Versatile Protein-A Coated Photoelectric Immunosensors with a Purple-Membrane Monolayer Transducer Fabricated by Affinity-Immobilization on a Graphene-Oxide Complexed Linker and by Shear Flow.

Bacteriorhodopsin-embedded purple membranes (PM) have been demonstrated to be a sensitive photoelectric transducer for microbial detection. To efficiently prepare versatile BR-based immunosensors with protein A as antibody captures, a large, high-coverage, and uniformly oriented PM monolayer was fabricated on an electrode as an effective foundation for protein A conjugation through bis-NHS esters, by first affinity-coating biotinylated PM on an aminated surface using a complex of oxidized avidin and graphene oxide as the planar linker and then washing the coating with a shear flow. Three different polyclonal antibodies, each against Escherichia coli, Lactobacillus acidophilus, and Streptococcus mutans, respectively, were individually, effectively and readily adsorbed on the protein A coated electrodes, leading to selective and sensitive quantitative detection of their respective target cells in a single step without any labeling. A single-cell detection limit was achieved for the former two cells. AFM, photocurrent, and Raman analyses all displayed each fabricated layer as well as the captured bacteria, with AFM particularly revealing the formation of a massive continuous PM monolayer on aminated mica. The facile cell-membrane monolayer fabrication and membrane surface conjugation techniques disclosed in this study may be widely applied to the preparation of different biomembrane-based biosensors.

Using random forest for reliable classification and cost-sensitive learning for medical diagnosis.

BACKGROUND: Most machine-learning classifiers output label predictions for new instances without indicating how reliable the predictions are. The applicability of these classifiers is limited in critical domains where incorrect predictions have serious consequences, like medical diagnosis. Further, the default assumption of equal misclassification costs is most likely violated in medical diagnosis. RESULTS: In this paper, we present a modified random forest classifier which is incorporated into the conformal predictor scheme. A conformal predictor is a transductive learning scheme, using Kolmogorov complexity to test the randomness of a particular sample with respect to the training sets. Our method show well-calibrated property that the performance can be set prior to classification and the accurate rate is exactly equal to the predefined confidence level. Further, to address the cost sensitive problem, we extend our method to a label-conditional predictor which takes into account different costs for misclassifications in different class and allows different confidence level to be specified for each class. Intensive experiments on benchmark datasets and real world applications show the resultant classifier is well-calibrated and able to control the specific risk of different class. CONCLUSION: The method of using RF outlier measure to design a nonconformity measure benefits the resultant predictor. Further, a label-conditional classifier is developed and turn to be an alternative approach to the cost sensitive learning problem that relies on label-wise predefined confidence level. The target of minimizing the risk of misclassification is achieved by specifying the different confidence level for different class.

Painless electroporation with a new needle-free microelectrode array to enhance transdermal drug delivery.

A microelectrode array was designed to minimize the pain sensation of electroporation for enhancing transdermal drug delivery. The influence of the size of the electrode-skin contact area and of the distance between electrodes on the pain sensation was tested on human volunteers. The pain level decreased with the dimension of electrode-skin contact area and with inter-electrode distance. When both reached about 0.5 mm, the pain level was not perceptible even at the threshold of transdermal electroporation level of sixty electric pulses at 150 V, 1 ms at 1-10 Hz. An array of 11 x 11 alternately connected electrodes with 0.6 x 0.6 mm dimension was fabricated. The electric thresholds for effective drug delivery, using toluidine blue O as a marker on mouse skin, was found to be the same for microelectrode arrays as for larger electrodes and wider inter-electrode distances. In vivo transdermal electroporation using microelectrode array with 180 pulses of 150 V, 0.2 ms at 1 Hz, followed by 30 min methotrexate (MTX) occlusion increased more than 4 fold the systemic MTX level in mice. The results demonstrated the potential of painless delivery of significant amounts of chemotherapeutic agents through skin with the new electrode arrays in a clinical setting.

Kekulé count in capped zigzag boron-nitride nanotubes.

Hemi-B16N16 capped zigzag boron-nitride nanotube is introduced, and its Kekulé count is studied. With a bond-allocating and coding scheme, recurrence formulas are established as well as for the case of a hemi-B36N36 capped zigzag nanotube. Numerical results reveal that the Kekulé counts increase exponentially with respect to the number of layers in the nanotubes concerned.