Silicon-Based Optical Sensors for Fungal Pathogen Diagnostics

The last years have witnessed a link between the COVID-19 pandemic with increasing numbers of vulnerable patients and globally emerging incidences of severe drug-resistant fungal infections, thus, calling for rapid, reliable, and sensitive diagnostic tools for fungal infections. However, despite strong warnings from health authorities, such as the World Health Organization, concerning the fatal consequences of the global spread of drug-resistant pathogenic fungi, progress in fungal infection diagnosis and therapy is still limited. Today, gold standard methods for revealing resistance and susceptibility in pathogenic fungi, namely antifungal susceptibility testing (AFST), require several days for completion, and thus this lengthy process can adversely affect antifungal therapy and further promote the spread of resistance. In this work, the use of photonic silicon chips consisting of micropatterned diffraction gratings as sensitive sensors for rapid AFST of clinically relevant fungal pathogens is investigated. These photonic chips provide a surface for the colonization of microbial pathogens at a liquid-solid interface and serve as the optical transducer element for label-free monitoring of fungal growth by detecting real-time changes in the white light reflectance. These sensor elements are used to track morphological changes of fungi in the presence of clinically relevant antifungals at varying concentrations to rapidly determine the minimum inhibitory concentration (MIC) values that help to classify pathogens as resistant or susceptible. We show that by careful design of the chip dimensions, this optical method can extend from bacteria, through yeasts, to filamentous fungi for accelerated AFST, which is at least three times faster than current gold standard methods and can provide same-day results. Moreover, a 3D-printed microfluidic gradient generator was designed to complement the assay and provide an integrated system, which can potentially be employed in point-of-care settings. This gradient generator produces the two-fold dilution series of clinically relevant antimicrobials in an automated manner and is interfaced with the photonic silicon chips to include a complete, on-chip, label-free, and phenotypic assay. Using the bacterial species Escherichia coli and ciprofloxacin as a model pathogen-drug combination, MIC values can be expeditiously determined within 90 minutes compared to current clinical practices, which typically require up to 24 h for bacterial species

Overconvergent Hilbert modular forms via perfectoid modular varieties

We give a new construction of $p$-adic overconvergent Hilbert modular forms by using Scholze's perfectoid Shimura varieties at infinite level and the Hodge--Tate period map. The definition is analytic, closely resembling that of complex Hilbert modular forms as holomorphic functions satisfying a transformation property under congruence subgroups. As a special case, we first revisit the case of elliptic modular forms, extending recent work of Chojecki, Hansen and Johansson. We then construct sheaves of geometric Hilbert modular forms, as well as subsheaves of integral modular forms, and vary our definitions in $p$-adic families. We show that the resulting spaces are isomorphic as Hecke modules to earlier constructions of Andreatta, Iovita and Pilloni. Finally, we give a new direct construction of sheaves of arithmetic Hilbert modular forms, and compare this to the construction via descent from the geometric case.Comment: Version 3. Minor improvements to abstract and introductio

Between the Histories of Art and Architecture: Critical Reception of Hans Vredeman de Vries

As an itinerant draughtsman, fortifications engineer, painter, and rhetorician, Hans Vredeman de Vries has never fit smoothly into 19th and 20th century historical narratives that insist upon the idea of ‘national schools’. The separation contemporary historians have often unwittingly placed between Vredeman’s work as a graphic designer and as an architect seems inconsistent with the reality of the sixteenth century, and is often predicated upon stylistic and periodic designations defined by the Italian Renaissance. This essay's survey of historiography on Vredeman reveals a picture where 19th and 20th century authors are often at odds with writers from the 16th, 17th and 18th centuries, who appear less apt to draw sharp distinctions between Vredeman's role as an architectural designer and artist. As pattern books, Vredeman's series' were by nature subject to widely varying uses and receptions, more so even than other types of prints bound to historical or propagandistic narratives. The market for and reception of Vredeman's architectural books and print series during the sixteenth, seventeenth and eighteenth centuries is also characterized by exceptional diversity in terms of distribution and classification. During Vredeman's stays in Antwerp between 1561-1570 and 1575-1586 demand for the new specialty of architectural prints appears to have remained relatively stable in the Netherlands, thanks largely to the initial popularity of imported ‘perspective’ designs by Jean Cousin and Jacques Androuet du Cerceau, as the collections of Philips II at the Escorial or Ferdinand of Tyrol at Ambras demonstrate. In such collections Vredeman's works also held an appeal for practicing artists and architects. Vincenzo Scamozzi, for example, owned an album that included plates from Vredeman's Den Eersten Boek and Das ander Beuch, as well as a complete edition of Architectura. Meanwhile from inventories it is clear that many Dutch 17th century. painters possessed ‘perspectiefboeken’ authored by Vredeman de Vries, specifically. Vredeman and his milieu became relatively unpopular in an atmosphere of architectural classicism after 1700. Only after a re-evaluation of ‘mannerist’ art and architecture had begun among Viennese art historians in the late nineteenth century, and increased authority was granted to the idea of Dutch (and Belgian) national schools was Hans Vredeman de Vries' work to again receive extensive consideration. In 1870 photolithographic reproductions of several Vredeman volumes from the Brussels library of G.A. van Trigt were published. Soon after monographic treatments by Schoy (1876) and Peters (1895) would independently claim Vredeman as part of divergent architectural heritages, introducing to the artist's reputation a kind of nationalistic tone which colored his subsequent study. Yet Schoy and Peters also insisted upon Vredeman's place in the idea of an Netherlandish architectural Renaissance. This idea has influenced many postwar studies of his undertakings, such as Mielke (1967) and Forssman (1956). Meanwhile, Vredeman's reputation as an indigenously Netherlandish specialist in perspectiven has placed him into many broader discussions about art practice as well as perception and optics, as in Alpers (1983). This at a time when Vredeman's eccentric reputation has made him again attractive to art- and architectural histories interested in materials traditionally excluded by older stylistic categories

Sensor integration into microfluidic systems: trends and challenges

The combination of sensors and microfluidics has become a promising approach for detecting a wide variety of targets relevant in biotechnology. Thanks to recent advances in the manufacturing of microfluidic systems, microfluidics can be manufactured faster, cheaper, and more accurately than ever before. These advances make microfluidic systems very appealing as a basis for constructing sensor systems, and microfluidic devices have been adapted to house (bio)sensors for various applications (e.g. protein biomarker detection, cell culture oxygen control, and pathogen detection). This review article highlights several successfully integrated microfluidic sensor systems, with a focus on work that has been published within the last two years. Different sensor integration methods are discussed, and the latest trends in wearable- and smartphone-based sensors are described

Sensor integration into microfluidic systems: trends and challenges

The combination of sensors and microfluidics has become a promising approach for detecting a wide variety of targets relevant in biotechnology. Thanks to recent advances in the manufacturing of microfluidic systems, microfluidics can be manufactured faster, cheaper, and more accurately than ever before. These advances make microfluidic systems very appealing as a basis for constructing sensor systems, and microfluidic devices have been adapted to house (bio)sensors for various applications (e.g. protein biomarker detection, cell culture oxygen control, and pathogen detection). This review article highlights several successfully integrated microfluidic sensor systems, with a focus on work that has been published within the last two years. Different sensor integration methods are discussed, and the latest trends in wearable- and smartphone-based sensors are described

Paving the way to overcome antifungal drug resistance: current practices and novel developments for rapid and reliable antifungal susceptibility testing

The past year has established the link between the COVID-19 pandemic and the global spread of severe fungal infections; thus, underscoring the critical need for rapid and realizable fungal disease diagnostics. While in recent years, health authorities, such as the Centers for Disease Control and Prevention, have reported the alarming emergence and spread of drug-resistant pathogenic fungi and warned against the devastating consequences, progress in the diagnosis and treatment of fungal infections is limited. Early diagnosis and patient-tailored therapy are established to be key in reducing morbidity and mortality associated with fungal (and cofungal) infections. As such, antifungal susceptibility testing (AFST) is crucial in revealing susceptibility or resistance of these pathogens and initiating correct antifungal therapy. Today, gold standard AFST methods require several days for completion, and thus this much delayed time for answer limits their clinical application. This review focuses on the advancements made in developing novel AFST techniques and discusses their implications in the context of the practiced clinical workflow. The aim of this work is to highlight the advantages and drawbacks of currently available methods and identify the main gaps hindering their progress toward clinical application

Aptasensors versus immunosensors—Which will prevail?

Since the invention of the first biosensors 70 years ago, they have turned into valuable and versatile tools for various applications, ranging from disease diagnosis to environmental monitoring. Traditionally, antibodies have been employed as the capture probes in most biosensors, owing to their innate ability to bind their target with high affinity and specificity, and are still considered as the gold standard. Yet, the resulting immunosensors often suffer from considerable limitations, which are mainly ascribed to the antibody size, conjugation chemistry, stability, and costs. Over the past decade, aptamers have emerged as promising alternative capture probes presenting some advantages over existing constraints of immunosensors, as well as new biosensing concepts. Herein, we review the employment of antibodies and aptamers as capture probes in biosensing platforms, addressing the main aspects of biosensor design and mechanism. We also aim to compare both capture probe classes from theoretical and experimental perspectives. Yet, we highlight that such comparisons are not straightforward, and these two families of capture probes should not be necessarily perceived as competing but rather as complementary. We, thus, elaborate on their combined use in hybrid biosensing schemes benefiting from the advantages of each biorecognition element

3D printing in biotechnology—An insight into miniaturized and microfluidic systems for applications from cell culture to bioanalytics

Since its invention in the 1980s, 3D printing has evolved into a versatile technique for the additive manufacturing of diverse objects and tools, using various materials. The relative flexibility, straightforwardness, and ability to enable rapid prototyping are tremendous advantages offered by this technique compared to conventional methods for miniaturized and microfluidic systems fabrication (such as soft lithography). The development of 3D printers exhibiting high printer resolution has enabled the fabrication of accurate miniaturized and microfluidic systems—which have, in turn, substantially reduced both device sizes and required sample volumes. Moreover, the continuing development of translucent, heat resistant, and biocompatible materials will make 3D printing more and more useful for applications in biotechnology in the coming years. Today, a wide variety of 3D-printed objects in biotechnology—ranging from miniaturized cultivation chambers to microfluidic lab-on-a-chip devices for diagnostics—are already being deployed in labs across the world. This review explains the 3D printing technologies that are currently used to fabricate such miniaturized microfluidic devices, and also seeks to offer some insight into recent developments demonstrating the use of these tools for biotechnological applications such as cell culture, separation techniques, and biosensors

PACE Solver Description: The KaPoCE Exact Cluster Editing Algorithm

The cluster editing problem is to transform an input graph into a cluster graph by performing a minimum number of edge editing operations. A cluster graph is a graph where each connected component is a clique. An edit operation can be either adding a new edge or removing an existing edge. In this write-up we outline the core techniques used in the exact cluster editing algorithm of the KaPoCE framework (contains also a heuristic solver), submitted to the exact track of the 2021 PACE challenge

PACE Solver Description: KaPoCE: A Heuristic Cluster Editing Algorithm

The cluster editing problem is to transform an input graph into a cluster graph by performing a minimum number of edge editing operations. A cluster graph is a graph where each connected component is a clique. An edit operation can be either adding a new edge or removing an existing edge. In this write-up we outline the core techniques used in the heuristic cluster editing algorithm of the Karlsruhe and Potsdam Cluster Editing (KaPoCE) framework, submitted to the heuristic track of the 2021 PACE challenge