Highly sensitive immunodiagnostics at the point of care employing alternative recognition elements and smartphones: hype,trend, or revolution?

Immunodiagnostic tests performed at the point of care (POC) today usually employ antibodies for biorecognition and are read out either visually or with specialized equipment. Availability of alternative biorecognition elements with promising features as well as smartphone-based approaches for signal readout, however, challenge the described established configuration in terms of analytical performance and practicability. Assessing these developments’ clinical relevance and their impact on POC immunodiagnostics is demanding. The first part of this review will therefore give an overview on suitable diagnostic biosensors based on alternative recognition elements (such as nucleic acid-based aptamers or engineered binding proteins) and exemplify advantages and drawbacks of these biomolecules on the base of selected assays. The second part of the review then focuses on smartphone-connected diagnostics and discusses the indispensable considerations required for successful future clinical POCT implementation. Together, the joint depiction of two of the most innovative and exciting developments in the field will enable the reader to cast a glance into the distant future of POC immunodiagnostics.

     

Rate measurement of D(0)-->K+pi(-)pi(0) and constraints on D(0) -- D(0) mixing

We present an observation and time-integrated rate measurement of the decay D(0)-->K(+)pi(-)pi(0) produced in 9 fb(-1) of e(+)e(-) collisions near the Upsilon(4S) resonance. The signal is inconsistent with an upward fluctuation of the background by 4.9 standard deviations. We measured the time-integrated rate of D(0)-->K(+)pi(-)pi(0) normalized to the rate of D(0)-->K(+)pi(-)pi(0) to be 0.0043(+0.0011)(-0.0010) (stat)+/-0.0007 (syst). This decay can be produced by doubly Cabibbo-suppressed decays or by the D(0) evolving into a D(0) through mixing, followed by a Cabibbo-favored decay to K(+)pi(-)pi(0). We also found the CP asymmetry A = (9(+25)(-22))% be consistent with zero.     

Study of exclusive radiative B meson decays

We have studied exclusive, radiative B meson decays to charmless mesons in 9.7x10(6) B&Bmacr; decays accumulated with the CLEO detector. We measure B(B0-->K(*0)(892)gamma) = (4.55(+0.72)(-0. 68)+/-0.34)x10(-5) and B(B+-->K(*+)(892)gamma) = (3.76(+0.89)(-0. 83)+/-0.28)x10(-5). We have searched for CP asymmetry in B-->K(*)(892)gamma decays and measure A(CP) = +0.08+/-0.13+/-0.03. We report the first observation of B-->K(*)(2)(1430)gamma decays with a branching fraction of (1.66(+0.59)(-0.53)+/-0.13)x10(-5). No evidence for the decays B-->rhogamma and B0-->omegagamma is found and we limit B(B-->(rho/omega)gamma)/B(B-->K(*)(892)gamma)<0.32 at 90% C.L.     

Transformations on [0, 1] with infinite invariant measures

Under certain regularity conditions a real transformation with indifferent fixed points has an infinite invariant measure equivalent to Lebesgue measure. In this paper several ergodic properties of such transformations are established.     

Zur Bestimmung von Ammoniak in Lebensmitteln

Zusammenfassung Ein von Burg u. Mook entwickelter, kleiner Vakuum-Destillationsapparat wurde das Gerät der Wahl: Nach den auch hier für ein schonendes Verfahren ermittelten optimalen Destillationsbedin-gungen können Ammoniakmengen im Mikrogrammbereich bei einer Mindestalkalität von pH 10 und einer Destillationstemperatur von etwa 25° C aus echten Lösungen innerhalb von 5 min, aus Suspensionen innerhalb von 15 min quantitativ freigesetzt werden.Das zur Beschleunigung des Übertreibens erforderliche Bewegen des ganzen Mikro-Vakuumapparates wurde durch ein selbstgebautes Sehüttelgerät mechanisiert und erlaubt Destillationen in Serie.Dabei wurden in Weizenmehlen nach verschiedenen Lagerungszeiten präformierte Ammoniumverbindungen, berechnet als Stickstoff, in einer Größenordnung von 10–30 mg/kg gefunden; darüber hinaus wurde jedoch keine Abspaltung von Ammoniak festgestellt.

---

Determination of ammonia in foodIV. Examination of the vacuum-micro-distillation methods, especially concerning the apparatus of Burg and Mook

A small apparatus for vacuum-micro-distillation developed by Burg and Mook finally gave satisfactory results: According to the optimum conditions for a careful procedure of distillation, which hereby were also tested, micrograms of ammonia can be liberated quantitatively from true solutions within 5 min and from suspensions within 15 min, provided that the alkalinity is at least pH 10 and the liquid mixture in the distillation flask has a temperature of approximately 25° C.In order to accelerate the procedure of distillation it is necessary to shake the whole apparatus; a selfmade shaker, which allows distillations in series, was employed for that purpose.Thereby, in wheat flours after different periods of storage, preformed ammonia compounds were found in a range of 10–30 mg/kg, calculated as nitrogen; but apart from this no releasing of ammonia was observed.

---

---

III. Mitteilung: diese Z. 250, 120 (1970).

---

Auszug aus der Dissertation W. Sturm: Zur Bestimmung von Ammoniak in Getreidemehlen und Backwaren. Technische Universität, Braunschweig 1967.     

Lithium-Salt Effects in Peptide Synthesis. Part I. Conditions for the Use of Lithium-Salts in Coupling Reactions

The influence of Li-salts on the course of peptide-coupling reactions was investigated. As a model for segment couplings, Ac-Phe-OH was coupled to HCl·H-Ala-OMe using the mixed anhydride, DCC1, DCCl/HOBt, BOP-Castro and TBTU-Knorr methods. As a model for stepwise synthesis Z-Phe-OH was coupled with HCl·Ala-O(t-Bu), using symmetrical anhydrides and active esters. The effects of salt additives such as LiCl, LiBr, LiC10₄, and ZnCl₂ on yields, side-product formation, racemisation, and reaction rates are reported.     

Copper(I) complexes, copper(I)/O(2) reactivity, and copper(II) complex adducts, with a series of tetradentate tripyridylalkylamine tripodal ligands

Copper(I) and copper(II) complexes possessing a series of related ligands with pyridyl-containing donors have been investigated. The ligands are tris(2-pyridylmethyl)amine (tmpa), bis[(2-pyridyl)methyl]-2-(2-pyridyl)ethylamine (pmea), bis[2-(2-pyridyl)ethyl]-(2-pyridyl)methylamine (pmap), and tris[2-(2-pyridyl)ethyl]amine (tepa). The crystal structures of the protonated ligand H(tepa)ClO(4), the copper(I) complexes [Cu(pmea)]PF(6) (1b-PF(6)), [Cu(pmap)]PF(6) (1c-PF(6)), and copper(II) complexes [Cu(pmea)Cl]ClO(4).H(2)O (2b-ClO(4).H(2)O), [Cu(pmap)Cl]ClO(4).H(2)O (2c-ClO(4).H(2)O), [Cu(pmap)Cl]ClO(4) (2c-ClO(4)), and [Cu(pmea)F](2)(PF(6))(2) (3b-PF(6)) were determined. Crystal data: H(tepa)ClO(4), formula C(21)H(25)ClN(4)O(4), triclinic space group P1, Z = 2, a = 10.386(2) A, b = 10.723(2) A, c = 11.663(2) A, alpha = 108.77(3) degrees, beta = 113.81(3) degrees, gamma = 90.39(3) degrees; 1b-PF(6), formula C(19)H(20)CuF(6)N(4)P, orthorhombic space group Pbca, Z = 8, a = 14.413(3) A, b = 16.043(3) A, c = 18.288(4) A, alpha = beta = gamma = 90 degrees; (1c-PF(6)), formula C(20)H(22)CuF(6)N(4)P, orthorhombic space group Pbca, Z = 8, a = 13.306(3) A, b = 16.936(3) A, c = 19.163(4) A, alpha = beta = gamma = 90 degrees; 2b-ClO(4).H(2)O, formula C(19)H(22)Cl(2)CuN(4)O(5), triclinic space group P1, Z = 4, a = 11.967(2) A, b = 12.445(3) A, c = 15.668(3) A, alpha = 84.65(3) degrees, beta = 68.57(3) degrees, gamma = 87.33(3) degrees; 2c-ClO(4).H(2)O, formula C(20)H(24)Cl(2)CuN(4)O(5), monoclinic space group P2(1)/c, Z = 4, a = 11.2927(5) A, b = 13.2389(4) A, c = 15.0939(8) A, alpha = gamma = 90 degrees, beta = 97.397(2) degrees; 2c-ClO(4), formula C(20)H(22)Cl(2)CuN(4)O(4), monoclinic space group P2(1)/c, Z = 4, a = 8.7682(4) A, b = 18.4968(10) A, c = 13.2575(8) A, alpha = gamma = 90 degrees, beta = 94.219(4) degrees; 3b-PF(6), formula [C(19)H(20)CuF(7)N(4)P](2), monoclinic space group P2(1)/n, Z = 2, a = 11.620(5) A, b = 12.752(5) A, c = 15.424(6) A, alpha = gamma = 90 degrees, beta = 109.56(3) degrees. The oxidation of the copper(I) complexes with dioxygen was studied. [Cu(tmpa)(CH(3)CN)](+) (1a) reacts with dioxygen to form a dinuclear peroxo complex that is stable at low temperatures. In contrast, only a very labile peroxo complex was observed spectroscopically when 1b was reacted with dioxygen at low temperatures using stopped-flow kinetic techniques. No dioxygen adduct was detected spectroscopically during the oxidation of 1c, and 1d was found to be unreactive toward dioxygen. Reaction of dioxygen with 1a-PF(6), 1b-PF(6), and 1c-PF(6) at ambient temperatures leads to fluoride-bridged dinuclear copper(II) complexes as products. All copper(II) complexes were characterized by UV-vis, EPR, and electrochemical measurements. The results manifest the dramatic effects of ligand variations and particularly chelate ring size on structure and reactivity.