bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA
Arrays: Preparation and Application
Authors: Whitaker Tom J. , Jacobson K. Bruce , Doktycz Mitchel J. 
Published: September 2006

Abstract

DNA arrays, which may also be called DNA chips, biochips, genosensors, GeneChips
®
, microarrays, or other names, are considered by many researchers and entrepreneurs to be the most promising technology for economically determining whether a specific sequence of bases exists in an unknown DNA sample. The sequence of bases in DNA is the source of genetic information; consequently, DNA arrays can be used for a number of applications, including diagnosis of genetic diseases or mutations, detection of polymorphisms, and identification of microorganisms. In addition, DNA arrays can also establish the amount of one or more particular messenger RNA (mRNA) in a cell or tissue to reveal gene activity.

DNA arrays take on many forms and there are exceptions to almost any statement describing them. However, a typical array will have multiple segments of single‐stranded DNA (ssDNA) attached to the surface of a substrate. These probes have a known sequence and, under the right conditions, an unknown DNA sequence will bind or “hybridize” to one or more of them only if the unknown DNA has sequence that is related to the probe's sequence. This selective hybridization allows DNA arrays to provide sequence information about the unknown DNA.
This article describes some of the primary considerations in the design, construction, and implementation of DNA arrays. Items discussed are probe selection and design, selection of a suitable substrate, probe immobilization, array construction, hybridization, hybrid detection, how the application affects each of these factors, and how decisions made at one point of the process may affect other decisions.
Electroanalysis and Biosensors in Clinical Chemistry
Authors: Killard Anthony J. , Sequeira Margaret , Diamond Dermot , Smyth Malcolm R. 
Published: September 2006

AbstractElectroanalysis involves the measurement or determination of a chemical or biochemical species, using a wide range of electrochemical methods. The species being measured can either bring about a direct electrochemical response that can be detected and measured, or can be induced to bring about such a response, resulting in a process that can be detected electrochemically. In both cases an interface is required between the chemical or biochemical species being measured, and the electrochemical system performing the measurement. This interface is referred to as an “electrode”. It is the transfer of electrons or ions between the electrode and the environment being sampled which is of concern in electroanalysis.The application of electrochemistry in clinical analysis is concerned with the measurement of chemical and biochemical species present in biological fluids (primarily blood but also urine and other body fluids and tissues). It is applied in several areas of critical care where its rapidity, sensitivity, precision, and accuracy at biologically relevant concentrations make it an ideal choice over other, typically slower, biochemical techniques. Indeed, it is the speed of electrochemical analysis that principally differentiates it from other methods. It is not universally applicable to clinical chemistry, however, and has only been applied in situations where such analyses are relevant. This has principally been in the analysis of blood gases and pH and blood electrolytes. Electrochemical methods are, however, gradually being extended to the analysis of small biochemical components such as sugars, amino acids and other metabolites, with the advent of enzyme‐based “biosensors”. There is also little doubt that the application of electrochemistry in clinical analysis will be further exploited by the use of such biosensor devices based on other forms of biorecognition, such as antibodies, cell ligands, membranes, tissues and whole cells. These biosensor devices are also amenable to other forms of detection such as acoustic wave and optical measurements. Together, these techniques offer a wide range of advantages over traditional analytical methodologies, and will undoubtedly have a rapidly increasing impact on many types of clinical analysis. This article focuses on the use of electrochemical techniques and electrochemical biosensors and their application in clinical chemistry.
Electrolytes, Blood Gases, and BloodpH
Authors: Elser Robert C. 
Published: September 2006

AbstractThe term electrolytes, in the clinical sense, refers to the principal ionic constituents of blood: sodium (Na+), potassium (K+), chloride (Cl−), and bicarbonate (HCO3−). Technology for the measurement of these ions has evolved from colorimetric and spectrophotometric methods to ion selective sensors. With the evolution of the technology has come an important reduction in the quantity of sample required to make the determination of concentrations of the ions in blood.The assessment of respiratory function and the acid–base balance of the blood is accomplished by the measurement of pH, PCO2, and PO2. These measurements are usually not made singly, but rather as a combination of determinations made at the same time on the same blood sample.In critically ill persons, these seven analytes are of major diagnostic importance.
Glucose Measurement
Authors: Cardosi Marco F. 
Published: September 2006

Abstract
Because of the pivotal role of glucose in physiological processes, much effort has been devoted to the development of methods for measuring glucose in food, microbiological and clinical matrices. The development of direct methods to measure glucose has been hindered by the lack of a suitable chromophore or indeed an electrophore. Consequently, more complex indirect methods have been developed based either on the chemical reactivity of the sugar, a particular enzymatic reaction or an indirect electrochemical measurement based upon the measurement of tensametric peaks or waves.
Although accurate and offering good sensitivity, chemical methods for the analysis of glucose such as the o‐toluidine approach are not specific for glucose. Other hexoses such as mannose and galactose, some of their derivatives, aldopentoses and some disaccharides may also react, thereby complicating the measurement.

Because of the lack of specificity associated with chemical methods of measuring glucose, enzymatic methods have gained in popularity. Enzymes are very selective biological catalysts which carry out the conversion of a particular substrate into a product under mild operating conditions, i.e. room temperature, low ionic strength and near neutral pH. An enzyme will usually catalyze a single chemical reaction or a set of closely related chemical reactions. Side reactions leading to wasteful formation of by‐products rarely occur. Thus, quantitative assays may be done on crude materials with little or no sample preparation. The enzymes which are currently used for the measurement of glucose include hexokinase (EC 2.7.1.1; adenosine triphosphate (ATP):
D
‐hexose‐6‐phosphotransferase), glucose oxidase (EC 1.1.3.4; β‐
D
‐glucose: oxygen 1‐oxidoreductase) and glucose dehydrogenase (EC 1.1.1.47; β‐
D
‐glucose: (nicotinamide adenine dinucleotide phosphate (oxidized form)) NAD(P)
+
1‐oxidoreductase). The mode of detection that is used to measure the activity and hence concentration of glucose, ultimately depends upon the nature of the enzymatic reaction itself and is usually colorimetric or electrochemical.

More recently, new analytical methodologies based upon the direct electrochemical detection of glucose using pulsed amperometric detection (PAD) have been developed. Coupled with liquid chromatography (LC), this technique is proving to be a highly selective and sensitive method for the measurement of glucose in a wide variety of sample matrices.
Immunochemistry
Authors: Price Christopher P. 
Published: September 2006

AbstractImmunochemistry is a generic term to describe all analytical methods that employ the reaction between an antigen and its complementary antibody for the recognition and/or quantitation of an analyte. The analyte may be the antigen or antibody and in each case the complementary species (antibody or antigen, respectively) will be the primary reagent in the analytical system. The analyte may be present in free solution (e.g. in blood, urine, fermentation broth, effluent, etc.) or may be structurally incorporated in a cell (e.g. red cell, bacterium, virus particle) or solid tissue. Our knowledge of the chemical structure and reactivity of the combining sites of antigens and antibodies (epitopes and paratopes, respectively) has meant that antigen‐ and antibody‐like species can now be synthesized. In the former case this may be undertaken to provide an appropriate immunogen or calibration material whilst several antibody mimics have been demonstrated.The immunoassay format will depend on the purpose for which the assay is to be used. In that the antigen–antibody reaction is unique to two complementary partners, in terms of cells and tissues, there is no other technique that will provide the same specificity – with the exception of DNA. Quantitative assays are usually required for the analysis of molecules in complex fluids. In the research phase, chromatographic techniques, e.g. high‐performance liquid chromatography (HPLC), gas chromatography (GC), or capillary zone electrophoresis (CZE) can provide the characterization and quantitation required; however, these techniques are not always applicable when the need for the assay is established and a large workload is envisaged. An immunoassay then provides the necessary specificity and workload capability. In addition, when assays are used outside the laboratory, e.g. at the bedside, then only immunoassays are applicable because they can be encapsulated in microfabricated devices.This article describes the underlying principles of immunoassay, the design of reagents and assay formats, and illustrates their application to a wide range of analytes.
Infrared Spectroscopy in Clinical Chemistry
Authors: Ng Lily M. , Simmons Reiko 
Published: September 2006

Abstract
Infrared (IR) spectroscopy measures the absorption of IR radiation by chemical bonds in a material. Chemical structural fragments of molecules, known as functional groups, tend to absorb IR radiation in the same frequency range regardless of the structure of the rest of the molecule in which the functional group is located. This correlation between the structure of a molecule and the frequencies at which it absorbs IR radiation allows the structures of unknown molecules to be identified and structural or chemical changes of the molecule to be followed. Traditionally, IR spectroscopy has been one of the most important physical methods in the chemical laboratory as it plays an important role in the elucidation of structures and the identification of organic and inorganic compounds. The quantitative analysis of samples is straightforward and is not affected by the physical state of the sample. Gaseous, liquid, and homogeneous and inhomogeneous solid samples all can be conveniently studied.
Applications of IR spectroscopy in clinical chemistry have progressed rapidly in recent years. IR pathological analysis is becoming increasingly important in the detection of biochemical changes in body fluids and tissues. Information obtained from their IR spectra can be used to identify diseases. Advanced investigations are carried out using different data‐analysis techniques such as multivariate analysis. Using a pattern‐recognition approach, IR spectroscopic data provide a nonsubjective aid in the diagnosis of the disease state and the staging of the disease. Unlike most colorimetric or electrochemical/enzymatic clinical chemistry assays, IR spectroscopic analysis is applicable to a variety of body fluids and tissues: whole blood, plasma or serum, synovial fluid, saliva, urine, cells, and membranes. The methodology is fast and readily automated. Sample preparation is simple and no special reagents or other consumables such as electrodes are required, making IR spectroscopy a low‐cost operation. The most attractive advantage of the method is the potential for a rapid multicomponent analysis to be carried out from a single spectrum.
Micro Total Analytical Systems in Clinical Chemistry
Authors: Hendrikse J. , van den Berg A. 
Published: September 2006

AbstractA micro total analytical system (μTAS) is a system that enhances the performance of a complete chemical analysis by minimizing the scale on which it is performed. The main advantages are automated analyses, higher speed and better separation performance as well as the ability to analyze extremely small (picoliter) sample volumes and reactions involving minute amounts of reagents. A complete analysis may involve taking a sample, its pretreatment and separation into its different components and their detection. In order to perform this sequence of functions, the sample is transported through microchannels that connect the various system parts performing these tasks, while the various (feedback) signals are transported through a separate microelectronic network. Examples of system parts in silicon, glass and polymers that perform tasks such as hydrodynamic and electroosmotic pumping, laminar and turbulent reagent mixing and (di)electrophoretic separations of DNA fragments and particles and cells are presented. Currently, μTAS are mainly being developed and used for remote environmental and process monitoring, patient monitoring and the analysis of nucleic acids. An integrated system in each of these areas is discussed.
Nucleic Acid Analysis in Clinical Chemistry
Authors: Thompson Michael , Deisingh Anil K. 
Published: September 2006

Abstract
This article examines the role of nucleic acid analysis in clinical chemistry. It is a broad‐based article and begins with the background knowledge which will be needed to appreciate the succeeding sections. In the Introduction, structure and function of nucleic acids, hybridization, probe labeling, hybridization protection, polymerase chain reaction (PCR) and sequencing are discussed. Major sections are devoted to microbiological analysis (with particular emphasis on bacteriology), genetic diseases and screening [discussions are provided for cystic fibrosis (CF), heriditary fructose intolerance (HFI) and hemochromatosis along with an introduction to the Human Genome Project and single nucleotide polymorphisms (SNP)], other areas of human medicine (oncology, colorectal cancer and Alzheimer's disease (AD) are considered) and the biosensor approach. A discussion of interesting current and future developments, not only in nucleic acid analysis, but also in gene therapy, concludes the article.
Pharmacogenetic Testing
Authors: Weber Wendell W. , Cronin Maureen T. 
Published: September 2006

AbstractDrugs are administered to patients with the intention of achieving a planned therapeutic response. Yet drug prescription is a medical art because of the wide variation in individual responses to standard drug doses. In the 1960s, the field of pharmacogenetics emerged from the dedicated work of a small group of investigators who began to enrich the discipline of pharmacology by integrating it with human genetics. Pharmacogenetics provides the experimental framework to understand variability in human reactions to drugs and other exogenous substances as a function of intrinsic human genetic variability. The maturation of the human genome initiative has provided a wealth of primary genetic information and functional genomic data to fuel the understanding of genetic polymorphism and its functional consequences. Today, the field of pharmacogenetics is a well‐integrated, worldwide network engaging a vast community of academic and industrial scientists.One hallmark of pharmacogenetics studies is the large amount of genetic data that must be accumulated and integrated for high‐resolution drug‐response genotyping and subsequent phenotype profiling. This need for highly parallel genetic analysis has, in turn, fueled a demand for technical innovation to provide the tools necessary for its execution. The response has been a flurry of inventions in microfluidics and nanotechnology, some of which are scaled down versions of existing technologies, such as capillary electrophoresis and mass spectrometry, and some are completely new inventions. Outstanding in this technical revolution are DNA microarrays. Array technology has emerged as the most versatile and widely applied tool to support pharmacogenetics, for several reasons: arrays have the largest and most scalable capacity for parallel analysis, their inherent flexibility permits them to be used as independent analysis tools or as integrated components of more complex microfluidic systems and, finally, a wide variety of methods can be used to design and fabricate them. Pharmacogenetics is experiencing a period of rapid growth and definition. Arrays have proven themselves to be a technology capable of responding to the growing and changing needs of the current research environment and are likely to be equally important as pharmacogenetics moves into the clinical arena.
Phosphorescence, Fluorescence, and Chemiluminescence in Clinical Chemistry
Authors: Schulman Joanna M. , Schulman Stephen G. 
Published: September 2006

AbstractMolecular luminescence spectroscopy, including fluorescence, phosphorescence, and chemiluminescence (CL), is among the most sensitive of analytical methods. Its use in clinical chemistry has been extensive since the late 1950s and is constantly expanding. Modern separation and immunoassay methods coupled with luminescence detection have revolutionized the detection and determination of endogenous substances, xenobiotics, and their metabolites. Newer techniques such as time‐resolved fluorimetry and phosphorimetry, detection by fiber‐optic sensors, and derivatization with infrared (IR)‐emitting dyes are expanding the range of clinical analysis into new realms of analytical selectivity, sensitivity, and expediency on a scale unimagined until recently. This article considers some of the aspects of fluorescence, phosphorescence, and CL spectroscopy that have contributed to important recent advances in clinical analysis.
Point‐of‐Care Testing
Authors: Kost Gerald J. 
Published: September 2006

AbstractPoint‐of‐care testing (POCT) is defined as testing at or near the site of patient care wherever that medical care is needed. The goal of POCT is to facilitate immediate evidence‐based medical decisions that improve patient outcomes and reduce patient acuity, criticality, morbidity, and mortality, especially during life‐threatening crises and emergency resuscitations. POCT is efficient and efficacious because it facilitates rapid diagnosis, faster treatment decisions, high‐quality trend monitoring, and patient and physician satisfaction. New point‐of‐care technologies are appearing rapidly. This article summarizes principles and analytical methods of whole‐blood analysis (WBA) for chemistry, hematology, and hemostasis analytes, cardiac injury markers, and other point‐of‐care diagnostic tests. Then, the article discusses important clinical aspects, including test clusters and medical indications, methods of monitoring and enhancing performance, and optimization strategies. In the next two decades, diagnostic testing will continue to shift to the point of care, necessitating collaborative integration, information consolidation, and Knowledge Optimization®in surgery, intensive care, emergency medicine, and other settings extending from the acute care center to the patient's home.
Product Development for the Clinical Laboratory
Authors: Krouwer Jan S. 
Published: September 2006

AbstractClinical assays have an important role in medical decision making. Test results help a clinician answer a fundamental question, “how should I treat the patient?” Whereas these assays used to be developed in hospital laboratories and were performed by skilled technicians, the availability of automated instruments has created an industry which now provides most of the assays. The industry is highly competitive – development of assay systems requires a product development process that is efficient. Most companies use a development process that breaks product development into stages: (1) researching new opportunities, (2) proving feasibility, (3) scheduled development, (4) validation, and (5) product launch. Each stage has methods and tools that help attain the commercial goal.
Serum Proteins
Authors: Ritchie Robert F. , Whicher John T. 
Published: September 2006

Abstract

Plasma contains a large number of different proteins with varying structural characteristics. The “plasma proteins” have been defined on the basis of plasma concentration and amenability to measurement in certain types of measurement systems. In the past, they were proteins present with concentrations above 0.05 g L
−1
, but more recently detection limits have been decreased to about 0.001 g L
−1
. However, the group of proteins is not defined on a pathophysiological basis and the definition remains idiosyncratic and incomprehensible to the noncognoscenti. The function of an increasing proportion of them is known and the evidence suggests that they are present either with a specific role in the plasma or that they represent cellular proteins shed into the circulation as a result of degradative processes. Many plasma proteins show characteristic changes in concentration or structure either resulting from genetic dictates that may give rise to disease directly or as a result of changes reflecting pathological or physiological processes. All the transcellular fluids, such as cerebrospinal fluid (CSF), urine, synovial fluid and saliva, contain most or all of the plasma proteins, but there are some additional proteins secreted specifically into these fluids.

This chapter reviews the many methods applied to proteins for clinical and research purposes. Also addressed are the pitfalls not often appreciated by the worker presented with a sample to be analyzed in an increasingly impenetrable “machine”.
Statistical Quality Control in Clinical Laboratories
Authors: Dechert Jerry 
Published: September 2006

AbstractThe importance of reporting quality patient results by clinical laboratories cannot be overstated. Maintaining and improving the quality of laboratory results is a never‐ending process, and the thoughtful application of statistical quality control techniques is the key to this continuous pursuit. Using statistical methods, laboratories can ensure that their patient results are reliable and can continue to improve their performance.It is clear that the method for monitoring quality control in the clinical laboratory will have a direct impact on the results reported by the laboratory. This article reviews the historical development of clinical quality control and details methods traditionally applied in the field. Recently proposed approaches are identified and their statistical performance is evaluated. Quality control methods involving clinical significance are also described, and economic modeling applicable to clinical quality control is presented.