We developed an integrated chip for real-time amplification and detection of nucleic acid using pH-sensing complementary metal-oxide semiconductor (CMOS) technology. Here we show an amplification-coupled detection method for directly measuring released hydrogen ions during nucleotide incorporation rather than relying on indirect measurements such as fluorescent dyes. This is a label-free, non-optical, real-time method for detecting and quantifying target sequences by monitoring pH signatures of native amplification chemistries. The chip has ion-sensitive field effect transistor (ISFET) sensors, temperature sensors, resistive heating, signal processing and control circuitry all integrated to create a full system-on-chip platform. We evaluated the platform using two amplification strategies: PCR and isothermal amplification. Using this platform, we genotyped and discriminated unique single-nucleotide polymorphism (SNP) variants of the cytochrome P450 family from crude human saliva. We anticipate this semiconductor technology will enable the creation of devices for cost-effective, portable and scalable real-time nucleic acid analysis.

There was no significant difference in the effectiveness of INF and IVM for prehospital analgesia.

The reaction kinetics for the addition of the muonium (Mu = Jl, + e-) atom to C 2 H 4 and C 2 D 4 have been measured over the temperature range 150-500 K at (N 2 ) moderator pressures near 1 atm. A factor of about 8 variation in moderator pressure was carried out for C 2 H 4 , with no significant change seen in the apparent rate constant k app , which is therefore taken to be at the high pressure limit, yielding the bimolecular rate constant k Mu for the addition step. This is also expected from the nature of the Jl,SR technique employed, which, in favorable cases, gives kapp = k Mu at any pressure. Comparisons with the H atom data of Lightfoot and Pilling, and Sugawara et al. and the D atom data of Sugawara et al. reveal large isotope effects. Only at the highest temperatures, near 500 K, is k Mulk H given by its classical value of2.9, from the mean velocity dependence ofthe collision rate but at the lowest temperatures kMulkH ~ 3011 is seen, reflecting the pronounced tunneling ofthe much lighter Mu atom (mIL = 1/9 m p )' The present Mu results should provide accurate tests of reaction theories on currently available ab initio surfaces.

Using the basic muon-spin-rotation technique, the fractions of energetic positive muons thermalizing in diamagnetic environments (f") or as the paramagnetic muonium atom M& ---, M&.Muons are produced with kinetic energies of 4.1 MeV or greater, far larger than the energy regime of atomic interest. During its slowing down process in matter, the p+ undergoes charge exchange with molecules X of the medium, @++X~(p+e ) +X+, in complete analogy with proton charge exchange. The neutral muonium atom (Mu) formed with cross section o. io has as its nucleus a positive muon but otherwise can be regarded simply as a light isotope of the hydrogen atom. ' ' The fraction of muons that thermalize in matter as either "free" p+ or as Mu atoms can easily be measured and interpreted in terms of well-established concepts in proton charge exchange.There are three basic things to be learned from 26 2527 1982 The American Physical Society FLEMING, MIKULA, AND) GARNER the present study.(1) Unlike the proton experiments, the p+ beam stops in the gas so that, in principle, one is able to probe the regime of charge exchange on the approach to thermal energies. In this regard, the information content is similar to that available from protons as thick target yields.