The development of biosensors has been astronomical with the advent of the rapid growth of nanomaterials and nanotechnology. Nanobiosensors are becoming ubiquitous in numerous biomedical applications. Thus, there is a great impetus to exploit smart nanoparticles and other nanomaterials for designing and fabricating smart nanobiosensors that are ultrasensitive and biocompatible. We are developing smart self-assembling biosensors that can detect specific biomolecules (e.g., enzymes, cofactors, metabolites, drugs, hormones, etc.) from micro- to nanomolar levels. Applications of the biosensors include detection of organ dysfunction and/or failure (e.g., liver malfunction, heart failure, etc.), early detection of malignant cancers, toxicant identification, and other biomarkers of diseases. Although nanobiosensors that possess high sensitivity and specificity have been designed and marketed, one fundamental issue remains to be resolved. This important issue is one concerning biocompatibility. Thus, in our development of smart biosensors using nanomaterials, we have adopted a dual purpose approach. (i) On the one hand, it is necessary to systematically and comprehensively evaluate the material properties, characterize and model the signal sensing ability, and determine the biocompatibility of materials to be employed for the design of nanobiosensors. (ii) On the other hand, it is imperative to identify the ideal criteria for the designs of fast-response smart self-assembling nanobiosensors for biomarker detection. Based on a critical review of the literature and consideration of the biocompatibility, functional characterization, and other related issues discussed above, we have identify a set of criteria for the design of fast-response smart self-assembling nanobiosensors for detection of multiple biomarkers. We have also identified many biomedical areas where such nanobiosensors can be applied to detect biomarkers for various diseases. Our dual purpose approach will ultimately lead to the design of much more biocompatible and highly sensitive nanobiosensors and diagnostic equipment (nanobiosensor arrays).

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