1. |
- Korten, Slobodanka, et al.
(author)
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Sample solution constraints on motor-driven diagnostic nanodevices
- 2013
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In: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 13:5, s. 866-876
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Journal article (peer-reviewed)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.
(author)
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Biocomputation Using Molecular Agents Moving in Microfluidic Channel Networks : An Alternative Platform for Information Technology
- 2022
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In: Cyber-Physical Systems : Intelligent Models and Algorithms - Intelligent Models and Algorithms. - Cham : Springer International Publishing. - 2198-4190 .- 2198-4182. - 9783030951160 - 9783030951153 ; 417, s. 15-27
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Book chapter (peer-reviewed)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.
(author)
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Fundamental energy cost of finite-time parallelizable computing
- 2023
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)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.
(author)
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Solving the subset sum problem with a nonideal biological computer
- 2021
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In: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 23:9
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Journal article (peer-reviewed)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.
(author)
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Design of network-based biocomputation circuits for the exact cover problem
- 2021
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In: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 23:8
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Journal article (peer-reviewed)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.
(author)
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Towards the application of cytoskeletal motor proteins in molecular detection and diagnostic devices
- 2010
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In: Current Opinion in Biotechnology. - : Elsevier BV. - 0958-1669 .- 1879-0429. ; 21:4, s. 477-488
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Journal article (peer-reviewed)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.
(author)
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Design and development of nanoimprint-enabled structures for molecular motor devices
- 2019
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In: Materials Research Express. - : IOP Publishing. - 2053-1591. ; 6:2
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Journal article (peer-reviewed)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.
(author)
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Nanolithographic Fabrication Technologies for Network-Based Biocomputation Devices
- 2023
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In: Materials. - : MDPI. - 1996-1944. ; 16:3
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Journal article (peer-reviewed)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.
(author)
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Parallel computation with molecular-motor-propelled agents in nanofabricated networks
- 2016
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In: 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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Journal article (peer-reviewed)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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11. |
- Reuther, Cordula, et al.
(author)
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Comparison of actin- and microtubule-based motility systems for application in functional nanodevices
- 2021
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In: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 23:7
-
Journal article (peer-reviewed)abstract
- Over the last 25 years, extensive progress has been made in developing a range of nanotechnological applications where cytoskeletal filaments and molecular motors are key elements. This includes novel, highly miniaturized lab on a chip systems for biosensing, nanoseparation etc but also new materials and parallel computation devices for solving otherwise intractable mathematical problems. For such approaches, both actin-based and microtubule-based cytoskeletal systems have been used. However, in accordance with their different cellular functions, actin filaments and microtubules have different properties and interaction kinetics with molecular motors. Therefore, the two systems obviously exhibit different advantages and encounter different challenges when exploited for applications. Specifically, the achievable filament velocities, the capability to guide filaments along nanopatterned tracks and the capability to attach and transport cargo differ between actin- and microtubule-based systems. Our aim here is to systematically elucidate these differences to facilitate design of new devices and optimize future developments. We first review the cellular functions and the fundamental physical and biochemical properties of actin filaments and microtubules. In this context we also consider their interaction with molecular motors and other regulatory proteins that are of relevance for applications. We then relate these properties to the advantages and challenges associated with the use of each of the motor-filament systems for different tasks. Finally, fundamental properties are considered in relation to some of the most interesting future development paths e.g. in biosensing and biocomputation.
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12. |
- Salhotra, Aseem, et al.
(author)
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Exploitation of Engineered Light-Switchable Myosin XI for Nanotechnological Applications
- 2023
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In: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 17:17, s. 17233-17244
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Journal article (peer-reviewed)abstract
- For certain nanotechnological applications of the contractile proteins actin and myosin, e.g., in biosensing and network-based biocomputation, it would be desirable to temporarily switch on/off motile function in parts of nanostructured devices, e.g., for sorting or programming. Myosin XI motor constructs, engineered with a light-switchable domain for switching actin motility between high and low velocities (light-sensitive motors (LSMs) below), are promising in this regard. However, they were not designed for use in nanotechnology, where longevity of operation, long shelf life, and selectivity of function in specific regions of a nanofabricated network are important. Here, we tested if these criteria can be fulfilled using existing LSM constructs or if additional developments will be required. We demonstrated extended shelf life as well as longevity of the actin-propelling function compared to those in previous studies. We also evaluated several approaches for selective immobilization with a maintained actin propelling function in dedicated nanochannels only. Whereas selectivity was feasible using certain nanopatterning combinations, the reproducibility was not satisfactory. In summary, the study demonstrates the feasibility of using engineered light-controlled myosin XI motors for myosin-driven actin transport in nanotechnological applications. Before use for, e.g., sorting or programming, additional work is however needed to achieve reproducibility of the nanofabrication and, further, optimize the motor properties.
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13. |
- Schroeder, Viktor, et al.
(author)
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Dynamic Guiding of Motor-Driven Microtubules on Electrically Heated, Smart Polymer Tracks
- 2013
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In: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 13:7, s. 3434-3438
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Journal article (peer-reviewed)abstract
- Biomolecular motor systems are attractive for future nanotechnological devices because they can replace nanofluidics by directed transport. However, the lack of methods to externally control motor-driven transport along complex paths limits their range of applications. Based on a thermo-responsive polymer, we developed a novel technique to guide microtubules propelled by kinesin-1 motors on a planar surface. Using electrically heated gold microstructures, the polymers were locally collapsed, creating dynamically switchable tracks that successfully guided microtubule movement.
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14. |
- Surendiran, Pradheebha, et al.
(author)
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Solving Exact Cover Instances with Molecular-Motor-Powered Network-Based Biocomputation
- 2022
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In: ACS Nanoscience Au. - : American Chemical Society (ACS). - 2694-2496 .- 2694-2496.
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Journal article (peer-reviewed)abstract
- Information processing by traditional, serial electronic processors consumes an ever-increasing part of the global electricity supply. An alternative, highly energy efficient, parallel computing paradigm is network-based biocomputation (NBC). In NBC a given combinatorial problem is encoded into a nanofabricated, modular network. Parallel exploration of the network by a very large number of independent molecular-motor-propelled protein filaments solves the encoded problem. Here we demonstrate a significant scale-up of this technology by solving four instances of Exact Cover, a nondeterministic polynomial time (NP) complete problem with applications in resource scheduling. The difficulty of the largest instances solved here is 128 times greater in comparison to the current state of the art for NBC.
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15. |
- van Delft, Falco C. M. J. M., et al.
(author)
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Roadmap for network-based biocomputation
- 2022
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In: Nano Futures. - : Institute of Physics Publishing (IOPP). - 2399-1984. ; 6:3
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Research review (peer-reviewed)abstract
- Network-based biocomputation (NBC) is an alternative, parallel computation approach that can potentially solve technologically important, combinatorial problems with much lower energy consumption than electronic processors. In NBC, a combinatorial problem is encoded into a physical, nanofabricated network. The problem is solved by biological agents (such as cytoskeletal filaments driven by molecular motors) that explore all possible pathways through the network in a massively parallel and highly energy-efficient manner. Whereas there is currently a rapid development in the size and types of problems that can be solved by NBC in proof-of-principle experiments, significant challenges still need to be overcome before NBC can be scaled up to fill a technological niche and reach an industrial level of manufacturing. Here, we provide a roadmap that identifies key scientific and technological needs. Specifically, we identify technology benchmarks that need to be reached or overcome, as well as possible solutions for how to achieve this. These include methods for large-scale production of nanoscale physical networks, for dynamically changing pathways in these networks, for encoding information onto biological agents, for single-molecule readout technology, as well as the integration of each of these approaches in large-scale production. We also introduce figures of merit that help analyze the scalability of various types of NBC networks and we use these to evaluate scenarios for major technological impact of NBC. A major milestone for NBC will be to increase parallelization to a point where the technology is able to outperform the current run time of electronic processors. If this can be achieved, NBC would offer a drastic advantage in terms of orders of magnitude lower energy consumption. In addition, the fundamentally different architecture of NBC compared to conventional electronic computers may make it more advantageous to use NBC to solve certain types of problems and instances that are easy to parallelize. To achieve these objectives, the purpose of this roadmap is to identify pre-competitive research domains, enabling cooperation between industry, institutes, and universities for sharing research and development efforts and reducing development cost and time.
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16. |
- Zhu, Jingyuan, et al.
(author)
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Physical requirements for scaling up network-based biocomputation
- 2021
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In: New Journal of Physics. - : Institute of Physics (IOP). - 1367-2630. ; 23:10
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Journal article (peer-reviewed)abstract
- The high energy consumption of electronic data processors, together with physical challenges limiting their further improvement, has triggered intensive interest in alternative computation paradigms. Here we focus on network-based biocomputation (NBC), a massively parallel approach where computational problems are encoded in planar networks implemented with nanoscale channels. These networks are explored by biological agents, such as biological molecular motor systems and bacteria, benefitting from their energy efficiency and availability in large numbers. We analyse and define the fundamental requirements that need to be fulfilled to scale up NBC computers to become a viable technology that can solve large NP-complete problem instances faster or with less energy consumption than electronic computers. Our work can serve as a guide for further efforts to contribute to elements of future NBC devices, and as the theoretical basis for a detailed NBC roadmap.
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17. |
- Zhu, Jingyuan, et al.
(author)
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Solving the 3-Satisfiability Problem Using Network-Based Biocomputation
- 2022
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In: Advanced Intelligent Systems. - : John Wiley & Sons. - 2640-4567. ; 4:12
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Journal article (peer-reviewed)abstract
- The 3-satisfiability Problem (3-SAT) is a demanding combinatorial problem that is of central importance among the nondeterministic polynomial (NP) complete problems, with applications in circuit design, artificial intelligence, and logistics. Even with optimized algorithms, the solution space that needs to be explored grows exponentially with the increasing size of 3-SAT instances. Thus, large 3-SAT instances require excessive amounts of energy to solve with serial electronic computers. Network-based biocomputation (NBC) is a parallel computation approach with drastically reduced energy consumption. NBC uses biomolecular motors to propel cytoskeletal filaments through nanofabricated networks that encode mathematical problems. By stochastically exploring possible paths through the networks, the cytoskeletal filaments find possible solutions. However, to date, no NBC algorithm for 3-SAT has been available. Herein, an algorithm that converts 3-SAT into an NBC-compatible network format is reported and four small 3-SAT instances (with up to three variables and five clauses) using the actin-myosin biomolecular motor system are experimentally solved. Because practical polynomial conversions to 3-SAT exist for many important NP complete problems, the result opens the door to enable NBC to solve small instances of a wide range of problems.
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