scholarly journals Recent Advances in Microfluidic Paper-Based Analytical Devices toward High-Throughput Screening

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 2970
Author(s):  
Siraprapa Boobphahom ◽  
Mai Nguyet Ly ◽  
Veasna Soum ◽  
Nayoon Pyun ◽  
Oh-Sun Kwon ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Point Of Care ◽  
Cost Effective ◽  
Drug Analysis ◽  
Detection Sensitivity ◽  
Detection Methods ◽  
Food And Beverage ◽  
Rapid Result ◽  
Recent Developments

Microfluidic paper-based analytical devices (µPADs) have become promising tools offering various analytical applications for chemical and biological assays at the point-of-care (POC). Compared to traditional microfluidic devices, µPADs offer notable advantages; they are cost-effective, easily fabricated, disposable, and portable. Because of our better understanding and advanced engineering of µPADs, multistep assays, high detection sensitivity, and rapid result readout have become possible, and recently developed µPADs have gained extensive interest in parallel analyses to detect biomarkers of interest. In this review, we focus on recent developments in order to achieve µPADs with high-throughput capability. We discuss existing fabrication techniques and designs, and we introduce and discuss current detection methods and their applications to multiplexed detection assays in relation to clinical diagnosis, drug analysis and screening, environmental monitoring, and food and beverage quality control. A summary with future perspectives for µPADs is also presented.

The Medicinal Chemistry of Therapeutic Peptides: Recent Developments in Synthesis and Design Optimizations

2019 ◽  
Vol 26 (13) ◽  
pp. 2330-2355 ◽  
Author(s):  
Anutthaman Parthasarathy ◽  
Sasikala K. Anandamma ◽  
Karunakaran A. Kalesh
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Therapeutic Potential ◽  
The Past ◽  
Recombinant Production ◽  
Tremendous Progress ◽  
Recent Developments ◽  
Therapeutic Peptides ◽  
Development Processes ◽  
Delivery Strategies

Peptide therapeutics has made tremendous progress in the past decade. Many of the inherent weaknesses of peptides which hampered their development as therapeutics are now more or less effectively tackled with recent scientific and technological advancements in integrated drug discovery settings. These include recent developments in synthetic organic chemistry, high-throughput recombinant production strategies, highresolution analytical methods, high-throughput screening options, ingenious drug delivery strategies and novel formulation preparations. Here, we will briefly describe the key methodologies and strategies used in the therapeutic peptide development processes with selected examples of the most recent developments in the field. The aim of this review is to highlight the viable options a medicinal chemist may consider in order to improve a specific pharmacological property of interest in a peptide lead entity and thereby rationally assess the therapeutic potential this class of molecules possesses while they are traditionally (and incorrectly) considered ‘undruggable’.

scholarly journals Paper-Based SERS Platform for One-Step Screening of Tetracycline in Milk

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ana Marques ◽  
Bruno Veigas ◽  
Andreia Araújo ◽  
Beatriz Pagará ◽  
Pedro Viana Baptista ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Point Of Care ◽  
Dairy Industry ◽  
Principal Component ◽  
Surface Enhanced Raman Spectroscopy ◽  
Economic Losses ◽  
Screening Methods ◽  
Sers Substrate ◽  
Molecular Signatures

AbstractThroughout the last decade, the expansion of food testing has been gradually moving towards ordinary high throughput screening methods performed on-site. The demand for point-of-care testing, able to distinguish molecular signatures with high accuracy, sensitivity and specificity has been significantly increasing. This new requirement relies on the on-site detection and monitorization of molecular signatures suitable for the surveillance of food production and processing. The widespread use of antibiotics has contributed to disease control of livestock but has also created problems for the dairy industry and consumers. Its therapeutic and subtherapeutic use has increased the risk of contamination in milk in enough concentrations to cause economic losses to the dairy industry and have a health impact in highly sensitive individuals. This study focuses on the development of a simple Surface-Enhanced Raman Spectroscopy (SERS) method for fast high throughput screening of tetracycline (TET) in milk. For this, we integrate a paper-based low-cost, fully recyclable and highly stable SERS platform, with a minimal sample preparation protocol. A two-microliter sample of milk solutions spiked with TET (from 0.01 to 1000 ppm) is dried on a silver nanoparticle coated cardboard substrate and measured via a Raman spectrophotometer. The SERS substrate showed to be extremely stable with a shelf life of several months. A global spectrum principal component analysis approach was used to test all the detected vibrational modes and their correlation with TET concentration. Peak intensity ratios (455 cm−1/1280 cm−1 and 874 cm−1/1397 cm−1) were found to be correlated with TET concentrations in milk, achieving a sensitivity as low as 0.1 ppm. Results indicate that this SERS method combined with portable Raman spectrometer is a potential tool that can be used on-site for the monitoring of TET residues and other antibiotics.

scholarly journals Long-Term Storage of Compound Solutions for High-Throughput Screening by Using a Novel 1536-Well Microplate

2009 ◽  
Vol 14 (5) ◽  
pp. 492-498 ◽  
Author(s):  
Martin Joseph Pfeifer ◽  
Guenther Scheel
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Cost Effective ◽  
The Novel ◽  
Long Term Storage ◽  
Plate Design ◽  
Minor Losses ◽  
Storage Times ◽  
Term Storage

This report describes the features and the performance of a new and significantly improved 1536-well microplate design. The design allows for simple, automation-friendly, and cost-effective storage of compound solutions for high-throughput screening. The plate design is based on Society for Biomolecular Sciences standards for microplates and can be molded from polystyrene or cycloolefin copolymer, thus making the plate suitable for use with acoustic dispensing as well as other conventional liquid dispensing in the nanoliter range. For a 9:1 DMSO/water mix as solvent, the novel plate design has shown to perform over 4 months with only minor losses in solvent. Thus, this novel plate design creates the basis for further reductions in compound storage volumes and allows for an increase in the storage times for microliter volumes for up to a year or more. The high protection against solvent evaporation is also visible for aqueous solutions, thus allowing for reduced edge effects during screening campaigns.

scholarly journals Upscaling of hiPS Cell–Derived Neurons for High-Throughput Screening

2016 ◽  
Vol 22 (3) ◽  
pp. 274-286
Author(s):  
Stefanie Traub ◽  
Heiko Stahl ◽  
Holger Rosenbrock ◽  
Eric Simon ◽  
Ralf Heilker
Keyword(s):  
Drug Discovery ◽  
High Throughput ◽  
High Throughput Screening ◽  
Detection Sensitivity ◽  
Neuronal Markers ◽  
Downstream Target ◽  
Electrophysiological Recordings ◽  
Downstream Target Gene ◽  
The Central Nervous System ◽  
Induced Pluripotent

The advent of human-induced pluripotent stem (hiPS) cell–derived neurons promised to provide better model cells for drug discovery in the context of the central nervous system. This work demonstrates both the upscaling of cellular expansion and the acceleration of neuronal differentiation to accommodate the immense material needs of a high-throughput screening (HTS) approach. Using GRowth factor–driven expansion and INhibition of NotCH (GRINCH) during maturation, the derived cells are here referred to as GRINCH neurons. GRINCH cells displayed neuronal markers, and their functional activity could be demonstrated by electrophysiological recordings. In an application of GRINCH neurons, the brain-derived neurotrophic factor (BDNF)–mediated activation of tropomyosin receptor kinase (TrkB) was investigated as a promising drug target to treat synaptic dysfunctions. To assess the phosphorylation of endogenous TrkB in the GRINCH cells, the highly sensitive amplified luminescent proximity homogeneous assay LISA (AlphaLISA) format was established as a primary screen. A high-throughput reverse transcription (RT)–PCR format was employed as a secondary assay to analyze TrkB-mediated downstream target gene expression. In summary, an optimized differentiation protocol, highly efficient cell upscaling, and advanced assay miniaturization, combined with increased detection sensitivity, pave the way for a new generation of predictive cell-based drug discovery.

scholarly journals Discovery of Acid-Stable Oxygen Evolution Catalysts : High-throughput Computational Screening of Equimolar Bimetallic Oxides

2020 ◽  
Author(s):  
Seoin Back ◽  
Kevin Tran ◽  
Zachary Ulissi
Keyword(s):  
Oxygen Evolution ◽  
High Throughput ◽  
High Throughput Screening ◽  
Noble Metals ◽  
Cost Effective ◽  
Oxide Catalysts ◽  
Computational Screening ◽  
Energy Conversion Systems ◽  
Acid Stable ◽  
Bimetallic Oxides

Discovering acid-stable, cost-effective and active catalysts for oxygen evolution reaction (OER) is critical since this reaction is bottlenecking many electrochemical energy conversion systems. Current systems use extremely expensive iridium oxide catalysts. Identifying Ir-free or catalysts with reduced Ir-composition has been suggested as goals, but no systematic strategy to discover such catalysts has been reported. In this work, we performed high-throughput computational screening to investigate bimetalic oxide catalysts with space groups derived from those of IrO$_x$, identified promising OER catalysts predicted to satisfy all the desired properties: Co-Ir, Fe-Ir and Mo-Ir bimetallic oxides. We find that for the given crystal structures explored, it is essential to include noble metals to maintain the acid-stability, although one-to-one mixing of noble and non-noble metal oxides could keep the materials survive under the acidic conditions. Based on the calculated results, we provide insights to efficiently perform future high-throughput screening to discover catalysts with desirable properties.

scholarly journals Sorting out antibiotics' mechanisms of action: a double fluorescent protein reporter for high throughput screening of ribosome and DNA biosynthesis inhibitors

2016 ◽  
pp. AAC.02117-16 ◽  
Author(s):  
Ilya A. Osterman ◽  
Ekaterina S. Komarova ◽  
Dmitry I. Shiryaev ◽  
Ilya A. Korniltsev ◽  
Irina M. Khven ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Protein Gene ◽  
Fluorescent Protein ◽  
Fluorescent Proteins ◽  
Cost Effective ◽  
High Signal ◽  
Red Fluorescent Protein ◽  
Reporter System ◽  
Ribosome Stalling

In order to accelerate drug discovery, a simple, reliable and cost-effective system for high-throughput identification of a potential antibiotic mechanism of action is required. To facilitate such screening of new antibiotics, we created a double reporter system for not only antimicrobial activity detection, but also for simultaneous sorting of potential antimicrobials into those that cause ribosome stalling, and others that induce SOS response due to DNA damage. In this reporter system the red fluorescent protein generfpwas placed under the control of the SOS-induciblesulApromoter. The far-red fluorescent protein genekatushka2Swas inserted downstream the tryptophan attenuator where two tryptophan codons were replaced by alanine codons, with simultaneous replacement of the complementary part of the attenuator, to preserve the ability to form secondary structures that influence transcription termination. This genetically modified attenuator makes possible Katushka2S expression only upon exposure to any ribosome stalling compounds. The application of red and far-red fluorescent proteins provides a high signal-to-background ratio without any need in enzymatic substrates for detection of the reporter activity. This reporter was shown to be efficient in high-throughput screening of both synthetic and natural chemicals.

scholarly journals Optimization of a Luminescence-Based High-Throughput Screening Assay for Detecting Apyrase Activity

2016 ◽  
Vol 22 (1) ◽  
pp. 94-101 ◽  
Author(s):  
John R. Veloria ◽  
Ashwini K. Devkota ◽  
Eun Jeong Cho ◽  
Kevin N. Dalby
Keyword(s):  
High Throughput ◽  
Herbicide Resistance ◽  
High Throughput Screening ◽  
Detection System ◽  
Cost Effective ◽  
Adenosine Monophosphate ◽  
Adenosine Diphosphate ◽  
Screening Assay ◽  
High Throughput Screening Assay ◽  
Automated Screening

Apyrase is a calcium-activated enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP), adenosine monophosphate (AMP), and Pi. It is currently used in studies involving cancer and platelet aggregation in humans, as well as herbicide resistance in plants. Inhibitors of apyrase are being investigated for their use to suppress tumors and combat herbicide resistance. Only a few inhibitors of apyrase have been reported, many of which were identified through automated screening using a 96-well plate format and colorimetric phosphate detection. However, these screens have had limitations, including large volumes, inconsistent reproducibility, high incidence of false hits, and lack of higher-throughput compatibility. A luciferin/luciferase-based detection system has been reported to examine potential inhibitors of apyrase; however, these reactions were performed in tubes with the assay completion in seconds, which necessitate the development of a high-throughput screening (HTS)–compatible format for screening. Therefore, a more cost-effective biochemical assay that improved the limitations of the previous assay formats using a commercially available luminescence-based detection system was developed. This new robust mix-and-read platform incorporates a low-volume luminescence-based protocol, formatted for use in 384-well microplates. This new format provides a simple and cost-effective method to screen for apyrase inhibitors and will facilitate larger HTS efforts to identify potent inhibitors of apyrase.

scholarly journals Highly sensitive and portable mRNA detection platform for early cancer detection

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hongxia Li ◽  
Antony R. Warden ◽  
Wenqiong Su ◽  
Jie He ◽  
Xiao Zhi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Early Stage ◽  
Point Of Care ◽  
Cancer Biomarker ◽  
Detection Sensitivity ◽  
Detection Methods ◽  
Mrna Detection ◽  
Amplification Method ◽  
Pancreatic Cancer Cells

AbstractPancreatic cancer, at unresectable advanced stages, presents poor prognoses, which could be prevented by early pancreatic cancer diagnosis methods. Recently, a promising early-stage pancreatic cancer biomarker, extracellular vesicles (EVs) related glypican-1 (GPC1) mRNA, is found to overexpress in pancreatic cancer cells. Current mRNA detection methods usually require expensive machinery, strict preservation environments, and time-consuming processes to guarantee detection sensitivity, specificity, and stability. Herein, we propose a novel two-step amplification method (CHAGE) via the target triggered Catalytic Hairpin Assembly strategy combined with Gold-Enhanced point-of-care-testing (POCT) technology for sensitive visual detection of pancreatic cancer biomarker. First, utilizing the catalyzed hairpin DNA circuit, low expression of the GPC1 mRNA was changed into amplification product 1 (AP1, a DNA duplex) as the next detection targets of the paper strips. Second, the AP1 was loaded onto a lateral flow assay and captured with the gold signal nanoparticles to visualize results. Finally, the detected results can be further enhanced by depositing gold to re-enlarge the sizes of gold nanoparticles in detection zones. As a result, the CHAGE methodology lowers the detection limit of mRNA to 100 fM and provides results within 2 h at 37 °C. Furthermore, we demonstrate the successful application in discriminating pancreatic cancer cells by analyzing EVs’ GPC1 mRNA expression levels. Hence, the CHAGE methodology proposed here provides a rapid and convenient POCT platform for sensitive detection of mRNAs through unique probes designs (COVID, HPV, etc.).

scholarly journals Discovery of Acid-Stable Oxygen Evolution Catalysts : High-throughput Computational Screening of Equimolar Bimetallic Oxides

2020 ◽  
Author(s):  
Seoin Back ◽  
Kevin Tran ◽  
Zachary Ulissi
Keyword(s):  
Oxygen Evolution ◽  
High Throughput ◽  
High Throughput Screening ◽  
Noble Metals ◽  
Cost Effective ◽  
Oxide Catalysts ◽  
Computational Screening ◽  
Energy Conversion Systems ◽  
Acid Stable ◽  
Bimetallic Oxides

Discovering acid-stable, cost-effective and active catalysts for oxygen evolution reaction (OER) is critical since this reaction is bottlenecking many electrochemical energy conversion systems. Current systems use extremely expensive iridium oxide catalysts. Identifying Ir-free or catalysts with reduced Ir-composition has been suggested as goals, but no systematic strategy to discover such catalysts has been reported. In this work, we performed high-throughput computational screening to investigate bimetalic oxide catalysts with space groups derived from those of IrO$_x$, identified promising OER catalysts predicted to satisfy all the desired properties: Co-Ir, Fe-Ir and Mo-Ir bimetallic oxides. We find that for the given crystal structures explored, it is essential to include noble metals to maintain the acid-stability, although one-to-one mixing of noble and non-noble metal oxides could keep the materials survive under the acidic conditions. Based on the calculated results, we provide insights to efficiently perform future high-throughput screening to discover catalysts with desirable properties.

scholarly journals High-Throughput Screening Fluorescence Polarization Assay for Tumor-Specific Hsp90

2007 ◽  
Vol 12 (7) ◽  
pp. 915-924 ◽  
Author(s):  
Yuhong Du ◽  
Kamalika Moulick ◽  
Anna Rodina ◽  
Julia Aguirre ◽  
Sara Felts ◽  
...  
Keyword(s):  
High Throughput ◽  
Fluorescence Polarization ◽  
High Throughput Screening ◽  
Small Cell Lung Carcinoma ◽  
Heat Shock Protein 90 ◽  
Cost Effective ◽  
Cell Lung Carcinoma ◽  
Lung Carcinoma Cells ◽  
Fluorescence Polarization Assay ◽  
Molecular Libraries

Heat shock protein 90 (Hsp90) is a molecular chaperone that has emerged as an important target in cancer and several other diseases, such as neurodegenerative diseases, nerve injuries, inflammation, and infection. Discovery of novel agents that inhibit Hsp90 and have druglike properties is therefore a major focus in several academic and industrial laboratories. In this study, the authors describe the development and optimization in a 384-well format of a novel assay for the identification of Hsp90 inhibitors using fluorescence polarization, which measures competitive binding of red-shifted fluorescently labeled geldanamycin (GM-cy3B) to Hsp90 found in the NCI-N417 small-cell lung carcinoma cells. The authors demonstrate that GMcy3B binds with high affinity and specificity to cellular Hsp90. The assay results in excellent signal-to-noise ratios (>10) and Z′ values (>0.75) at tracer concentrations greater than 4 nM and 1 µg/well of total NCI-N417 protein, indicating a robust assay. It also equilibrates after 5 h of incubation at room temperature and remains stable for up to 24 h. Furthermore, it is a simple mix-and-read format that is cost-effective and uses only low amounts of fluorophore and cell lysates. A study using more than 15,000 compounds from the National Institutes of Health Molecular Libraries Screening Center Network was performed to validate its performance in a high-throughput screening format. ( Journal of Biomolecular Screening 2007:915-924)

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