A methodological combined framework for roadmapping biosensor research: a fault tree analysis approach within a strategic technology evaluation frame

Abstract

Biosensor technology began in the 1960s to revolutionize instrumentation and measurement. Despite the glucose sensor market success that revolutionized medical diagnostics, and artificial pancreas promise currently the approval stage, the industry is reluctant to capitalize on other relevant university-produced knowledge and innovation. On the other hand, the scientific literature is extensive and persisting, while the number of university-hosted biosensor groups is growing. Considering the limited marketability of biosensors compared to the available research output, the biosensor field has been used by the present authors as a suitable paradigm for developing a methodological combined framework for “roadmapping” university research output in this discipline. This framework adopts the basic principles of the Analytic Hierarchy Process (AHP), replacing the lower level of technology alternatives with internal barriers (drawbacks, limitations, disadvantages), modeled through fault tree analysis (FTA) relying on fuzzy reasoning to count for uncertainty. The proposed methodology is validated retrospectively using ion selective field effect transistor (ISFET) – based biosensors as a case example, and then implemented prospectively membrane biosensors, putting an emphasis on the manufacturability issues. The analysis performed the trajectory of membrane platforms differently than the available market roadmaps that, considering the vast industrial experience in tailoring and handling crystallic forms, suggest the technology path of biomimetic and synthetic materials. The results presented herein indicate that future trajectories lie along with nanotechnology, and especially nanofabrication and nano-bioinformatics, and focused, more on the science-path, that is, on controlling the natural process of self-assembly and the thermodynamics of bioelement-lipid interaction. This retained the nature-derived sensitivity of the biosensor platform, pointing out the differences between the scope of academic research and the market viewpoint.

• Analytic hierarchy process
• biosensors
• fault tree analysis
• fuzzy reasoning
• systems of innovation

Notes

¹Thévenot et al. (1999, p. 2334): “An electrochemical biosensor is a self-contained integrated device, which is capable of providing specific quantitative or semi-quantitative analytical information using a biological recognition element (biochemical receptor) which is retained in direct spatial contact with an electrochemical transduction element. Because of its ability to be repeatedly calibrated, we recommend that a biosensor should be clearly distinguished from a bioanalytical system, which requires additional processing steps, such as reagent addition. A device which is both disposable after one measurement, i.e., single use, and unable to monitor the analyte concentration continuously or after rapid and reproducible regeneration should be designated a single use biosensor.”

²These misconceptions on terminology may be justified by the scale that these devices are usually developed and tested within the university environment. Because bench-scale devices (experimental set-ups or prototypes) exhibit limited operation time at carefully controlled environments, lifetime is indeed determined primarily by the structural stability of the biological element, and secondarily by the effect of the electrode drift on the calibration curve (commonly, whatever strikes first). At real operation, however, extreme conditions may prevail (e.g. temperature, unanticipated interference, overflows, pH), even as abrupt changes, that may be proven detrimental to the device itself, let alone its operation (see e.g. Batzias and Siontorou, 2005; Khanna, 2007; Siontorou et al., 2010).

³ISFETs commonly operate in two modes. In the feedback mode, the drain current, I_ds, is kept constant by applying a compensating feedback voltage, V_gs, to the solution side of the gate (e.g. using a double junction type calomel reference electrode). Ideally, the changes in this feedback voltage correspond to ISFET’s response to variations in the ion concentration. Alternatively, a constant gate voltage can be applied to the reference electrode using a DC power supply, in which case ISFET’s response is characterized by changes in the drain current.