Villingen-Schwenningen, Germany
Villingen-Schwenningen, Germany
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Leicht J.,Albert Ludwigs University of Freiburg | Amayreh M.,Albert Ludwigs University of Freiburg | Moranz C.,Albert Ludwigs University of Freiburg | Maurath D.,Albert Ludwigs University of Freiburg | And 2 more authors.
Digest of Technical Papers - IEEE International Solid-State Circuits Conference | Year: 2015

An electromagnetic vibration energy harvester (EMH) is an electromechanical mass-spring-damper system transducing electrical energy out of ambient vibrations. Resistive load matching [1] as well as maximum power point (MPP) AC-DC conversion [2] are highly suitable techniques for enhancing the electrical energy output of an EMH. The presented interface IC (Fig. 20.6.1) enables MPP AC-DC conversion by tracking the optimum conduction angle and by employing a hysteretic input voltage controlled inductive DC-DC boost converter. All control signals are derived from the harvester voltage itself. Thus, no additional sensor, harvester disconnection, or DC-DC converter duty-cycle control are needed. Additionally, the implemented voltage conditioning provides over-voltage protection (OVP) and application voltage regulation (VR). © 2015 IEEE.

Karle M.,HSG IMIT | Miwa J.,Albert Ludwigs University of Freiburg | Czilwik G.,HSG IMIT | Auwarter V.,Albert Ludwigs University of Freiburg | And 6 more authors.
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2010

This paper reports a novel microfluidic-chip based platform using "phase-transfer magnetophoresis" enabling continuous biomolecule processing. As an example we demonstrate for the first time continuous DNA extraction from cell lysate on a microfluidic chip. After mixing bacterial Escherichia coli culture with superparamagnetic bead suspension, lysis and binding buffers, DNA is released from cells and captured by the beads. These DNA carrying beads are continuously transported across the interfaces between co-flowing laminar streams of sample mixture, washing and elution buffer. Bead actuation is achieved by applying a time-varying magnetic field generated by a rotating permanent magnet. Flagella-like chains of magnetic beads are formed and transported along the microfluidic channels by an interplay of fluid drag and periodic magnetic entrapment. The turnover time for DNA extraction was approximately 2 minutes with a sample flow rate of 0.75 l s -1 and an eluate flow rate of 0.35 l s -1. DNA recovery was 147% (on average) compared to bead based batch-wise extraction in reference tubes within a dilution series experiment over 7 orders of magnitude. The novel platform is suggested for automation of various magnetic bead based applications that require continuous sample processing, e.g. continuous DNA extraction for flow-through PCR, capture and analysis of cells and continuous immunoassays. Potential applications are seen in the field of biological safety monitoring, bioprocess control, environmental monitoring, or epidemiological studies such as monitoring the load of antibiotic resistant bacteria in waste water from hospitals. © 2010 The Royal Society of Chemistry.

Lutz S.,HSG IMIT | Weber P.,HSG IMIT | Focke M.,Albert Ludwigs University of Freiburg | Faltin B.,Albert Ludwigs University of Freiburg | And 11 more authors.
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2010

For the first time we demonstrate a self-sufficient lab-on-a-foil system for the fully automated analysis of nucleic acids which is based on the recently available isothermal recombinase polymerase amplification (RPA). The system consists of a novel, foil-based centrifugal microfluidic cartridge including prestored liquid and dry reagents, and a commercially available centrifugal analyzer for incubation at 37 °C and real-time fluorescence detection. The system was characterized with an assay for the detection of the antibiotic resistance gene mecA of Staphylococcus aureus. The limit of detection was <10 copies and time-to-result was <20 min. Microfluidic unit operations comprise storage and release of liquid reagents, reconstitution of lyophilized reagents, aliquoting the sample into ≤30 independent reaction cavities, and mixing of reagents with the DNA samples. The foil-based cartridge was produced by blow-molding and sealed with a self-adhesive tape. The demonstrated system excels existing PCR based lab-on-a-chip platforms in terms of energy efficiency and time-to-result. Applications are suggested in the field of mobile point-of-care analysis, B-detection, or in combination with continuous monitoring systems. © 2010 The Royal Society of Chemistry.

Hoffmann J.,Albert Ludwigs University of Freiburg | Mark D.,HSG IMIT | Lutz S.,HSG IMIT | Zengerle R.,Albert Ludwigs University of Freiburg | Von Stetten F.,Albert Ludwigs University of Freiburg
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2010

Self-containing, ready-to-use cartridges are essential for mobile Lab-on-a-Chip (LoaC) systems intended for Point-of-Care (POC) use. Up to now, a common weak point in many LoaC developments is the need to dispense liquid reagents into the test cartridge before or during processing of the assay. To address this issue we have developed an efficient method for fusing liquid reagents into glass ampoules, which are then sealed into a centrifugally operated cartridge. For on-demand reagent release, the ampoules are disrupted through the flexible lid of the cartridge. Upon centrifugation, 98.7 L out of 100 L (CV = 2.5%) of the pre-stored contents are released into the microfluidic system. No liquid loss is observed for ethanol and H 2O stored for 300 days at room temperature. Frozen storage is possible without damage to the ampoules. Applicability of this concept is demonstrated by performing a LoaC integrated DNA extraction after 140 days of reagent pre-storage. DNA yield from 32 L of whole blood was up to 199 ng, which is 77% of an off-chip reference extraction. The presented approach allows the improvement of existing LoaC cartridges where pre-storage of liquid reagents was not implemented yet. © The Royal Society of Chemistry 2010.

Vosseler M.,HSG IMIT | Jugl M.,HSG IMIT | Zengerle R.,HSG IMIT | Zengerle R.,Albert Ludwigs University of Freiburg
Pharmaceutical Research | Year: 2011

Purpose: We present a smart intradermal interface suitable for skin-attached drug delivery devices. Our solution enables injections or infusions that are less invasive compared to subcutaneous injections and are leakage-free at the location of penetration. Methods: The intradermal interface is based on a 31-gauge cannula embedded in a slider, movable relative to a carrier plate that can easily be fixed onto the skin. By simply pushing the slider, the cannula is inserted into the dermis. Results: We performed injections and infusions with stained water and polyethylene glycol (PEG) solution in ex vivo pig skin. The sizes of coloured spots in the skin range from 3.5 mm 2 to 15.4 mm 2 for stained water depending on the infused volume. Infusing stained PEG solution resulted in stained tissue areas about one order of magnitude larger. One of three investigated leakage modes is unacceptable but can be reliably avoided by proper site selection. At low flow rates and at the beginning of an infusion an initial back pressure overshoot was identified. This effect was identified as the limiting parameter for the design of small programmable or intelligent devices based on micro actuators. Conclusions: With the proposed easy-to-use interface, intradermal injections and infusions can be performed reliably. Therefore, it is supposed to be an ideal and clinically relevant solution for self-administration of parenteral drugs in home care applications. © 2011 Springer Science+Business Media, LLC.

Focke M.,Albert Ludwigs University of Freiburg | Kosse D.,HSG IMIT | Muller C.,Albert Ludwigs University of Freiburg | Reinecke H.,Albert Ludwigs University of Freiburg | And 2 more authors.
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2010

This critical review is motivated by an increasing interest of the microfluidics community in developing complete Lab-on-a-Chip solutions based on thin and flexible films (Lab-on-a-Foil). Those implementations benefit from a broad range of fabrication methods that are partly adopted from well-established macroscale processes or are completely new and promising. In addition, thin and flexible foils enable various features like low thermal resistance for efficient thermocycling or integration of easily deformable chambers paving the way for new means of on-chip reagent storage or fluid transport. From an economical perspective, Lab-on-a-Foil systems are characterised by low material consumption and often low-cost materials which are attractive for cost-effective high-volume fabrication of self-contained disposable chips. The first part of this review focuses on available materials, fabrication processes and approaches for integration of microfluidic functions including liquid control and transport as well as storage and release of reagents. In the second part, an analysis of the state of Lab-on-a-Foil applications is provided with a special focus on nucleic acid analysis, immunoassays, cell-based assays and home care testing. We conclude that the Lab-on-a-Foil approach is very versatile and significantly expands the toolbox for the development of Lab-on-a-Chip solutions. © The Royal Society of Chemistry 2010.

Strohmeier O.,Albert Ludwigs University of Freiburg | Emperle A.,Albert Ludwigs University of Freiburg | Roth G.,Albert Ludwigs University of Freiburg | Mark D.,HSG IMIT | And 2 more authors.
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2013

Transportation of magnetic beads between different reagents plays a crucial role in many biological assays e.g. for purification of biomolecules or cells where the beads act as a mobile solid support. Therefore, usually a complex set-up either for fluidic processing or for manipulation of magnetic beads is required. To circumvent these drawbacks, we present a facile and automated method for the transportation of magnetic beads between multiple microfluidic chambers on a centrifugal microfluidic cartridge "LabDisk". The method excels by requiring only one stack of stationary permanent magnets, a specific microfluidic layout without actively controlled valves and a predefined frequency protocol for rotation of the LabDisk. Magnetic beads were transported through three fluidically separated chambers with a yield of 82.6% ± 3.6%. Bead based DNA purification from a dilution series of a Listeria innocua lysate and from a lambda phage DNA standard was demonstrated where the three chambers were used for binding, washing and elution of DNA. Recovery of L. innocua DNA was up to 68% ± 24% and for lambda phage DNA 43% ± 10% compared to manual reference purification in test tubes. Complete purification was conducted automatically within 12.5 min. Since all reagents can be preloaded onto the LabDisk prior to purification, no further hands-on steps are required during processing. Due to its modular and generic character, the presented method could also be adapted to other magnetic bead based assays e.g. to immunoassays or protein affinity purification, solely requiring the adjustment of number and volumes of the fluidic chambers. © The Royal Society of Chemistry.

Landenberger B.,Albert Ludwigs University of Freiburg | Hofemann H.,HSG IMIT | Wadle S.,Albert Ludwigs University of Freiburg | Rohrbach A.,Albert Ludwigs University of Freiburg
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2012

Optical gradient forces generated by fast steerable optical tweezers are highly effective for sorting small populations of cells in a lab-on-a-chip environment. The presented system can sort a broad range of different biological specimens by an automated optimisation of the tweezer path and velocity profile. The optimal grab positions for subsequent trap and cell displacements are estimated from the intensity of the bright field image, which is derived theoretically and proven experimentally. We exhibit rapid displacements of 2 μm small mitochondria, yeast cells, rod-shaped bacteria and 30 μm large protoplasts. Reliable sorting of yeast cells in a microfluidic chamber by both morphological criteria and by fluorescence emission is demonstrated. © 2012 The Royal Society of Chemistry.

Mark D.,HSG IMIT | Weber P.,Albert Ludwigs University of Freiburg | Lutz S.,HSG IMIT | Focke M.,Albert Ludwigs University of Freiburg | And 4 more authors.
Microfluidics and Nanofluidics | Year: 2011

We present a new method for aliquoting liquids on the centrifugal microfluidic platform. Aliquoting is an essential unit operation to perform multiple parallel assays ("geometric multiplexing") from one individual sample, such as genotyping by real-time polymerase chain reactions (PCR), or homogeneous immunoassay panels. Our method is a two-stage process with an initial metering phase and a subsequent transport phase initiated by switching a centrifugo-pneumatic valve. The method enables aliquoting liquids into completely separated reaction cavities. It includes precise metering that is independent on the volume of pre-stored reagents in the receiving cavities. It further excludes any cross-contamination between the receiving cavities. We characterized the performance for prototypes fabricated by three different technologies: micro-milling, thermoforming of foils, and injection molding. An initial volume of ~90 μl was split into 8 aliquots of 10 μl volume each plus a waste reservoir on a thermoformed foil disk resulting in a coefficient of variation (CV) of the metered volumes of 3.6%. A similar volume of ~105 μl was split into 16 aliquots of 6 μl volume each on micro-milled and injection-molded disks and the corresponding CVs were 2.8 and 2.2%, respectively. Thus, the compatibility of the novel aliquoting structure to the aforementioned prototyping and production technologies is demonstrated. Additionally, the important question of achievable volume precision of the aliquoting structure with respect to the production tolerances inherent to each of these production technologies is addressed experimentally and theoretically. The new method is amenable to low cost mass production, since it does not require any post-replication surface modifications like hydrophobic patches. © 2011 Springer-Verlag.

Campisi G.,University of Palermo | Giannola L.I.,University of Palermo | Florena A.M.,University of Palermo | De Caro V.,University of Palermo | And 4 more authors.
Journal of Controlled Release | Year: 2010

Naltrexone (NLX), an opioid antagonist, is widely used in the treatment of opiate addiction, alcoholism and smoking cessation. Its current peroral administration induces various adverse side effects and has limited efficacy since bioavailability and patient compliance are poor. The development of a long-acting drug delivery system of NLX may overcome the current drawbacks and help in the improvement of treatment of addiction. The primary endpoints of this study were: a) to compare the NLX bioavailability and pharmacokinetics after delivering a single transbuccal dose, released by a prototype of intraoral device, . versus an intravenous (I.V.) bolus of the same drug dose; b) to verify the functioning of a prototype of a new intraoral device . in vivo; c) to evaluate the permeation enhancement effect of iontophoresis; d) to assess any histomorphological changes in the buccal mucosa after transbuccal delivery. The system was tested on 6 pigs in a cross-over trial. Venous blood samples were drawn at a fixed timetable from the beginning of drug administration and analyzed for the presence of NLX, using an LC/MS/MS method. A punch biopsy was performed for histological analysis after the final experiment. The administration of I.V. NLX induced a sharp increase in blood levels after 5. min and then a steep decrease. In contrast, transmucosal delivery resulted in a gradual increase in blood NLX levels, reaching its peak after 90. min, followed by a slow decrease. After 6. h the blood levels of NLX delivered through the buccal mucosa were higher as compared to I.V. administration. No signs of flogosis or tissue damage were histologically highlighted. These results suggest that buccal delivery by an intraoral electronic device could potentially induce long-lasting, continuous and controlled blood levels of NLX, avoiding at the same time spikes of drug plasma levels typical of the I.V. administration route. © 2010 Elsevier B.V.

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