Optimization of Trustworthy Biomolecular Quantitative Analysis Using Cyber-Physical Microfluidic Platforms

1 Introduction 
1.1 Overview of Digital Microfluidics 
1.2 Overview of Continuous-Flow Microfluidics 
1.3 Design Automation and Optimization of Micro fluidic Biochips 
1.4 Cyber-physical Adaptation for Quantitative Analysis 
1.5 Security Assessment of Biomolecular Quantitative Analysis 
1.6 Proposed Research Methodology 
1.7 Book Outline 
I Real-Time Execution of Multi-Sample Biomolecular Analysis 
2 Synthesis for Multiple Sample Pathways: Gene-Expression Analysis 
2.1 Benchtop Protocol for Gene-Expression Analysis 
2.2 Digital Microfluidics for Gene-Expression Analysis 
2.3 Spatial Reconfiguration 
2.4 Shared-Resource Allocation
2.5 Firmware for Quantitative Analysis 
2.6 Simulation Results 
2.7 Chapter Summary 
3 Synthesis of Protocols with Temporal Constraints: Epigenetic Analysis
3.1 Miniaturization of Epigenetic-Regulation Analysis
3.2 System Model 
3.3 Task Assignment and Scheduling 
3.4 Simulation Results and Experimental Demonstration 
3.5 Chapter Summary 
4 A Micro fluidics-Driven Cloud Service: Genomic Association Studies 
4.1 Background 
4.2 Biological Pathway of Gene Expression and Omic Data 
4.3 Case Study: Integrative Multi-Omic Investigation of Breast Cancer
4.4 The Proposed Framework: BioCyBig
4.5 BioCyBig Application Stack
4.6 Design of Microfluidics for Genomic Association Studies 
4.7 Distributed-System Interfacing and Integration 
4.8 Chapter Summary 
II High-Throughput Single-Cell Analysis 
5 Synthesis of Protocols with Indexed Samples: Single-Cell Analysis 
5.1 Hybrid Platform and Single-Cell Analysis
5.2 Mapping to Algorithmic Models
5.3 Co-Synthesis Methodology 
5.4 Valve-Based Synthesizer 
5.5 Protocol Modeling Using Markov Chains 
5.6 Simulation Results
5.7 Chapter Summary 
6 Timing-Driven Synthesis with Pin Constraints: Single-Cell Screening 
6.1 Preliminaries 
6.2 Multiplexed Control and Delay
6.3 Sortex: Synthesis Solution
6.4 Experimental Results 
6.5 Chapter Summary 
III Parameter-Space Exploration and Error Recovery
7 Synthesis for Parameter-Space Exploration: Synthetic Bio-circuits 
7.1 Background 
7.2 PSE Based on MEDA Biochips 
7.3 Sampling of Concentration Factor Space
7.4 Synthesis Methodology 
7.5 High-Level Synthesis 
7.6 Physical-Level Synthesis 
7.7 Simulation Results 
7.8 Chapter Summary 
8 Fault-Tolerant Realization of Biomolecular Assays 
8.1 Physical Defects and Prior Error-Recovery Solutions 
8.2 Adaptation of the C5 Architecture to Error Recovery 
8.3 System Design
8.4 Dictionary-Based Error Recovery 
8.5 Experiment Results and Demonstration 
8.6 Chapter Summary 
IV Security Vulnerabilities and Countermeasures 
9 Security Vulnerabilities of Quantitative-Analysis Frame-works 
9.1 Threats Assessment of DMFBs 
9.2 Manipulation Attacks on Glucose-Test Results 
9.3 Attacks in the Presence of Cyber-Physical Integration 
9.4 DNA-Forgery Attacks on DNA Preparation 
9.5 Chapter Summary
10 Security Countermeasures of Quantitative-Analysis Frame-works 
10.1 Microfluidic Encryption 
10.2 Aging Reinforces DMFB Security 
10.3 Encryption Security Analysis and Simulation Results 
10.4 DNA Barcoding as a Biochemical-Level Defense Mechanism 
10.5 Benchtop Demonstration of DNA Barcoding 
10.6 Chapter Summary 
11 Conclusion and Future Outlook 
11.1 Book Summary 
11.2 Future Research Directions 
Appendix A Proof of Theorem 5.1: A Fully Connected Routing Crossbar 
Appendix B Modeling a Fully Connected Routing Crossbar 
Appendix C Proof of Lemma 6.1: Derivation of Control Delay Vector  
Appendix D Proof of Theorem 6.1: Derivation of Control Latency
Appendix E Proof of Lemma 7.1: Properties of Aliquot-Generation Trees 
E.1 Overlapping-Subproblems Property 
E.2 Optimal-Substructure Property 
Appendix F Proof of Theorem 7.1: Recursion in Aliquot-Generation Trees 
Bibliography