Development of a conductivity-based photothermal absorbance detection microchip using polyelectrolytic gel electrodes.

The development and application of polyelectrolytic gel electrodes (PGEs) for a microfluidic photothermal absorbance detection system is described. The PGEs are used to measure changes in conductivity based on heat generation by analytes absorbing light and changing the solution viscosity. The PGEs are suitable for direct contact conductivity measurements since they do not degrade with exposure to high electric fields. Both a 2-electrode system with DC voltages and a 3-electrode system with AC voltages were investigated. Experimental factors including excitation voltage, excitation frequency, laser modulation frequency, laser power, and path length were tested. The limits of detection for the 3-electrode and 2-electrode systems are 500nM and 0.55nM for DABSYL-tagged glucosamine, respectively. In addition, an electrokinetic separation of a potassium, DABSYL-tagged glucosamine, Rhodamine 6G, and Rhodamine B mixture was demonstrated.

Low voltage picoliter droplet manipulation utilizing electrowetting-on-dielectric platforms.

Picoliter droplets actuated on an electrowetting-on-dielectric (EWD) actuator are demonstrated. In this study, the physical scaling of electrodes for 33 µm and 21 µm EWD devices resulted in droplets of 12 pl and 5 pl being dispensed respectively in conjunction with 3 µm SU8 gaskets. The stacked multi-layer insulators in the actuators consisted of 200 nm tantalum pentoxide (Ta2O5) and 200 nm parylene C films deposited and coated with 70 nm of CYTOP. The voltages for dispensing droplets on chips without any external pressure sources are 17.1 Vrms and 22 Vrms for these two sets of devices. A 12 pl droplet can be split into two 6 pl daughter droplets at 18.7 Vrms with 33 µm electrode devices. Droplet manipulation is also demonstrated with paramagnetic beads and buffer solutions with proteins. In addition, electrodes with interlocking protrusions and special featured reservoir gasket are designed to facilitate droplet dispensing on these scaled EWD devices. In order to improve sealing of the two-piece sandwich EWD structure, a soft material, Norland Optical Adhesive (NOA), was coated on the top plate along with pressure on top. We demonstrate that based on fundamental theories and experiments, the dimensional scaling of EWD devices has not yet met a limitation as long as the EWD device can be sealed well.

Picoliter DNA sequencing chemistry on an electrowetting-based digital microfluidic platform.

The results of investigations into performing DNA sequencing chemistry on a picoliter-scale electrowetting digital microfluidic platform are reported. Pyrosequencing utilizes pyrophosphate produced during nucleotide base addition to initiate a process ending with detection through a chemiluminescence reaction using firefly luciferase. The intensity of light produced during the reaction can be quantified to determine the number of bases added to the DNA strand. The logic-based control and discrete fluid droplets of a digital microfluidic device lend themselves well to the pyrosequencing process. Bead-bound DNA is magnetically held in a single location, and wash or reagent droplets added or split from it to circumvent product dilution. Here we discuss the dispensing, control, and magnetic manipulation of the paramagnetic beads used to hold target DNA. We also demonstrate and characterize the picoliter-scale reaction of luciferase with adenosine triphosphate to represent the detection steps of pyrosequencing and all necessary alterations for working on this scale.

Low Voltage Electrowetting-on-Dielectric Platform using Multi-Layer Insulators.

A low voltage, two-level-metal, and multi-layer insulator electrowetting-on-dielectric (EWD) platform is presented. Dispensing 300pl droplets from 140nl closed on-chip reservoirs was accomplished with as little as 11.4V solely through EWD forces, and the actuation threshold voltage was 7.2V with a 1Hz voltage switching rate between electrodes. EWD devices were fabricated with a multilayer insulator consisting of 135nm sputtered tantalum pentoxide (Ta(2)O(5)) and 180nm parylene C coated with 70nm of CYTOP. Furthermore, the minimum actuation threshold voltage followed a previously published scaling model for the threshold voltage, V(T), which is proportional to (t/ε(r))(1/2), where t and ε(r) are the insulator thickness and dielectric constant respectively. Device threshold voltages are compared for several insulator thicknesses (200nm, 500nm, and 1µm), different dielectric materials (parylene C and tantalum pentoxide), and homogeneous versus heterogeneous compositions. Additionally, we used a two-level-metal fabrication process, which enables the fabrication of smaller and denser electrodes with high interconnect routing flexibility. We also have achieved low dispensing and actuation voltages for scaled devices with 30pl droplets.

Noninvasive assessment of dermal carotenoids as a biomarker of fruit and vegetable intake.

BACKGROUND: Resonance Raman spectroscopy (RRS) has been suggested as a feasible method for noninvasive carotenoid measurement of human skin. However, before RRS measures of dermal carotenoids can be used as a biomarker, data on intra- and intersubject variability and validity are needed. OBJECTIVE: The purpose of this study was to evaluate the reproducibility and validity of RRS measures of dermal total carotenoids and lycopene in humans. DESIGN: In study 1, 74 men and women with diverse skin pigmentation were recruited. RRS measures of the palm, inner arm, and outer arm were obtained at baseline, 1 wk, 2 wk, 1 mo, 3 mo, and 6 mo (to maximize seasonal variation). The RRS device used visible light at 488 nm to estimate total carotenoids and at 514 nm to estimate lycopene. Reproducibility was assessed by intraclass correlation coefficients (ICCs). In study 2, we recruited 28 subjects and assessed dietary carotenoid intake, obtained blood for HPLC analyses, performed RRS measures of dermal carotenoid status, and performed dermal biopsies (3-mm punch biopsy) with dermal carotenoids assessed by HPLC. RESULTS: ICCs for total carotenoids across time were 0.97 (palm), 0.95 (inner arm), and 0.93 (outer arm). Total dermal carotenoids assessed by RRS were significantly correlated with total dermal carotenoids assessed by HPLC of dermal biopsies (r = 0.66, P = 0.0001). Similarly, lycopene assessed by RRS was significantly correlated with lycopene assessed by HPLC of dermal biopsies (r = 0.74, P < 0.0001). CONCLUSION: RRS is a feasible and valid method for noninvasively assessing dermal carotenoids as a biomarker for studies of nutrition and health.

Significant correlations of dermal total carotenoids and dermal lycopene with their respective plasma levels in healthy adults.

Carotenoids in skin have been known to play a role in photoprotection against UV radiation. We performed dermal biopsies of healthy humans (N=27) and collected blood samples for pair-wise correlation analyses of total and individual carotenoid content by high performance liquid chromatography (HPLC). The hydrocarbon carotenoids (lycopene and beta-carotene) made up the majority of carotenoids in both skin and plasma, and skin was somewhat enriched in these carotenoids relative to plasma. Beta-cryptoxanthin, a monohydroxycarotenoid, was found in similar proportions in skin as in plasma. In contrast, the dihydroxycarotenoids, lutein and zeaxanthin, were relatively lacking in human skin in absolute and relative levels as compared to plasma. Total carotenoids were significantly correlated in skin and plasma (r=0.53, p<0.01). Our findings suggest that human skin is relatively enriched in lycopene and beta-carotene, compared to lutein and zeaxanthin, possibly reflecting a specific function of hydrocarbon carotenoids in human skin photoprotection.

Development of a photothermal absorbance detector for use with microfluidic devices.

The development of a photothermal absorbance detector for use with microfluidic devices is described. Unlike thermo-optical techniques that rely on measuring refractive index changes, the solution viscosity is probed by continuously monitoring solution conductivity. Platinum electrodes microfabricated on a quartz substrate and bonded to a substrate containing the microchannels enable contact conductivity measurements. The effects of excitation frequency and voltage, electrode spacing, laser power, and laser modulation (chopping) frequency were evaluated experimentally. In the current configuration, a limit of detection of 5 nM for DABSYL-tagged glucosamine was obtained using long injections (to give flat-topped peaks). This corresponds to an absorbance of 4.4 x 10(-7) AU. Separation and detection of DABSYL-tagged glycine, proline, and tryptophan are also shown to demonstrate the feasibility of the method. In addition, simulations were used to investigate the applicability of the technique to small volume platforms.

Assessment of the impact of medication therapy management delivered to home-based Medicare beneficiaries.

BACKGROUND: Medication Therapy Management (MTM) is a voluntary patient participation program mandated for Medicare Part D sponsors by the Centers for Medicare and Medicaid Services for chronically ill beneficiaries with high medication costs/utilization. OBJECTIVE: To assess the impact of an MTM program on mortality, healthcare utilization, and prescription medication costs and to quantify drug-related problems (DRPs) identified during MTM. METHODS: This nonrandomized controlled study was conducted among beneficiaries who were targeted for MTM in 2006. The MTM intervention was designed to identify potential DRPs, educate the patient/caregiver about appropriate medication use, and ensure that the patient was appropriately integrated into clinical services. Data were collected from administrative databases and manual chart abstractions. Study outcomes included all-cause death (primary outcome), hospitalization, and emergency department (ED) visit rates and medication cost changes in the 180 days following MTM targeting and quantification of DRPs. Multivariate logistic regression was used to adjust the outcomes for baseline risk and other potential confounders. A mock MTM intervention was performed for beneficiaries who declined MTM and died, were hospitalized, and/or made an ED visit. RESULTS: A total of 459 opt-in and 336 opt-out beneficiaries who agreed and declined, respectively, to receive MTM were included in the analysis. Beneficiaries who opted in were less likely to die compared with beneficiaries who opted out (adjusted OR [AOR] 0.5; 95% CI 0.3 to 0.9) but were more likely to have had a hospitalization (AOR 1.4; 95% CI 1.1 to 2.0) and an increase in medication costs (AOR 1.4; 95% CI 1.1 to 1.9) during follow-up. There was no difference in ED visit rates. At least one DRP was identified in more than 83% of beneficiaries in both groups, with the most common DRP being drug-drug interaction. CONCLUSIONS: Our investigation supports the use of MTM, with its increased coordination of information between healthcare providers and patients, since it may impact mortality positively in a population of high-risk Medicare beneficiaries.

Management of nonmelanoma skin cancer in 2007.

As the incidence of nonmelanoma skin cancer (NMSC) increases, so does the number of modalities used to treat this condition. Surgery is the most frequent approach used to treat NMSC, and clinicians usually perform Mohs micrographic surgery, conventional excision, electrodesiccation and curettage or cryosurgery. The 'gold standard' for treatment continues to be Mohs micrographic surgery, but owing to the time and expense involved with this procedure, it is indicated only in patients with aggressive tumors or those where disfigurement or functional impairment is a risk. Although radiation therapy is effective, its use is limited because of the side effects induced; radiation therapy can be used in certain patients who are not surgical candidates. Newer noninvasive options for NMSC include topical chemotherapeutics, biological-immune-response modifiers, retinoids, and photodynamic therapy, which can be used particularly in patients with superficial tumors. Treatments should be tailored to tumor type, location, size, and histological pattern, and although surgical methods remain the most frequently used, newer noninvasive treatments can be used in select tumors and may reduce morbidity.

Patterns of characterization in folktales across geographic regions and levels of cultural complexity : Literature as a neglected source of quantitative data.

Literary scholars are generally suspicious of the concept of universals: there are presently no candidates for literary universals that a high proportion of literary scholars would accept as valid. This paper reports results from a content analysis of patterns of characterization in folktales from 48 culture areas, aimed at identifying patterns of characterization that apply across regions of the world and levels of cultural complexity. The search for these patterns was guided by evolutionary theory and the findings are consistent with previous research on patterns of altruism, sex differences in mate preferences, sex differences in reproductive strategy, and differing emphases on male and female physical attractiveness. World literature, especially originally oral literature, represents a vast and neglected repository of information that researchers can use to more precisely map the contours of human nature.