154 research outputs found

    Volume Management for Pin-Constrained Continuous-Flow Microfluidic Biochips

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    Strengthening Privacy and Data Security in Biomedical Microelectromechanical Systems by IoT Communication Security and Protection in Smart Healthcare.

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    Biomedical Microelectromechanical Systems (BioMEMS) serve as a crucial catalyst in enhancing IoT communication security and safeguarding smart healthcare systems. Situated at the nexus of advanced technology and healthcare, BioMEMS are instrumental in pioneering personalized diagnostics, monitoring, and therapeutic applications. Nonetheless, this integration brings forth a complex array of security and privacy challenges intrinsic to IoT communications within smart healthcare ecosystems, demanding comprehensive scrutiny. In this manuscript, we embark on an extensive analysis of the intricate security terrain associated with IoT communications in the realm of BioMEMS, addressing a spectrum of vulnerabilities that spans cyber threats, data manipulation, and interception of communications. The integration of real-world case studies serves to illuminate the direct repercussions of security breaches within smart healthcare systems, highlighting the imperative to safeguard both patient safety and the integrity of medical data. We delve into a suite of security solutions, encompassing rigorous authentication processes, data encryption, designs resistant to attacks, and continuous monitoring mechanisms, all tailored to fortify BioMEMS in the face of ever-evolving threats within smart healthcare environments. Furthermore, the paper underscores the vital role of ethical and regulatory considerations, emphasizing the need to uphold patient autonomy, ensure the confidentiality of data, and maintain equitable access to healthcare in the context of IoT communication security. Looking forward, we explore the impending landscape of BioMEMS security as it intertwines with emerging technologies such as AI-driven diagnostics, quantum computing, and genomic integration, anticipating potential challenges and strategizing for the future. In doing so, this paper highlights the paramount importance of adopting an integrated approach that seamlessly blends technological innovation, ethical foresight, and collaborative ingenuity, thereby steering BioMEMS towards a secure and resilient future within smart healthcare systems, in the ambit of IoT communication security and protection

    Static mode microfluidic cantilevers for detection of waterborne pathogens

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    This paper reports on the first demonstration of polymeric microfluidic cantilever sensors. Microcantilever sensors, magnetic beads, and microfluidic technology have been combined to create a polymer based biosensor. Using cheap materials like polyimide, a simple fabrication method has been developed to produce cantilevers with an embedded microfluidic channel. The advantage of this approach is that the addition of a microfluidic channel enables the analysis of smaller volumes and increases the capture efficiency in applications detecting rare analytes. As a proof of principle the system has been applied for the detection of the waterborne protozoan parasite Cryptosporidium, achieving sensitivity comparable to QCM, whereas a previous set-up without the microfluidic channel was unable to detect the parasite

    Usability and Applicability of Microfluidic Cell Culture Systems

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    Evolvable Smartphone-Based Platforms for Point-Of-Care In-Vitro Diagnostics Applications

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    The association of smart mobile devices and lab-on-chip technologies offers unprecedented opportunities for the emergence of direct-to-consumer in vitro medical diagnostics applications. Despite their clear transformative potential, obstacles remain to the large-scale disruption and long-lasting success of these systems in the consumer market. For instance, the increasing level of complexity of instrumented lab-on-chip devices, coupled to the sporadic nature of point-of-care testing, threatens the viability of a business model mainly relying on disposable/consumable lab-on-chips. We argued recently that system evolvability, defined as the design characteristic that facilitates more manageable transitions between system generations via the modification of an inherited design, can help remedy these limitations. In this paper, we discuss how platform-based design can constitute a formal entry point to the design and implementation of evolvable smart device/lab-on-chip systems. We present both a hardware/software design framework and the implementation details of a platform prototype enabling at this stage the interfacing of several lab-on-chip variants relying on current- or impedance-based biosensors. Our findings suggest that several change-enabling mechanisms implemented in the higher abstraction software layers of the system can promote evolvability, together with the design of change-absorbing hardware/software interfaces. Our platform architecture is based on a mobile software application programming interface coupled to a modular hardware accessory. It allows the specification of lab-on-chip operation and post-analytic functions at the mobile software layer. We demonstrate its potential by operating a simple lab-on-chip to carry out the detection of dopamine using various electroanalytical methods

    MakerFluidics: low cost microfluidics for synthetic biology

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    Recent advancements in multilayer, multicellular, genetic logic circuits often rely on manual intervention throughout the computation cycle and orthogonal signals for each chemical “wire”. These constraints can prevent genetic circuits from scaling. Microfluidic devices can be used to mitigate these constraints. However, continuous-flow microfluidics are largely designed through artisanal processes involving hand-drawing features and accomplishing design rule checks visually: processes that are also inextensible. Additionally, continuous-flow microfluidic routing is only a consideration during chip design and, once built, the routing structure becomes “frozen in silicon,” or for many microfluidic chips “frozen in polydimethylsiloxane (PDMS)”; any changes to fluid routing often require an entirely new device and control infrastructure. The cost of fabricating and controlling a new device is high in terms of time and money; attempts to reduce one cost measure are, generally, paid through increases in the other. This work has three main thrusts: to create a microfluidic fabrication framework, called MakerFluidics, that lowers the barrier to entry for designing and fabricating microfluidics in a manner amenable to automation; to prove this methodology can design, fabricate, and control complex and novel microfluidic devices; and to demonstrate the methodology can be used to solve biologically-relevant problems. Utilizing accessible technologies, rapid prototyping, and scalable design practices, the MakerFluidics framework has demonstrated its ability to design, fabricate and control novel, complex and scalable microfludic devices. This was proven through the development of a reconfigurable, continuous-flow routing fabric driven by a modular, scalable primitive called a transposer. In addition to creating complex microfluidic networks, MakerFluidics was deployed in support of cutting-edge, application-focused research at the Charles Stark Draper Laboratory. Informed by a design of experiments approach using the parametric rapid prototyping capabilities made possible by MakerFluidics, a plastic blood--bacteria separation device was optimized, demonstrating that the new device geometry can separate bacteria from blood while operating at 275% greater flow rate as well as reduce the power requirement by 82% for equivalent separation performance when compared to the state of the art. Ultimately, MakerFluidics demonstrated the ability to design, fabricate, and control complex and practical microfluidic devices while lowering the barrier to entry to continuous-flow microfluidics, thus democratizing cutting edge technology beyond a handful of well-resourced and specialized labs

    A housekeeping prognostic health management framework for microfluidic systems

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    Micro-Electro-Mechanical Systems (MEMS) and Microfluidics are becoming popular solutions for sensing, diagnostics and control applications. Reliability and validation of function is of increasing importance in the majority of these applications. On-line testing strategies for these devices have the potential to provide real-time condition monitoring information. It is shown that this information can be used to diagnose and prognose the health of the device. This information can also be used to provide an early failure warning system by predicting the remaining useful life. Diagnostic and prognostic outcomes can also be leveraged to improve the reliability, dependability and availability of these devices. This work has delivered a methodology for a “lightweight” prognostics solution for a microfluidic device based on real-time diagnostics. An oscillation based test methodology is used to extract diagnostic information that is processed using a Linear Discriminant Analysis based classifier. This enables the identification of current health based on pre-defined health levels. As the deteriorating device is periodically classified, the rate at which the device degrades is used to predict the devices remaining useful life

    Putting Synthesis into Biology: A Viral View of Genetic Engineering through De Novo Gene and Genome Synthesis

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    SummaryThe rapid improvements in DNA synthesis technology hold the potential to revolutionize biosciences in the near future. Traditional genetic engineering methods are template dependent and make extensive but laborious use of site-directed mutagenesis to explore the impact of small variations on an existing sequence “theme.” De novo gene and genome synthesis frees the investigator from the restrictions of the pre-existing template and allows for the rational design of any conceivable new sequence theme.Viruses, being among the simplest replicating entities, have been at the forefront of the advancing biosciences since the dawn of molecular biology. Viral genomes, especially those of RNA viruses, are relatively short, often less than 10,000 bases long, making them amenable to whole genome synthesis with the currently available technology. For this reason viruses are once again poised to lead the way in the budding field of synthetic biology—for better or worse

    Optimisation of microfluidic experiments for model calibration of a synthetic promoter in S. cerevisiae

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    This thesis explores, implements, and examines the methods to improve the efficiency of model calibration experiments for synthetic biological circuits in three aspects: experimental technique, optimal experimental design (OED), and automatic experiment abnormality screening (AEAS). Moreover, to obtain a specific benchmark that provides clear-cut evidence of the utility, an integrated synthetic orthogonal promoter in yeast (S. cerevisiae) and a corresponded model is selected as the experiment object. This work first focuses on the “wet-lab” part of the experiment. It verifies the theoretical benefit of adopting microfluidic technique by carrying out a series of in-vivo experiments on a developed automatic microfluidic experimental platform. Statistical analysis shows that compared to the models calibrated with flow-cytometry data (a representative traditional experimental technique), the models based on microfluidic data of the same experiment time give significantly more accurate behaviour predictions of never-encountered stimuli patterns. In other words, compare to flow-cytometry experiments, microfluidics can obtain models of the required prediction accuracy within less experiment time. The next aspect is to optimise the “dry-lab” part, i.e., the design of experiments and data processing. Previous works have proven that the informativeness of experiments can be improved by optimising the input design (OID). However, the amount of work and the time cost of the current OID approach rise dramatically with large and complex synthetic networks and mathematical models. To address this problem, this thesis introduces the parameter clustering analysis and visualisation (PCAV) to speed up the OID by narrowing down the parameters of interest. For the first time, this thesis proposes a parameter clustering algorithm based on the Fisher information matrix (FIMPC). Practices with in-silico experiments on the benchmarking promoter show that PCAV reduces the complexity of OID and provides a new way to explore the connections between parameters. Moreover, the analysis shows that experiments with FIMPC-based OID lead to significantly more accurate parameter estimations than the current OID approach. Automatic abnormality screening is the third aspect. For microfluidic experiments, the current identification of invalid microfluidic experiments is carried out by visual checks of the microscope images by experts after the experiments. To improve the automation level and robustness of this quality control process, this work develops an automatic experiment abnormality screening (AEAS) system supported by convolutional neural networks (CNNs). The system learns the features of six abnormal experiment conditions from images taken in actual microfluidic experiments and achieves identification within seconds in the application. The training and validation of six representative CNNs of different network depths and design strategies show that some shallow CNNs can already diagnose abnormal conditions with the desired accuracy. Moreover, to improve the training convergence of deep CNNs with small data sets, this thesis proposes a levelled-training method and improves the chance of convergence from 30% to 90%. With a benchmark of a synthetic promoter model in yeast, this thesis optimises model calibration experiments in three aspects to achieve a more efficient procedure: experimental technique, optimal experimental design (OED), and automatic experiment abnormality screening (AEAS). In this study, the efficiency of model calibration experiments for the benchmarking model can be improved by: adopting microfluidics technology, applying CAVP parameter analysis and FIMPC-based OID, and setting up an AEAS system supported by CNN. These contributions have the potential to be exploited for designing more efficient in-vivo experiments for model calibration in similar studies
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