Quick chip assay using locked nucleic acid modified epithelial cell adhesion molecule and nucleolin aptamers for the capture of circulating tumor cells

The role of circulating tumor cells (CTCs) in disease diagnosis, prognosis, monitoring of the therapeutic efficacy, and clinical decision making is immense and has attracted tremendous focus in the last decade. We designed and fabricated simple, flat channel microfluidic devices polydimethylsiloxane (PDMS based) functionalized with locked nucleic acid (LNA) modified aptamers (targeting epithelial cell adhesion molecule (EpCAM) and nucleolin expression) for quick and efficient capture of CTCs and cancer cells. With optimized flow rates (10 μl/min), it was revealed that the aptamer modified devices offered reusability for up to six times while retaining optimal capture efficiency (>90%) and specificity. High capture sensitivity (92%) and specificity (100%) was observed in whole blood samples spiked with Caco-2 cells (10-100 cells/ml). Analysis of blood samples obtained from 25 head and neck cancer patients on the EpCAM LNA aptamer functionalized chip revealed that an average count of 5 ± 3 CTCs/ml of blood were captured from 22/25 samples (88%). EpCAM intracellular domain (EpICD) immunohistochemistry on 9 oral squamous cell carcinomas showed the EpICD positivity in the tumor cells, confirming the EpCAM expression in CTCs from head and neck cancers. These microfluidic devices also maintained viability for in vitro culture and characterization. Use of LNA modified aptamers provided added benefits in terms of cost effectiveness due to increased reusability and sustainability of the devices. Our results present a robust, quick, and efficient CTC capture platform with the use of simple PDMS based devices that are easy to fabricate at low cost and have an immense potential in cancer diagnosis, prognosis, and therapeutic planning.

Visual impairment in Australia: distance visual acuity, near vision, and visual field findings of the Melbourne Visual Impairment Project

PURPOSE: To describe the age-specific and gender-specific rates of blindness and visual impairment in urban adults aged 40 years and older. METHODS: A population-based sample of residents was recruited. Presenting and best-corrected distance visual acuities were assessed. Functional near vision was measured at each participant's preferred distance. Visual field examination was performed with a Humphrey Field Analyzer (HFA); those unable to perform the field analyzer test attempted a Bjerrum screen or confrontation field. RESULTS: The study population comprised 3,271 residents (83% of eligible) from ages 40 to 98 years; 54% were women. Overall, 56% of the study population wore distance correction; this was significantly lower in men but higher in the older age groups. Age-adjusted rates of blindness were 0.066% in men and 0.170% in women. Vision with current correction improved after refraction by gender and age. Direct age-standardized rates of functional near vision did not vary significantly by gender. Forty-six people had significant visual field loss in their better eye. The proportion of participants with constriction of the visual field to within 20 degrees of fixation was similar for men and women when controlled for age (odds ratio, 0.81; 95% confidence interval, 0.44 to 1.49) but increased significantly with age controlled for gender. Visual field abnormalities were detected in 548 right eyes (17%) and 533 left eyes (16%). CONCLUSIONS: Although overall rates of blindness because of visual acuity loss were relatively low, nearly three times more people had visual impairment because of visual field loss than visual acuity loss. These results highlight the need to target blindness prevention programs to the aging population, with a special emphasis on women.

Lab-on-a-chip or chip-in-a-lab: challenges of commercialization lost in translation

Lab-on-a-chip technology has been long envisaged to have tremendous commercial potential, owing to the ability of such devices to encapsulate a full range of laboratory processes in a single instrument and operate in a portable manner, rapidly and at low cost. Devices are believed to have potential in fields ranging across medical diagnostics, environmental sampling and a range of consumer products, however, to date very few devices have attained commercial success. This review examines the challenges relating to the commercialization of lab-on-a-chip technology from fundamental research to mass manufacturing and aims to provide insight to both academics and product development specialists the perceived hindrances to commercialization and a strategy by which future work could be translated into commercial success.