Better biomarkers are urgently needed to improve diagnosis, guide molecularly targeted therapy and monitor activity and therapeutic response across a wide spectrum of disease. Proteomics methods based on mass spectrometry hold special promise for the discovery of novel biomarkers that might form the foundation for new clinical blood tests, but to date their contribution to the diagnostic armamentarium has been disappointing. This is due in part to the lack of a coherent pipeline connecting marker discovery with well-established methods for validation. Advances in methods and technology now enable construction of a comprehensive biomarker pipeline from six essential process components: candidate discovery, qualification, verification, research assay optimization, biomarker validation and commercialization. Better understanding of the overall process of biomarker discovery and validation and of the challenges and strategies inherent in each phase should improve experimental study design, in turn increasing the efficiency of biomarker development and facilitating the delivery and deployment of novel clinical tests.

Protein biomarker discovery and validation: the long and uncertain path to clinical utility.

A gas sensor, fabricated by the simple casting of single-walled carbon nanotubes (SWNTs) on an interdigitated electrode (IDE), is presented for gas and organic vapor detection at room temperature. The sensor responses are linear for concentrations of sub ppm to hundreds of ppm with detection limits of 44 ppb for NO2 and 262 ppb for nitrotoluene. The time is on the order of seconds for the detection response and minutes for the recovery. The variation of the sensitivity is less than 6% for all of the tested devices, comparable with commercial metal oxide or polymer microfilm sensors while retaining the room-temperature high sensitivity of the SWNT transistor sensors and manufacturability of the commercial sensors. The extended detection capability from gas to organic vapors is attributed to direct charge transfer on individual semiconducting SWNT conductivity with additional electron hopping effects on intertube conductivity through physically adsorbed molecules between SWNTs.

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Carbon Nanotube Sensors for Gas and Organic Vapor Detection

Nomenclature in evaluation of analytical methods including detection and quantification capabilities (IUPAC Recommendations 1995)

Mass cytometry enables high-dimensional, single-cell analysis of cell type and state. In mass cytometry, rare earth metals are used as reporters on antibodies. Analysis of metal abundances using the mass cytometer allows determination of marker expression in individual cells. Mass cytometry has previously been applied only to cell suspensions. To gain spatial information, we have coupled immunohistochemical and immunocytochemical methods with high-resolution laser ablation to CyTOF mass cytometry. This approach enables the simultaneous imaging of 32 proteins and protein modifications at subcellular resolution; with the availability of additional isotopes, measurement of over 100 markers will be possible. We applied imaging mass cytometry to human breast cancer samples, allowing delineation of cell subpopulations and cell-cell interactions and highlighting tumor heterogeneity. Imaging mass cytometry complements existing imaging approaches. It will enable basic studies of tissue heterogeneity and function and support the transition of medicine toward individualized molecularly targeted diagnosis and therapies.

Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry

Achieving high sensitivity in solid-state gas sensors can allow the precise detection of chemical agents. In particular, detection of volatile organic compounds (VOCs) at the parts per billion (ppb) level is critical for the early diagnosis of diseases. To obtain high sensitivity, two requirements need to be simultaneously satisfied: (i) low electrical noise and (ii) strong signal, which existing sensor materials cannot meet. Here, we demonstrate that 2D metal carbide MXenes, which possess high metallic conductivity for low noise and a fully functionalized surface for a strong signal, greatly outperform the sensitivity of conventional semiconductor channel materials. Ti3C2Tx MXene gas sensors exhibited a very low limit of detection of 50–100 ppb for VOC gases at room temperature. Also, the extremely low noise led to a signal-to-noise ratio 2 orders of magnitude higher than that of other 2D materials, surpassing the best sensors known. Our results provide insight in utilizing highly functionalized metallic...

Metallic Ti3C2Tx MXene Gas Sensors with Ultrahigh Signal-to-Noise Ratio

Guidelines for calibration in analytical chemistry. Part I. Fundamentals and single component calibration (IUPAC Recommendations 1998)

Chairman: G. Svehla (UK), Secretary: S . P. Perone (USA). Titular Members: C. A. M. G. Cramers (Netherlands), R. W. Frei (Netherlands), R. E. van Grieken (Belgium), D. Klockow (FRG). Associate Members: L. Currie (USA), L. S . Ettre (USA), A. Fein (USA), H. Freiser (USA), W. Horwitz (USA), M. A. Leonard (UK), D. Leyden (USA), R. F. Martin (USA), B. Schreiber (Switzerland). National Representatives: K. Doerffel (GDR), I. Giolito (Brazil), E. Grushka (Israel), W. E. Harris (Canada), H. M. N. H. Irving ( S . African Republic), D. Jagner (Sweden), W. Rosset (France), J. Stary (Czechoslovakia).

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Nomenclature for the presentation of results of chemical analysis (IUPAC Recommendations 1994)

Calibration in analytical chemistry refers to the relation between sample domain and measurement domain (signal domain) expressed by an analytical function x = fs(Q) representing a pattern of chemical species Q and their amounts or concentrations x in a given test sample on the one hand and a measured function y = f(z) that may be a spectrum, chromatogram, etc. Simultaneous multispecies analyses are carried out mainly by spectroscopic and chromatographic methods in a more or less selective way. For the determination of n species Qi (i = 1,2 …n), at least n signals must be measured which should be well separated in the ideal case. In analytical practice, the situation can be different.

Guidelines for calibration in analytical chemistry. Part 2: Multicomponent calibration (IUPAC Technical Report)

Calibration in analytical chemistry refers to the relation between sample domain and measurement domain (signal domain) expressed by an analytical function x = fs(Q) representing a pattern of chemical species Q and their amounts or concentrations x in a given test sample on the one hand and a measured function y = f(z) that may be a spectrum, chromatogram, etc. Simultaneous multispecies analyses are carried out mainly by spectroscopic and chromatographic methods in a more or less selective way. For the determination of n species Qi (i = 1, 2...n), at least n signals must be measured which should be well separated in the ideal case. In analytical practice, the situation can be different. CONTENTS

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Lloyd A. Currie

Papers

Nomenclature in evaluation of analytical methods including detection and quantification capabilities (IUPAC Recommendations 1995)

Guidelines for calibration in analytical chemistry. Part I. Fundamentals and single component calibration (IUPAC Recommendations 1998)

Nomenclature for the presentation of results of chemical analysis (IUPAC Recommendations 1994)

Guidelines for calibration in analytical chemistry. Part 2: Multicomponent calibration (IUPAC Technical Report)

Guidelines for calibration in analytical chemistry part 2. multispecies calibration