Spherical nucleic acids Cutler, Joshua I; Auyeung, Evelyn; Mirkin, Chad A
Journal of the American Chemical Society,
01/2012, Letnik:
134, Številka:
3
Journal Article
Recenzirano
A historical perspective of the development of spherical nucleic acid (SNA) conjugates and other three-dimensional nucleic acid nanostructures is provided. This Perspective details the synthetic ...methods for preparing them, followed by a discussion of their unique properties and theoretical and experimental models for understanding them. Important examples of technological advances made possible by their fundamental properties spanning the fields of chemistry, molecular diagnostics, gene regulation, medicine, and materials science are also presented.
The inclusion of dynamical and static electron correlation (SEC) is mandatory for accurate quantum chemistry (QC). SEC is particularly difficult to calculate and hence a qualitative understanding is ...important to judge the applicability of approximate QC methods. Existing scalar SEC diagnostics, however, lack the important information where the SEC effects occur in a molecule. We introduce an analysis tool based on a fractional occupation number weighted electron density (ρFOD) that is plotted in 3D for a pre‐defined contour surface value. The scalar field is obtained by finite‐temperature DFT calculations with pre‐defined electronic temperature (e.g. TPSS at 5000 K). FOD plots only show the contribution of the “hot” (strongly correlated) electrons. We discuss illustrative plots for a broad range of chemical systems from small molecules to large conjugated molecules with polyradicaloid character. Spatial integration yields a single number which can be used to globally quantify SEC.
Hot FOD: The inclusion of static electron correlation (SEC) is mandatory for accurate quantum chemistry yet is particularly difficult to calculate. An analysis tool is developed based on a fractional occupation number weighted electron density (ρFOD) that is plotted as an isosurface and shows the “hot” (strongly correlated) electrons. Spatial integration of ρFOD yields a single number which can be used to globally quantify SEC.
"Paper Machine" for Molecular Diagnostics Connelly, John T; Rolland, Jason P; Whitesides, George M
Analytical chemistry (Washington),
08/2015, Letnik:
87, Številka:
15
Journal Article
Recenzirano
Odprti dostop
Clinical tests based on primer-initiated amplification of specific nucleic acid sequences achieve high levels of sensitivity and specificity. Despite these desirable characteristics, these tests have ...not reached their full potential because their complexity and expense limit their usefulness to centralized laboratories. This paper describes a device that integrates sample preparation and loop-mediated isothermal amplification (LAMP) with end point detection using a hand-held UV source and camera phone. The prototype device integrates paper microfluidics (to enable fluid handling) and a multilayer structure, or a "paper machine", that allows a central patterned paper strip to slide in and out of fluidic path and thus allows introduction of sample, wash buffers, amplification master mix, and detection reagents with minimal pipetting, in a hand-held, disposable device intended for point-of-care use in resource-limited environments. This device creates a dynamic seal that prevents evaporation during incubation at 65 °C for 1 h. This interval is sufficient to allow a LAMP reaction for the Escherichia coli malB gene to proceed with an analytical sensitivity of 1 double-stranded DNA target copy. Starting with human plasma spiked with whole, live E. coli cells, this paper demonstrates full integration of sample preparation with LAMP amplification and end point detection with a limit of detection of 5 cells. Further, it shows that the method used to prepare sample enables concentration of DNA from sample volumes commonly available from fingerstick blood draw.
In this article, I discuss some of the emerging applications and the future opportunities and challenges created by the use of mobile phones and their embedded components for the development of ...next-generation imaging, sensing, diagnostics and measurement tools. The massive volume of mobile phone users, which has now reached ~7 billion, drives the rapid improvements of the hardware, software and high-end imaging and sensing technologies embedded in our phones, transforming the mobile phone into a cost-effective and yet extremely powerful platform to run, e.g., biomedical tests, and perform scientific measurements that would normally require advanced laboratory instruments. This rapidly evolving and continuing trend will help us transform how medicine, engineering and sciences are practiced and taught globally.
Der empfindliche Nachweis von bakteriellen Infektionen ist eine Voraussetzung für deren erfolgreiche Behandlung. Die Verwendung von chemilumineszenten Sonden wurde bisher durch deren unzureichende ...Anreicherung in den Erregern erschwert. Wir koppelten Siderophoreinheiten, welche über das bakterielle Eisentransportsystem in Pathogenen angereichert werden, mit enzymatisch aktivierbaren Dioxetanen und erhielten sieben trifunktionale Sonden, die hohe Signal‐zu‐Hintergrund‐Verhältnisse (S/H=426‐859) aufwiesen. Die Eisentransportfähigkeit der Sonden wurde durch Experimente zur Wiederherstellung des Wachstums in Siderophor‐defizienten Mutanten gezeigt. Desferrioxamin‐Konjugate markierten alle Erreger des ESKAPE‐Panels mit einem hellen Chemilumineszenzsignal, während die Signale von Catechol‐Konjugaten aufgrund von Selbstquenchingeffekten generell schwächer ausfielen. Die Sonden konnten Bakterien in infizierten Lungenepithelzellen nachweisen. Die beste Sonde 8 wies 9.1×103 KBE mL−1 von S. aureus und 5.0×104 KBE mL−1 von P. aeruginosa nach, während die strukturell ähnliche Fluoreszenzsonde 10 205–305fach weniger empfindlich war. Die Daten qualifizieren Siderophor‐Dioxetan‐Sonden für den selektiven und empfindlichen Nachweis von Bakterien.
Eine sensitive Diagnostik ist für die erfolgreiche Behandlung von bakteriellen Infektionen entscheidend. Die Konjugation von Bakterien‐spezifischen, aktiv transportierten Siderophor‐Vektoren an enzyminduzierbare, chemilumineszente Dioxetanen ermöglichte den Nachweis eines breiten Spektrums von „ESKAPE“‐Pathogenen. Die Sonden zeigten eine hohe Empfindlichkeit in menschlichem Plasma und wiesen zudem intrazelluläre gram‐positive und ‐negative Bakterien nach.
Separation and sorting of micron-sized particles has great importance in diagnostics, chemical and biological analyses, food and chemical processing and environmental assessment. By employing the ...unique characteristics of microscale flow phenomena, various techniques have been established for fast and accurate separation and sorting of microparticles in a continuous manner. The advancements in microfluidics enable sorting technologies that combine the benefits of continuous operation with small-sized scale suitable for manipulation and probing of individual particles or cells. Microfluidic sorting platforms require smaller sample volume, which has several benefits in terms of reduced cost of reagents, analysis time and less invasiveness to patients for sample extraction. Additionally, smaller size of device together with lower fabrication cost allows massive parallelization, which makes high-throughput sorting possible. Both passive and active separation and sorting techniques have been reported in literature. Passive techniques utilize the interaction between particles, flow field and the channel structure and do not require external fields. On the other hand, active techniques make use of external fields in various forms but offer better performance. This paper provides an extensive review of various passive and active separation techniques including basic theories and experimental details. The working principles are explained in detail, and performances of the devices are discussed.
The ability of mass spectrometry imaging (MSI) to localize panels of biomolecules in tissues, without prior knowledge of their presence and in a label-free manner, has led to a rapid and substantial ...impact in clinical and pharmacological research, uncovering biomolecular changes associated with disease and providing low cost imaging of pharmaceuticals. This Feature article will give an introduction to the capabilities and role of MSI in the clinical analysis of patient tissues and discusses those improvements that are necessary for the progression of MSI toward routine clinical application.
PDF
