Integrated Control of Microfluidics – Application in Fluid Routing, Sensor Synchronization, and Real-Time Feedback Control

Microfluidic applications range from combinatorial chemical synthesis to high-throughput screening, with platforms integrating analog perfusion components, digitally controlled microvalves, and a range of sensors that demand a variety of communication protocols. A comprehensive solution for microfluidic control has to support an arbitrary combination of microfluidic components and to meet the demand for easy-to-operate system as it arises from the growing community of unspecialized microfluidics users. It should also be an easy to modify and extendable platform, which offer an adequate computational resources, preferably without a need for a local computer terminal for increased mobility. Here we will describe several implementation of microfluidics control technologies and propose a microprocessor-based unit that unifies them. Integrated control can streamline the generation process of complex perfusion sequences required for sensor-integrated microfluidic platforms that demand iterative operation procedures such as calibration, sensing, data acquisition, and decision making. It also enables the implementation of intricate optimization protocols, which often require significant computational resources. System integration is an imperative developmental milestone for the field of microfluidics, both in terms of the scalability of increasingly complex platforms that still lack standardization, and the incorporation and adoption of emerging technologies in biomedical research. Here we describe a modular integration and synchronization of a complex multicomponent microfluidic platform

Hydrogel-based logic circuits for planar microfluidics and lab-on-a-chip automation

The transport of vital nutrient supply in fluids as well as the exchange of specific chemical signals from cell to cell has been optimized over billion years of natural evolution. This model from nature is a driving factor in the field of microfluidics, which investigates the manipulation of the smallest amounts of fluid with the aim of applying these effects in fluidic microsystems for technical solutions. Currently, microfluidic systems are receiving attention, especially in diagnostics, \textit{e.g.} as SARS-CoV-2 antigen tests, or in the field of high-throughput analysis, \textit{e.g.} for cancer research. Either simple-to-use or large-scale integrated microfluidic systems that perform biological and chemical laboratory investigations on a so called Lab-on-a-Chip (LoC) provide fast analysis, high functionality, outstanding reproducibility at low cost per sample, and small demand of reagents due to system miniaturization. Despite the great progress of different LoC technology platforms in the last 30 years, there is still a lack of standardized microfluidic components, as well as a high-performance, fully integrated on-chip automation. Quite promising for the microfluidic system design is the similarity of the Kirchhoff's laws from electronics to predict pressure and flow rate in microchannel structures. One specific LoC platform technology approach controls fluids by active polymers which respond to specific physical and chemical signals in the fluid. Analogue to (micro-)electronics, these active polymer materials can be realized by various photolithographic and micro patterning methods to generate functional elements at high scalability. The so called chemofluidic circuits have a high-functional potential and provide “real” on-chip automation, but are complex in system design. In this work, an advanced circuit concept for the planar microfluidic chip architecture, originating from the early era of the semiconductor-based resistor-transistor-logic (RTL) will be presented. Beginning with the state of the art of microfluidic technologies, materials, and methods of this work will be further described. Then the preferred fabrication technology is evaluated and various microfluidic components are discussed in function and design. The most important component to be characterized is the hydrogel-based chemical volume phase transition transistor (CVPT) which is the key to approach microfluidic logic gate operations. This circuit concept (CVPT-RTL) is robust and simple in design, feasible with common materials and manufacturing techniques. Finally, application scenarios for the CVPT-RTL concept are presented and further development recommendations are proposed.:1 The transistor: invention of the 20th century 2 Introduction to fluidic microsystems and the theoretical basics 2.1 Fluidic systems at the microscale 2.2 Overview of microfluidic chip fabrication 2.2.1 Common substrate materials for fluidic microsystems 2.2.2 Structuring polymer substrates for microfluidics 2.2.3 Polymer chip bonding technologies 2.3 Fundamentals and microfluidic transport processes 2.3.1 Fluid dynamics in miniaturized systems 2.3.2 Hagen-Poiseuille law: the fluidic resistance 2.3.3 Electronic and microfluidic circuit model analogy 2.3.4 Limits of the electro-fluidic analogy 2.4 Active components for microfluidic control 2.4.1 Fluid transport by integrated micropumps 2.4.2 Controlling fluids by on-chip microvalves 2.4.3 Hydrogel-based microvalve archetypes 2.5 LoC technologies: lost in translation? 2.6 Microfluidic platforms providing logic operations 2.6.1 Hybrids: MEMS-based logic concepts 2.6.2 Intrinsic logic operators for microfluidic circuits 2.7 Research objective: microfluidic hydrogel-based logic circuits 3 Stimuli-responsive polymers for microfluidics 3.1 Introduction to hydrogels 3.1.1 Application variety of hydrogels 3.1.2 Hydrogel microstructuring methods 3.2 Theory: stimuli-responsive hydrogels 3.3 PNIPAAm: a multi-responsive hydrogel 4 Design, production and characterization methods of hydrogel-based microfluidic systems 4.1 The semi-automated computer aided design approach for microfluidic systems 4.2 The applied design process 4.3 Fabrication of microfluidic chips 4.3.1 Photoresist master fabrication 4.3.2 Soft lithography for PDMS chip production 4.3.3 Assembling PDMS chips by plasma bonding 4.4 Integration of functional hydrogels in microfluidic chips 4.4.1 Preparation of a monomer solution for hydrogel synthesis 4.4.2 Integration methods 4.5 Effects on hydrogel photopolymerization and the role of integration method 4.5.1 Photopolymerization from monomer solutions: managing the diffusion of free radicals 4.5.2 Hydrogel adhesion and UV light intensity distribution in the polymerization chamber 4.5.3 Hydrogel shrinkage behavior of different adhesion types 4.6 Comparison of the integration methods 4.7 Characterization setups for hydrogel actuators and microfluidic measurements . 71 4.7.1 Optical characterization method to describe swelling behavior 4.7.2 Setup of a microfluidic test stand 4.8 Conclusion: design, production and characterization methods 5 VLSI technology for hydrogel-based microfluidics 5.1 Overview of photolithography methods 5.2 Standard UV photolithography system for microfluidic structures 5.3 Self-made UV lithography system suitable for the mVLSI 5.3.1 Lithography setup for the DFR and SU-8 master exposure 5.3.2 Comparison of mask-based UV induced crosslinking for DFR and SU-8 5.4 Mask-based UV photopolymerization for mVLSI hydrogel patterning 5.4.1 Lithography setup for the photopolymerization of hydrogels 5.4.2 Hydrogel photopolymerization: experiments and results 5.4.3 Troubleshooting: photopolymerization of hydrogels 5.5 Conclusion: mVLSI technologies for hydrogel-based LoCs 6 Components for chemofluidic circuit design 6.1 Passive components in microfluidics 6.1.1 Microfluidic resistor 6.1.2 Planar-passive microfluidic signal mixer 6.1.3 Phase separation: laminar flow signal splitter 6.1.4 Hydrogel-based microfluidic one-directional valves 6.2 Hydrogel-based active components 6.2.1 Reversible hydrogel-based valves 6.2.2 Hydrogel-based variable resistors 6.2.3 CVPT: the microfluidic transistor 6.3 Conclusion: components for chemofluidic circuits 7 Hydrogel-based logic circuits in planar microfluidics 7.1 Development of a planar CVPT logic concept 7.1.1 Challenges of planar microfluidics 7.1.2 Preparatory work and conceptional basis 7.2 The microfluidic CVPT-RTL concept 7.3 The CVPT-RTL NAND gate 7.3.1 Circuit optimization stabilizing the NAND operating mode 7.3.2 Role of laminar flow for the CVPT-RTL concept 7.3.3 Hydrogel-based components for improved switching reliability 7.4 One design fits all: the NOR, AND and OR gate 7.5 Control measures for cascaded systems 7.6 Application scenarios for the CVPT-RTL concept 7.6.1 Use case: automated cell growth system 7.6.2 Use case: chemofluidic converter 7.7 Conclusion: Hydrogel-based logic circuits 8 Summary and outlook 8.1 Scientific achievements 8.2 Summarized recommendations from this work Supplementary information SI.1 Swelling degree of BIS-pNIPAAm gels SI.2 Simulated ray tracing of UV lithography setup by WinLens® SI.3 Determination of the resolution using the intercept theorem SI.4 Microfluidic master mold test structures SI.4.1 Polymer and glass mask comparison SI.4.2 Resolution Siemens star in DFR SI.4.3 Resolution Siemens star in SU-8 SI.4.4 Integration test array 300 μm for DFR and SU-8 SI.4.5 Integration test array 100 μm for SU-8 SI.4.6 Microfluidic structure for different technology parameters SI.5 Microfluidic test setups SI.6 Supplementary information: microfluidic components SI.6.1 Compensation methods for flow stabilization in microfluidic chips SI.6.2 Planar-passive microfluidic signal mixer SI.6.3 Laminar flow signal splitter SI.6.4 Variable fluidic resistors: flow rate characteristics SI.6.5 CVPT flow rate characteristics for high Rout Standard operation proceduresDer Transport von lebenswichtigen Nährstoffen in Flüssigkeiten sowie der Austausch spezifischer chemischer Signale von Zelle zu Zelle wurde in Milliarden Jahren natürlicher Evolution optimiert. Dieses Vorbild aus der Natur ist ein treibender Faktor im Fachgebiet der Mikrofluidik, welches die Manipulation kleinster Flüssigkeitsmengen erforscht um diese Effekte in fluidischen Mikrosystemen für technische Lösungen zu nutzen. Derzeit finden mikrofluidische Systeme vor allem in der Diagnostik, z.B. wie SARS-CoV-2-Antigentests, oder im Bereich der Hochdurchsatzanalyse, z.B. in der Krebsforschung, besondere Beachtung. Entweder einfach zu bedienende oder hochintegrierte mikrofluidische Systeme, die biologische und chemische Laboruntersuchungen auf einem sogenannten Lab-on-a-Chip (LoC) durchführen, bieten schnelle Analysen, hohe Funktionalität, hervorragende Reproduzierbarkeit bei niedrigen Kosten pro Probe und einen geringen Bedarf an Reagenzien durch die Miniaturisierung des Systems. Trotz des großen Fortschritts verschiedener LoC-Technologieplattformen in den letzten 30 Jahren mangelt es noch an standardisierten mikrofluidischen Komponenten sowie an einer leistungsstarken, vollintegrierten On-Chip-Automatisierung. Vielversprechend für das Design mikrofluidischer Systeme ist die Ähnlichkeit der Kirchhoff'schen Gesetze aus der Elektronik zur Vorhersage von Druck und Flussrate in Mikrokanalstrukturen. Ein spezifischer Ansatz der LoC-Plattformtechnologie steuert Flüssigkeiten durch aktive Polymere, die auf spezifische physikalische und chemische Signale in der Flüssigkeit reagieren. Analog zur (Mikro-)Elektronik können diese aktiven Polymermaterialien durch verschiedene fotolithografische und mikrostrukturelle Methoden realisiert werden, um funktionelle Elemente mit hoher Skalierbarkeit zu erzeugen.\\ Die sogenannten chemofluidischen Schaltungen haben ein hohes funktionales Potenzial und ermöglichen eine 'wirkliche' on-chip Automatisierung, sind jedoch komplex im Systemdesign. In dieser Arbeit wird ein fortgeschrittenes Schaltungskonzept für eine planare mikrofluidische Chiparchitektur vorgestellt, das aus der frühen Ära der halbleiterbasierten Resistor-Transistor-Logik (RTL) hervorgeht. Beginnend mit dem Stand der Technik der mikrofluidischen Technologien, werden Materialien und Methoden dieser Arbeit näher beschrieben. Daraufhin wird die bevorzugte Herstellungstechnologie bewertet und verschiedene mikrofluidische Komponenten werden in Funktion und Design diskutiert. Die wichtigste Komponente, die es zu charakterisieren gilt, ist der auf Hydrogel basierende chemische Volumen-Phasenübergangstransistor (CVPT), der den Schlüssel zur Realisierung mikrofluidische Logikgatteroperationen darstellt. Dieses Schaltungskonzept (CVPT-RTL) ist robust und einfach im Design und kann mit gängigen Materialien und Fertigungstechniken realisiert werden. Zuletzt werden Anwendungsszenarien für das CVPT-RTL-Konzept vorgestellt und Empfehlungen für die fortlaufende Entwicklung angestellt.:1 The transistor: invention of the 20th century 2 Introduction to fluidic microsystems and the theoretical basics 2.1 Fluidic systems at the microscale 2.2 Overview of microfluidic chip fabrication 2.2.1 Common substrate materials for fluidic microsystems 2.2.2 Structuring polymer substrates for microfluidics 2.2.3 Polymer chip bonding technologies 2.3 Fundamentals and microfluidic transport processes 2.3.1 Fluid dynamics in miniaturized systems 2.3.2 Hagen-Poiseuille law: the fluidic resistance 2.3.3 Electronic and microfluidic circuit model analogy 2.3.4 Limits of the electro-fluidic analogy 2.4 Active components for microfluidic control 2.4.1 Fluid transport by integrated micropumps 2.4.2 Controlling fluids by on-chip microvalves 2.4.3 Hydrogel-based microvalve archetypes 2.5 LoC technologies: lost in translation? 2.6 Microfluidic platforms providing logic operations 2.6.1 Hybrids: MEMS-based logic concepts 2.6.2 Intrinsic logic operators for microfluidic circuits 2.7 Research objective: microfluidic hydrogel-based logic circuits 3 Stimuli-responsive polymers for microfluidics 3.1 Introduction to hydrogels 3.1.1 Application variety of hydrogels 3.1.2 Hydrogel microstructuring methods 3.2 Theory: stimuli-responsive hydrogels 3.3 PNIPAAm: a multi-responsive hydrogel 4 Design, production and characterization methods of hydrogel-based microfluidic systems 4.1 The semi-automated computer aided design approach for microfluidic systems 4.2 The applied design process 4.3 Fabrication of microfluidic chips 4.3.1 Photoresist master fabrication 4.3.2 Soft lithography for PDMS chip production 4.3.3 Assembling PDMS chips by plasma bonding 4.4 Integration of functional hydrogels in microfluidic chips 4.4.1 Preparation of a monomer solution for hydrogel synthesis 4.4.2 Integration methods 4.5 Effects on hydrogel photopolymerization and the role of integration method 4.5.1 Photopolymerization from monomer solutions: managing the diffusion of free radicals 4.5.2 Hydrogel adhesion and UV light intensity distribution in the polymerization chamber 4.5.3 Hydrogel shrinkage behavior of different adhesion types 4.6 Comparison of the integration methods 4.7 Characterization setups for hydrogel actuators and microfluidic measurements . 71 4.7.1 Optical characterization method to describe swelling behavior 4.7.2 Setup of a microfluidic test stand 4.8 Conclusion: design, production and characterization methods 5 VLSI technology for hydrogel-based microfluidics 5.1 Overview of photolithography methods 5.2 Standard UV photolithography system for microfluidic structures 5.3 Self-made UV lithography system suitable for the mVLSI 5.3.1 Lithography setup for the DFR and SU-8 master exposure 5.3.2 Comparison of mask-based UV induced crosslinking for DFR and SU-8 5.4 Mask-based UV photopolymerization for mVLSI hydrogel patterning 5.4.1 Lithography setup for the photopolymerization of hydrogels 5.4.2 Hydrogel photopolymerization: experiments and results 5.4.3 Troubleshooting: photopolymerization of hydrogels 5.5 Conclusion: mVLSI technologies for hydrogel-based LoCs 6 Components for chemofluidic circuit design 6.1 Passive components in microfluidics 6.1.1 Microfluidic resistor 6.1.2 Planar-passive microfluidic signal mixer 6.1.3 Phase separation: laminar flow signal splitter 6.1.4 Hydrogel-based microfluidic one-directional valves 6.2 Hydrogel-based active components 6.2.1 Reversible hydrogel-based valves 6.2.2 Hydrogel-based variable resistors 6.2.3 CVPT: the microfluidic transistor 6.3 Conclusion: components for chemofluidic circuits 7 Hydrogel-based logic circuits in planar microfluidics 7.1 Development of a planar CVPT logic concept 7.1.1 Challenges of planar microfluidics 7.1.2 Preparatory work and conceptional basis 7.2 The microfluidic CVPT-RTL concept 7.3 The CVPT-RTL NAND gate 7.3.1 Circuit optimization stabilizing the NAND operating mode 7.3.2 Role of laminar flow for the CVPT-RTL concept 7.3.3 Hydrogel-based components for improved switching reliability 7.4 One design fits all: the NOR, AND and OR gate 7.5 Control measures for cascaded systems 7.6 Application scenarios for the CVPT-RTL concept 7.6.1 Use case: automated cell growth system 7.6.2 Use case: chemofluidic converter 7.7 Conclusion: Hydrogel-based logic circuits 8 Summary and outlook 8.1 Scientific achievements 8.2 Summarized recommendations from this work Supplementary information SI.1 Swelling degree of BIS-pNIPAAm gels SI.2 Simulated ray tracing of UV lithography setup by WinLens® SI.3 Determination of the resolution using the intercept theorem SI.4 Microfluidic master mold test structures SI.4.1 Polymer and glass mask comparison SI.4.2 Resolution Siemens star in DFR SI.4.3 Resolution Siemens star in SU-8 SI.4.4 Integration test array 300 μm for DFR and SU-8 SI.4.5 Integration test array 100 μm for SU-8 SI.4.6 Microfluidic structure for different technology parameters SI.5 Microfluidic test setups SI.6 Supplementary information: microfluidic components SI.6.1 Compensation methods for flow stabilization in microfluidic chips SI.6.2 Planar-passive microfluidic signal mixer SI.6.3 Laminar flow signal splitter SI.6.4 Variable fluidic resistors: flow rate characteristics SI.6.5 CVPT flow rate characteristics for high Rout Standard operation procedure

Design and manufacture of edible microfluidic logic gates

Edible robotics is an emerging research field with potential use in environmental, food, and medical scenarios. In this context, the design of edible control circuits could increase the behavioral complexity of edible robots and reduce their dependence on inedible components. Here we describe a method to design and manufacture edible control circuits based on microfluidic logic gates. We focus on the choice of materials and fabrication procedure to produce edible logic gates based on recently available soft microfluidic logic. We validate the proposed design with the production of a functional NOT gate and suggest further research avenues for scaling up the method to more complex circuits.Comment: 7 pages, 6 figure

Microfluidic-based Bacterial Molecular Computing on a Chip

Biocomputing systems based on engineered bacteria can lead to novel tools for environmental monitoring and detection of metabolic diseases. In this paper, we propose a Bacterial Molecular Computing on a Chip (BMCoC) using microfluidic and electrochemical sensing technologies. The computing can be flexibly integrated into the chip, but we focus on engineered bacterial AND Boolean logic gate and ON-OFF switch sensors that produces secondary signals to change the pH and dissolved oxygen concentrations. We present a prototype with experimental results that shows the electrochemical sensors can detect small pH and dissolved oxygen concentration changes created by the engineered bacterial populations’ molecular signals. Additionally, we present a theoretical model analysis of the BMCoC computation reliability when subjected to unwanted effects, i.e., molecular signal delays and noise, and electrochemical sensors threshold settings that are based on either standard or blind detectors. Our numerical analysis found that the variations in the production delay and the molecular output signal concentration can impact on the computation reliability for the AND logic gate and ON-OFF switch. The molecular communications of synthetic engineered cells for logic gates integrated with sensing systems can lead to a new breed of biochips that can be used for numerous diagnostic applications

A portable device for time-resolved fluorescence based on an array of CMOS SPADs with integrated microfluidics

[eng] Traditionally, molecular analysis is performed in laboratories equipped with desktop instruments operated by specialized technicians. This paradigm has been changing in recent decades, as biosensor technology has become as accurate as desktop instruments, providing results in much shorter periods and miniaturizing the instrumentation, moving the diagnostic tests gradually out of the central laboratory. However, despite the inherent advantages of time-resolved fluorescence spectroscopy applied to molecular diagnosis, it is only in the last decade that POC (Point Of Care) devices have begun to be developed based on the detection of fluorescence, due to the challenge of developing high-performance, portable and low-cost spectroscopic sensors. This thesis presents the development of a compact, robust and low-cost system for molecular diagnosis based on time-resolved fluorescence spectroscopy, which serves as a general-purpose platform for the optical detection of a variety of biomarkers, bridging the gap between the laboratory and the POC of the fluorescence lifetime based bioassays. In particular, two systems with different levels of integration have been developed that combine a one-dimensional array of SPAD (Single-Photon Avalanch Diode) pixels capable of detecting a single photon, with an interchangeable microfluidic cartridge used to insert the sample and a laser diode Pulsed low-cost UV as a source of excitation. The contact-oriented design of the binomial formed by the sensor and the microfluidic, together with the timed operation of the sensors, makes it possible to dispense with the use of lenses and filters. In turn, custom packaging of the sensor chip allows the microfluidic cartridge to be positioned directly on the sensor array without any alignment procedure. Both systems have been validated, determining the decomposition time of quantum dots in 20 nl of solution for different concentrations, emulating a molecular test in a POC device.[cat] Tradicionalment, l'anàlisi molecular es realitza en laboratoris equipats amb instruments de sobretaula operats per tècnics especialitzats. Aquest paradigma ha anat canviant en les últimes dècades, a mesura que la tecnologia de biosensor s'ha tornat tan precisa com els instruments de sobretaula, proporcionant resultats en períodes molt més curts de temps i miniaturitzant la instrumentació, permetent així, traslladar gradualment les proves de diagnòstic fora de laboratori central. No obstant això i malgrat els avantatges inherents de l'espectroscòpia de fluorescència resolta en el temps aplicada a la diagnosi molecular, no ha estat fins a l'última dècada que s'han començat a desenvolupar dispositius POC (Point Of Care) basats en la detecció de la fluorescència, degut al desafiament que suposa el desenvolupament de sensors espectroscòpics d'alt rendiment, portàtils i de baix cost. Aquesta tesi presenta el desenvolupament d'un sistema compacte, robust i de baix cost per al diagnòstic molecular basat en l'espectroscòpia de fluorescència resolta en el temps, que serveixi com a plataforma d'ús general per a la detecció òptica d'una varietat de biomarcadors, tancant la bretxa entre el laboratori i el POC dels bioassaigs basats en l'anàlisi de la pèrdua de la fluorescència. En particular, s'han desenvolupat dos sistemes amb diferents nivells d'integració que combinen una matriu unidimensional de píxels SPAD (Single-Photon Avalanch Diode) capaços de detectar un sol fotó, amb un cartutx microfluídic intercanviable emprat per inserir la mostra, així com un díode làser UV premut de baix cost com a font d'excitació. El disseny orientat a la detecció per contacte de l'binomi format pel sensor i la microfluídica, juntament amb l'operació temporitzada dels sensors, permet prescindir de l'ús de lents i filtres. Al seu torn, l'empaquetat a mida de l'xip sensor permet posicionar el cartutx microfluídic directament sobre la matriu de sensors sense cap procediment d'alineament. Tots dos sistemes han estat validats determinant el temps de descomposició de "quantum dots" en 20 nl de solució per a diferents concentracions, emulant així un assaig molecular en un dispositiu POC

Micro-mechanical logic for field produceable gate arrays

Thesis (S.M.)--Massachusetts Institute of Technology, School of Architecture and Planning, Program in Media Arts and Sciences, 2005.Includes bibliographical references (leaves 106-110).A paradigm of micro-mechanical gates for field produceable logic is explored. A desktop manufacturing system is sought after which is capable of printing functional logic devices in the field. A logic scheme which induces non-linearities via geometrical properties is considered. Logic devices in two-phase air-water fluid-dynamic system at micron scales are constructed. A systematic study of non-linearities and relevant force fields in fluid dynamics at low Reynolds Number is undertaken. Viscous forces dominate inertial forces at low Reynolds Number flows at low pressure. Thus devices based on non-linear inertial effects at high Reynolds numbers can not be scaled down to micron-sizes. Bubble microfluidic logic gates are invented to tackle the above problem, thus producing low Reynolds Number logic in Newtonian fluids. Various devices including AND/OR gates, NOT gate, nonvolatile bistable memory, shift registers and ON/OFF flow valves, based on this new scheme of bubble bubble interaction in microfluidic devices to induce non-linearity, are designed and characterized. On-chip bubble generators and annihilators are used for encoding and destroying information in bubble logic devices.(cont.) Applications of the above described logic devices as a flow control strategy for droplet based Lab-on-chip devices is explored. A simple to construct in-situ pressure sensor based on the principle of compressibility of an air bubble in microfluidic devices is invented. A scheme of controlled bubble/droplet movement in shift registers via pulsating pressure fields for precise temporal control of start of microfluidic reactions is proposed. Excimer laser micro-machining of boro-silicate glass is developed to direct write 3D microfluidic structures. Laser ablation process using a ArF based 193nm laser for machining is characterized using laser confocal microscopy techniques. Single bubble cavitation induced by laser pulses is developed as a process for writing micro-bubbles at precise locations in microfluidic channels.by Manu Prakash.S.M

Strategic Optimization Techniques For FRTU Deployment and Chip Physical Design

Combinatorial optimization is a complex engineering subject. Although formulation often depends on the nature of problems that differs from their setup, design, constraints, and implications, establishing a unifying framework is essential. This dissertation investigates the unique features of three important optimization problems that can span from small-scale design automation to large-scale power system planning: (1) Feeder remote terminal unit (FRTU) planning strategy by considering the cybersecurity of secondary distribution network in electrical distribution grid, (2) physical-level synthesis for microfluidic lab-on-a-chip, and (3) discrete gate sizing in very-large-scale integration (VLSI) circuit. First, an optimization technique by cross entropy is proposed to handle FRTU deployment in primary network considering cybersecurity of secondary distribution network. While it is constrained by monetary budget on the number of deployed FRTUs, the proposed algorithm identi?es pivotal locations of a distribution feeder to install the FRTUs in different time horizons. Then, multi-scale optimization techniques are proposed for digital micro?uidic lab-on-a-chip physical level synthesis. The proposed techniques handle the variation-aware lab-on-a-chip placement and routing co-design while satisfying all constraints, and considering contamination and defect. Last, the first fully polynomial time approximation scheme (FPTAS) is proposed for the delay driven discrete gate sizing problem, which explores the theoretical view since the existing works are heuristics with no performance guarantee. The intellectual contribution of the proposed methods establishes a novel paradigm bridging the gaps between professional communities

Biosensing by “Growing” Antennas and Error-correcting Codes

Food-borne disease outbreaks not only cause numerous fatalities every year but also contribute to significant economic losses. While end-to-end supply chain monitoring can be one of the keys to preventing these outbreaks, screening every food product in the supply chain is not feasible considering the sheer volume and prohibitive test costs. Fortunately, two converging economic trends promise to make this end-to-end supply chain monitoring possible. The first trend is that passive radio-frequency identification (RFID) tags and quick response (QR) codes are now widely accepted for food packaging. The second trend is that smartphones are now equipped with the capability to interrogate RFID tags or to decode QR codes. Together, they have opened up the possibility of monitoring food quality by endowing these tags and error-correcting codes with the capability to detect pathogenic contaminants. This dissertation investigates a biosensing paradigm of growing\u27\u27 transducer structures, such as RFID tags and QR codes, which is triggered only when analytes of interest are present in the sample. This transducer growth or self-assembly process relies on a silver enhancement technique through which silver ions reduce into metallic form in the presence of a target analyte, which in turn leads to changes in electrical or optical properties. By exploiting this, we first demonstrate two remote biosensor platforms, a RFID tag-based biosensor and a QR code-based biosensor, respectively. For the RFID-based biosensor, a chain of silver-shelled particles is assembled during the analyte detection process, which directly modulates the antenna\u27s effective impedance, and hence leads to an improvement in the tag\u27s reflection efficiency. For the QR code-based biosensor, the operating principle relies on the optical absorption changes resulting from silver enhancement. The target detection process assembles an invalid code-word into a valid QR code. This self-assembly sensing approach should produce few false positives since it is a process which transits from a high entropy state (disassembled transducer) to a low entropy state (assembled transducer). While there can be numerous states of a disassembled transducer structure, there are only a few configurations representing the assembled transducer state. Given that there are no active power sources on the RFID tag or the QR code, it is challenging for the proposed biosensors to perform sample acquisition and pre-processing since they are envisioned to be embedded inside food packages eventually. Paper-based microfluidics have been explored and integrated on the biosensors to provide a self-powered approach for reagent sampling and processing. One use case is to trigger target detection remotely by an end consumer. Thermal absorption properties of graphite have been exploited such that the end user can initiate the process of analyte sampling in paper-based biosensors by shining a beam of light on the sensor

MakerFluidics: low cost microfluidics for synthetic biology

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