18,875 research outputs found
Liquid chromatography-tandem mass spectrometry - Application in the clinical laboratory
This review provides a concise survey of liquid chromatography tandem mass spectrometry (LCTMS) as an emerging technology in clinical chemistry. The combination of two mass spectrometers with an interposed collision cell characterizes LCTMS as an analytical technology on its own and not just as a more specific detector for HPLC compared with conventional techniques. In LCTMS, liquid chromatography is rather used for sample preparation but not for complete resolution of compounds of interest. The instrument technology of LCTMS is complex and comparatively expensive; however, in routine use, methods are far more rugged compared to conventional chromatographic techniques and enable highthroughput analyses with very limited manual handling steps. Moreover, compared to both gas chromatographymass spectrometry (GCMS) and conventional HPLC techniques, LCTMS is substantially more versatile with respect to the spectrum of analyzable compounds. For these reasons it is likely that LCTMS will gain far more widespread use in the clinical laboratory than HPLC and GCMS ever did. In this article, the key features of LCTMS are described, method development is explained, typical fields of application are discussed, and personal experiences are related
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A Systematic Framework to Optimize and Control Monoclonal Antibody Manufacturing Process
Since the approval of the first therapeutic monoclonal antibody in 1986, monoclonal antibody has become an important class of drugs within the biopharmaceutical industry, with indications and superior efficacy across multiple therapeutic areas, such as oncology and immunology. Although there has been great advance in this field, there are still challenges that hinder or delay the development and approval of new antibodies.
For example, we have seen issues in manufacturing, such as quality, process inconsistency and large manufacturing cost, which can be attributed to production failure, delay in approval and drug shortage. Recently, the development of new technologies, such as Process Analytical Tools (PCT), and the use of statistical tools, such as quality by design (QbD), Design of Experiment (DoE) and Statistical Process Control (SPC), has enabled us to identify critical process parameters and attributes, and monitor manufacturing performance.
However, these methods might not be reliable or comprehensive enough to accurately describe the relationship between critical process parameters and attributes, or still lack the ability to forecast manufacturing performance. In this work, by utilizing multiple modeling approaches, we have developed a systematic framework to optimize and control monoclonal antibody manufacturing process.
In our first study, we leverage DoE-PCA approach to unambiguously identify critical process parameters to improve process yield and cost of goods, followed by the use of Monte Carlo simulation to validate the impact of parameters on these attributes. In our second study, we use a Bayesian approach to predict product quality for future manufacturing batches, and hence mitigation strategies can be put in place if the data suggest a potential deviation. Finally, we use neural network model to accurately characterize the impurity reduction of each purification step, and ultimately use this model to develop acceptance criteria for the feed based on the predetermined process specifications. Overall, the work in this thesis demonstrates that the framework is powerful and more reliable for process optimization, monitoring and control
Polymorph Impact on the Bioavailability and Stability of Poorly Soluble Drugs
Drugs with low water solubility are predisposed to poor and variable oral bioavailability and, therefore, to variability in clinical response, that might be overcome through an appropriate formulation of the drug. Polymorphs (anhydrous and solvate/hydrate forms) may resolve these bioavailability problems, but they can be a challenge to ensure physicochemical stability for the entire shelf life of the drug product. Since clinical failures of polymorph drugs have not been uncommon, and some of them have been entirely unexpected, the Food and Drug Administration (FDA) and the International Conference on Harmonization (ICH) has required preliminary and exhaustive screening studies to identify and characterize all the polymorph crystal forms for each drug. In the past, the polymorphism of many drugs was detected fortuitously or through manual time consuming methods; today, drug crystal engineering, in particular, combinatorial chemistry and high-throughput screening, makes it possible to easily and exhaustively identify stable polymorphic and/or hydrate/dehydrate forms of poorly soluble drugs, in order to overcome bioavailability related problems or clinical failures. This review describes the concepts involved, provides examples of drugs characterized by poor solubility for which polymorphism has proven important, outlines the state-of-the-art technologies and discusses the pertinent regulations
Nanoscale integration of single cell biologics discovery processes using optofluidic manipulation and monitoring.
The new and rapid advancement in the complexity of biologics drug discovery has been driven by a deeper understanding of biological systems combined with innovative new therapeutic modalities, paving the way to breakthrough therapies for previously intractable diseases. These exciting times in biomedical innovation require the development of novel technologies to facilitate the sophisticated, multifaceted, high-paced workflows necessary to support modern large molecule drug discovery. A high-level aspiration is a true integration of "lab-on-a-chip" methods that vastly miniaturize cellulmical experiments could transform the speed, cost, and success of multiple workstreams in biologics development. Several microscale bioprocess technologies have been established that incrementally address these needs, yet each is inflexibly designed for a very specific process thus limiting an integrated holistic application. A more fully integrated nanoscale approach that incorporates manipulation, culture, analytics, and traceable digital record keeping of thousands of single cells in a relevant nanoenvironment would be a transformative technology capable of keeping pace with today's rapid and complex drug discovery demands. The recent advent of optical manipulation of cells using light-induced electrokinetics with micro- and nanoscale cell culture is poised to revolutionize both fundamental and applied biological research. In this review, we summarize the current state of the art for optical manipulation techniques and discuss emerging biological applications of this technology. In particular, we focus on promising prospects for drug discovery workflows, including antibody discovery, bioassay development, antibody engineering, and cell line development, which are enabled by the automation and industrialization of an integrated optoelectronic single-cell manipulation and culture platform. Continued development of such platforms will be well positioned to overcome many of the challenges currently associated with fragmented, low-throughput bioprocess workflows in biopharma and life science research
Application of microfluidic chips in anticancer drug screening
With the continuous development of drug screening technology, new screening methodologies and technologies are constantly emerging, driving drug screening into rapid, efficient and high-throughput development. Microfluidics is a rising star in the development of innovative approaches in drug discovery. In this article, we summarize the recent years' progress of microfluidic chip technology in drug screening, including the developmental history, structural design, and applications in different aspects of microfluidic chips on drug screening. Herein, the existing microfluidic chip screening platforms are summarized from four aspects: chip structure design, sample injection and drive system, cell culture technology on a chip, and efficient remote detection technology. Furthermore, this review discusses the application and developmental prospects of using microfluidic chips in drug screening, particularly in screening natural product anticancer drugs based on chemical properties, pharmacological effects, and drug cytotoxicity.Peer reviewe
ΠΠΈΠΊΡΠΎΡΠ»ΡΠΈΠ΄Π½ΡΠΉ ΠΌΠ΅ΡΠΎΠ΄ ΠΊΠ°ΠΊ ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π½Π°Ρ ΡΠ΅Ρ Π½ΠΎΠ»ΠΎΠ³ΠΈΡ Π΄Π»Ρ ΡΠΈΠ½ΡΠ΅Π·Π° Π°Π½ΡΠΈΠΌΠΈΠΊΡΠΎΠ±Π½ΡΡ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ
Objectives. The study aimed to analyze the current antiseptics and disinfectants, explore the possibility of synthesizing various antiseptics including oligohexamethylene guanidine hydrochloride (OHMG-HC) using microfluidic technology, and investigate the main synthesis parameters affecting the properties of the resulting product.Methods. This article presented a review of literature sources associated with investigations of antimicrobial resistance, the uses of agents based on polyhexamethylene guanidine hydrochloride, oligohexamethylene guanidine hydrochloride, and other salts, obained using modern synthesis technologies with microreactors.Results. The relevance of developing production technologies for the βOHMG-HC branchedβ substance was determined. The microfluidic method for the synthesis of polymers, and its application prospects for obtaining the target substance were compared with the existing methods. Advantages of the microfluidic method were indicated.Conclusions. Microreactor technologies allow for more accurate control of the conditions of the polycondensation reaction of the starting monomers and increase the yield and selectivity of the oligomers obtained, leading to an increase in the product purity and process efficiency, in contrast with other known methods. The use of microreactor technologies for the synthesis of branched oligohexamethylene guanidine hydrochloride products is a promising strategy.Π¦Π΅Π»ΠΈ. Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΠΏΡΠΎΠ°Π½Π°Π»ΠΈΠ·Π°ΡΠΎΠ²Π°ΡΡ ΠΏΡΠΈΠΌΠ΅Π½ΡΡΡΠΈΠ΅ΡΡ Π°Π½ΡΠΈΡΠ΅ΠΏΡΠΈΠΊΠΈ ΠΈ Π΄Π΅Π·ΠΈΠ½ΡΠ΅ΠΊΡΠ°Π½ΡΡ, ΡΠ°ΡΡΠΌΠΎΡΡΠ΅ΡΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΡΠΈΠ½ΡΠ΅Π·Π° ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
Π°Π½ΡΠΈΡΠ΅ΠΏΡΠΈΠΊΠΎΠ² ΠΈ ΠΎΡΠ΄Π΅Π»ΡΠ½ΠΎ ΡΠΈΠ½ΡΠ΅Π·Π° ΠΎΠ»ΠΈΠ³ΠΎΠ³Π΅ΠΊΡΠ°ΠΌΠ΅ΡΠΈΠ»Π΅Π½Π³ΡΠ°Π½ΠΈΠ΄ΠΈΠ½Π° Π³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄Π° (ΠΠΠΠ-ΠΠ₯) Ρ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ΠΌ ΠΌΠΈΠΊΡΠΎΡΠ»ΡΠΈΠ΄Π½ΠΎΠΉ ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΈΠ·ΡΡΠΈΡΡ ΠΎΡΠ½ΠΎΠ²Π½ΡΠ΅ ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡΡ ΡΠΈΠ½ΡΠ΅Π·Π°, Π²Π»ΠΈΡΡΡΠΈΠ΅ Π½Π° Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ ΠΏΠΎΠ»ΡΡΠ°Π΅ΠΌΠΎΠ³ΠΎ ΠΏΡΠΎΠ΄ΡΠΊΡΠ°.ΠΠ΅ΡΠΎΠ΄Ρ. ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ ΠΎΠ±Π·ΠΎΡ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΠ½ΡΡ
ΠΈΡΡΠΎΡΠ½ΠΈΠΊΠΎΠ², ΡΠ²ΡΠ·Π°Π½Π½ΡΡ
Ρ ΠΈΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡΠΌΠΈ Π°Π½ΡΠΈΠΌΠΈΠΊΡΠΎΠ±Π½ΠΎΠΉ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΠΈ, ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ΠΌ ΡΡΠ΅Π΄ΡΡΠ² Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΠΏΠΎΠ»ΠΈΠ³Π΅ΠΊΡΠ°ΠΌΠ΅ΡΠΈΠ»Π΅Π½Π³ΡΠ°Π½ΠΈΠ΄ΠΈΠ½Π° Π³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄Π°, ΠΎΠ»ΠΈΠ³ΠΎΠ³Π΅ΠΊΡΠ°ΠΌΠ΅ΡΠΈΠ»Π΅Π½Π³ΡΠ°Π½ΠΈΠ΄ΠΈΠ½Π° Π³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄Π°, Π° ΡΠ°ΠΊΠΆΠ΅ Π΄ΡΡΠ³ΠΈΡ
ΡΠΎΠ»Π΅ΠΉ, ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ
ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠΌΠΈ ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΡΠΌΠΈ ΡΠΈΠ½ΡΠ΅Π·Π° Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΌΠΈΠΊΡΠΎΡΠ΅Π°ΠΊΡΠΎΡΠΎΠ².Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π° Π°ΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠΈ ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΡΡΠ±ΡΡΠ°Π½ΡΠΈΠΈ Β«ΠΠΠΠβΠΠ₯ ΡΠ°Π·Π²Π΅ΡΠ²Π»Π΅Π½Π½ΡΠΉΒ». Π Π°ΡΡΠΌΠΎΡΡΠ΅Π½Ρ ΡΡΡΠ΅ΡΡΠ²ΡΡΡΠΈΠ΅ ΡΠΏΠΎΡΠΎΠ±Ρ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΡΡΠ±ΡΡΠ°Π½ΡΠΈΠΈ ΠΈ ΠΈΡ
Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΊΠΈ. Π’Π°ΠΊΠΆΠ΅ ΡΠ°ΡΡΠΌΠΎΡΡΠ΅Π½ ΠΌΠΈΠΊΡΠΎΡΠ»ΡΠΈΠ΄Π½ΡΠΉ ΡΠΏΠΎΡΠΎΠ± ΡΠΈΠ½ΡΠ΅Π·Π° ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΎΠ², Π΅Π³ΠΎ Π΄ΠΎΡΡΠΎΠΈΠ½ΡΡΠ²Π° ΠΈ ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Ρ Π΅Π³ΠΎ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ Π΄Π»Ρ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΡΠ΅Π»Π΅Π²ΠΎΠΉ ΡΡΠ±ΡΡΠ°Π½ΡΠΈΠΈ.ΠΡΠ²ΠΎΠ΄Ρ. ΠΠΈΠΊΡΠΎΡΠ΅Π°ΠΊΡΠΎΡΠ½ΡΠ΅ ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡ Π±ΠΎΠ»Π΅Π΅ ΡΠΎΡΠ½ΠΎ ΠΊΠΎΠ½ΡΡΠΎΠ»ΠΈΡΠΎΠ²Π°ΡΡ ΡΡΠ»ΠΎΠ²ΠΈΡ ΡΠ΅Π°ΠΊΡΠΈΠΈ ΠΏΠΎΠ»ΠΈΠΊΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΠΈΠΈ ΠΈΡΡ
ΠΎΠ΄Π½ΡΡ
ΠΌΠΎΠ½ΠΎΠΌΠ΅ΡΠΎΠ² ΠΈ ΠΏΠΎΠ²ΡΡΠ°ΡΡ Π²ΡΡ
ΠΎΠ΄ ΠΈ ΡΠ΅Π»Π΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ
ΠΎΠ»ΠΈΠ³ΠΎΠΌΠ΅ΡΠΎΠ², ΡΡΠΎ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΡ ΡΠΈΡΡΠΎΡΡ ΠΏΡΠΎΠ΄ΡΠΊΡΠ° ΠΈ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΏΡΠΎΡΠ΅ΡΡΠ°, Π² ΠΎΡΠ»ΠΈΡΠΈΠ΅ ΠΎΡ Π΄ΡΡΠ³ΠΈΡ
ΠΈΠ·Π²Π΅ΡΡΠ½ΡΡ
ΡΠΏΠΎΡΠΎΠ±ΠΎΠ². ΠΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΌΠΈΠΊΡΠΎΡΠ΅Π°ΠΊΡΠΎΡΠ½ΡΡ
ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΉ Π΄Π»Ρ ΡΠΈΠ½ΡΠ΅Π·Π° ΡΠ°Π·Π²Π΅ΡΠ²Π»Π΅Π½Π½ΡΡ
ΠΏΡΠΎΠ΄ΡΠΊΡΠΎΠ² Π³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄Π° ΠΎΠ»ΠΈΠ³ΠΎΠ³Π΅ΠΊΡΠ°ΠΌΠ΅ΡΠΈΠ»Π΅Π½Π³ΡΠ°Π½ΠΈΠ΄ΠΈΠ½Π° ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠΉ ΡΡΡΠ°ΡΠ΅Π³ΠΈΠ΅ΠΉ
A combined high-throughput and high-content platform for unified on-chip synthesis, characterization and biological screening
Acceleration and unification of drug discovery is important to reduce the effort and cost of new drug development. Diverse chemical and biological conditions, specialized infrastructure and incompatibility between existing analytical methods with high-throughput, nanoliter scale chemistry make the whole drug discovery process lengthy and expensive. Here, we demonstrate a chemBIOS platform combining on-chip chemical synthesis, characterization and biological screening. We developed a dendrimer-based surface patterning that enables the generation of high-density nanodroplet arrays for both organic and aqueous liquids. Each droplet (amongβ>β50,000 droplets per plate) functions as an individual, spatially separated nanovessel, that can be used for solution-based synthesis or analytical assays. An additional indium-tin oxide coating enables ultra-fast on-chip detection down to the attomole per droplet by matrix-assisted laser desorption/ionization mass spectrometry. The excellent optical properties of the chemBIOS platform allow for on-chip characterization and in-situ reaction monitoring in the ultraviolet, visible (on-chip UV-Vis spectroscopy and optical microscopy) and infrared (on-chip IR spectroscopy) regions. The platform is compatible with various cell-biological screenings, which opens new avenues in the fields of high-throughput synthesis and drug discovery
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