinked, electrospun 25 wt% hydroxyapatite (HA)-gelatin and pure gelatin fiber scaffolds, seeded with human foetal osteoblasts (hFOBs), were studied for up to 18 days in static and dynamic cell culture. Two types of stack models were investigated: a four-layer stack with cells seeded at the bottom surface of the first/top layer and the top surface of the fourth/bottom layer, so that the two middle layers were not seeded with cells with the aim to act as continuing conduits of culture medium and nutrients supply to the adjacent cell-populated zones; a three-layer stack with cells seeded at the bottom surface of each layer. hFOBs exhibited lower migration rate through the stack thickness for the 25 wt% HA-gelatin scaffolds compared to the pure gelatin scaffolds, due to the small pores of the former. Hence, the regularly seeded three-layer stack maintained cell-free porous zones in all layers through which the culture medium could continuously perfuse, while good fusion was achieved at the interface of all layers via the cross-migrating cells with a preference to downwards vertical migration attributed to gravity. Dynamic cell culture conditions enhanced overall cell growth by about 6% for the regularly seeded three-layer stack.

  • Henslee EA, Torcal Serrano RM, Labeed FH, Jabr RI, Fry CH, Hughes MP, Hoettges KF. (2016) 'Accurate quantification of apoptosis progression and toxicity using a dielectrophoretic approach'. Analyst, 141, pp. 6408-6415.

    Abstract

    A loss of ability of cells to undergo apoptosis (programmed cell death, whereby the cell ceases to function and destroys itself) is commonly associated with cancer, and many anti-cancer interventions aim to restart the process. Consequently, the accurate quantification of apoptosis is essential in understanding the function and performance of new anti-cancer drugs. Dielectrophoresis has previously been demonstrated to detect apoptosis more rapidly than other methods, and is low-cost, label-free and rapid, but has previously been unable to accurately quantify cells through the apoptotic process because cells in late apoptosis disintegrate, making cell tracking impossible. In this paper we use a novel method based on light absorbance and multi-population tracking to quantify the progress of apoptosis, benchmarking against conventional assays including MTT, Trypan Blue and Annexin-V. Analyses are performed on suspension and adherent cells, and using two apoptosis-inducing agents. IC50 measurements compared favourably to MTT and were superior to Trypan Blue, whilst also detecting apoptotic progression faster than Annexin-V.

  • Elsayed Y, Lekakou C, Labeed F, Tomlins P. (2016) 'Fabrication and characterisation of biomimetic, electrospun gelatin fibre scaffolds for tunica media-equivalent, tissue engineered vascular grafts'. MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS, 61, pp. 473-483.
  • Elsayed Y, Lekakou C, Labeed F, Tomlins P. (2015) 'Smooth muscle tissue engineering in crosslinked electrospun gelatin scaffolds'. JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 104 (1), pp. 313-321.
  • Mulhall HJ, Cardnell A, Hoettges KF, Labeed FH, Hughes MP. (2015) 'Apoptosis progression studied using parallel dielectrophoresis electrophysiological analysis and flow cytometry'. INTEGRATIVE BIOLOGY, 7 (11), pp. 1396-1401.
  • Graham KA, Mulhall HJ, Labeed FH, Lewis MP, Hoettges KF, Kalavrezos N, McCaul J, Liew C, Porter S, Fedele S, Hughes MP. (2015) 'A dielectrophoretic method of discrimination between normal oral epithelium, and oral and oropharyngeal cancer in a clinical setting.'. Analyst, England: 140 (15), pp. 5198-5204.

    Abstract

    Despite the accessibility of the oral cavity to clinical examination, delays in diagnosis of oral and oropharyngeal carcinoma (OOPC) are observed in a large majority of patients, with negative impact on prognosis. Diagnostic aids might help detection and improve early diagnosis, but there remains little robust evidence supporting the use of any particular diagnostic technology at the moment. The aim of the present feasibility first-in-human study was to evaluate the preliminary diagnostic validity of a novel technology platform based on dielectrophoresis (DEP). DEP does not require labeling with antibodies or stains and it is an ideal tool for rapid analysis of cell properties. Cells from OOPC/dysplasia tissue and healthy oral mucosa were collected from 57 study participants via minimally-invasive brush biopsies and tested with a prototype DEP platform using median membrane midpoint frequency as main analysis parameter. Results indicate that the current DEP platform can discriminate between brush biopsy samples from cancerous and healthy oral tissue with a diagnostic sensitivity of 81.6% and a specificity of 81.0%. The present ex vivo results support the potential application of DEP testing for identification of OOPC. This result indicates that DEP has the potential to be developed into a low-cost, rapid platform as an assistive tool for the early identification of oral cancer in primary care; given the rapid, minimally-invasive and non-expensive nature of the test, dielectric characterization represents a promising platform for cost-effective early cancer detection.

  • Mahabadi S, Labeed FH, Hughes MP. (2015) 'Effects of cell detachment methods on the dielectric properties of adherent and suspension cells.'. Electrophoresis, Germany: 36 (13), pp. 1493-1498.

    Abstract

    Cell analyses such as flow cytometry, dielectrophoresis, and some patch-clamp techniques require that cells be in monodisperse suspension in order for analysis to occur. Where cells have a normally adherent phenotype in vivo, this requires that cells be removed from the surface of the culture flask or vessel. This can be achieved in many ways, but most commonly either by the use of a dissociation medium of some form, or by scraping the cells from the surface. Both methods have potential drawbacks; chemical methods may alter the properties of the cells to such a degree that the measurement might be regarded as meaningless, whilst scraping could cause physical damage to the structure of the cells. In this paper, we use dielectrophoresis to analyse the electrical properties of two adherent cell lines detached by multiple methods, and compare these against a control cell line of suspension cells, examined in both the native state and when subject to the same chemical treatments. The results indicate that most chemical agents do not alter the electrophysiology of cells directly, though they may trigger some potential cell deterioration processes such as apoptosis in the cells. This can be observed in the production of apoptotic body-like particles and the alteration of cytoplasmic conductivity (which has been associated with apoptotic water efflux). However, cells detached by scraping exhibited statistically significant differences in their electrophysiological properties when compared to those detached by the chemical methods, indicating that this method is unsuitable for detachment of adherent cells prior to analysis of isolates suspension cells.

  • Ismail A, Hughes M, Mulhall H, Oreffo R, Labeed F. (2015) 'Characterization of human skeletal stem and bone cell populations using dielectrophoresis'. Journal of Tissue Engineering and Regenerative Medicine, 9 (2), pp. 162-168.

    Abstract

    © 2012 John Wiley & Sons, Ltd.Dielectrophoresis (DEP) is a non-invasive cell analysis method that uses differences in electrical properties between particles and surrounding medium to determine a unique set of cellular properties that can be used as a basis for cell separation. Cell-based therapies using skeletal stem cells are currently one of the most promising areas for treating a variety of skeletal and muscular disorders. However, identifying and sorting these cells remains a challenge in the absence of unique skeletal stem cell markers. DEP provides an ideal method for identifying subsets of cells without the need for markers by using their dielectric properties. This study used a 3D dielectrophoretic well chip device to determine the dielectric characteristics of two osteosarcoma cell lines (MG-63 and SAOS-2) and an immunoselected enriched skeletal stem cell fraction (STRO-1 positive cell) of human bone marrow. Skeletal cells were exposed to a series of different frequencies to induce dielectrophoretic cell movement, and a model was developed to generate the membrane and cytoplasmic properties of the cell populations. Differences were observed in the dielectric properties of MG-63, SAOS-2 and STRO-1 enriched skeletal populations, which could potentially be used to sort cells in mixed populations. This study provide evidence of the ability to characterize different human skeletal stem and mature cell populations, and acts as a proof-of-concept that dielectrophoresis can be exploited to detect, isolate and separate skeletal cell populations from heterogeneous bone marrow cell populations.

  • Liang X, Graham KA, Johannessen AC, Costea DE, Labeed FH. (2014) 'Human oral cancer cells with increasing tumorigenic abilities exhibit higher effective membrane capacitance'. OMICS: A Journal of Integrative Biology,
  • Abdul Razak MA, Hoettges KF, Fatoyinbo HO, Labeed FH, Hughes MP. (2013) 'Efficient dielectrophoretic cell enrichment using a dielectrophoresis-well based system.'. Biomicrofluidics, United States: 7 (6)

    Abstract

    Whilst laboratory-on-chip cell separation systems using dielectrophoresis are increasingly reported in the literature, many systems are afflicted by factors which impede "real world" performance, chief among these being cell loss (in dead spaces, attached to glass and tubing surfaces, or sedimentation from flow), and designs with large channel height-to-width ratios (large channel widths, small channel heights) that make the systems difficult to interface with other microfluidic systems. In this paper, we present a scalable structure based on 3D wells with approximately unity height-to-width ratios (based on tubes with electrodes on the sides), which is capable of enriching yeast cell populations whilst ensuring that up to 94.3% of cells processed through the device can be collected in tubes beyond the output.

  • Mulhall HJ, Hughes MP, Kazmi B, Lewis MP, Labeed FH. (2013) 'Epithelial cancer cells exhibit different electrical properties when cultured in 2D and 3D environments.'. Biochim Biophys Acta, Netherlands: 1830 (11), pp. 5136-5141.

    Abstract

    BACKGROUND: Many drug development and toxicology studies are performed using cells grown in monolayers in well-plates and flasks, despite the fact that these are widely held to be different to cells found in the native environment. 3D, tissue engineered, organotypical tissue culture systems have been developed to be more representative of the native tissue environment than standard monolayer cultures. Whilst the biochemical differences between cells grown in 2D and 3D culture have been explored, the changes on the electrophysiological properties of the cells have not. METHODS: We compared the electrophysiological properties of primary normal oral keratinocytes (nOK) and cancerous abnormal oral keratinocytes (aOK), cultured in standard monolayer and reconstituted 3D organotypical tissue cultures. The electrophysiological properties of populations of the cells were analysed using dielectrophoresis. The intracellular conductivity of aOK was significantly increased when grown in organotypical cultures compared to counterpart cells grown in monolayer cultures. RESULTS: 3D cultured aOK showed almost identical intracellular conductivity to nOK also grown in organotypical cultures, but significantly different to aOK grown in monolayers. The effective membrane capacitance of aOK grown in 3D was found to be significantly higher than nOK, but there was no significant difference between the electrophysiological properties of nOK grown in 2D and 3D cultures. GENERAL SIGNIFICANCE: This work suggests that factors such as cell shape and cytoplasmic trafficking between cells play an important role in their electrophysiology, and highlights the need to use in vitro models more representative of native tissue when studying cell electrophysiological properties.

  • Abdallat RG, Ahmad Tajuddin AS, Gould DH, Hughes MP, Fatoyinbo HO, Labeed FH. (2013) 'Process development for cell aggregate arrays encapsulated in a synthetic hydrogel using negative dielectrophoresis.'. Electrophoresis, Germany: 34 (7), pp. 1059-1067.

    Abstract

    Spatial patterning of cells is of great importance in tissue engineering and biotechnology, enabling, for example the creation of bottom-up histoarchitectures of heterogeneous cells, or cell aggregates for in vitro high-throughput toxicological and therapeutic studies within 3D microenvironments. In this paper, a single-step process for creating peelable and resilient hydrogels, encapsulating arrays of biological cell aggregates formed by negative DEP has been devised. The dielectrophoretic trapping within low-energy regions of the DEP-dot array reduces cell exposure to high field stresses while creating distinguishable, evenly spaced arrays of aggregates. In addition to using an optimal combination of PEG diacrylate pre-polymer solution concentration and a novel UV exposure mechanism, total processing time was reduced. With a continuous phase medium of PEG diacrylate at 15% v/v concentration, effective dielectrophoretic cell patterned arrays and photo-polymerisation of the mixture was achieved within a 4 min period. This unique single-step process was achieved using a 30 s UV exposure time frame within a dedicated, wide exposure area DEP light box system. To demonstrate the developed process, aggregates of yeast, human leukemic (K562) and HeLa cells were immobilised in an array format within the hydrogel. Relative cell viability for both cells within the hydrogels, after maintaining them in appropriate iso-osmotic media, over a week period was greater than 90%.

  • Abdallat RG, Ahmad Tajuddin AS, Gould DH, Hughes MP, Fatoyinbo HO, Labeed FH. (2013) 'Process development for cell aggregate arrays encapsulated in a synthetic hydrogel using negative dielectrophoresis'. Electrophoresis, 34 (7), pp. 1059-1067.

    Abstract

    Spatial patterning of cells is of great importance in tissue engineering and biotechnology, enabling, for example the creation of bottom-up histoarchitectures of heterogeneous cells, or cell aggregates for in vitro high-throughput toxicological and therapeutic studies within 3D microenvironments. In this paper, a single-step process for creating peelable and resilient hydrogels, encapsulating arrays of biological cell aggregates formed by negative DEP has been devised. The dielectrophoretic trapping within low-energy regions of the DEP-dot array reduces cell exposure to high field stresses while creating distinguishable, evenly spaced arrays of aggregates. In addition to using an optimal combination of PEG diacrylate pre-polymer solution concentration and a novel UV exposure mechanism, total processing time was reduced. With a continuous phase medium of PEG diacrylate at 15% v/v concentration, effective dielectrophoretic cell patterned arrays and photo-polymerisation of the mixture was achieved within a 4 min period. This unique single-step process was achieved using a 30 s UV exposure time frame within a dedicated, wide exposure area DEP light box system. To demonstrate the developed process, aggregates of yeast, human leukemic (K562) and HeLa cells were immobilised in an array format within the hydrogel. Relative cell viability for both cells within the hydrogels, after maintaining them in appropriate iso-osmotic media, over a week period was greater than 90%. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  • Fry CH, Salvage SC, Manazza A, Dupont E, Labeed FH, Hughes MP, Jabr RI. (2012) 'Cytoplasm resistivity of mammalian atrial myocardium determined by dielectrophoresis and impedance methods'. Biophysical Journal, 103 (11), pp. 2287-2294.

    Abstract

    Many cardiac arrhythmias are caused by slowed conduction of action potentials, which in turn can be due to an abnormal increase of intracellular myocardial resistance. Intracellular resistivity is a linear sum of that offered by gap junctions between contiguous cells and the cytoplasm of the myocytes themselves. However, the relative contribution of the two components is unclear, especially in atrial myocardium, as there are no precise measurements of cytoplasmic resistivity, Rc. In this study, Rc was measured in atrial tissue using several methods: a dielectrophoresis technique with isolated cells and impedance measurements with both isolated cells and multicellular preparations. All methods yielded similar values for R c, with a mean of 138 ± 5 Ω·cm at 23°C, and a Q10 value of 1.20. This value is about half that of total intracellular resistivity and thus will be a significant determinant of the actual value of action potential conduction velocity. The dielectrophoresis experiments demonstrated the importance of including divalent cations (Ca 2+ and Mg2+) in the suspension medium, as their omission reduced cell integrity by lowering membrane resistivity and increasing cytoplasm resistivity. Accurate measurement of Rc is essential to develop quantitative computational models that determine the key factors contributing to the development of cardiac arrhythmias. © 2012 Biophysical Society.

  • Mulhall HJ, Labeed FH, Kazmi B, Costea DE, Hughes MP, Lewis MP. (2011) 'Cancer, pre-cancer and normal oral cells distinguished by dielectrophoresis.'. Anal Bioanal Chem, Germany: 401 (8), pp. 2455-2463.

    Abstract

    Most oral cancers are oral squamous cell carcinomas (OSCC) that arise from the epithelial lining of the oral mucosa. Given that the oral cavity is easily accessible, the disease lends itself to early detection; however, most oral cancers are diagnosed at a late stage, and approximately half of oral cancer sufferers do not survive beyond five years, post-diagnosis. The low survival rate has been attributed to late detection, but there is no accepted, reliable and convenient method for the detection of oral cancer and oral pre-cancer. Dielectrophoresis (DEP) is a label-free technique which can be used to obtain multi-parametric measurements of cell electrical properties. Parameters such as cytoplasmic conductivity and effective membrane capacitance (C(Eff)) can be non-invasively determined by the technique. In this study, a novel lab-on-a-chip device was used to determine the cytoplasmic conductivity and C(Eff) of primary normal oral keratinocytes, and pre-cancerous and cancerous oral keratinocyte cell lines. Our results show that the electrical properties of normal, pre-cancerous and cancerous oral keratinocytes are distinct. Furthermore, increasing C (Eff) and decreasing cytoplasmic conductivity correlate with disease progression which could prove significant for diagnostic and prognostic applications. DEP has the potential to be used as a non-invasive technique to detect oral cancer and oral pre-cancer. Clinical investigation is needed to establish the reliability and temporal relationship of the correlation between oncologic disease progression and the electrical parameters identified in this study. To use this technique as an OSCC detection tool in a clinical setting, further characterisation and refinement is warranted.

  • Duncan LA, Labeed FH, Abel M-L, Kamali A, Watts JF. (2011) 'Effects of thermal treatments on protein adsorption of Co-Cr-Mo ASTM-F75 alloys'. Journal of Materials Science: Materials in Medicine, , pp. 1-10.
  • Labeed FH, Lu J, Mulhall HJ, Marchenko SA, Hoettges KF, Estrada LC, Lee AP, Hughes MP, Flanagan LA. (2011) 'Biophysical characteristics reveal neural stem cell differentiation potential.'. PLoS One, United States: 6 (9)

    Abstract

    Distinguishing human neural stem/progenitor cell (huNSPC) populations that will predominantly generate neurons from those that produce glia is currently hampered by a lack of sufficient cell type-specific surface markers predictive of fate potential. This limits investigation of lineage-biased progenitors and their potential use as therapeutic agents. A live-cell biophysical and label-free measure of fate potential would solve this problem by obviating the need for specific cell surface markers.

  • Fatoyinbo HO, Kadri NA, Gould DH, Hoettges KF, Labeed FH. (2011) 'Real-time cell electrophysiology using a multi-channel dielectrophoretic-dot microelectrode array.'. Electrophoresis, Germany: 32 (18), pp. 2541-2549.

    Abstract

    Dielectrophoresis (DEP) has been used for many years for the analysis of the electrophysiological properties of cells. However, such analyses have in the past been time-consuming, such that it can take 30 min or more to collect sufficient data to make valid interpretations from a single DEP spectrum. This has limited the application of the technology to a rapid tool for non-invasive, label-free research in areas from drug discovery to diagnostics. In this paper we present the development of a programmable, multi-channel DEP system for rapid biophysical assessment of populations of biological cells. A new assay format has been developed for continuous near-real-time monitoring, using simultaneous application of up to eight alternating current electrical signals to independently addressable dot microelectrodes in an array format, allowing a DEP spectrum to be measured in 20 s, with a total cycle time between measurements of 90 s. To demonstrate the system, human leukaemic K562 cells were monitored after exposure to staurosporine and valinomycin. The DEP response curves showed the timing and manner in which the membrane properties changed for the actions of these two drugs at the early phase of induction. This technology shows the great potential for increasing our understanding of the role of electrophysiology in drug action, by observing the changes in electrical characteristics as they occur.

  • Lamprou D, Zhdan P, Labeed F, Lekakou C. (2011) 'Gelatine and gelatine/elastin nanocomposites for vascular grafts: processing and characterization.'. J Biomater Appl, England: 26 (2), pp. 209-226.

    Abstract

    This study involves the preparation, microstructural, physical, mechanical, and biological characterization of novel gelatine and gelatine/elastin gels for their use in the tissue engineering of vascular grafts. Gelatine and gelatine/elastin nanocomposite gels were prepared via a sol-gel process, using soluble gelatine. Gelatine was subsequently cross-linked by leaving the gels in 1% glutaraldehyde. The cross-linking time was optimized by assessing the mass loss of the cross-linked gels in water and examining their mechanical properties in dynamic mechanical tests. Atomic force microscopy (AFM) studies revealed elastin nanodomains, homogeneously distributed and embedded in a bed of gelatine nanofibrils in the 30/70 elastin/gelatine gel. It was concluded that the manufactured nanocomposite gels resembled natural arteries in terms of microstructure and stiffness. The biological characterization involved the culture of rat smooth muscle cells (SMCs) on tubular gelatine and gelatine/ elastin nanocomposite gels, and measurements of the scaffold diameter and the cell density as a function of time.

  • Duncan LA, Labeed FH, Abel ML, Kamali A, Watts JF. (2011) 'Effects of thermal treatments on protein adsorption of Co-Cr-Mo ASTM-F75 alloys'. Journal of Materials Science: Materials in Medicine, 22 (6), pp. 1455-1464.

    Abstract

    Post-manufacturing thermal treatments are commonly employed in the production of hip replacements to reduce shrinkage voids which can occur in cast components. Several studies have investigated the consequences of these treatments upon the alloy microstructure and tribological properties but none have determined if there are any biological ramifications. In this study the adsorption of proteins from foetal bovine serum (FBS) on three Co-Cr-Mo ASTM-F75 alloy samples with different metallurgical histories, has been studied as a function of protein concentration. Adsorption isotherms have been plotted using the surface concentration of nitrogen as a diagnostic of protein uptake as measured by X-ray photoelectron spectroscopy. The data was a good fit to the Langmuir adsorption isotherm up to the concentration at which critical protein saturation occurred. Differences in protein adsorption on each alloy have been observed. This suggests that development of the tissue/implant interface, although similar, may differ between as-cast (AC) and heat treated samples. © Springer Science+Business Media, LLC 2011.

  • Bushnak IA, Labeed FH, Sear RP, Keddie JL. (2010) 'Adhesion of microorganisms to bovine submaxillary mucin coatings: effect of coating deposition conditions'. BIOFOULING, 26 (4), pp. 387-397.
  • Fatoyinbo HO, Gould DH, Labeed FH. (2010) 'A bio-analytical system for rapid cellular electrophysiological assays.'. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference, , pp. 6510-6513.

    Abstract

    In this paper, the use of non-uniform ac electric fields on biological cells for bioanalysis, through multiple, independently configurable channels is presented. The programmable system has been used to obtain the dielectrophoretic spectra of cells in near real time, within 90 seconds. This is a significant improvement on existing dielectrophoretic techniques as simultaneous parallel measurement of the dielectrophoretic forces at different frequencies has potential of revealing subtle changes to the electrophysiology of cells, as they occur. The results show that with continuous on-chip monitoring, cells exposed to a chemical agent that induces apoptosis begin to exhibit a spectrum that differs from untreated cells, as indicated from shifts in the observed crossover frequency values.

  • Labeed FH. (2010) 'AC-electrokinetic applications in a biological setting.'. Methods in molecular biology (Clifton, N.J.), 583, pp. 199-219.
  • Jaber FT, Labeed FH, Hughes MP. (2009) 'Action potential recording from dielectrophoretically positioned neurons inside micro-wells of a planar microelectrode array'. JOURNAL OF NEUROSCIENCE METHODS, 182 (2), pp. 225-235.
  • Duncan L, Shelmerdine H, Hughes MP, Coley HM, Huebner Y, Labeed FH. (2008) 'Dielectrophoretic analysis of changes in cytoplasmic ion levels due to ion channel blocker action reveals underlying differences between drug-sensitive and multidrug-resistant leukaemic cells'. PHYSICS IN MEDICINE AND BIOLOGY, 53 (2), pp. N1-N7.
  • Coley HM, Labeed FH, Thomas H, Hughes MP. (2007) 'Biophysical characterization of MDR breast cancer cell lines reveals the cytoplasm is critical in determining drug sensitivity'. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1770 (4), pp. 601-608.
  • Broche LM, Bhadal N, Lewis MP, Porter S, Hughes MP, Labeed FH. (2007) 'Early detection of oral cancer - Is dielectrophoresis the answer?'. ORAL ONCOLOGY, 43 (2), pp. 199-203.
  • Fatoyinbo HO, Hughes MP, Martin SP, Pashby P, Labeed FH. (2007) 'Dielectrophoretic separation of Bacillus subtilis spores from environmental diesel particles'. JOURNAL OF ENVIRONMENTAL MONITORING, 9 (1), pp. 87-90.
  • Labeed FH, Coley HM, Hughes MP. (2006) 'Differences in the biophysical properties of membrane and cytoplasm of apoptotic cells revealed using dielectrophoresis'. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1760 (6), pp. 922-929.
  • Duncan L, Shelmerdine H, Coley HM, Labeed FH. (2006) 'Assessment of the dielectric properties of drug sensitive and resistant leukaemic cells before and after ion channel blockers using dielectroplioresis'. 2006 NSTI Nanotechnology Conference and Trade Show - NSTI Nanotech 2006 Technical Proceedings, 2, pp. 45-48.

    Abstract

    Dielectrophoresis (DEP) is a phenomenon of induced particle motion in non-uniform electric fields. The effect is frequency dependent; by monitoring the motion of particles in AC fields and analysing the change in motion with frequency, it is possible to determine the electrical properties of single cells in lab-on-a-chip systems. In this paper we use DEP to study the electrical properties of drug-sensitive and drug-resistant cancer cells before and after treatment with ion channel blocking agents, which give insight into the origin of cytoplasmic differences shown to have a significant bearing on the origin of drug resistance in cancer.

  • Chin S, Hughes MP, Coley HM, Labeed FH. (2006) 'Rapid assessment of early biophysical changes in K562 cells during apoptosis determined using dielectrophoresis'. INTERNATIONAL JOURNAL OF NANOMEDICINE, 1 (3), pp. 333-337.
  • Labeed F, Broche LM, Hughes MP. (2005) 'Extraction of dielectric properties of multiple populations from dielectrophoretic collection spectrum data'. Physics in Medicine and Biology, 50, pp. 2267-2274.
  • Labeed F, Coley HM, Thomas H, Hughes MP. (2003) 'ASSESSMENT OF MULTIDRUG RESISTANCE REVERSAL USING DIELECTROPHORESIS AND FLOW CYTOMETRY'. Biophysical Journal, 85, pp. 2028-2034.

Conference papers

  • Jaber FT, Labeed FH, Hughes MP. (2013) 'A dielectrophoresis and image processing based system for loading single-neurons per micro-well in planar microelectrode arrays'. 2013 8th International Workshop on Systems, Signal Processing and Their Applications, WoSSPA 2013, , pp. 180-184.

    Abstract

    In this article, which is related to the biomedical signal processing applications area of the workshop, we present a system for positioning a single-neuron inside each micro-well of a 4-by-4 planar microelectrode array (MEA). Neurons are moved toward the electrode sites of the MEA (located at the bottom of the wells) using dielectrophoresis. The system utilizes the image acquisition and processing capabilities of MATLAB to detect the presence of a neuron inside each micro-well and stop the dielectrophoretic force, thus preventing more cells from being loaded. This method provides a fast, simple and relatively inexpensive way for loading cells on MEAs embedded with micro-wells for the purpose of acquiring and processing action potentials from geometrically defined biological neural networks at the single-cell level. Recordings from neurons that were positioned using this system have been obtained and are presented. © 2013 IEEE.

  • Kadri NA, Fatoyinbo HO, Hughes MP, Labeed FH. (2011) 'Semi-automated dielectrophoretic cell characterisation module for lab-on-chip applications'. Springer IFMBE Proceedings, Kuala Lumpur, Malaysia: BIOMED 2011: 5th Kuala Lumpur International Conference on Biomedical Engineering 35 (14), pp. 582-586.

    Abstract

    Dielectrophoresis is an electrical phenomenon that occurs when a polarisable particle is placed in non-uniform electrical fields. The magnitude of the generated force is dependent upon the electrophysiological make-up of the particle, therefore the specific DEP profile may be attained for any polarisable particles based on the intrinsic electrical properties alone. Any changes to these parameters may be detected by observing the corresponding DEP spectra. Despite having the advantages of being non-invasive, DEP applications are still not widely used due to the time-consuming processes involved. This study presents the preliminary outcomes in the development of a semi-automated DEP-based cell characterisation tool that allowed concurrent DEP experiments to be conducted serially, thus significantly reducing the time taken to complete the required sets of experiments. The results showed that the system is capable of producing a DEP spectrum for K562 leukaemic cells between the 10 kHz to 1 MHz range in less than 10 minutes, when recorded at eight points per decade.

  • Fatoyinbo HO, Gould DH, Labeed FH. (2010) 'A bio-analytical system for rapid cellular electrophysiological assays.'. Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Buenos Aires, Argentina: EMBC 2010 2010, pp. 6510-6513.

    Abstract

    In this paper, the use of non-uniform ac electric fields on biological cells for bioanalysis, through multiple, independently configurable channels is presented. The programmable system has been used to obtain the dielectrophoretic spectra of cells in near real time, within 90 seconds. This is a significant improvement on existing dielectrophoretic techniques as simultaneous parallel measurement of the dielectrophoretic forces at different frequencies has potential of revealing subtle changes to the electrophysiology of cells, as they occur. The results show that with continuous on-chip monitoring, cells exposed to a chemical agent that induces apoptosis begin to exhibit a spectrum that differs from untreated cells, as indicated from shifts in the observed crossover frequency values.

  • Mulhall HJ, Abdallat R, Liang X, Fedele S, Lewis MP, Porter S, Tsinkalovsky O, Johannessen AC, Hughes MP, Costea DE, Labeed FH. (2010) 'Rapid detection of oral cancer: Electrophysiological characterization by dielectrophoresis technology'. Technical Proceedings of the 2010 NSTI Nanotechnology Conference and Expo, Anaheim, USA: Nanotech Conference & Expo 2010 3, pp. 35-38.
  • Liang X, Labeed FH, Abdallat R, Johannessen AC, Tsinkalovsky O, Wang J, Costea DE. (2010) 'Rapid adherence to collagen IV enriches for tumour initiating cells'. EJC SUPPLEMENTS, 8 (5), pp. 124-124.
  • Fatoyino HO, Huebner Y, Hoettges KF, Hughes MP, Labeed FH. (2006) 'Applications of Dielectrophoretic / electrohydrodynamic electrodes for concentration of biological nanoparticles'. 2006 NSTI Nanotechnology Conference and Trade Show - NSTI Nanotech 2006 Technical Proceedings, 2, pp. 275-277.

    Abstract

    Dielectrophoresis (DEP) is a phenomenon of induced particle motion in non-uniform electric fields. The effect is frequency dependent; by monitoring the motion of particles in AC fields and analyzing the change in motion with frequency, it is possible to determine the electrical properties of single cells in lab-on-a-chip systems. By combining two common electrokinetic phenomena dielectrophoresis and electrohydrodynamic fluid flow - we demonstrate that it is possible to manipulate, concentrate and trap particles from cell to molecular scale, and show how the trapping phenomenon is not related to particle size. We also discuss application of the phenomenon, from particle preconcentration in sensor systems to the deposition of particles on sensor surfaces.

Book chapters

  • Labeed F. (2009) 'AC-electrokinetic applications in a biological setting'. in Hughes MP, Hoettges K (eds.) Microengineering in Biotechnology Humana Press
  • Labeed F, Hughes MP, Hoettges K, Fatoyinbo HO. (2004) 'AC Electrokinetics of Particles'. in Dorf RC (ed.) Handbook of Engineering Boca Raton : CRC Press

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