2022 CONFERENCE REVIEW (10-11 May 2022)

BioCHIPS & Solutions

Microfluidic physiological flows to test Ultrasound-controlled Swarmbots

Navigation of microrobots in living vasculatures is essential in realizing targeted drug delivery and advancing non-invasive surgeries. However, in the present there are still few functional microrobots when implemented inside a vasculature environment. The complexity of microrobotic manipulation, makes it difficult for these platforms to be translated to real applications, and still a thorough characterization of microrobotic handling is needed. We developed a microfluidic platform to test the acoustic control of “swarmbots”, based on the self-assembly of clinically approved microbubbles. We performed an in-depth characterization of microrobot self-assembly and propulsion mechanisms, exploiting microfluidic to mimic physiological flow rates. We demonstrate controlled propulsion towards both ends of an artificial vessel and we combine the microrobot propulsion with real-time imaging.

Fine micro- and nanofabrication of biocompatible hydrogel materials for biomedical application

We have developed a synthetic, ECM-mimicking hydrogel platform and have shown its promising characteristics for soft prosthesis and xeno-free explant expansion applications. Also, our previous work has demonstrated chip-format compatible modelling of neural and cancerous processes based on the tuneable biointeractivity of the self-supporting hydrogel. Here we will present microfabrication capabilities of this new biomaterial displaying elastomechanical characteristics similar to those of PDMS. We have fabricated and characterised topographic features down to the scale of sub-500 nm. This microscaffold fabrication is scaleable without relying on 3D printing techniques. We demonstrate how this system is exploited in contractile tissue-on-a-chip devices, e.g. skeletal muscle modelling.

Centrifugal microfluidic toolbox for liquid biopsy applications

Liquid biopsy is a revolutionary concept in oncology, utilizing analytes in body fluids as biomarkers for diagnosis of cancer. However, isolation and analysis of such analytes in a complex background, such as blood, is still challenging and standardization of liquid biopsy analysis remains an unsolved task. We propose using centrifugal microfluidics as a toolbox for automation and standardization of liquid biopsy applications. Demonstrated workflows cover microfluidic isolation of circulating cell-free nucleic acids (cfDNA), isolation of extracellular vesicles, analysis of cfDNA by digital droplet PCR and automated library preparation for next generation sequencing (NGS). To reach the next level of workflow standardization, we propose a concept of using a robotic station for microfluidic cartridge handling.

An innovative microfluidic platform with optical tweezers for screening and retrieval of B cells: its applicability demonstrated by discovering anti-SARS-CoV-2 monoclonal antibodies
KU Leuven

Digging deep into single-cell properties and collecting cells of interest for downstream processing is recently made possible by advancements in microfabrication and microfluidics. In this context, we present a powerful platform in which microwells and optical tweezers are integrated with a microfluidic chip, enabling microscopic screening and efficient and specific isolation of individual cells. Using the platform, we screened and isolated single human B cells from convalescent COVID-19 patients, resulting in the discovery of 2 monoclonal antibodies with high affinity and in vitro neutralizing potential against SARS-CoV-2. Owing to its performance, we envision this platform to contribute to the discovery of unique mAbs and other cell products, and to gain insights in numerous biological mechanisms, thereby advancing life science research.

An apparatus for single molecule DNA-identification using antenna-enhanced fluorescence
Fraunhofer-Institut für Physikalische Messtechnik IPM

Single molecule detection via plasmonic amplification of fluorescence may become an alternative to PCR. We present a novel apparatus designed for the point-of-care, which can prepare, conduct and analyze plasmonic assays on a chip. In comparison to conventional PCR methods, the device benefits from a reduced technical complexity. This is reflected in the small sized low cost device, and a fast analysis. Additionally, the method can – in principle – also be applied to different targets like antibodies/antigens. A disposable cartridge is used to process the chemical reactions. Fluorescence signals from a microarray are detected in a miniaturized microscope with < 2 µm resolution. The technical realization and first results for amplified DNA-detection are subject to this presentation. Funded by BMBF, 03VP03892

Multi-Responsive Hydrogel Microneedle Sensors for Multiplexed Chemical Analytics
MacEwan University

In this presentation we will demonstrate our flexible microneedle electrochemical probes based on biomimetric redox responsive composite hydrogels for in-situ multiplex detection of biologically relevant chemical markers, e.g., redox biomarkers, pH, biogenic amines, antioxidants, lactate, cortisol, and adrenaline. The composite hydrogels in these sensors simultaneously serve as an interface for biological fluid sampling and a medium for electrochemical sensing. Our presentation will demonstrate our e-skin sensory devices for real-time wireless monitoring of on-plant stress diagnostics, on-packaging food spoilage analytics, and wearable ‘emotion’ sensing in humans. In all cases, the sensors utilize non-invasive biological fluids, e.g., sweat and interstitial fluids for animals, and plants apoplastic exudates. The wearable sensors are aimed for applications in precision agri-food &nutrition, and health&wellness monitoring.

Ultimate flexibility in dispensing technology
M24You GmbH

M24You is focused on supplying instruments for dispensing technology from R&D up to fully automated production lines. These instruments enable various volume ranges - from picolitre (pL) till microlitre (µL) volumes, with the most accurate cv (<= 2%) available. By controlling all variables, the manufacturer M2-Automation, implements necessary conditions for biomolecules to have enough time for their binding on the target surface. In the binding process, there are many factors, which play an important role in receiving excellent result – the crucial factors are hydrophobicity, surface tension, temperature, humidity, viscosity and stability of the molecule. Within M24You/ M2-Automation we manage to control them successfully. Together with our application specialist team, we design and manufacture specific dispensing solution for your specific application.

Systems biology of organ-on-chip models
Hans Knöll Institute Jena

Organ-on-chip systems provide excellent tools to study the behavior of various biological structures under physiological and pathological conditions. We have investigated the effects of bacterial, viral and fungal infections in lung-, intestine-, and liver-on-chip models by means of an image-based systems biology approach. This aspect combines automated image processing and mathematical modeling to quantify biological processes. For instance, fungal invasion in the lung-on-chip model provided quantifiable measures of the behavior of hyphae under the effect of immune cells or antifungal agents. We measured the orientation distribution of the hyphae growing to the endothelial side of the tissue. Similarly, the (co-)infections by bacteria and viruses in the on-chip organs were evaluated by the image-based quantification of epithelial and endothelial cell damage.

Development of a 4D-in vitro-test system for specificity and potency of 3rd generation chimeric antigen receptor-T-cells (CAR-T-cells) based on microcavity array-bioreactors
Karlsruhe Institute of Technbology

We have developed a model of a leukemic bone marrow for the in vitro evaluation of chimeric antigen receptor-T- cell (CAR) specificity and potency. The model is based on a polymer microcavity array that is arranged on a chip which is then inserted into a bioreactor housing. For the establishment of the model we used human mesenchymal stromal cells and the ALL line Nalm-6. After 24 h of co-culture we added CAR-T-cells (effector:target-ratio = 10:1) and cultivated the chip for 72 h. With this model we were able to show that CAR-T-cells attack leukemic cells in their niche and that after 72 h only 12% of the leukemic cells could be detected.

A universal platform for nucleic acid based point-of-care diagnostics
Fraunhofer-Institut für Physikalische Messtechnik IPM

We developed a novel platform based on polymerase chain reaction (PCR). By combining microfluidic integration and a fully automated processing unit, we achieve an overall processing of about 45 minutes. The microfluidic elements are combined into a disposable disk with no active elements which has all reagents prestored. All active components, particularly the rotation unit, the heating unit, and the fluorescence readout module are integrated into a fully automated device designed for the point-of-care. The functional units of the platform will be presented. Special emphasis is given on the fast thermocycling based on a non-equilibrium approach with direct infrared liquid heating. The platform has been tested with assays for resistant pathogens. Funded by BMBF, 031A586C.

3D Printing: An Accelerator for Customized Microfluidic Applications
Leibniz Universität Hannover - Institut für Technische Chemie

Driven by its ever-increasing resolution, 3D printing is revolutionizing the access to microfluidic fabrication: Rapid prototyping of complex internal structures using biocompatible materials enables the fabrication of customized microfluidic systems, which are being used in a growing number of laboratories in life sciences and biotechnology. This presentation will provide guidance for the successful transfer from design to application of microfluidic systems using 3D printing. A particular focus will be on two 3D-printed platforms as feasible and cost-effective solutions for passive or active parallelization and automatization of microfluidic devices. By including small fittings (e.g., Luer lock), micromixers, or servo-controlled microvalves, the potential integration of customizable 3D-printed microfluidic systems into biotechnological applications such as antimicrobial susceptibility testing, organ-on-a-chip, or live-cell-imaging will be highlighted.

Miniaturization, multiplexing and single cell handling– an excellent foundation for next generation diagnostics

SCIENION’s proprietary non-contact dispensing technology is a central hub seamlessly integrated with upstream and downstream processing steps for many next generation diagnostic products. Further development of array based analytics focuses on new components and methods as surface functionalized substrates, probe deposition techniques, strategies of probe immobilization, target preparation and incubation as well as label and label free detection methods to improve sensitivity, reproducibility and to minimize material consumption. The transfer of these systems from open R&D platforms using e.g. microplates to cartridge systems using fully integrated microfluidic chips or biosensors is another goal to enable fully automated diagnostics in the clinical laboratory and Point of Care applications. We will present recent results on miniaturization of DNA or protein based diagnostic test and single cell application using SCIENION technologies.

Magnetic surface microrollers against physiological flows in living microfluidic chips
Max Planck Institute for Intelligent Systems

Controlled microrobotic navigation in blood vessels holds significant potential to revolutionize targeted drug delivery. We use microfluidic platforms to test the performance of the magnetic microrollers in physiological flows. The microrobotic system consist of cell-sized silica microparticles half-coated with magnetic material, while the silica face has cancer cell selective antibodies and drugs. The microfluidic setup is composed of a poly(methyl methacrylate) (PMMA) top piece encompassing fluidic connections, a double-sided tape defining the channel shape and height, and a glass bottom piece. The endothelialized microfluidic channels provide robust platform for the testing of surface microrollers in physiological flows.

Gate-coupling and Single-trap Effects for Sensitivity Enhancement in Nanowire Field-effect Transistor Biosensors
Forschungszentrum Jülich, Bioelectronics (IBI-3)

Nanowires are unique nanomaterial promising for many fundamental studies as well as for nano - and bioelectronics applications. We develop biosensors based on nanowires for the early detection of cardiovascular and Alzheimer’s diseases. Based on our comprehensive studies on transport and noise phenomena in the fabricated devices, we propose novel approaches on the basis of gate-coupling and single-trap effects for the detection of the target biomarkers with enhanced sensitivity for advanced biosensing. The developed approach opens prospects for diagnosis of the diseases in real-time at the early stages when therapy can be effectively applied to restore the healthy state of the patient.

Precise Contactless Spotting for Lab-on-Chip Application

Lab-on-chip devices as small microfluidic devices equipped with microchannels carry out diagnostic tests by enabling reactions between patient samples and reagents. The devices deliver test results with very small sample volumes in a short period of time. For production of lab-on-chip devices a precise, fast material deposition method is needed. Typically, the devices are produced at high numbers under high throughput conditions. The substrates may be made of different materials but all have a structured surface like channels. Deposition or Spotting of reagents onto the chip is a demanding task and requires filling of small cavities and microchannels with a high accuracy. This can be done with a microspotting platform based on in inkjet technology. The flexibility of this technology allows solutions adapted to the specific customer needs. It is demonstrated how high accurate the volume of spotted reagents and precise of placement is achieved under high throughput production conditions. www.microdrop.de


R&D Solutions Using Mass-Producible Versatile Acoustofluidic Chips
Leibniz IFW Dresden

Surface acoustic wave (SAW)-based acoustofluidics is a promising technology for versatile applications in the manipulation of liquids, cells and (bio-) particles. This includes, among others, the generation of aerosols, liquid mixing, focusing and sorting of different cells or particles. Current limits for their production and application in an industrial scale are complex fabrication process, low performing materials and non-optimized periphery. We present our developments of new-generation SAW-based acoustofluidic devices employing chips with precisely integrated microchannels, task-specific periphery and automation solutions to support a variety of your application scenarios.

PowderMEMS - Integration of porous structures on wafer-level
Fraunhofer Institute for Silicon Technology ISIT

This talk presents PowderMEMS, a novel technology for the creation of porous microstructures on wafer-level. The PowderMEMS process solidifies micron-sized particles via atomic layer deposition (ALD) to create three-dimensional microstructures on planar substrates. The process offers numerous degrees of freedom for the design of functional (Bio-)MEMS, such as a wide choice of different materials and the precise fabrication of 3D volumes at substrate level with a defined degree of porosity. Porous PowderMEMS microstructures tolerate post-processing to integrate additional functional structures such as electrodes or heaters. The potential of PowderMEMS towards bioanalysis and biosensors is discussed and applications such as microscale chromatography and catalysis are presented.

Scanning Probe-Based Rapid Prototyping of Single Cell Chips
Center for Physical Sciences and Technology

We present scanning-probe based techniques for fabrication of sub-micron surface features for single-cell arraying and controlled adhesion. Such rapid prototyping can be implemented by commercial scanning probe (SP) microscopy instrumentation, in the regular chemical laboratory environment. Our key process is direct chemical writing at a speed up to 100 µm s-1, with an SP functioning as a nanofluidic pen for transferring mixtures of surface-selective bifunctional compounds and lipids. We fabricate and subsequently replicate a few mm-sized chip areas, consisting of protein features of virtually any geometry, at a submicron resolution. We demonstrate the utility of the SP nanolithography in the design of subcellular patterns for programming cytoskeletal architectures and developing new single-cell sensing platforms.

Innovative approach for dynamic flow regimes on cerebral organoid maturation
Department of Bioengineering, Faculty of Engineering, University of Ege

A bioengineered whole brain organoids that can be widely self-organized by iPSCs-derived cells, have become imperative for modelling various neurological disease in a physiological and functional manner. One of the most critical points in brain organoid development is the initiation of dynamic flow conditions that support oxygen and nutrient diffusion to the tissue while promoting neuronal self-organization and organoid survival. In addition to traditional methods, microfluidic systems have been investigated that provide controlled dynamic flow conditions by imitating laminar blood flow in the brain, support growth factor diffusion, metabolite exchange in larger sizes and survival for a long time. A molecularly-functionally-structurally matured brain organoids have been formed with high harvestability using the microfluidic platform that is designed in our group.

Fabrication of 3D Amphiphilic Shape-Coded Microparticles to Spontaneously Form Uniform Reaction Volumes for Amplified Immunoassays

Here, we present a versatile platform to compartmentalize and perform reactions in uniform nanoliter-scale volumes using microscale multi-material particles that form a single droplet per particle for an amplification assay. Our system provides customizable shape-coded particle for multiplexing, flexibility to be scaled up, and ease of implementation with existing amplified assay workflows, enabling 100s of parallel reactions upon simple mixing of reagents. We manufacture the multi-material particles using a 3D printed device to run a hydrodynamically stable co-flow of four different streams of polymer precursors that take a cylindrical co-axial shape. We have fabricated particles with distinct cross-sectional shapes and different dimensions. These particles with a hydrophilic inner hollow layer and hydrophobic outer layer provide a versatile and scalable platform to form highly uniform aqueous droplets (200pL to 6nL) in the center of the particles suspended in an oil phase.

3D microfabrication for biological and biomedical applications. Introducing the first bioprinter enabling sub-micron printing resolution.

The Quantum X bio is the first 3D bioprinter of its kind; enabling sub-micron printing resolution, and raising the bar for high-precision 3D bioprinting. Powered by NANOSCRIBE’s proprietary Two-Photon Grayscale Lithography (2GL®) technology and CELLINK’s award-winning cell-friendly solutions, the Quantum X bio has been customized and reimagined for cell biologists and biomedical engineers. High-throughput batch production and precision printing meet patented Clean Chamber sterilization technologies, advanced temperature controls, metadata collection, and biocompatibility to empower scientists and engineers with the fastest and most shape-accurate 3D printer on the market. In this live product demo, we will discuss how the Quantum X bio will accelerate innovation and production in critical application areas for biomedical technologies, tissue engineering, cell biology, and regenerative medicine.

Advanced methods for the production of next generation flow reactors out of glass
Little Things Factory GmbH

Flow chemistry and the controlled generation of liquid micro droplets with uniform characteristics will be one of the future key technologies in research and in industrial production. The phase separation of liquids will be another one. This work describes recent innovations in the field of laser etching in glass and the application of this technology in these fields of flow chemistry.

Development of a microfluidic platform for high sensitive, in-flow living samples detection
Istituto Italiano di Tecnologia

In this talk an innovative configuration for in-flow detection of living samples in a lab-on-chip will be presented. By the exploitment of a hydrodynamic focus designed with an innovative configuration we are able to exactly localize the samples at the center of the microchannels. This allows us to detect them by collecting the fluorescence light emitted by pre-treated samples, or by collecting their scattered light. This kind of chip can offer a solid protocol for several applications, for example it can be used as a high sensitive, high throughput device for the detection of different kind of pollutants inside water, e.g. bacteria or metals.

2019 CONFERENCE REVIEW (7-8 May 2019)

Laser-assisted generation of microarrays for diagnostics and disease research
Max Planck Institute of Colloids and Interfaces

We have developed the next-generation method for microarray synthesis: For the first time, it will be possible to cost-efficiently generate any kind of large scale high-density molecule microarray. For example, this will allow us to screen the whole malaria peptidome at once for vaccine research. Key feature of the new method is a laser transfer process. Tiny solid material spots are rapidly transferred from a donor film to an acceptor surface, requiring only minute amounts of materials. The transfer is performed with different and easy-to-produce donor slides. Each donor slide bears a thin polymer film, embedding one type of monomer. The coupling reaction occurs in a separate heating step, where the matrix becomes viscous and building blocks can diffuse and couple to the acceptor surface. This novel method allows us to incorporate any synthetic or commercial building block into the array’s molecules with a density of 10,000 spots per cm².

Low volume (pL, nL, µL) dispensing application within biochip or microfluidics

M24You/ M2-Automation enabling low volume dispensing technology for different volume (pL, nL, µL) ranges by just exchanging the dispenser (Click & Go) within the one device or multi-dispenser system for research, iTWO-Cube, up till a fully automated Production line, iZERO. During our presentation we like to point out dispensing features supported by customer applications from request till accomplishing results. Find more at www.M24You.com

Fluidic platform for vascularized Organs-on-a-Chip
Karlsruhe Institute of Technology

Especially in the area of drug discovery, tissue engineering and organ-on-chips are becoming more important. However, handling is often time consuming and difficult due to a lack of automatized systems. We present a microfluidic platform that is used to cultivate slide-sized organ-chips. Within the chip, endothelial cells grow on a curved microchannel, to create an artificial blood vessel. Several organ-models can be built in a surrounding compartment, which can be used for various applications like drug testing. The platform itself consists of a micro annular gear pump that enables flow rates down to approx. 1.5 µl/min and several miniaturevalves. The platform is controlled by a connected touch display. Because of the dimensions of a multi-well plate (127.8 x 85.5 mm2), the platform fits to standard devices, like microscopes. Furthermore, there are fluidic connections for sampling as well as the possibility to integrate sensors (e.g. O2, CO2) via Luer-Locks.

Roll-to-roll printed graphene biosensor

We have printed sensors for usage in cell-based assays. Graphene platelets are the main component of the ink. Roll-to-roll gravure printing is used for printing 5 µm thick interdigital electrode structures. Inline drying of printed structures is performed with near-infrared dryers. Thin polymer films comprising the printed sensor structures in multiwell plate format are bonded to bottomless well plates and electrically connected with an impedance analyzer. The TZM-bl / HIV-1 pseudovirus (PV) system is used for sensor validation. In the validation experiments 10,000 TZM-bl cells are seeded per well. The PV PVO.4 (in a concentration usually used in neutralisation assays) or PVO.4 plus 1 µM Efavirenz are added to the wells 24 h after cell seeding. We have shown that the developed sensors are suitable for online monitoring of the viral effect on cell culture and inhibition of the virus-induced cytopathic effect by antiviral substances.

Customer-specific integrated microelectronics for the application in life-sciences
IMMS Institut

IMMS serves enterprises through preliminary research. It acts as their strategic partner in the development of microelectronic and mechatronic products and of systems technology. IMMS’ life science focus is the research and development of application-specific integrated electronic circuits (ASICs) and sensor systems for quantitative rapid tests and in-vitro diagnosis and for the monitoring of therapeutic progress. The biotechnological know-how of its partners is the starting point for joint development of customised systems. For those systems, IMMS concentrates on optical and electrochemical detection in combination with wireless data transfer. Examples from previous research projects will be presented, as for example a wireless, battery-free temperature sensor and a mobile box for the detection of antigen-antibody interactions. For future developments IMMS will combine optical or electrochemical sensing with wireless energy supply and data transfer for the development of sensors which can be read out e.g. by smartphones.

3D printing of micromechanical structures for personal medicine

Personalized medicine calls for new ways to manufacture functional structures that could be tuned by the needs of the specific patient and case. Multiphoton polymerization (MPP) based 3D printing is a powerful technique to manufacture true 3D structures in the size range from µm to mm. We present a possibility to use MPP for efficient biomedical micromechanical device fabrication. First, we discuss a concept of ultra-precise integrated flow meters with measuring capacity down to 10 µL/min. Also, medicine-oriented 3D microrobots with unrestricted movement capability are proposed with the intent of using them as a personalized diagnostic and curing tool inside a human body. Biocompatibility and specific application cases are evaluated. Overall, it is demonstrated that MPP is a unique tool allowing to create integrated and/or mechanical objects capable of performing highly complex tasks in-vitro and in-vivo at a micro-level. Find more at www.femtika.lt

Microfluidics for Marine Science
Jade University of Applied Science

The usage of microfluidics for marine science is shown in two examples: one analytical instrument (nutrient analyzer) and one sample treatment device to mimic environmental conditions.

The OrganoPlate: Human organ-on-a-chip tissue models for predictive drug testing in high throughput

Organ-on-a-chip has recently emerged as the new paradigm in enhanced, 3D tissue culture. The field builds on almost 26 years of developments in microfluidic and associated microfabrication techniques on the one hand and an urge towards ever more physiologically relevant cell and tissue culture approaches on the other hand. Application of microengineering techniques in cell culture enables structured co-culture, 3D culture, the use of flow and associated shear stress and application of controlled gradients. MIMETAS develops a commercially available platform based on a microtiter plate format that harbors up to 96 chips and enables perfused 3D co-culture in a membrane-free manner. The OrganoPlate® facilitates growth of tubules and blood vessels under continuous flow of medium, it allows engineering of organ complexity without usage of artificial membranes. The OrganoPlate® is fully compatible with liquid handling equipment and high-content readers and is easily adopted by end-users. Current flagship models in OrganoPlates® comprise the human kidney proximal tubule, central nervous system, colon, liver and blood vessels. These models are unsurpassed in terms of physiological relevance and throughput.

Fluorescence lifetime-activated droplet sorting (FLADS) in microfluidic chip systems
University Leipzig

In context of droplet microfluidics, fluorescence activated droplet sorting is one of the most widely used sorting technique. The herein predominantly used method for droplet detection based on fluorescence intensity is easy to realize but can be error prone. An interesting alternative is to read the fluorescence lifetimes of individual droplets rather than just the intensity. Furthermore, it allows to better differentiate between analytes and also enables to probe the environment of the fluorescent molecule, e.g. for sensing applications. We manifest a novel technique to sort droplets by on-the-fly fluorescence lifetime determination. The system enables sorting of droplets containing fluorescence compounds as Fluorescein and Pyranine by average fluorescence lifetime with a high accuracy of sorting.

Microfluidic infrastructure for biochip integration
Fraunhofer ENAS

In the talk we will present our technology for integrated micro pumps based on electrolysis. The technology was used to develop microfluidic cartridges, which are open for integration of various biosensors. The talk will give an overview about biosensors that were already integrated, applications(human diagnostics, food quality/safety, environmental testing) and challenges during biosensors integration. Find more at www.enas.fraunhofer.de

Stimuli-Responsive Protein Polymers for Bioseparations and Assays
ETH Zurich & University of Basel

Tropoelastin is an extracellular matrix protein containing long stretches of disordered amino acid sequence. By utilizing tropoelastin’s repetitive VPGXG motif, we have engineered versions of artificial elastin-like polypeptides (ELPs) for bioseparations and biosensing. ELPs are useful reagents for biochip systems because they undergo a reversible phase transition in response to small changes in environmental conditions, such as changes in ionic strength and pH. After describing the relevant background on ELPs, I will present two systems involving newly engineered ELPs. The first system uses bio-orthogonal ELPs for fabrication of biosensor surfaces with improved sensitivity, while the second system demonstrates magnetic nanoparticle-based separations of ELP fusion proteins. These technologies demonstrate the broad range of biochip applications where ELPs can be of use.

Online Monitoring of Metabolic Activity or Growth Conditions in Microfluidics

Cell and μ-tissue culture in microfluidics gained huge popularity during the past years. Small volumes and controlled geometry makes microfluidics a perfect tool to conduct fast and reproducible experiments. On the way towards mimicking physiological in vivo conditions in microfluidics, the volume restrictions and its implications on e.g. oxygen and nutrient availability have to carefully kept in mind. Cells or tissue in vivo each fact their own special physiological conditions, which are mostly far off, of the standard 5%CO2 and air saturated growth conditions in incubators. Furthermore, O2 in such a small the medium volumes with a high amount of cells can quickly drop to hypoxia or anoxia, and pH changes occur fast, event in perfused systems. We present optical chemical sensor techniques that can measure online O2, pH or CO2 in a minimally or even non-invasive way and which can be integrated in nearly all types of microfluidic chips. Find more at www.PreSens.de

Scalable wafer level production of consumables for Life Science and Diagnostics Applications made of non-CMOS compatible materials on Glass. Challenges and opportunities by addressing Manufacturing and Standardization in a foundry concept

Microfluidics, a technology characterized by the engineered manipulation of fluids at the submillimetre scale, has shown considerable promise for improving diagnostics and biology research. Currently the state-of-the-art is characterized by the best-conduct practiced at each foundry determined by the technologies available (polymer, glass and silicon), leading to a lack of standardization and interoperability. The lab-on-chip is created by structuring micro channels, -mixers, -reservoirs and diffusion chambers into the substrate material. The integration of surface functionalization as well as electronical, optical elements and valves provides a comprehensive biosensor made of a single substandard device. Moreover, hybrid integration of diverse materials such as polymers, silicon with glass can provide novel multilayer hybrid microfluidic devices. The overall complexity is addressed by transferring MEMS standardization protocols, methodologies and equipment available in the MEMS into the field of microfluidics. In this presentation, we discuss the challenges and solutions of implementing WLP processes for LOAC products. Find more at www.imtag.ch

A BiCMOS high-frequency biosensor for dielectric spectroscopy of bio-fluids for medical diagnostics

Chronic Obstructive Pulmonary Disease (COPD) is one of the most common chronic lung disease worldwide. Although majority of patients with objective COPD go undiagnosed until late stages of their disease, recent studies suggest that the viscosity variation of sputum samples collected from patients could be an indicator of the disease progression. Since, the viscosity of the sputum is defined by its water and protein contents, it is possible to use dielectric sensors for rapid screening and detection of sputum variations. Therefore, the main content of my presentation at BioCHIP conference will be to introduce our BiCMOS biochip/biosensor which is developed for rapid diagnosis of COPD through dielectric characterization methods. The small size, DC readout mechanism, and low power consumption of the developed sensor made its fully integration into a handheld device possible. The operating frequency of the dielectric sensor was chosen to be 30 GHz to achieve a high signal-to-noise-ratio.

Roll-to-Roll Imprinting and Microarray Spotting of Biosensors

Roll-to-roll (R2R) production is applied in many fields ranging from print industry to organic electronics and lab-on-a-chip technology and brings an increase in throughput, decrease of production cost and simplification of substrate handling. In this study, a foil based biosensor for chemiluminescence based DNA quick tests is presented. The sensor microchannels were produced by R2R UV-NIL, showing the transfer of the chip concept from classic injection molding to R2R based production. In addition, R2R produced optical microstructures for signal enhancement were implemented on the chip bottom. Optical signals, generated inside the microfluidic channels, are coupled out of the chip with higher efficiency and signal strength is increased. The implementation of DNA printing of the biosensor is also transferred to a R2R process. A novel R2R Microarray-spotter is presented, which allows high resolution printing of multiplexed biomolecule arrays on R2R imprinted microstructures. This technology enables high throughput production of biosensor chips.

Scalable hybrid microelectronic-microfluidic integration of highly sensitive biosensors
TU Berlin

The increasing distribution and acceptance of Point-of-Care devices creates the need for disposable highly sensitive biosensor devices. Specialized microelectronic sensor chips combining superior sensitivity compared to paper strips and better miniaturization potential, production scalability and readout simplicity compared to optical systems are emerging from science to application. Packaging of these sensors into a disposable component needs to comprise electronic connection as well as sensor-to-fluid exposure and the respective interfaces to the “macro world”. Reaching feasible costs for such integrated hybrid microelectronic-microfluidic components is possible by saving highly expensive silicon substrate area and place the non-active functionality such as electronic and fluidic wiring onto cheaper substrates. During the presentation two packaging technologies addressing different product requirements will described. Therefore, the development of two dedicated process flows will be outlined, that allow the packaging of two sensor variants by using microelectronic packaging processes suitable for cost effective medium to high volume manufacturing. Both sensor packaging process variants have been validated by actual sensor embedding and functional testing in cooperation with sensor developers.

Personal biochips
University of Colorado Boulder

We investigate how to ubiquitize healthcare by moving the process of diagnosis closer to the patient. What if instead of laboratories, doctors themselves could perform the tests while patients wait? Or, what if we could empower patients to perform selected tests at home, as part of their decision whether to see a doctor? I pursue this vision by creating cyber-physical systems based on biochips, electronic devices that manipulate droplets of fluids to execute “bio-protocols”. Biochips automate processes traditionally performed in wet labs. Instead of going to a specialist, a patient could download a bio-protocol. This transforms diagnosis into a software problem that has the potential to scale the way software scales. I design biochips that can be operated at the level of expertise of doctors and patients. Specifically, I develop biochip hardware, write compilation software, and I am currently working on a user-facing system to edit bio-protocol interactively.

A Fluid-Walled Microfluidic Device for Cell Migration Studies
University of Oxford

Various microfluidic platforms have been developed in the past couple of decades offering experimental methods for the study of cell migration, yet their implementation in the laboratory has remained limited. This is mainly due to technical complexity, high failure rate due to gas-bubbles, as well as questionable bio-compatibility of polydimethylsiloxane (PDMS). We have designed and implemented a system that creates microfluidic circuits using only materials commonly used by biologists - standard cell culture dishes and media. The media is shaped into microfluidic patterns onto a petri dish and overlaid with an immiscible perfluorocarbon to form fluid-walled circuits. Cells may be added anywhere to the open microfluidic format and flow driven from any point within the circuit by passive or active means using principles of Laplace pressure. Novel devices were fabricated, and to demonstrate the functionality of this system we performed cell migration based assays.

Precise Contactless Spotting for Lab-on-Chip Applications

Lab-on-chip devices as small microfluidic devices equipped with microchannels carry out diagnostic tests by enabling reactions between patient samples and reagents. The devices deliver test results with very small sample volumes in a short period of time. For production of lab-on-chip devices a precise, fast material deposition method is needed. Typically, the devices are produced at high numbers under high throughput conditions. The substrates may be made of different materials but all have a structured surface like channels. Deposition or Spotting of reagents onto the chip is a demanding task and requires filling of small cavities and microchannels with a high accuracy. This can be done with a microspotting platform based on in inkjet technology. The flexibility of this technology allows solutions adapted to the specific customer needs. It is demonstrated how high accurate the volume of spotted reagents and precise of placement is achieved under high throughput production conditions. Find more at www.microdrop.de

Biochip for detection of bacteria using surface enhanced Raman spectroscopy (SERS)
French National Center for Scientific Research (CNRS) - Ecole Polytechnique

Rapid and accurate detection of pathogens is a major challenge in many areas including health, food safety or military applications. For this purpose, biochips are particularly attractive as they allow multiplex detection of pathogens at relatively low costs and fast. Different methods with good sensitivities were already developed however they are not able to verify the nature of the detected pathogens or to identify their strains. Thus, we aim to develop a new architecture of biochip for the multiplex and spectroscopic identification of pathogens by SERS imaging. Our biochip design is based on amorphous silicon carbon alloy and plasmonic nanostructures. Briefly, the amorphous layer allows the reproducible fixation of different probes (mannoside or antibody) via robust covalent Si-C bonds and the plasmonic nanostructures are responsible for the exaltation of Raman signal of the targets. Afterwards we will focus on selectivity, sensitivity and on the limit of detection of our method.

World’s first fully (hybrid) integrated and wafer scale manufacturable photonic interferometric biosensor-array chip-module with unparalleled sensitivity, applicable in both companion/complementary diagnostics and drug screening/optimization
LioniX International BV

The platform uses proprietary Si3N4 based waveguide technology and is based on a proprietary ‘asymmetric Mach-Zehnder Interferometer’ (aMZI), that intrinsically is orders more sensitive than other label-free optical sensor systems such as based on Surface Plasmon Resonance. The performance of the aMZI is further enhanced by material-selective functionalization of Si3N4 vs. SiO2. This allows for bioreceptor immobilization on the waveguide alone, resulting in minimized analyte depletion and a The platform combines two innovative improvements of state-of-the-art biosensing technology, while it the whole optical system is implemented on a solid-state chip-module, allowing for POC and (high) volume manufacturing. Next to this, the platform is being developed by a consortium of complementary SME/companies leading in their own field of expertise. This development has received funding from the European Union's Horizon 2020 programme under grant agreement No 732309 (BioCDx) and European Regional Development Fund under No PROJ-00697 (BioMEANDER). Find more at www.lionix-int.com

Protein microarray for SIRS detection
University of Freiburg

In clinical diagnostics complex patterns of biomarkers such as cytokines, e.g. for Systemisches inflammatory Response-Syndrom (SIRS) diagnostic play a vital role. The mortality rate of SIRS patients is 10 %. Therefore, it is important to detect SIRS in a fast way. The SIRS relevant biomarkers (IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma and PCT) are low concentrated (pg/ml) in a sample. Hence, it is essential to develop a high sensitive biochip to detect these markers in parallel within a small sample volume (25 µl). Here, we present a microarray based assay with a high sensitivity for a fast diagnosis of SIRS on one chip. The results show the detection of all six biomarkers with a high sensitivity and broad dynamic measurement range in one chip. Especially for Procalcitonin, the dynamic measurement range is between five decades.

Autonomous Plug&Play Multi-Organ-Chips with Integrated Pumping and Sensing
Fraunhofer IWS

Multi-organ platforms have an enormous potential to lead to a paradigm shift in a multitude of research domains including drug development, toxicological screening, personalized medicine as well as disease modeling. We have developed a plug&play multi-organ system that combines a microfluidic base chip, featuring integrated micro pumps, valves, reservoirs and oxygenators, with ultra-compact microphysiological tissue modules, comprising various types of µ-tissues. Both systems can be interconnected with temporal flexibility, whereby pre-cultivation of the individual modules is possible. Since both the individual modules and the base chip are transparent, it is possible to monitor the µ-tissues as well as the flow architecture using (fluorescence) microscopy. The concept moreover allows the integration of multiple individual μ-tissue modules with the superordinate basis chip. This approach creates for the first time a fully customizable multi-organ-chip platform within a closed circulation system. For this purpose, defined fluidic interfaces have been developed and established.

A versatile microfluidic system to emulate human physiology applied to organ on a chip and 3D cell culture
Cherry Biotech

CubiX is a plug & play and versatile microfluidic platform to cultivate for long term (1 to 7 days) complex 3D biological models (spheroids, organ on a chip and tumor biopsies) in physiological conditions. We already internally developed and designed a series of microfluidic chips to support specific biological applications. In this presentation, we will focus on presenting the results obtained with skin and melanoma on a chip as well as kidney tumor on a chip. Both of these results were generated using either a proprietary microfluidic chip or commercially available solutions. A special emphasis will be given on the specific chip requirements related to each model to highlight the versatility of CubiX.

Nanocomposite based Biochip for detection of choline as an essential nutritive in food industry and as a biomarker for early diagnosis of neurological disorders
TU Bergakademie Freiberg

Choline is an essential nutrient that is crucial for normal cellular function and its deficiency has an impact on disorders such as liver disease, atherosclerosis and possibly neurological disorders and increases the risk of multiple cancers. Therefore, it is necessary to develop a fast and sensitive method for choline detection. The development of innovative biochips holds a great promise for the fabrication of smart and low-cost portable devices, which play an important role in future food industry, healthcare and diagnosis of mentioned diseases. Screen-printed electrodes (SPE) proved to be suitable for further modification and miniaturization, which make them more attractive and ideal for commercial development of biosensors. Consequently, modification of SPEs with hybrid composites based on carbon nanomaterials and ionic liquid with unique and highly attractive properties will provide the best candidates for choline oxidase immobilization and develop a choline-chip for choline detection in food samples or biological matrices.