Thomas Maeke

Microfabrication of a BioModule composed of microfluidics and digitally controlled microelectrodes for processing biomolecules

This work focuses on the development of an online programmable microfluidic bioprocessing unit (BioModule) using digital logic microelectrodes for rapid pipelined selection and transfer of deoxyribonucleic acid (DNA) molecules and other charged biopolymers. The design and construction technique for this hybrid programmable biopolymer processing device is presented along with the first proof of principle functionality. The electronically controlled collection, separation and channel transfer of the biomolecules is monitored by a sensitive fluorescence set-up. This hybrid reconfigurable architecture couples electronic and biomolecular information processing via a single module combination of fluidics and electronics and opens new fields of applications not only in DNA computing and molecular diagnostics but also in applications of combinatorial chemistry and lab-on-a-chip biotechnology to the drug discovery process. Fundamentals of the design and silicon–polydimethylsiloxane (PDMS)-based construction of these electronic microfluidic devices and their functions are described as well as the experimental results.

An Electronically Controlled Microfluidic Approach towards Artificial Cells

This work focuses on the application of on-line programmable microfluidic bioprocessing as a complementation vehicle towards the design of artificial cells. The electronically controlled collection, separation and channel transfer of the biomolecules are monitored by a sensitive fluorescence setup. Two different physical effects, electrophoresis and electroosmotic flow, are used to allow for a detailed micro-control of fluids in micro-reaction environments. A combination of these two basic electronically controlled input reaction chambers makes combinatorial fluidic networks and indefinitely sustained biochemical or chemical reaction networks feasible. Experimental data showing the power of this approach is presented. Not only does this processing power pave the way towards the development of artificial cells (using a technology to complement not yet established autonomous metabolic or replication capabilities) but it also opens up new processes for applications of combinatorial chemistry and lab-on-a-chip biotechnology to drug discovery and diagnosis.

EVOLVING INDUCTIVE GENERALIZATION VIA GENETIC SELF-ASSEMBLY

We propose that genetic encoding of self-assembling components greatly enhances the evolution of complex systems and provides an efficient platform for inductive generalization, i.e. the inductive derivation of a solution to a problem with a potentially infinite number of instances from a limited set of test examples. We exemplify this in simulations by evolving scalable circuitry for several problems. One of them, digital multiplication, has been intensively studied in recent years, where hitherto the evolutionary design of only specific small multipliers was achieved. The fact that this and other problems can be solved in full generality employing self-assembly sheds light on the evolutionary role of self-assembly in biology and is of relevance for the design of complex systems in nano- and bionanotechnology.

Field programmable chemistry: Integrated chemical and electronic processing of informational molecules towards electronic chemical cells

The topic addressed is that of combining self-constructing chemical systems with electronic computation to form unconventional embedded computation systems performing complex nano-scale chemical tasks autonomously. The hybrid route to complex programmable chemistry, and ultimately to artificial cells based on novel chemistry, requires a solution of the two-way massively parallel coupling problem between digital electronics and chemical systems. We present a chemical microprocessor technology and show how it can provide a generic programmable platform for complex molecular processing tasks in Field Programmable Chemistry, including steps towards the grand challenge of constructing the first electronic chemical cells. Field programmable chemistry employs a massively parallel field of electrodes, under the control of latched voltages, which are used to modulate chemical activity. We implement such a field programmable chemistry which links to chemistry in rather generic, two-phase microfluidic channel networks that are separated into weakly coupled domains. Electric fields, produced by the high-density array of electrodes embedded in the channel floors, are used to control the transport of chemicals across the hydrodynamic barriers separating domains. In the absence of electric fields, separate microfluidic domains are essentially independent with only slow diffusional interchange of chemicals. Electronic chemical cells, based on chemical microprocessors, exploit a spatially resolved sandwich structure in which the electronic and chemical systems are locally coupled through homogeneous fine-grained actuation and sensor networks and play symmetric and complementary roles. We describe how these systems are fabricated, experimentally test their basic functionality, simulate their potential (e.g. for feed forward digital electrophoretic (FFDE) separation) and outline the application to building electronic chemical cells.

Molecular systems on-chip (MSoC) steps forward for programmable biosystems

This work describes online programmable microfluidic bioprocessing units using digital logic microelectrodes for rapid pipelined translocation of DNA molecules and other charged biopolymers as well as nanoparticles. Fundamentals of the design and fabrication technique both the silicon-PDMS and a polyimide-PDMS based construction (a new method based on conventional printed circuit board materials) of these electronic microfluidic devices and their functions are described as well as the experimental results along with the first proof of principle functionality. The electronically controlled collection, separation and channel transfer of the biomolecules and nanosized beads are monitored by a sen-sitive fluorescence setup and controlled by a custom-designed hardware for camera-control and feature selection. This hybrid reconfigurable architecture couples electronic and biomolecular information processing via a single module combination of fluidics and electronics and opens new fields of applications not only in DNA computing and molecular diagnostics but also in applications of combinatorial chemistry and lab-on-a-chip biotechnology to the drug discovery process.

NGEN: A Massively Parallel Reconfigurable Computer for Biological Simulation: Towards a Self-Organizing Computer

NGEN is a flexible computer hardware for rapid custom-circuit simulation of fine grained physical processes via a massively parallel architecture. It is optimized to implement dataflow architectures and systolic algorithms for large problems. High speed distributed SRAM on the chip-to chip interconnect enables a transparent extension of problem size beyond the limits posed by the number of available processors. For simulated evolution tasks for example, this takes the effective population sizes up into the range of millions of strings without computational bottlenecks. Using FPGA technology, multiple processors per chip may be configured down to the level of individual gates if need be. 144 agent FPGAs are grouped in blocks of 4 and connected with one another via one of several possible broad band electronic frontplanes (36 channels per chip) which implement 2D, 3D or higher geometries. The communication of the parallel computation with a UNIX host workstation via VME-bus is mediated also by configurable interface FPGAs allowing problem specific communication needs to be respected. A separate 100 Mhz clock card frees the machine from the 16 MHz VME clock and allows designs to run at their optimum speed. Configuration files may be downloaded in series or parallel from the host workstation in less than a second. They may be created by user programs or commercial schematic entry or VHDL products. A run-time library for writing simulations in C which use the configurable hardware has been completed including a graphical interface allowing parallel symbolic debugging and display. The machine is a logical consequence of the shift of programming effort to effective communication in massively parallel applications. Its flexible structure also admits applications to real-time intelligent data acquistion tasks.

Spatially resolved simulations of membrane reactions and dynamics: Multipolar reaction DPD

Biophysical chemistry of mesoscale systems and quantitative modeling in systems biology now require a simulation methodology unifying chemical reaction kinetics with essential collective physics. This will enable the study of the collective dynamics of complex chemical and structural systems in a spatially resolved manner with a combinatorially complex variety of different system constituents. In order to allow a direct link-up with experimental data (e.g. high-throughput fluorescence images) the simulations must be constructed locally, i.e. mesoscale phenomena have to emerge from local composition and interactions that can be extracted from experimental data. Under suitable conditions, the simulation of such local interactions must lead to processes such as vesicle budding, transport of membrane-bounded compartments and protein sorting, all of which result from a sophisticated interplay between chemical and mechanical processes and require the link-up of different length scales. In this work, we show that introducing multipolar interactions between particles in dissipative particle dynamics (DPD) leads to extended membrane structures emerging in a self-organized manner and exhibiting the necessary mechanical stability for transport, correct scaling behavior, and membrane fluidity so as to provide a two-dimensional self-organizing dynamic reaction environment for kinetic studies in the context of cell biology.

A CMOS 16k microelectrode array as docking platform for autonomous microsystems

A microelectrode array (MEA) system based on an active pixel architecture is presented, which has been fabricated in 180nm CMOS technology, featuring 16384 active pixels (36×36×m2). Each pixel consists of 4 electrodes (each 12×12μm2): two (connected together) for actuating and two for differential sensing. The pixels are arranged in a square grid of 4.6×4.6mm2. Schematic and layout of the MEA were generated by a SKILL script. The MEA is designed as a docking platform for charging and communicating with autonomous microsystems, called lablets, as well as combinatorial electrochemistry. Experiments in aqueous electrolyte solutions confirm the functionality of the MEA to fulfill the requirements of a flexible configuration of the pixels and the possibility of charging microsystems in a solution.

Corrigendum to: “Field programmable chemistry: Integrated chemical and electronic processing of informational molecules towards electronic chemical cells” [Biosystems, (2012) 109: 2–17]

The final second part of the acknowledgement section for the above said article was: We wish to acknowledge financial support from the Europen Commission FP7 Program in ISTFET (projects ECCell, #222422, and MATCHIT, #249032), and networking support from the COST network in Systems Chemistry (CM0703), from the Interfacial Systems Chemistry Initiative IFSC at the Ruhr-Universitat Bochum, from the European Center for Living Technology, Venice, Italy and in the EU Coordination Action COBRA (#270371) on BioChem-IT. The authors regret that the CADMAD project was not acknowledged in the publication. The final second part of the acknowledgement section for the above said article is: We wish to acknowledge financial support from the Europen Commission FP7 Program in ISTFET (projects ECCell, #222422, MATCHIT, #249032 and CADMAD, #265505), and networking support from the COST network in Systems Chemistry (CM0703), from the Interfacial Systems Chemistry Initiative IFSC at the Ruhr-Universitat Bochum, from the European Center for Living Technology, Venice, Italy and in the EU Coordination Action COBRA (#270371) on BioChem-IT. The authors would like to apologise for any inconvenience caused in making this correction.

Construction of an integrated biomodule composed of microfluidics and digitally controlled microelectrodes for processing biomolecules

This work focuses on the development of an online programmable microfluidic bioprocessing unit (BioModule) using digital logic microelectrodes for rapid pipelined selection and transfer of DNA molecules and other charged biopolymers. The design and construction technique for this hybrid programmable biopolymer processing device is presented along with the first proof of principle functionality. The electronically controlled collection, separation and channel transfer of the biomolecules is monitored by a sensitive fluorescence setup. This hybrid reconfigurable architecture couples electronic and biomolecular information processing via a single module combination of fluidics and electronics and opens new fields of applications not only in DNA computing and molecular diagnostics but also in applications of combinatorial chemistry and lab-on-a-chip biotechnology to the drug discovery process. Fundamentals of the design and silicon-PDMS-based construction of these electronic microfluidic devices and their functions are described as well as the experimental results.