| 1. |
- Korten, Slobodanka, et al.
(författare)
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Sample solution constraints on motor-driven diagnostic nanodevices
- 2013
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Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 13:5, s. 866-876
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Tidskriftsartikel (refereegranskat)abstract
- The last decade has seen appreciable advancements in efforts towards increased portability of lab-on-a-chip devices by substituting microfluidics with molecular motor-based transportation. As of now, first proof-of-principle devices have analyzed protein mixtures of low complexity, such as target protein molecules in buffer solutions optimized for molecular motor performance. However, in a diagnostic workup, lab-on-a-chip devices need to be compatible with complex biological samples. While it has been shown that such samples do not interfere with crucial steps in molecular diagnostics (for example antibody-antigen recognition), their effect on molecular motors is unknown. This critical and long overlooked issue is addressed here. In particular, we studied the effects of blood, cell lysates and solutions containing genomic DNA extracts on actomyosin and kinesin-microtubule-based transport, the two biomolecular motor systems that are most promising for lab-on-a-chip applications. We found that motor function is well preserved at defined dilutions of most of the investigated biological samples and demonstrated a molecular motor-driven label-free blood type test. Our results support the feasibility of molecular-motor driven nanodevices for diagnostic point-of-care applications and also demonstrate important constraints imposed by sample composition and device design that apply both to kinesin-microtubule and actomyosin driven applications.
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| 2. |
- Blaudeck, Thomas, et al.
(författare)
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Biocomputation Using Molecular Agents Moving in Microfluidic Channel Networks : An Alternative Platform for Information Technology
- 2022
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Ingår i: Cyber-Physical Systems : Intelligent Models and Algorithms - Intelligent Models and Algorithms. - Cham : Springer International Publishing. - 2198-4190 .- 2198-4182. - 9783030951153 - 9783030951160 ; 417, s. 15-27
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Bokkapitel (refereegranskat)abstract
- Deficiencies in software or computer chips cause computers or smartphones to crash and allow hackers to steal passwords. Automated test procedures could avoid these problems. However, the computing power and cooling requirements of conventional computers increase exponentially with the size of the problem, so that the technological limits for solving these problems will soon be reached. The EU project Bio4Comp aims to develop concepts for a bio-computer to help overcome these two main problems. Compared to conventional computers, computers based on biological molecular motors only consume a fraction of the energy per arithmetic operation and scale very well for problems that can be parallelized (“multitasking”). In this article, the topic network-based biocomputation (NBC) i.e. computing with biological molecules as agents that are driven by molecular motors in microfluidic networks, is presented as an alternative approach to computing, data processing, and information technology.
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| 3. |
- Konopik, Michael, et al.
(författare)
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Fundamental energy cost of finite-time parallelizable computing
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The fundamental energy cost of irreversible computing is given by the Landauer bound of kTln 2 /bit, where k is the Boltzmann constant and T is the temperature in Kelvin. However, this limit is only achievable for infinite-time processes. We here determine the fundamental energy cost of finite-time parallelizable computing within the framework of nonequilibrium thermodynamics. We apply these results to quantify the energetic advantage of parallel computing over serial computing. We find that the energy cost per operation of a parallel computer can be kept close to the Landauer limit even for large problem sizes, whereas that of a serial computer fundamentally diverges. We analyze, in particular, the effects of different degrees of parallelization and amounts of overhead, as well as the influence of non-ideal electronic hardware. We further discuss their implications in the context of current technology. Our findings provide a physical basis for the design of energy-efficient computers.
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| 4. |
- Konopik, Michael, et al.
(författare)
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Solving the subset sum problem with a nonideal biological computer
- 2021
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 23:9
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Tidskriftsartikel (refereegranskat)abstract
- We consider the solution of the subset sum problem based on a parallel computer consisting of self-propelled biological agents moving in a nanostructured network that encodes the computing task in its geometry. We develop an approximate analytical method to analyze the effects of small errors in the nonideal junctions composing the computing network by using a Gaussian confidence interval approximation of the multinomial distribution. We concretely evaluate the probability distribution for error-induced paths and determine the minimal number of agents required to obtain a proper solution. We finally validate our theoretical results with exact numerical simulations of the subset sum problem for different set sizes and error probabilities, and discuss the scalability of the nonideal problem using realistic experimental error probabilities.
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| 5. |
- Korten, Till, et al.
(författare)
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Design of network-based biocomputation circuits for the exact cover problem
- 2021
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 23:8
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Tidskriftsartikel (refereegranskat)abstract
- Exact cover is a non-deterministic polynomial time (NP)-complete problem that is central to optimization challenges such as airline fleet planning and allocation of cloud computing resources. Solving exact cover requires the exploration of a solution space that increases exponentially with cardinality. Hence, it is time- and energy consuming to solve large instances of exact cover by serial computers. One approach to address these challenges is to utilize the inherent parallelism and high energy efficiency of biological systems in a network-based biocomputation (NBC) device. NBC is a parallel computing paradigm in which a given combinatorial problem is encoded into a graphical, modular network that is embedded in a nanofabricated planar device. The network is then explored in parallel using a large number of biological agents, such as molecular-motor-propelled protein filaments. The answer to the combinatorial problem can then be inferred by measuring the positions through which the agents exit the network. Here, we (i) show how exact cover can be encoded and solved in an NBC device, (ii) define a formalization that allows to prove the correctness of our approach and provides a mathematical basis for further studying NBC, and (iii) demonstrate various optimizations that significantly improve the computing performance of NBC. This work lays the ground for fabricating and scaling NBC devices to solve significantly larger combinatorial problems than have been demonstrated so far.
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| 6. |
- Korten, Till, et al.
(författare)
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Towards the application of cytoskeletal motor proteins in molecular detection and diagnostic devices
- 2010
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Ingår i: Current Opinion in Biotechnology. - : Elsevier BV. - 0958-1669 .- 1879-0429. ; 21:4, s. 477-488
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Tidskriftsartikel (refereegranskat)abstract
- Over the past ten years, great advancements have been made towards using biomolecular motors for nanotechnological applications. In particular, devices using cytoskeletal motor proteins for molecular transport are maturing. First efforts towards designing such devices used motor proteins attached to micro-structured substrates for the directed transport of microtubules and actin filaments. Soon thereafter, the specific capture, transport and detection of target analytes like viruses were demonstrated. Recently, spatial guiding of the gliding filaments was added to increase the sensitivity of detection and allow parallelization. Whereas molecular motor powered devices have not yet demonstrated performance beyond the level of existing detection techniques, the potential is great: Replacing microfluidics with transport powered by molecular motors allows integration of the energy source (ATP) into the assay solution. This opens up the opportunity to design highly integrated, miniaturized, autonomous detection devices. Such devices, in turn, may allow fast and cheap on-site diagnosis of diseases and detection of environmental pathogens and toxins.
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| 7. |
- Lindberg, Frida W., et al.
(författare)
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Design and development of nanoimprint-enabled structures for molecular motor devices
- 2019
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Ingår i: Materials Research Express. - : IOP Publishing. - 2053-1591. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Devices based on molecular motor-driven cytoskeletal filaments, e.g., actin filaments, have been developed both for biosensing and biocomputational applications. Commonly, these devices require nanoscaled tracks for guidance of the actin filaments which has limited the patterning technique to electron beam lithography. Thus, large scale systems become intractable to fabricate at a high throughput within a reasonable time-frame. We have studied the possibility to fabricate molecular motor-based devices using the high throughput, high resolution technique of nanoimprint lithography. Molecular motor-based devices require wide open regions (loading zones) to allow filaments to land for later propulsion into the nanoscale tracks. Such open zones are challenging to fabricate using nanoimprint lithography due to the large amount of material displaced in the process. We found that this challenge can be overcome by introducing nanoscaled pillars inside the loading zones, into which material can be displaced during imprint. By optimising the resist thickness, we were able to decrease the amount of material displaced without suffering from insufficient filling of the stamp. Furthermore, simulations suggest that the shape and positioning of the pillars can be used to tailor the overall cytoskeletal filament transportation direction and behaviour. This is a potentially promising design feature for future applications that however, requires further optimisations before experimental realisation.
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| 8. |
- Meinecke, Christoph R., et al.
(författare)
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Nanolithographic Fabrication Technologies for Network-Based Biocomputation Devices
- 2023
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Ingår i: Materials. - : MDPI. - 1996-1944. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- Network-based biocomputation (NBC) relies on accurate guiding of biological agents through nanofabricated channels produced by lithographic patterning techniques. Here, we report on the large-scale, wafer-level fabrication of optimized microfluidic channel networks (NBC networks) using electron-beam lithography as the central method. To confirm the functionality of these NBC networks, we solve an instance of a classical non-deterministic-polynomial-time complete ("NP-complete") problem, the subset-sum problem. The propagation of cytoskeletal filaments, e.g., molecular motor-propelled microtubules or actin filaments, relies on a combination of physical and chemical guiding along the channels of an NBC network. Therefore, the nanofabricated channels have to fulfill specific requirements with respect to the biochemical treatment as well as the geometrical confienement, with walls surrounding the floors where functional molecular motors attach. We show how the material stack used for the NBC network can be optimized so that the motor-proteins attach themselves in functional form only to the floor of the channels. Further optimizations in the nanolithographic fabrication processes greatly improve the smoothness of the channel walls and floors, while optimizations in motor-protein expression and purification improve the activity of the motor proteins, and therefore, the motility of the filaments. Together, these optimizations provide us with the opportunity to increase the reliability of our NBC devices. In the future, we expect that these nanolithographic fabrication technologies will enable production of large-scale NBC networks intended to solve substantially larger combinatorial problems that are currently outside the capabilities of conventional software-based solvers.
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| 9. |
- Nicolau, Dan V., Jr., et al.
(författare)
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Parallel computation with molecular-motor-propelled agents in nanofabricated networks
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:10, s. 2591-2596
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Tidskriftsartikel (refereegranskat)abstract
- The combinatorial nature of many important mathematical problems, including nondeterministic-polynomial-time (NP)-complete problems, places a severe limitation on the problem size that can be solved with conventional, sequentially operating electronic computers. There have been significant efforts in conceiving parallel-computation approaches in the past, for example: DNA computation, quantum computation, and microfluidics-based computation. However, these approaches have not proven, so far, to be scalable and practical from a fabrication and operational perspective. Here, we report the foundations of an alternative parallel-computation system in which a given combinatorial problem is encoded into a graphical, modular network that is embedded in a nanofabricated planar device. Exploring the network in a parallel fashion using a large number of independent, molecular-motor-propelled agents then solves the mathematical problem. This approach uses orders of magnitude less energy than conventional computers, thus addressing issues related to power consumption and heat dissipation. We provide a proof-of-concept demonstration of such a device by solving, in a parallel fashion, the small instance {2, 5, 9} of the subset sum problem, which is a benchmark NP-complete problem. Finally, we discuss the technical advances necessary to make our system scalable with presently available technology.
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| 10. |
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