Nanodiagnostics to Face SARS-CoV-2 and Future Pandemics: From an Idea to the Market and beyond

The COVID-19 pandemic made clear how our society requires quickly available tools to address emerging healthcare issues. Diagnostic assays and devices are used every day to screen for COVID-19 positive patients, with the aim to decide the appropriate treatment and containment measures. In this context, we would have expected to see the use of the most recent diagnostic technologies worldwide, including the advanced ones such as nano-biosensors capable to provide faster, more sensitive, cheaper, and high-throughput results than the standard polymerase chain reaction and lateral flow assays. Here we discuss why that has not been the case and why all the exciting diagnostic strategies published on a daily basis in peer-reviewed journals are not yet successful in reaching the market and being implemented in the clinical practice.We acknowledge funding from the European Union Horizon2020 Programme under Grant No. 881603 (Graphene Flagship Core 3). We acknowledge Consejo Superior de Investigaciones Científicas (CSIC) for the project “COVID19-122” granted in the call “Nuevas ayudas extraordinarias a proyectos de investigación en el marco de las medidas urgentes extraordinarias para hacer frente al impacto económico y social del COVID-19 (Ayudas CSIC–COVID-19)”. We acknowledge the MICROB-PREDICT Project for partially supporting the work. The MICROB-PREDICT project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant No. 825694. This reflects only the author’s view, and the European Commission is not responsible for any use that may be made of the information it contains. We also acknowledge Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) for the project MAT2017-87202-P. A.I. was supported by a PROBIST postdoctoral fellowship funded by European Research Council (Marie Skłodowska-Curie Grant No. 754510). C.C.C.S. acknowledges funding through CAPES–PRINT (Programa Institucional de Internacionalização; Grant Nos. 88887.310281/2018-00 and 88887.467442/2019-00) and Mackpesquisa-UPM. L.H. acknowledges funding through the China Scholarship Council. ICN2 is funded by the CERCA Programme/Generalitat de Catalunya and supported by the Severo Ochoa programme (MINECO Grant No. SEV-2017-0706)

Quaternary Stereogenic Carbons in Complex Molecules by an Asymmetric, Organocatalytic, Triple Cascade Reaction

A novel organocatalytic triple cascade that allows the stereoselective construction of all-carbon quaternary sterogenic centers in complex organic molecules has been disclosed. The method provides a flexible and direct access to cyclohexene carbaldehydes with three or four stereogenic carbon atoms with high diastereomeric and complete enantiomeric control, and can be extended to the preparation of enantiopure cyclohexanes with five chiral centers and two quaternary carbons

Technological development of intracellular polysilicon–chromium–gold chips for orthogonal chemical functionalization

Increasingly, advances in microtechnologies are focused on obtaining new chips intended for applications in fields such as nanomedicine and cell biology, taking advantage of the ability of microelectronics to manufacture devices with cell dimensions and a large variety of features. Here, we report a technology for the fabrication of multi-material chips, using polysilicon and gold as device layers, to be used as bi-functional cell-internalizable devices. In our case, one of the main technological challenges is to overcome the low adherence between these two materials, especially because of their small contact-area, only 9 μm2. Thus, in order to circumvent this difficulty a chromium adherent-layer was deposited in between. After fabrication, the devices following this design can be successfully internalized inside living macrophages without affecting their viability. The advantage of having multiple material layers in one device is the potential to render multi-tasking chips, as once they are appropriately functionalized, we can provide the chip the ability of being multi-functional. Hence, and as a proof of concept, two different proteins, Wheat Germ Agglutinin (WGA) and Concanavalin (ConA), were immobilized on the chip surface through self-assembled monolayers using orthogonal chemistry. The results of this work show a well-controlled fabrication, the bi-functional capabilities and no cell-toxicity of intracellular polysilicon–chromium–gold chips. Eventually, two different dyes (Oregon Green® 488 and BODIPY® 581/591) were used to bi-functionalize each surface of the multi-material chip in order to demonstrate that functional chips can also be internalized in living cells. These devices have a promising future as intracellular functional platforms for biosensing, drug delivery and diagnosis

Technological development of intracellular polysilicon-chromium-gold chips for orthogonal chemical functionalization

© 2014 Elsevier B.V. Increasingly, advances in microtechnologies are focused on obtaining new chips intended for applications in fields such as nanomedicine and cell biology, taking advantage of the ability of microelectronics to manufacture devices with cell dimensions and a large variety of features. Here, we report a technology for the fabrication of multi-material chips, using polysilicon and gold as device layers, to be used as bi-functional cell-internalizable devices. In our case, one of the main technological challenges is to overcome the low adherence between these two materials, especially because of their small contact-area, only 9 μm2. Thus, in order to circumvent this difficulty a chromium adherent-layer was deposited in between. After fabrication, the devices following this design can be successfully internalized inside living macrophages without affecting their viability. The advantage of having multiple material layers in one device is the potential to render multi-tasking chips, as once they are appropriately functionalized, we can provide the chip the ability of being multi-functional. Hence, and as a proof of concept, two different proteins, Wheat Germ Agglutinin (WGA) and Concanavalin (ConA), were immobilized on the chip surface through self-assembled monolayers using orthogonal chemistry. The results of this work show a well-controlled fabrication, the bi-functional capabilities and no cell-toxicity of intracellular polysilicon-chromium-gold chips. Eventually, two different dyes (Oregon Green® 488 and BODIPY® 581/591) were used to bi-functionalize each surface of the multi-material chip in order to demonstrate that functional chips can also be internalized in living cells. These devices have a promising future as intracellular functional platforms for biosensing, drug delivery and diagnosis.Peer Reviewe

The logic of the partial λ-calculus with equality

Abstract. We investigate the logical aspects of the partial λ-calculus with equality, exploiting an equivalence between partial λ-theories and partial cartesian closed categories (pcccs) established here. The partial λ-calculus with equality provides a full-blown intuitionistic higher order logic, which in a precise sense turns out to be almost the logic of toposes, the distinctive feature of the latter being unique choice. We give a linguistic proof of the generalization of the fundamental theorem of toposes to pcccs with equality; type theoretically, one thus obtains that the partial λ-calculus with equality encompasses a Martin-Löf-style dependent type theory. This work forms part of the semantical foundations for the higher order algebraic specification language HasCasl