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.

BackgroundThe number of ambulatory patients seeking treatment for skin and skin structure infections (SSSI) are increasing. The objective of this study is to determine recent trends in hospital admissions and healthcare resource utilization and identify covariates associated with hospital costs and mortality for hospitalized adult patients with a primary SSSI diagnosis in the United States.MethodsWe performed a retrospective cross-sectional analysis (years 2005–2011) of data from the US Healthcare Cost and Utilization Project National Inpatient Sample. Recent trends, patient characteristics, and healthcare resource utilization for patients hospitalized with a primary SSSI diagnosis were evaluated. Descriptive and bivariate analyses were conducted to assess patient and hospital characteristics.ResultsA total of 1.8% of hospital admissions for the years 2005 through 2011 were for adult patients with a SSSI primary diagnosis. SSSI-related hospital admissions significantly changed during the study period (P < .001 for trend) ranging from 1.6% (in 2005) to 2.0% (in 2011). Mean hospital length of stay (LOS) decreased from 5.4 days in the year 2005 to 5.0 days in the year 2011 (overall change, P < .001) with no change in hospital costs. Patients with postoperative wound infections had the longest hospital stays (adjusted mean, 5.81 days; 95% confidence interval (CI), 5.80–5.83) and highest total costs (adjusted mean, $9388; 95% CI, $9366-$9410). Year of hospital admission was strongly associated with mortality; infection type, all patient refined diagnosis related group severity of illness level, and LOS were strongly associated with hospital costs.ConclusionsHospital admissions for adult patients in the United States with a SSSI primary diagnosis continue to increase. Decreasing hospital inpatient LOS and mortality rate may be due to improved early treatment. Future research should focus on identifying alternative treatment processes for patients with SSSI that could shift management from inpatient to outpatient treatment settings.

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A convenient and clean procedure of esterification is reported by direct condensation of equimolar amounts of carboxylic acids with alcohols catalyzed by an easy to prepare catalyst system of perchloric acid immobilized on silica gel (HClO(4)-SiO(2)). The direct condensation of aryl, heteroaryl, styryl, aryl alkyl, alkyl, cycloalkyl, and long-chain aliphatic carboxylic acids with primary/secondary alkyl/cycloalkyl, allyl, propargyl, and long-chain aliphatic alcohols has been achieved to afford the corresponding esters in excellent yields. Chiral alcohol and N-t-Boc protected chiral amino acid also resulted in ester formation with the representative carboxylic acid or alcohol without competitive N-t-Boc deprotection and detrimental effect on the optical purity of the product demonstrating the mildness and chemoselectivity of the procedure. The esters of long-chain (>C(10)) acids and alcohols are obtained in high yields. The catalyst is recovered and recycled without significant loss of activity. The industrial application of the esterification process is demonstrated by the synthesis of prodrugs of ibuprofen and a few commercial flavoring agents. Other protic acids such as H(2)SO(4), HBr, TfOH, HBF(4), and TFA that were adsorbed on silica gel were less effective compared to HClO(4)-SiO(2) following the order HClO(4)-SiO(2) >> H(2)SO(4)-SiO(2) > HBr-SiO(2) > TfOH-SiO(2) >> HBF(4)-SiO(2) approximately TFA-SiO(2). When HClO(4) was immobilized on other solid supports the catalytic efficiency followed the order HClO(4)-SiO(2) > HClO(4)-K10 > HClO(4)-Al(2)O(3) (neutral) > HClO(4)-Al(2)O(3) (acidic) > HClO(4)-Al(2)O(3) (basic).

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