Day 2 :
Center for Pharmaceutical Engineering (PVZ), Germany
Keynote: Microfluidic systems for pharma technology - the manipulation of cells, droplets and particles
Time : 09:00-09:40
Andreas Dietzel studied Physics and completed his PhD at University of Göttingen in 1990. In the years 1990 to 2003, he worked in different organizations of IBM including the Research Laboratory in Rüschlikon. In 2004, he joined TU Eindhoven as a Full Professor of Micro and Nanoscale Engineering. In 2012, he was appointed as Professor at TU Braunschweig and Director of the Institute of Micro-technology. His research interest focuses on “The design and fabrication of microsystems and especially of microfluidic systems with applications in the life sciences”
In a world that becomes increasingly concerned about affordable health care, fast and effective screening methods for drugs in different formulations are required in the course of their development. In addition, the trend towards personalized medicine demands production of drugs in very small volumes. For both, the microfluidic approach is ideally suited. With miniaturized systems that can be realized by micro- or nanofabrication processes, new tools for pharmaceutical research and development become available. As new and better technologies for pre-clinical screening of drug dosage formulations microfluidic cell culture models that can mimic in-vivo conditions have attracted much attention. Recently developed organ-on-chip platforms providing dynamic flow conditions like cornea-on-chip and pancreas-on-chip will be presented including aspects of their microfluidic design, their fabrication and application. These systems are equipped with integrated sensors but also allow microscopic access at low background auto fluorescence. Furthermore recent work on the production of nanoparticles formulations within microfluidic droplet flows and plug flows will be discussed. In thereby obtained smallest fluid volumes mixing is accelerated and very controlled precipitation occurs. This leads to nanoparticle formulations in which particle sizes can be tuned by external flow controls. These approaches offer new possibilities for production at smallest scales and for improving the bioavailability of poorly soluble drugs.
Tsinghua-Berkeley Shenzhen Institute, China
Time : 09:40-10:20
Xiaohao Wang completed his Bachelor and Doctor degree both at Tsinghua University in 1994 and 1999, respectively. From 1998, he worked at Tsinghua University as a Faculty member, and was promoted to Full Professor at 2000. From 2007 to 2008, he was at Technical University of Berlin as a Visiting Scholar. He serves as the Deputy Dean of Graduate School at Shenzhen, Tsinghua University, now. His research interests cover MEMS based sensors and actuators, ionizing sources and portable analytical instrument. He has published over 200 technical papers and holds tens of patents.
Ionization source is a vital component of the mass spectrometer. In recent years, with the development of the mass spectrometer miniaturization and the microfluidic chip integration technologies, increasing research efforts have been devoted to the coupling of microfluidic chip ionization source to mass spectrometry. Facing requirement of portable MS used for on-site rapid detection, a microfluidic chip ionization source is developed. Multi-layer soft photolithography technology is chosen as the fabrication craft for the microfluidic chip template, and three novel microfluidic chip ionization sources were proposed, such as a microfluidic chip-based multi-channel ionization (MCMCI) was developed to extend the application of microfluidic chip ionization to MS. This MCMCI implemented extraction of untreated compounds in complex matrices without sample pretreatments and dual sprays with high DC voltages simultaneously.
- Nanotechnology in Biosensors
Biochips & Nucleic Acid Sensors
Bioinstrumentation & Equipments
Photonic Sensor Technologies
Center for Pharmaceutical Engineering(PVZ), Germany
Sarmiza Elena Stanca
Leibniz Institute of Photonic Technology , Germany
California Institute of Technology, USA
Title: Recent and upcoming potential spacecraft missions requiring biosensor technologies: Current examples, what are we looking for and remaining challenges
Time : 10:20-10:50
Ike Chi is a Materials and Processing Engineer at NASA’s Jet Propulsion Laboratory. He is the integrated product team (IPT) lead for Skutterudite Technology Maturation (STM) program and the device development task lead for Advanced Thermoelectric Couples (ATEC) program. He is also currently a member of Multi-Mission Radioisotope Thermoelectric Generator (MMRTG) Pyroshock project. He received his PhD from the Johns Hopkins University in 2014. He had several years of experience in fabricating biocompatible ceramics/semiconductors and ultra-high surface area materials. He is also interested in the area of biomedical implants/scaffolds and biosensing.
The National Aeronautics and Space Administration (NASA) has upcoming spacecraft missions to Mars (i.e., Mars 2020) and future potential missions (e.g., landers, penetrators) in the planning stages to Mars, Europa, Enceladus and Titan that could require unique biosensor systems to search for critical biomarkers in those environments. In-situ sensing capability under extreme environmental conditions is particularly critical for these current and potential NASA space exploration missions. JPL/NASA’s future planned Europa Clipper multiple flyby mission and a potential Europa lander or the planned Mars 2020 (ESA ExoMars mission) will encounter extreme environmental conditions. This presentation will report on our to-date accomplishments at the Jet Propulsion Laboratory (JPL) on Mars and potential plans in these other extreme deep space environments. Those missions will need ultra-sensitive sensors capable of reliable operation across a very wide range of temperatures. The applications of the highly sensitive sensor developed can include habitat health monitoring for a space station and/or for life detection on an Earth-like planet. In order to help fulfill scientific needs, we have developed a portable and low power in-situ biosensor to detect amino acids using an electrochemical spectroscopy technique. We have also enhanced chemical sensitivity of the sensor to parts-per-billion (ppb) range by integrating novel nanostructured electrode materials with improved surface properties. This novel engineered nanostructured micro-device tailored to sense specific analytes (e.g., amino acids) could be integrated with multiple flight-proven sensing platforms for a wide range of missions. This presentation will report on the progress for validating performance of this multi-platform in-situ bio-sensing device developed and tested by JPL.
Leibniz Institute of Photonic Technology, Germany
Time : 11:10-11:40
Sarmiza Elena Stanca has her expertise in electrochemical and optical nanosensors achieved during her research activity at the EPFL Lausanne (Swiss Confederation Fellow), UCD Dublin (Marie-Curie-Fellow), UKJ Jena (Marie-Curie-Fellow), University Babes-Bolyai Cluj-Napoca, Research Centre Karlsruhe and IPHT Jena (DAAD Fellow). She is currently a Scientist at the Leibniz Institute of Photonic Technology, Jena.
The plasma membrane regulates the selective interchange of matter between the interior and the exterior of the cell. Understanding this complex process requires knowledge of the plasma membrane´s molecular constituents. Topical reports prove the access to the molecular level of the synthetic membrane by atomic force microscopy (AFM). This technique also permits an electrochemical investigation in the immediate vicinity of the tip. An electrochemical and topographic study of the living cell membrane, by the mean of an AFM-probe integrated amperometric biosensors is employed to localize specific molecules in the natural cellular membrane (Figure 1). Several materials and shapes of the AFM probes integrated in different systems are presented. It is underlined that the selection of control experiment is decisive in achieving accurate findings. The central concern of this study is how to preserve the sensor response accuracy while increasing its precision.
Figure 1: (A) Height, amplitude and phase atomic force micrographs (110 µm x 110 µm) of the cells immobilized on conductive glass; (B) Height, amplitude and phase AFMs in one location of 1.5 µm x 1.5 µm of the plasma membrane; (C) AFM probe integrated sensor signal on two different points: green and red marked on the AFM image (200 nm x 200 nm).
University of Calabria, Italy
Title: Detection of gold nanoparticles aggregation growth induced by nucleic acid through laser scanning confocal microscopy
Time : 11:40-12:10
Ramla Gary has completed her PhD in 2017 from the Laboratory of Liquid Crystals and Interfaces in Physics department in collaboration with the Biological department at University of Calabria, Italy, and Post-doctoral studies from the same University. She has published more than five papers in reputed journals, and has participated in more than eight international and national conferences.
The gold nanoparticle (GNP) aggregation growth induced by deoxyribonucleic acid (DNA) is studied by laser scanning confocal and environmental scanning electron microscope. As in the investigated case, the direct light scattering analysis is not suitable, we observe the behavior of the ﬂuorescence produced by a dye and we detect the aggregation by the shift and the broadening of the ﬂuorescence peak. Results of laser scanning confocal microscopy images and the ﬂuorescence emission spectra from lambda scan mode suggest, in fact, that the intruding of the hydrophobic moiety of the probe within the cationic surfactants bilayer ﬁlm coating GNPs results in a Förster resonance energy transfer. The environmental scanning electron microscopy images show that DNA molecules act as template to assemble GNPs into three-dimensional structures which are reminiscent of the DNA helix. This study is useful to design better nano-biotechnological devices using GNPs and DNA.
Chang Gung University, Taiwan
Title: Detection of pH/H2O2 and prostrate/breast cancer biomarker by using nickel-oxide/iridium-oxide sensing membrane in electrolyte-insulator-semiconductor structure
Time : 12:10-12:40
Siddheswar Maikap has completed PhD in Department of Physics and Meteorology at IIT Kharagpur on February, 2003. He is Professor at Chang Gung University, Taiwan, since August 2014. He is the holder of three US patents on memory/bio-sensor, eight US/Taiwan patent files, and has more than 100 SCI journal papers, more than 150 international conference papers, 26 keynote/invited talks, and four best paper awards. His recent research focuses on cross-point resistive switching memory for high-density memory as well as bio-sensor applications
Quantification of pH/H2O2 attracts a lot of attentions due to its importance in chemical industries as well as biomedical diagnostic. For the detection of pH and H2O2 by using electrolyte-insulator-semiconductor (EIS) is preferred due to label-free detection, easy fabrication process, and low cost. The NiOx based sensor has shown good pH sensitivity of 50.25 mV/pH. X-ray photo-electron spectroscopy of Ni 2p3/2 has shown two different oxidation states of NiOx membrane and those are Ni2+ and Ni3+ having binding energy 854.5 eV and 856.5 eV, respectively. Existence of these two oxidation states resembles the reduction-oxidation (redox) characteristics of NiOx membrane toward the electroactive species like H2O2. A reference voltage shift of 41 mV is obtained for H2O2 concentration of 10 µM and has shown good linearity up to 100 µM for the first time. In addition, the IrOx membrane shows a record pH sensitivity of 150.4 mV/pH for the first time. This IrOx sensor demonstrated good catalytic behavior as well as the breast cancer biomarker LOXL2 with a concentration of approximately 150 nM is detected. This IrOx nano-net sensor demonstrates good catalytic behavior for H2O2 reduction with a concentration of 100 fM because the oxidation state changes from Ir3+ to Ir4+, whereas a pure SiO2 membrane could not sense H2O2. The oxidation states are confirmed by X-ray photo-electron spectroscopy (XPS). Similarly, prostate cancer is also detected by using NiOx membrane. Therefore, good pH response and redox characteristics of the IrOx/NiOx sensing membrane allow it to diagnosis human disease in future.
University of Belgrade, Serbia
Slobodan J Petricevic completed his BSc in Electrical Engineering (EE) in 1996; MSc in EE in 2001 and; PhD in EE in 2007 at School of Electrical Engineering, University of Belgrade, Serbia. His field of research is Optoelectronic and Fiber Optic Instrumentation. He has published 18 scientific papers in SCI listed journal with 105 citations and two patents. He is currently employed as an Associate Professor at School of Electrical Engineering since 2008.
Faraday crystals (FC) have been under intense investigation in magnetic field sensing applications for several decades due to several desirable properties, but mostly due to low interaction with magnetic field that does not disturb the field during measurement. FC requires an optical carrier to sense the magnetic field since interaction of the field and light in the crystal affects the state of polarization of the light. Development of production technology for optical fibers for mass use in telecommunication industry has made design of fiber-optic magnetic field sensor (FOMS) based on Faraday crystal an interesting research field. A class of diamagnetic materials known as sillenites of which BiGeO is an interesting example has been used to sense magnetic field in optical sensor in various configuration and adopted to various application. This paper will discuss an extrinsic, fiber optic, magnetic field sensor, designed for direct point magnetic field measurement constructed using Bi12GeO20 crystal. A configuration suitable for measurement will be presented together with analyses of the test results obtained from a calibrated magnetic field setup. Compensation of temperature effect on magnetic field measurement will be presented and its implication will be discussed.
Cukurova University, Turkey
Umut Kokbas has studied Biotechnology and Biochemistry at Ege University. He is a Research Assistant in Medical Biochemistry department at Cukurova University, working on Thalassemia, which the most common genetic disorder in Turkey. He is also pursuing PhD in the same department.
Statement of the Problem: β-thalassemia is one of the most monogenic autosomal recessive disorders characterized by defective production of the β-chain of hemoglobin. Definition of the β-globin genotype is necessary for genetic counseling in the carriers, and for predicting prognosis and management options in the patients with thalassemia. DNA-based prenatal diagnosis of β-thalassemia routinely relies on polymerase chain reaction (PCR) and gel electrophoresis. The aim of this study is to develop a new procedure, a DNA-based piezoelectric biosensor, for the detection of β-thalassemia IVSI-110 mutation fetuses cell free DNA from maternal blood, the most common β-thalassemia mutation in Turkey.
Methodology & Theoretical Orientation: Cell-free fetal DNA was taken from maternal whole blood. Bioactive layer was constituted by binding 2-hidroxymetacrilate metacriloamidoscystein (HEMA-MAC) nano-polymers on the electrode’s surface. Single oligonucleotide probes specific for IVSI-110 mutation of β-thalassemia were attached to the nano-polymer. The measurements were executed by piezoelectric resonance frequency which is caused by binding of the cell-free fetal DNA in media with single oligonucleotide probe on the electrode surface. The results were confirmed by the conventional molecular method as ARMS.
Findings: The piezoelectric resonance frequencies obtained by hybridization of the cell free fetal DNA on bioactive layer were found 216±12, 273±6, and 321±9 Hz for the samples of normal β-globin, heterozygote, and homozygote of IVSI-110 mutation, respectively.
Conclusion & Significance: The developed biosensor serves as a specific result to IVSI- 110 mutation. It could accurately discriminate between normal and IVSI-110 mutation samples. Because of low costs, fast results, specificity and high detection/information effectiveness as compared with conventional prenatal diagnosis methods, we can offer this technique as an alternative to conventional molecular methods.
Murdoch University, Australia
Mahamudul Hassan has completed his BSc (honors) and MS in Microbiology from University of Chittagong, Bangladesh. Currently, he is persuing his PhD at Murdoch Univesity and he aims to investigate the role of electron mediators in microbial extracellular electron transfer (EET) processes.
Electron mediators often play a key role in facilitating microbial extracellular electron transfer (EET) to oxygen or insoluble compounds. This study aims at developing a novel electrochemical cell consisting of two closely (250 µm) mounted working electrodes (WEs), hence Twin-WE; to detect and quantify redox active compounds in a micro-scale (304 µL) environment. A fixed voltage window between two WEs using common counter and reference electrodes was maintained and the individual currents of both WEs were monitored. To detect electron mediators, an optimized voltage window (50 mV) was shifted through a defined potential range (between –1 V and +0.5 V vs. Ag/AgCl) by changing a fixed voltage step (12.5 mV) after the establishment of steady equilibrium current in both WEs. When the voltage window was maintained at the midpoint potential of a mediator, concurrent oxidation and reduction of the mediator occurred as evidence by the concurrent maximal anodic and cathodic current recorded at the two WEs. The electrical current difference plot against the potential scale enabled the identification (by peak location in the potential scale) and quantification (by peak height) of the mediators tested. Our technique enabled a precise determination of riboflavin, anthraquinone-2, 6-disulfonate (AQDS) and two mediators from a pyocyanin producing Pseudomonas aeruginosa (WACC 91) culture both individually and from their mixture. The described Twin-WE cell device is suitable for studying microbial electron transfer processes under a simulated redox environment which prevails in natural habitat. The bio-electrochemical principle underpinning this new method may also be useful for advancing biosensor development.
Technische Universität Braunschweig, Germany
Dr. Stefan Dübel is Full Professor of Biotechnology and Director of the respective department at the Technische Universität Braunschweig, Germany. Stefan Dübel serves as a Chair of Biotechnology. He serves as Consultant to biotech and pharma companies. He is initiator of Antibody Factory of the German National Genome Research Network and Editor of the four volumes "Handbook of Therapeutic Antibodies" and other antibody engineering books. He is Co-founder of several biotech companies, most recently of the human antibody provider Yumab GmbH.
The development of biosensors using antibodies for detection of an analyte is frequently hampered by the limited choice of sensor molecules, if antibodies were generated by classical animal immunization. For some antigens or desired fine specificity, no antibodies could be obtained at all. Here, recombinant methods based on a complete in vitro selection pipeline, typically phage display, offer several new opportunities. Antibodies with particular, pre-designed biochemical properties can be selected from the start, as the biochemical milieu during the in vitro selection can be exactly controlled. Further, properties of existing antibodies can be changed or improved in various directions to adapt the sensor molecule to the requirements of a particular biosensor system. We present examples of successful generation of antibodies binding to extremely toxic molecules of antibodies specifically selected to detect very small differences in the antigen structure, matching sandwich pairs, improvement of affinity or stability, and the change of the kinetic binding properties, and successful applications of such recombinant designer antibodies on biosensors.