François Patou

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

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.

A Smart Mobile Lab-on-Chip-Based Medical Diagnostics System Architecture Designed for Evolvability

Unprecedented knowledge levels in life sciences along with technological advances in micro-and nanotechnologies and microfluidics have recently conditioned the advent of Lab-on-Chip (LoC) devices for In-Vitro Medical Testing (IVMT). Combined with smart-mobile technologies, LoCs are pervasively giving rise to opportunities to better diagnose disease, predict and monitor personalised treatment efficacy, or provide healthcare decision-making support at the Point-of-Care (PoC). Although made increasingly available to the consumer market, the adoption of LoC-based PoC In-Vitro Medical Testing (IVMT) systems is still in its infancy. This attrition partly pertains to the intricacy of designing and developing complex systems, destined to be used sporadically, in a fast-pace evolving technological paradigm. System evolvability is therefore key in the design process and constitutes the main motivation for this work. We introduce a smart-mobile and LoC-based system architecture designed for evolvability. By propagating LoC programmability, instrumentation, and control tools to the high-level abstraction smart-mobile software layer, our architecture facilitates the realisation of new use-cases and the accommodation for incremental LoC-technology developments. We demonstrate these features with an implementation allowing the interfacing of LoCs embedding current-or impedance-based biosensors such as Silicon Nanowire Field Effect Transistors (SiNW-FETs) or electrochemical transducers. Structural modifications of these LoCs or changes in their specific operation may be addressed by the sole reengineering of the mobile-software layer, minimising system upgrade development and validation costs and efforts.

System-Level Sensitivity Analysis of SiNW-bioFET-Based Biosensing Using Lock-In Amplification

Although silicon nanowire biological field-effect transistors (SiNW-bioFETs) have steadily demonstrated their ability to detect biological markers at ultra-low concentration, they have not yet translated into routine diagnostics applications. One of the challenges inherent to the technology is that it requires an instrumentation capable of recovering ultra-low signal variations from sensors usually designed and operated in a highly resistive configuration. Often overlooked, the SiNW-bioFET/instrument interactions are yet critical factors in determining overall system biodetection performances. Here, we carry out, for the first time, the system-level sensitivity analysis of a generic SiNW-bioFET model coupled to a custom-design instrument based on the lock-in amplifier. By investigating a large parametric space spanning over both sensor and instrumentation specifications, we demonstrate that system-wide investigations can be instrumental in identifying the design trade-offs that will ensure the lowest limits of detection. The generic character of our analytical model allows us to elaborate on the most general SiNW-bioFET/instrument interactions and their overall implications on detection performances. Our model can be adapted to better match specific sensor or instrument designs to either ensure that ultra-high sensitivity SiNW-bioFETs are coupled with an appropriately sensitive and noise-rejecting instrumentation, or to best tailor SiNW-bioFET design to the specifications of an existing instrument.

Smartphone-based biosensing platform evolution: Implementation of electrochemical analysis capabilities

Lab-on-Chip technologies offer great opportunities for the democratization of in-vitro medical diagnostics to the consumer-market. Despite the limitations set by the strict instrumentation and control requirements of certain families of these devices, new solutions are emerging. Smartphones now routinely demonstrate their potential as an interface of choice for operating complex, instrumented Lab-on-Chips. The sporadic nature of home-based in-vitro medical diagnostics testing calls for the development of systems capable of evolving with new applications or new technologies for Lab-on-Chip devices. We present in this work how we evolved the first generation of a smartphone/Lab-on-Chip platform designed for evolvability. We demonstrate how reengineering efforts can be confined to the mobile-software layer and illustrate some of the benefits of building evolvable systems. We implement electrochemical capabilities on our platform prototype and carry out cyclic voltammetry to measure dopamine concentrations over several orders of magnitude.

Model-Based Evaluation of System Scalability: Bandwidth Analysis for Smartphone-Based Biosensing Applications

Scalability is a design principle often valued for the engineering of complex systems. Scalability is the ability of a system to change the current value of one of its specification parameters. Although targeted frameworks are available for the evaluation of scalability for specific digital systems, methodologies enabling scalability analysis of multi-domain, complex systems, are still missing. In acknowledgment of the importance for complex systems to present the ability to change or evolve, we present in this work a system-level model-based methodology allowing the multidisciplinary parametric evaluation of scalability. Our approach can be used to determine how a set of limited changes to targeted system modules could affect design specifications of interest. It can also help predict and trace system bottlenecks over several product generations, offering system designers the chance to to better plan re-engineering efforts for scaling a system specification efficaciously. We demonstrate the value of our methodology by investigating a smartphone-based biosensing instrumentation platform. Specifically, we carry out scalability analysis for the systems bandwidth specification: the maximum analog voltage waveform excitation frequency the system could output while allowing continuous acquisition and wireless streaming of bioimpedance measurements. We rely on several SysML modelling tools, including dependency matrices, as well as a fault-detection Simulink Stateflow executable model to conclude on how the successive re-engineering of 5 independent system modules, from the replacement of a wireless Bluetooth interface, to the revision of the ADC sample-and-hold operation could help increase system bandwidth.