Biosensors for Biomolecular Computing: a Review and Future Perspectives

Biomolecular computing is the field of engineering where computation, storage, communication, and coding are obtained by exploiting interactions between biomolecules, especially DNA, RNA, and enzymes. They are a promising solution in a long-term vision, bringing huge parallelism and negligible power consumption. Despite significant efforts in taking advantage of the massive computational power of biomolecules, many issues are still open along the way for considering biomolecular circuits as an alternative or a complement to competing with complementary metal–oxide–semiconductor (CMOS) architectures. According to the Von Neumann architecture, computing systems are composed of a central processing unit, a storage unit, and input and output (I/O). I/O operations are crucial to drive and read the computing core and to interface it to other devices. In emerging technologies, the complexity overhead and the bottleneck of I/O systems are usually limiting factors. While computing units and memories based on biomolecular systems have been successfully presented in literature, the published I/O operations are still based on laboratory equipment without a real development of integrated I/O. Biosensors are suitable devices for transducing biomolecular interactions by converting them into electrical signals. In this work, we explore the latest advancements in biomolecular computing, as well as in biosensors, with focus on technology suitable to provide the required and still missing I/O devices. Therefore, our goal is to picture out the present and future perspectives about DNA, RNA, and enzymatic-based computing according to the progression in its I/O technologies, and to understand how the field of biosensors contributes to the research beyond CMOS

All-in-Fiber Electrochemical Sensing

Electrochemical sensors have found a wide range of applications in analytical chemistry thanks to the advent of high-throughput printing technologies. However, these techniques are usually limited to two-dimensional (2D) geometry with relatively large minimal feature sizes. Here, we report on the scalable fabrication of monolithically integrated electrochemical devices with novel and customizable fiber-based architectures. The multimaterial thermal drawing technique is employed to co-process polymer composites and metallic glass into uniform electroactive and pseudoreference electrodes embedded in an insulating polymer cladding fiber. To demonstrate the versatility of the process, we tailor the fiber microstructure to two configurations: a small-footprint fiber tip sensor and a high-surface-area capillary cell. We demonstrate the performance of our devices using cyclic voltammetry and chronoamperometry for the direct detection and quantification of paracetamol, a common anesthetic drug. Finally, we showcase a fully portable pipet-based analyzer using low-power electronics and an "electrochemical pipet tip" for direct sampling and analysis of microliter-range volumes. Our approach paves the way toward novel materials and architectures for efficient electrochemical sensing to be deployed in existing and novel personal care and surgical configurations

A 6 day course of liposomal amphotericin B in the treatment of infantile visceral leishmaniasis: the Italian experience

OBJECTIVES: To evaluate in a retrospective analysis the efficacy and safety of a 6 day course of liposomal amphotericin B (L-AmB) in infantile cases of Mediterranean visceral leishmaniasis (VL) diagnosed over a 10 year period in Italy. PATIENTS AND METHODS: Patients included were diagnosed as having VL consecutively admitted from December 1992 to December 2001 at four main referral children's hospitals in Italy and treated with six intravenous doses of 3 mg/kg L-AmB given on days 1-5 and 10 (a total dose of 18 mg/kg). Demographic data, nutritional status, underlying diseases, clinical and laboratory findings, and therapy outcome were considered. RESULTS: A total of 164 HIV-negative children (median age 1.6 years; range 4 months to 14 years) were enrolled. All patients were initially cured by the given treatment, and did not present adverse events related to drug infusion. Seven patients (4.3%) had a clinical and parasitological relapse 3-15 months after therapy. All relapses were successfully retreated with 3 mg/kg L-AmB for 10 consecutive days (a total dose of 30 mg/kg). CONCLUSIONS: This study highlights the efficacy (>95%) and safety of the six dose L-AmB regimen and validates it as a first-line treatment for Mediterranean VL in children

Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks

The workshop titled “Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks” was co-organized by the Evidence-based Toxicology Collaboration and the European Food Safety Authority (EFSA) and hosted by EFSA at its headquarters in Parma, Italy on October 2 and 3, 2019. The goal was to explore integration of systematic review with mechanistic evidence evaluation. Participants were invited to work on concrete products to advance the exploration of how evidence-based approaches can support the development and application of adverse outcome pathways (AOP) in chemical risk assessment. The workshop discussions were centered around three related themes: 1) assessing certainty in AOPs, 2) literature-based AOP development, and 3) integrating certainty in AOPs and non-animal evidence into decision frameworks. Several challenges, mostly related to methodology, were identified and largely determined the workshop recommendations. The workshop recommendations included the comparison and potential alignment of processes used to develop AOP and systematic review methodology, including the translation of vocabulary of evidence-based methods to AOP and vice versa, the development and improvement of evidence mapping and text mining methods and tools, as well as a call for a fundamental change in chemical risk and uncertainty assessment methodology if to be conducted based on AOPs and new approach methodologies (NAM). The usefulness of evidence-based approaches for mechanism-based chemical risk assessments was stressed, particularly the potential contribution of the rigor and transparency inherent to such approaches in building stakeholders’ trust for implementation of NAM evidence and AOPs into chemical risk assessment

All-in-Fiber Electrochemical Sensing

Electrochemical sensors have found a wide range of applications in analytical chemistry thanks to the advent of high-throughput printing technologies. However, these techniques are usually limited to two-dimensional (2D) geometry with relatively large minimal feature sizes. Here, we report on the scalable fabrication of monolithically integrated electrochemical devices with novel and customizable fiber-based architectures. The multimaterial thermal drawing technique is employed to co-process polymer composites and metallic glass into uniform electroactive and pseudoreference electrodes embedded in an insulating polymer cladding fiber. To demonstrate the versatility of the process, we tailor the fiber microstructure to two configurations: a small-footprint fiber tip sensor and a high-surface-area capillary cell. We demonstrate the performance of our devices using cyclic voltammetry and chronoamperometry for the direct detection and quantification of paracetamol, a common anesthetic drug. Finally, we showcase a fully portable pipet-based analyzer using low-power electronics and an "electrochemical pipet tip" for direct sampling and analysis of microliter-range volumes. Our approach paves the way toward novel materials and architectures for efficient electrochemical sensing to be deployed in existing and novel personal care and surgical configurations.ICLABFIMA