LCaos Newsletter - Issue no.4


Dear Readers,
You are welcome to our new issue of the LCaos Newsletter.  As you know, the purpose of this newsletter is to bring you the latest news coming from our FP7 LCaos consortium activities and achievements.
The opening section, Former Events, describes activities or actions organized or related to the LCaos project. The following section, LCaos Activities & Achievements, refers to the General Assembly Meeting that took place on 13 June 2013 in Saarbrücken/Wallerfangen, Germany. The LCaos Technical Developments section contains information about the technical developments and current work status, as well as some major outcomes and plans for the future. The next section, LCaos Events, Publications and Awards advertises relevant workshops and conferences, and a list of publications and awards resulting from the project’s activities. Finally, the LCaos Exchanges and Position Openings section is dedicated to exchange opportunities and position openings. This is the place for each partner to advertise any M.Sc, Ph.D or post-doctoral open position, or any opportunities and exchanges for visiting researchers.
We really hope you will enjoy reading this newsletter! In the same time, we highly encourage all our readers to send us feedbacks and comments. We would also be pleased to receive more pictures and contributions from all our project partners!
Wishing you success in your research and lectures!
Prof. Hossam Haick and Dr. Silvia Birsan
LCaos Newsletter

LCaos Former Events

The first LCaos workshop and the ISOCS training sessions – one big success for LCaos Consortium!

The first Workshop on Lung Cancer Artificial Olfactory System (LCaos( was organized on June 13, 2013, in Saarbrücken/Wallerfangen, Germany.
The LCaos workshop was jointly organized by the LCaos Consortium, the Breath Analysis Summit 2013 (June 9-12, 2013) and the ISOCS Short Course on Chemical Sensors for Breath Analysis (June 14, 2013). All events took place in the same location. The LCaos workshop aimed to bring the latest updates on volatile markers for early diagnosis and classification of lung cancer. Additionally, the workshop aimed to pass to the audience the latest updates on chemical sensors and nanoarrays for the diagnosis of lung cancer via volatile markers. The LCaos workshop brought together scientists, clinicians, industry executives, and entrepreneurs who discussed key trends, future directions, and technologies available for chemical sensors and nanoarrays for lung cancer diagnosis via volatile markers.
ISOCS Short Course was organized on June 14, 2013 in the same place: Wallerfangen, Germany and most of the LCaos Consortium partners joined it as organizers or/and lectures.
The Short Course explored chemical sensors in breath analysis, provided knowledge on chemical sensors, covered the field of data analysis and breath analysis for lung cancer detection, and established medical practices for lung cancer detection. The main objective was to give an overview on the available technologies and current research, with a focus on practical applicability and real life problems. The short course was intended for medical scientists, clinicians and industrialists who want to get a head start on chemical sensors in breath analysis, as well as for researchers and engineers who want to use their technology in lung cancer breath analysis.

LCaos Activities and Achievements

4th General Assembly Meeting

On 13 June 2013 the 4th General Assembly Meeting of LCaos project took place in Wallerfangen, Germany – an event organized by our project partner JLM Innovation together with the Technion. The Public Session welcomed the LCaos members as well as other invited participants. Each WP leader presented the evolution of the project from the scientific and technical points of view, as well as the progress and results achieved during the last six-month period until June 2013. During the Internal Session, there were consultations on future project plans, on dissemination and administrative issues, and on the reporting process. All the participants valued the meeting that gave a comprehensive vision on the progress we made and on our future plans.


LCaos Technical Developments

The Max Planck Institute for the Science of Light has fabricated silicon nanowires (Si NWs) by bottom-up (growth) and top-down (etching) methods. The different processes are fully understood and can be used to form SiNWs of different aspect ratios, doping and structural / chemical surface properties and Si NW arrays of different geometries.  Si NWs were grown by the vapor liquid solid (VLS) method with an average diameter of 50-100 nm, average lengths of 1-20 µm and different doping levels. The array geometries can be tuned by controlled deposition of the VLS catalysts by lithographic techniques.  Further SiNWs were produced by reactive ion etching (RIE) in combination with polystyrene nanosphere (PS) lithography. Here average diameters of 0.5-1µm and average lengths of 1-6µm could be achieved. The chemical / physical properties of SiNW surfaces were modified, in order to optimize junctions / interfaces in SiNW based device applications. The surface roughness as well as the passivation of dangling bonds could be modified by various wet chemical approaches. Further, the SiNW doping and the work function could be tuned by controlled oxidation of the SiNW surfaces. Si NWs were characterized by advanced imaging techniques, such as scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The surface properties of the Si NW were analyzed by X-ray photoelectron spectroscopy (XPS) whereas electronic properties could be monitored by contacting single NW device structures and performing photo- and cathodoluminescence (PL, CL) studies.
                                    SEM micrograph of the Si NW fabricated by: (a) RIE (top down) and (b) CVD.
The Technion has developed selective detection of lung cancer biomarkers in the gas. The Technion team have shown that an ensemble of independent device parameters extracted from single Si Nanowire Field Effect Transistor (SiNW FET) in combination with artficial intelligence could provide high selectivity towards specific VOCs. The effect of the backbone and functional (head) groups of the recognition layer attached to the Si NW surface on the obtained sensing results is presented and discussed. We show additionally that this approach can’t only detect specific VOCs, but, also, can predict their concentrations in the gas phase. The selectivity of the examined devices towards a single VOC that is found in a mixture of VOCs has been achieved.    
Following the fabrication of the exposure cells in the first year of the project, Micronit Partner has developed a holder that forms the fluidic and electrical interface between the exposure cells and external equipment. The holder accommodates two exposure cells equipped with 8 sensor chips each which can be run in parallel analyzing the sample from one source or two sources simultaneously. The exposure cells can be exchanged in a matter of seconds for example to switch to an alternate set of sensor chips with different response characteristics for the samples that are being analyzed. A picture of the holder is shown below:
The Liverpool University and Technion partners have completed a series of experiments on in-vitro headspace VOC analysis for cell-lines that represent normal airway epithelial cells and the earliest precursors of lung cancer with defined genetic alterations. The has been extended to include discriminant factor analysis with NaNose sensor arrays, with between 1 and 3 sensor features being demonstrated to accurately identify each of 4 cell-lines with single mutation differences. This work will be presented at the LCAOS workshop in June.
In support of both the in vitro cancer cell-line analysis of the Tel-Aviv University partner and the identification of cancer risk biomarkers by the Liverpool University partner, next-generation genomic DNA sequencing is being carried out. The risk biomarker work includes on-going bioinformatic analysis of microRNA and DNA methylation data. Epidemiology-based lung cancer risk scores including the Liverpool Lung Project (LLP) model are also being integrated into VOC analysis of breath samples in collaboration between Liverpool University, Tel-Aviv University and Technion partners. In Liverpool, these samples are now being collected within LLP clinics, hospital and community medicine settings.
The Tel-Aviv University has achieved important milestones in the early detection of lung cancer by the sensors array developed in the LCaos project. The Tel-Aviv University team has achieved high accuracy in discriminating malignant nodules vs. non-malignant pulmonary nodules. Moreover, this team could discriminate between subtypes of lung cancer, NSCLC vs. SCLC, as describes in the following figure:
Up to date, the Tel-Aviv University collected exhaled breath samples from 112 participating: 80 are lung cancer patients, 22 individuals with nodules for follow-up, 4 participants are COPD patients or heavy smokers and 6 participants are healthy controls. The exhaled breath samples were delivered to the Technion for sensors array and GC-MS analyses. The Tel-Aviv University team constructed a clinical database gathering clinical and epidemiological information from each patient including health status, pathological classification, scan results (CT, PET-CT and SUV avidity), size and tumor location, disease status and epidemiological data (age, gender, smoking history, respiratory diseases, pollutant exposure etc.).  The team has also monitored patients who are under systemic therapy for lung cancer, aiming to allocate the specific VOCs that might have association with response (or progression).  So far, the team enrolled 27 patients; 24 patients have NSCLC and 3 patients have SCLC. The subsets have been determined as follows: (a) conventional chemotherapy regimen; (b) targeted therapy (e.g. EGFR, TKI, erlotinib); Breath samples are collected and the signatures are crossed-matched with tumor response, which is assessed by routine CT scan imaging, and be measured by the RECIST criteria. This follow up is still on-going.
In parallel to the breath analysis of lung cancer, the Tel-Aviv University team has reported that nanomaterial-based sensors array can discriminate between lung cancer subtypes, i.e. adenocarcinomas and squamous cell carcinoma. Moreover, the team has shown that the sensors array is also sensitive to genes abnormality, i.e. discriminating between EGFR, KRAS and ALK-EML4 mutants, as describes hereafter: 
Last 7 June 2013 the 1st Multidisciplinary Conference of Cancer took place at the Complutense University in Madrid (Spain). The reached objective of this event, which was run by Dr. José S. Torrecilla, Professor of the Chemical Engineering Department of the same university, was to help understand the multiple fields that are involved and necessary for cancer research. The close and dynamic attitude of the presentations favored the participation of the audience, which led to an active debate and interesting Q&A after every speech. All of the invited speakers, which were professors and researchers, highlighted that numerous disciplines must find the way to cooperate in order to attain one clear goal: win the fight against cancer by achieving its early diagnosis. Because of this, and after the success of this 1st Multidisciplinary Conference of Cancer, the organization will encourage the creation of future events meant for anyone interested in this matter.
In the current project period our project partner Ionimed has further tested the developed Liquid Calibration Unit (LCU) for simulation of artificial breath. The product itself and scientific posters have been presented at the PITTCON Conference & Expo 2013 (Philadelphia, USA), at spring meeting of the American Chemical Society (New Orleans, USA) and at the PTR-MS Conference (Obergurgl, Austria).  In order to extend the range of usable solvents to others than water, a suitable micro-pump has been selected, with a better range of resistivity. To re-calibrate the flow-meters to other solvents a volumetric calibration procedure has been defined and tested. This allows also to use pure compounds to a large extend.  The measurement of clinical breath samples with PTR-MS in Israel is currently ongoing.  For the real-time analysis of breath samples from patients, Ionimed has developed a Buffered-End-Tidal breath sampler, which has recently passed the certification for clinical use. This breath sampling interface, development outside the LCAOS project, allows employing analyzer which do not comply with regulatory requirements to be used for clinical breath analysis. This would allow to rapidly bring a prototype of a sensor-based analyzers to a clinical level. The potential integration has been discussed with other work packages concerned with development of the NA-NOSE sampling setup.  Furthermore, Ionimed has recently been merged with its parent company Ionicon Analytik. The necessary administrative procedures affecting Ionimed’s part in the LCAOS project have been investigated and are currently executed.

LCaos Events, Publications and Awards

Here is a selection of some relevant workshops and conferences attended by various LCaos teams during the last period:

  • E-MRS Spring Meeting, Strassbourg, France, 27-31 May 2013: Semiconductor nanowires in energy research
  • PVCT 2013, Aix-en-Provence, France, 22-24 May 2013: Semiconductor nanowires in energy research
  • GDR Nanofils Semiconducteurs, Montpellier, France, 02-05 April 2013: Semiconductor nanowires in energy research
  • MRS Spring Meeting, San Francisco, USA, 01-05 April 2013: Semiconductor nanowires in energy research
  • DPG 13, Regensburg, Germany, 10-15 March 2013: Semiconductor Nanowires in Energy Research
  • Annual meeting Photonic Devices - ZIB, Berlin, Germany, 21-22 February 2013: Semiconductor nanowires in energy research
  • OSA International Congress on Renewable Energy and the Environment, Eindhoven, Netherlands, 11-15 November 2012: Semiconductor Nanowires in Energy Research
  • Asia Communication & Photonics Conference- ACP2012, Guangzhou, China, 07-10 November 2012: Semiconductor Nanowires in Photovoltaic and Sensing Applications
  • SPIE Optics & Photonics: Conference 8471: Next Generation (Nano) Photonic & Cell Technologies for Solar Energy Conversion, San Diego, USA, 14-17 September 2012: Semiconductor Nanowires for Photovoltaic Applications


Relevant publications issued by LCaos teams:

  • Bashouti, Y. M.; Pietsch, M.; Brönstrup, G.; Sivakov, V.; Ristein, J.; Christiansen, S. Hybrid polymer/silicon nanowire solar cell with high efficiency through covalent Si-C terminated surface passivation, Prog. Photovolt: Res. Appl. (accepted) (2013).
  • Bashouti, M. Y.; Sardashti, K.; Ristein, J.; Christiansen, S. Kinetic study of H-terminated silicon nanowires oxidation in very first stages, Nanoscale Res. Lett. 8, 41 (2013).
  • Bashouti, M. Y.; Pietsch, M.; Brönstrup, G.; Sivakov, V.; Ristein, J.; Christiansen, S. Hybrid polymer / silicon nanowire solar cell with high efficiency through covalent Si-C terminated surface passivation. Prog. Photovolt: Res. Appl. (ASAP) (2013).
  • Schmitt, W. S.; Schechtel, F.; Amkreutz, D.; Bashouti, M., Srivastava, S. K.; Hoffmann, B.; Dieker, C.; Spiecker, E.; Rech, B.; Christiansen, H. S. Nanowire Arrays in Multicrystalline Silicon Thin Films on Glass: A Promising Material for Research and Applications in Nanotechnology, Nano Lett. 12, 4050–4054 (2013).
  • Pietsch, M.; Bashouti, M. Y.; Christiansen, S. The Role of Hole Transport in Hybrid Inorganic/Organic Silicon/Poly(3,4-ethylenedioxy-thiophene):Poly(styrenesulfonate) Heterojunction Solar Cells, J. Phys. Chem. C 117, 9049–9055 (2013).
  • Konvalina, G; Haick, H.* Sensors for Breath Testing: From Nanomaterials to Comprehensive Disease Detection. Acc. Chem. Res. (2013) (DOI: 10.1021/ar400070m)
  • Broza, Y.; Haick, H.* Nanomaterial-based Sensors for Detection of Disease by Volatile Organic Compounds.  Nanomedicine (London, UK) 8, 785-806 (2013)
  • Broza, Y.; Kremer, R.; Tisch, U.; Gevorkyan, A.; Abdah-Bortnyak, R.; Shiban, A.; Best, L. A.; Haick, H.* A Nanomaterial-Based Breath Test for Short-Term Follow-Up after Lung Tumor Resection. Nanomedicine (New York, NY, US) 9(1), 15-21 (2013).
  • Peled, N.; Barash, O.; Tisch, U.; Ionescu, R.; Ilouze, M.; Mattei, M.; Bunn, P. A. Jr R., Hirsch, F. R.; Haick, H.*Volatile Fingerprints of Cancer Specific Genetic Mutations. Nanomedicine (New York, NY, US) 9(6), 758-766 (2013).
  • Hakim, M.; Broza, Y. Y.; Barash, O.; Peled, N.; Phillips, M.; Amann, A.; Haick, H.* Volatile Organic Compounds of Lung Cancer and Possible Biochemical Pathways. Chem. Rev. 112 (11), 5949–5966 (2012) – An Invited Review.
  • Peled, N.; Hakim, M.; Tisch, U.; Bunn, P. A. Jr. R.; Miller, Y. E.; Kennedy, T. C.; Mattei, J.; Mitchell, J. D.; Weyant, M. J.; Hirsch, F. R.; Haick, H.*Non-invasive Breath Analysis of Pulmonary Nodules. J. Thorac. Oncol. 7(10), 1528-1533 (2012).
  • Tisch, U.; Billan, S.; Ilouze, M.; Phillips, M.; Peled, N.; Haick, H. Volatile Organic Compounds in the Exhaled Breath as Biomarkers for the Early Detection and Screening of Lung Cancer. CML – Lung Cancer 5(4), 107-117 (2012)


LCaos Exchanges and Position Openings

We are pleased to announce an open position on the team of Dr. Nir Peled (Tel Aviv University):
Position: M. Sc. student.
Responsibilities: Analyzing the PTR-MS results, comparing to molecules libraries, and identification of the metabolic pathways that the VOCs have originated from.
Education: M.Sc. student in Organic chemistry field.