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Background Eponyms are commonly used in medicine, but there are no specific studies of the use of eponyms in clinical chemistry. Methods Clinical chemistry eponyms were manually collected from books, review articles and journal articles from 1847 through 2020. Eponym usage was examined by searching titles and abstracts in PubMed. Custom Python scripts were used to first permute eponyms into multiple forms, and then to search PubMed using Biopython. The eponyms identified in PubMed were further focused on 2 clinical chemistry journals Clinica Chimica Acta [CCA] and Clinical Chemistry [CCJ]. Results The manual collection identified >300 eponyms in clinical chemistry. The Biopython search of PubMed identified a subset of 97 unique eponyms in 33,232 articles. PubMed identified 26 eponyms used in 130 CCA articles; whereas a full-text search identified 1187 articles. In comparison, PubMed identified 36 eponyms used in 158 CCJ articles; whereas a full-text CCJ search identified 708 articles. PubMed shows that the journals CCA and CCJ had a peak number of eponym citations in 1977 followed by a steady decline. Conclusions Eponyms have been frequently used in clinical chemistry with 97 eponyms in common use in PubMed. Overall, the use of clinical chemistry eponyms appears to be declining.

Background In the 1880s, concern over the inconvenience of hazardous chemical solutions used for bedside urinalysis sparked an interest in the development of dry reagents for a range of common urine tests. Content This article examines the history of Dr Pavy’s Pellets and Dr Oliver’s Papers, 2 different dry reagent systems developed in the 1880s for bedside urine testing. It sets these developments in the context of the earlier dry chemistry work (e.g., indicator papers) and the subsequent work that led to modern day reagent tablets and dipstick devices. Summary Tests based on dry reagents can be traced back to the 1st century, but active development, in the form of indicator papers, dates from the 1600s. In the 1880s, spurred by dissatisfaction with liquid-based bedside urine testing among clinicians, Dr Frederick William Pavy and Dr George Oliver developed dry reagent tests, based on pellets (Dr Pavy’s Pellets) and chemically impregnated papers (Dr Oliver’s Papers) for urine sugar and urine albumin. These reagents were commercialized by a number of companies and provided in convenient cases (Physician’s Pocket Reagent Case). Eventually, these tests lost popularity and were replaced by the type of tablets and dipsticks developed by both Eli Lilly, and the Ames Division of Miles Laboratories (subsequently Bayer, and currently Siemens Healthineers) during the 1940s and 1950s.

We began work on the development of a microfluidic sperm chip in the early 1990s as part of a larger project that developed chips for a wide range of diagnostic tests. Our rationale in developing the sperm chip was to provide an easy-to-use disposable test device for assessing semen quality (e.g., motility) at the point of care as part of the workup of male infertility (Fig. 1, A and B). A more ambitious goal was to provide a range of tests on a single microchip that would assess a series of factors relevant to male fertility testing (e.g., sperm motility and count, sperm–hyaluronic acid interaction, sperm antibodies) (1) (Fig. 1C). Although our sperm studies were targeted toward improving the understanding of fertility in humans, we also had a clear awareness of the implications of an effective sperm selection and testing technology in animal husbandry. Fig. 1. Sperm motility chips. (A) and (B), The silicon chip A enables testing in triplicate, and the scale (1–10) etched next to the channel provides for semiquantitative assessment of progression of sperm along the channel. In the glass chip B, the parallel grooves in the central semen application areas serve to direct sperm toward the curved analytical channels (4 per test), which prevent delay of sperm migration observed for 90° turns (compare with chip A). (C), Semen testing chip (motility, sperm–hyaluronic acid interaction, and 3 areas for other testing). (D), Lithographic mask for various designs of sperm chip and in vitro fertilization (IVF) chips. Mask location 1 …

This review advances the discussion about the future of laboratory medicine in the 2020s. In five major topic areas: 1. the “big picture” of healthcare; 2. pre-analytical factors; 3. Analytical factors; 4. post-analytical factors;and 5. relationships, which explores a next decade perspective on laboratory medicine and the likely impact of the predicted changes by means of a number of carefully focused questions that draw upon predictions made since 2013. The “big picture” of healthcare explores the effects of changing patient populations, the brain-to brain loop, direct access testing, robots and total laboratory automation, and green technologies and sustainability.The pre-analytical section considers the role of different sample types, drones, and biobanks. The analytical section examines advances in point-of-care testing, mass spectrometry, genomics, gene and immunotherapy,3D-printing, and total laboratory quality. The post-analytical section discusses the value of laboratory medicine, the emerging role of artificial intelligence, the management and interpretation of omics data, and common reference intervals and decision limits. Finally, the relationships section explores the role of aboratory medicine scientific societies, the educational needs of laboratory professionals, communication, the relationship between laboratory professionals and clinicians, laboratory medicine financing, and the anticipated economic opportunities and outcomes in the 2020's. Refereed/Peer-reviewed

Important and emerging trends at the interface of luminescence, nucleic acids and nanotechnology are: (i) the conventional luminescence labeling of nucleic acid nanostructures (e.g. DNA tetrahedron); (ii) the labeling of bulk nucleic acids (e.g. single-stranded DNA, double-stranded DNA) with nanostructured luminescent labels (e.g. copper nanoclusters); and (iii) the labeling of nucleic acid nanostructures (e.g. origami DNA) with nanostructured luminescent labels (e.g. silver nanoclusters). This review surveys recent advances in these three different approaches to the generation of nanostructured luminescently labeled nucleic acids, and includes both direct and indirect labeling methods.

Multiplexed assays are now a common form of analysis in routine clinical and research laboratories. Assuring the quality of this type of complex, massively-parallel testing poses challenges not encountered in the traditional single-plex assay. A range of quality assurance measures is implemented at different stages in a multiplex assay, beginning in the manufacturing process, and the ensuing analytical and data interpretation stages. This article explores quality issues and the quality assurance measures that have been devised for multiplex assays ranging from simple two-plex assays to the types of assays that involve simultaneous testing on millions of test sites on a single analytical device.

Predictions about the future of laboratory medicine have had a mixed success, and in some instances they have been overambitious and incorrectly assessed the future impact of emerging technologies. Current predictions suggest a more highly automated and connected future for diagnostic testing. The central laboratory of the future may be dominated by more robotics and more connectivity in order to take advantage of the benefits of the Internet of Things and artificial intelligence (AI)-based systems (e.g. decision support software and imaging analytics). For point-of-care testing, mobile health (mHealth) may be in the ascendancy driven by healthcare initiatives from technology companies such as Amazon, Apple, Facebook, Google, IBM, Microsoft and Uber.

Radioactive reagents have been gradually replaced by nonisotopic reagents for some tasks in molecular biology. Concern over laboratory safety and the economic and environmental aspects of radioactive waste disposal have been key factors in this change. Generally, the new nonisotopic systems have improved in terms of analytical sensitivity and the time required to obtain a result. The most prominent nonisotopic analytical methods exploit chemiluminescence, described here. This technique has been particularly effective when used in combination with an enzyme label, so that the amplifying properties of an enzyme label and the high sensitivity of a chemiluminescent detection reaction are combined to produce an ultrasensitive assay (e.g., chemiluminescent detection of peroxidase- and alkaline phosphatase-labeled proteins and nucleic acid probes). In all of the commonly used applications in molecular biology, the analytical performance of the chemiluminescent systems approaches that of 125I- or 32P-based systems. Chemiluminescent systems also avoid the lengthy signal detection times required with 32P-based methods, yielding results in minutes rather than days. In addition, chemiluminescent probes can be easily stripped from membranes, allowing the membranes to be reprobed many times without significant loss of resolution. Experimental protocols for directly attaching nonisotopic labels to nucleic acids and indirect labeling methods based on biotin, fluorescein, and digoxigenin labels are now well established. The ancillary reagents (e.g., avidin, streptavidin, antidigoxigenin, and antifluorescein enzyme conjugates) required for the indirect methods are widely available.

BACKGROUNDPoint-of-care technology (POCT) provides actionable information at the site of care to allow rapid clinical decision-making. With healthcare emphasis shifting toward precision medicine, population health, and chronic disease management, the potential impact of POCT continues to grow, and several prominent POCT trends have emerged or strengthened in the last decade.CONTENTThis review summarizes current and emerging trends in POCT, including technologies approved or cleared by the Food and Drug Administration or in development. Technologies included have either impacted existing clinical diagnostics applications (e.g., continuous monitoring and targeted nucleic acid testing) or are likely to impact diagnostics delivery in the near future. The focus is limited to in vitro diagnostics applications, although in some sections, technologies beyond in vitro diagnostics are also included given the commonalities (e.g., ultrasound plug-ins for smart phones). For technologies in development (e.g., wearables, noninvasive testing, mass spectrometry and nuclear magnetic resonance, paper-based diagnostics, nanopore-based devices, and digital microfluidics), we also discuss their potential clinical applications and provide perspectives on strategies beyond technological and analytical proof of concept, with the end goal of clinical implementation and impact.SUMMARYThe field of POCT has witnessed strong growth over the past decade, as evidenced by new clinical or consumer products or research and development directions. Combined with the appropriate strategies for clinical needs assessment, validation, and implementation, these and future POCTs may significantly impact care delivery and associated outcomes and costs.

Aim: We present the potential false-negative rate of exome sequencing for the detection of pharmacogenomic variants. Materials & Methods: Depth of coverage of 1928 pharmacogenomically relevant variant positions was ascertained from 62 exome-sequenced samples. Results: Approximately 14% of the 1928 variant locations examined had inadequate depth of coverage (

Important and emerging trends at the interface of luminescence, nucleic acids and nanotechnology are: (i) the conventional luminescence labeling of nucleic acid nanostructures (e.g. DNA tetrahedron); (ii) the labeling of bulk nucleic acids (e.g. single-stranded DNA, double-stranded DNA) with nanostructured luminescent labels (e.g. copper nanoclusters); and (iii) the labeling of nucleic acid nanostructures (e.g. origami DNA) with nanostructured luminescent labels (e.g. silver nanoclusters). This review surveys recent advances in these three different approaches to the generation of nanostructured luminescently labeled nucleic acids, and includes both direct and indirect labeling methods.

Commercial chemiluminescent reagents emit across a broad portion of the electromagnetic spectrum (400–500 nm). A challenge to the use of chemiluminescence to monitor biological processes is the presence of interfering substances in the biological optical window. In the present study, longer wavelength emitting fluorophores (the organic dyes Alexa 568 and Alexa 647), and a semiconductor nanoparticle (QDOT800) were used to red-shift the emission from commercially available 1,2-dioxetane-based chemiluminescent substrate reactions. By adding non-conjugated fluorescent emitters into chemiluminescent reaction mixtures, an emission peak occurred at the predicted wavelength of the fluorescent emitter. The excitation and emission from QDOT800 was preserved in the presence of a 100 µm-thick glass barrier separating it from the chemiluminescent reaction components. The maximum tissue phantom penetration by QDOT800 emission was 8.5 mm; in comparison, the native chemiluminescent emission at 500 nm was unable to penetrate the thinnest tissue phantom of 2.5 mm. The described method for red-shifted emissions from chemiluminescent reactions does not require direct interaction between the chemiluminescent reaction and the fluorescent emitters. This suggests that the mechanism of chemiluminescent excitation of fluorophores and QDOT800 is not exclusive to chemiluminescence resonance energy transfer or sensitized chemiluminescence, but rather by broad energization from the native chemiluminescent emission. Copyright © 2014 John Wiley & Sons, Ltd.

Chemiluminescent reactions have found application in a number of commercial point-of-care and on-site testing devices. Notable examples include allergy tests (e.g., MASTpette, OPTIGEN® systems), flu tests (e.g., ZstatFlu®-II), cartridge-based immunoassay systems (FastPack® IP System, PATHFAST®), forensic tests for bloodstains, portable analyzers for biochip array assays (Evidence MultiStat), water quality tests (Eclox), air pollutants (e.g., oxides of nitrogen), and handheld devices for detecting explosives (e.g., E3500 Chemilux®). Many other point-of-care or on-site testing devices with a chemiluminescent end point have been devised on the basis of a variety of formats (e.g., cuvette, cassette, dipstick, test strip, microchip), but most have not progressed beyond a proof-of-principle or prototype stage.

In March 1876, when the telephone pioneer Alexander Graham Bell made his historic call to his assistant, Thomas Watson, it is unlikely that either one of them envisaged other applications for a phone, let alone the medical application of a phone that was published in March 2017 by Shafiee and colleagues in Science Translational Medicine (1) (Figure 1). It is equally unlikely that they would have believed that nearly 150 years later there would be mobile phones or that there would be more mobile phones than people on the planet. Fig. 1. Historical progress of the telephone from Alexander Graham Bell to modern-day smartphone-based semen analysis. Bell on the telephone in New York calling Chicago in 1892 \[Gilbert H. Grosvenor Collection, Prints and Photographs Division, Library of Congress. (Public domain), via Wikimedia Commons\] (https://commons.wikimedia.org/wiki/File:Alexander\_Graham\_Telephone\_in\_Newyork.jpg) (Accessed April 2017) (A). Smartphone semen testing (a. optical attachment, b. microfluidic chip) (Image courtesy of Hadi Shafiee) (1) (B). Modern-day hand-held mobile telephony can be traced back to the early 1970s, and the technology has evolved into the current app-laden “smartphone” that combines communication (voice, data, internet) and data storage capabilities with the features of other devices, such as an MP3 player and a digital camera/video camera. Smartphones have created interesting opportunities in wellness medical care and in diagnostic testing. There are now many apps available aimed at …

Photographic film and film technology have been put to many uses including an art medium as illustrated by the abstract landscape that I created in 1985. I simply took undeveloped Polaroid film and carefully squashed the developer pod to release developer and form the yellow-orange colored silhouette of a sulfurous cloud-shrouded landscape viewed through a window (Fig. 1). Others have also used Polaroid film for a similar purpose and created more spectacular and diverse abstract images either using a malfunctioning Polaroid SX-70 camera (1) or applying high voltage to instant film (2). Fig. 1. Polaroid art—a silhouette of a sulfurous cloud-shrouded landscape viewed through a window. This was created by squashing the developer pods of 4 undeveloped Polaroid instant film sheets and assembling them into a 2 × 2 grid (Larry J. Kricka, 1985) (photograph by Lorna Ebert, Lorna Ebert Photography, NC). Just as film technology has been unusually repurposed in …

Several emerging or disruptive technologies can be identified that might, at some point in the future, displace established laboratory medicine technologies and practices. These include increased automation in the form of robots, 3-D printing, technology convergence (e.g., plug-in glucose meters for smart phones), new point-of-care technologies (e.g., contact lenses with sensors, digital and wireless enabled pregnancy tests) and testing locations (e.g., Retail Health Clinics, new at-home testing formats), new types of specimens (e.g., cell free DNA), big biology/data (e.g., million genome projects), and new regulations (e.g., for laboratory developed tests). In addition, there are many emerging technologies (e.g., planar arrays, mass spectrometry) that might find even broader application in the future and therefore also disrupt current practice. One interesting source of disruptive technology may prove to be the Qualcomm Tricorder XPrize, currently in its final stages.

In a recent issue of Science Translational Medicine (1), Yock and colleagues of Stanford University discuss the merits and challenges of developing a discipline of medical technology innovation. Innovation is defined as “inventiveness put to use”; a discovery that results in a commercial product or service. In this provocative article, the authors discuss two main streams of educational theory and practice that together form the basis for teaching innovation: design thinking and entrepreneurship education (Fig. 1). Design thinking focuses on identifying the opportunity and need, developing the idea to solve the problem, building the prototype, and testing the product, while entrepreneurship education provides an introduction to the skills and approaches required to take a product or a service and successfully commercialize it. The authors argue that medical technology innovation is the ideal environment for interdisciplinary team building combining physicians, engineers, scientists, and business professionals. Fig. 1. Components of innovation as suggested in a recent review on biomedical technology innovation as a discipline [Yock et al. (1)]. Design thinking encompasses the creative roadmap toward innovation, including awareness of the opportunity or unsolved problem, an idea to fill the opportunity, development work to design and prototype the solution, and experimental testing as a reality check. Multiple cycles of ideas, prototyping, and testing may be required before a viable product emerges. Entrepreneurship assesses the feasibility of commercializing the product, including components of uniqueness (intellectual property) and market potential. Regulatory requirements and business strategy often suggest outcomes that may include in-house manufacturing, licensing, mergers/acquisitions, or an initial public offering (IPA). In laboratory medicine, numerous scientists and physicians have been able to successfully launch their inventions into the marketplace; inventions that changed the practice of medicine. Six of those inventors were invited to share their success stories with the readers of Clinical Chemistry. How did they do it? What influenced most their success? What were the major drivers for their pursuits? Did they have formal training in …

BACKGROUNDThis review was written as part of the celebration of the International Year of Chemistry 2011.CONTENTIn this review we provide a chronicle of the history of clinical chemistry, with a focus on North America. We outline major methodological advances and trace the development of professional societies and journals dedicated to clinical chemistry. This review also serves as a guide to reference materials for those interested in the history of clinical chemistry. The various resources available, in sound recordings, videos, moving images, image and document archives, museums, and websites dedicated to diagnostic company timelines, are surveyed.SUMMARYThese resources provide a map of how the medical subspecialty of clinical chemistry arrived at its present state. This information will undoubtedly help visionaries to determine in which direction clinical chemistry will move in the future.

Background: The inherent fluorescent properties of nucleosides, nucleotides, and nucleic acids are limited, and thus the need has arisen for fluorescent labeling of these molecules for a variety of analytical applications.Content: This review traces the analytical ancestry of fluorescent labeling of nucleosides, nucleotides, and nucleic acids, with an emphasis on the first to publish or patent. The scope of labeling includes (a) direct labeling by covalent labeling of nucleic acids with a fluorescent label or noncovalent binding or intercalation of a fluorescent dye to nucleic acids and (b) indirect labeling via covalent attachment of a secondary label to a nucleic acid, and then binding this to a fluorescently labeled ligand binder. An alternative indirect strategy involves binding of a nucleic acid to a nucleic acid binder molecule (e.g., antibody, antibiotic, histone, antibody, nuclease) that is labeled with a fluorophore. Fluorescent labels for nucleic acids include organic fluorescent dyes, metal chelates, carbon nanotubes, quantum dots, gold particles, and fluorescent minerals.Summary: Fluorescently labeled nucleosides, nucleotides, and nucleic acids are important types of reagents for biological assay methods and underpin current methods of chromosome analysis, gel staining, DNA sequencing and quantitative PCR. Although these methods use predominantly organic fluorophores, new types of particulate fluorophores in the form of nanoparticles, nanorods, and nanotubes may provide the basis of a new generation of fluorescent labels and nucleic acid detection methods.

The noncovalent immobilization of alkaline phosphatase (ALP) onto aqueous dispersed nylon 6 nanorods ( approximately 310 nm mean diameter; approximately 6 microm mean length) prepared by anodic aluminum oxide (AAO) membrane templating was studied. Using multi-stacked layer-by-layer (LBL) assembly with the cationic quaternary ammonium polymer Sapphire II , the amount of ALP enzyme loaded onto the polymer nanostructures was found to be 115+/-7 microg mg(-1) nanorod. The biofunctionalized nanorods were also characterized for their chemiluminescent activity with the dioxetane substrate, CSPD . The results indicate that the kinetic parameters, K(m) and V(max), for the catalytic activity of the nanostructure-bound ALP enzyme are different from those of soluble ('free') ALP. While the K(m) value was measured to be 156 microM for free ALP, the apparent K(m) value determined for the LBL-immobilized ALP is approximately 20% lower (122 microM). Furthermore, despite the relatively high enzyme loading capacity of the nanorods, the specific activity of the bound ALP enzyme was found to be almost nine times lower than that measured for free ALP. Finally, additional experiments revealed that the catalytic activities of both free ALP and nanorod-conjugated ALP are affected similarly by changes in pH, with optimal performance levels occurring under conditions of pH 9.5. To the best of our knowledge, this study represents the first report examining the preparation of aqueous dispersed, AAO-templated polymer nanorods for potential application as enzyme scaffolds in chemiluminescent-based assay systems.

Aqueous suspendible polymer nanostructures were prepared by simple microtome processing of electrospun nylon 6 nanofibers and were used to immobilize calf intestinal alkaline phosphatase (ALP) by either covalent or noncovalent bioconjugation chemistries. It was found that noncovalent immobilization of ALP to the mechanically cut nanofibers (mean length approximately 4 microm; mean diameter approximately 80 nm) using a multi-stacked, layer-by-layer (LBL) approach with the cationic polymer Sapphire II resulted in the highest enzyme loading (48.1 +/- 0.4 microg . mg(-1) nanofiber) when compared to other covalent immobilization methods based on glutaraldehyde crosslinking. The biofunctionalized nanofibers were also characterized for their chemiluminescent activity with the dioxetane substrate, CSPD. The results indicate that the kinetic parameters, K(m) and V(max), for the catalytic activity of the nanostructure-bound ALP enzyme were influenced by the particular types of immobilization methods employed. In terms of the overall catalytic performance of the various immobilized ALP systems, a single-stacked LBL assembly approach resulted in the highest level of enzymatic activity per unit mass of nanofiber support. To the best of our knowledge, this study represents the first report examining the preparation of mechanically shortened, aqueous dispersed electrospun polymer nanofibers for potential application as enzyme scaffolds in chemiluminescent-based assay systems.

Background: The NIH is committed to improving healthcare quality in the US and has set up initiatives to address problems such as the fragmented nature of healthcare provision. A hypothesis has been developed that testing closer to the point at which care is delivered may reduce fragmentation of care and improve outcomes. Methods: The National Institute of Biomedical Imaging and Bioengineering (NIBIB), the NIH’s National Heart, Lung, and Blood Institute, and the National Science Foundation sponsored a workshop, “Improving Health Care Accessibility through Point-of-Care Technologies,” in April 2006. The workshop assessed the clinical needs and opportunities for point-of-care (POC) technologies in primary care, the home, and emergency medical services and reviewed minimally invasive and noninvasive testing, including imaging, and conventional testing based on sensor and lab-on-a-chip technologies. Emerging needs of informatics and telehealth and healthcare systems engineering were considered in the POC testing context. Additionally, implications of evidence-based decision-making were reviewed, particularly as it related to the challenges in producing reliable evidence, undertaking regulation, implementing evidence responsibly, and integrating evidence into health policy. Results: Many testing procedures were considered to be valuable in the clinical settings discussed. Technological solutions were proposed to meet these needs, as well as the practical requirements around clinical process change and regulation. From these considerations, a series of recommendations was formulated for development of POC technologies based on input from the symposium attendees. Conclusion: NIBIB has developed a funding initiative to establish a Point-of-Care Technologies Research Network that will work to bridge the technology/clinical gap and provide the partnerships necessary for the application of technologies to pressing clinical needs in POC testing.

Nylon nanorods and nanotubes (200 nm diameter) were fabricated by the membrane wetting technique (solvent and melt wetting) from a range of nylons (6; 6,6; 6,9; 6,10; 6,12; 11; 12, 6(3)T) and nylon blended with different dyes (Nylon Cast Blue, Nylon 6/6 Black) or with molybdenum disulfide (Nylon cast MDS). The 65-μm long nylon nanotubes and nanorods were characterized by scanning electron microscopy. The nanoscale nylon 6,6 served as an effective high surface area alternative to a nylon membrane as a solid support in a chemiluminescent assay for nylon-bound biotinylated nucleic acids based on streptavidin- alkaline phosphatase and chemiluminescent detection of the bound alkaline phosphatase label with the dioxetane substrate, CDP-Star. Layer-by-layer deposition of the cationic polymer (Sapphire-II™; Tropix) onto the nylon 6,6 nanostructures prior to UV-cross-linking with biotinylated DNA resulted in further enhancement of binding and detection of biotinylated DNA.

The microarray has emerged as an important format for simultaneous analysis of tens of thousands of substances present in a sample. Successful adaptation of microarray assays to clinical diagnostics will require particular attention to issues of quality control and quality assurance. Results of an assay can be compromised by a number of preanalytical factors including the quality of the reagents (e.g., the microarray and the detection reagents) and the integrity of the sample. Similarly, numerous factors in the analytical phase of a microarray assay, including changes in the reaction conditions and calibration, can contribute to inaccuracy and imprecision. Furthermore, a microarray combines many reagents or samples in a single device and therefore presents additional issues not usually encountered in discrete testing of a single analyte in a single sample. Various strategies (e.g., replicate analysis, array orientation control features, on-array controls, normalization) have been implemented to control and assess analytical factors that might compromise data generated from a microarray. The current range of measures taken to ensure the analytical accuracy and quality of data generated from protein microarrays is reviewed in the context of the lessons learned from DNA microarrays. The special considerations for protein microarrays as they transition from research into routine clinical analysis and the resulting quality control of clinical test results generated using such devices are discussed.

Nanotechnology has considerable promise for the detection, staging and treatment of cancer. Here, we outline one such promising application: the use of nanostructures with surface-bound ligands for the targeted delivery and ablation of colorectal cancer (CRC), the third most common malignancy and the second most common cause of cancer-related mortality in the US. Normal colonic epithelial cells as well as primary CRC and metastatic tumors all express a unique surface-bound guanylyl cyclase C (GCC), which binds the diarrheagenic bacterial heat-stable peptide enterotoxin ST. This makes GCC a potential target for metastatic tumor ablation using ST-bound nanoparticles in combination with thermal ablation with near-infrared or radiofrequency energy absorption. Furthermore, the incorporation of iron or iron oxide into such structures would provide advantages for magnetic resonance imaging (MRI). Although the scenarios outlined in this article are hypothetical, they might stimulate ideas about how other cancers could be attacked using nanotechnology.

Multiplexed protein analysis using planar microarrays or microbeads is growing in popularity for simultaneous assays of antibodies, cytokines, allergens, drugs and hormones. However, this new assay format presents several new operational issues for the clinical laboratory, such as the quality control of protein-microarray-based assays, the release of unrequested test data and the use of diagnostic algorithms to transform microarray data into diagnostic results.

Clinical analysis often requires rapid, automated, and high-throughput analytical systems. Microchip capillary electrophoresis (CE) has the potential to achieve very rapid analysis (typically seconds), easy integration of multiple analytical steps, and parallel operation. Although it is currently still in an early stage of development, there are already many reports in the literature describing the applications of microchip CE in clinical analysis. At the same time, more fully automated and higher throughput commercial instruments for microchip CE are becoming available and are expected to further enhance the development of applications of microchip CE in routine clinical testing. To put into perspective its potential, we briefly compare microchip CE with conventional CE and review developments in this technique that may be useful in diagnosis of major diseases.

There is no formal terminology used to describe the scope and use of microtechnology in the clinical laboratory. For many laboratory scientists, the word "microchip" is synonymous with high-density microarrays used primarily for investigating gene expression. The document proposes a system of "categories" and "descriptors" that facilitates the classification of a device in a way that communicates details of its function and analytical role, and describes the analytical principle involved and the methods and materials used for its manufacture. Adoption of this system would enable scientists to employ four descriptors that clearly delineate the function, analytical role, and chemical or physical principle involved in the device. Examples of existing commercial devices are given to illustrate the utility of the system.

We report the fabrication of silicon chips containing a row of 667 pillars, 10 by 20 microm in cross-section, etched to a depth of 80 microm with adjacent pillars being separated by 3.5 microm. The chips were used to separate white blood cells from whole blood in less than 2 min and for subsequent PCR of a genomic target (eNOS). Chip fluid dynamics were validated experimentally using CoventorWare microfluidic simulation software. The amplicon concentrations were determined using microchip capillary electrophoresis and were >40% of that observed in conventional PCR tubes for chips with and without pillars. Reproducible on-chip PCR was achieved using white blood cell preparations isolated from whole human blood pumped through the chip.

As more clinically relevant cancer genes are identified, comprehensive diagnostic approaches are needed to match patients to therapies, raising the challenge of optimization and analytical validation of assays that interrogate millions of bases of cancer genomes altered by multiple mechanisms. Here we describe a test based on massively parallel DNA sequencing to characterize base substitutions, short insertions and deletions (indels), copy number alterations and selected fusions across 287 cancer-related genes from routine formalin-fixed and paraffin-embedded (FFPE) clinical specimens. We implemented a practical validation strategy with reference samples of pooled cell lines that model key determinants of accuracy, including mutant allele frequency, indel length and amplitude of copy change. Test sensitivity achieved was 95–99% across alteration types, with high specificity (positive predictive value >99%). We confirmed accuracy using 249 FFPE cancer specimens characterized by established assays. Application of the test to 2,221 clinical cases revealed clinically actionable alterations in 76% of tumors, three times the number of actionable alterations detected by current diagnostic tests.

This article reviews the clinical applications of chemiluminescence in routine testing and surveys the diverse applications of chemiluminescence in clinical research. In routine clinical testing, chemiluminescent labels (acridinium ester, acridinium sulfonamide) and detection reactions for peroxidase and alkaline phosphatase enzyme labels (luminol and adamantyl 1,2-dioxetane-based reactions, respectively) are widely used in immunoassay and nucleic acid probe assays (e.g. hybridization protection assay, Hybrid Capture® assay). In clinical research the sensitivity, dynamic range and diversity of chemiluminescent assays has led to a vast range of applications, notably in protein and nucleic acid blotting, microarray-based assays, monitoring reactive oxygen species, and as detection reactions for substances separated by HPLC, capillary electrophoresis (CE), and flow-injection analysis.