Mechanism of anomalously increased oil displacement with aqueous viscoelastic polymer solutions.

Single-phase flows of viscoelastic polymer solutions in both microfluidic devices and rock cores exhibit apparent flow thickening. We demonstrate that this thickening occurs above a critical Deborah number corresponding to the onset of spatio-temporal fluctuations. These fluctuations are observed to occur over a broad range of spatial and temporal scales consistent with elastic turbulence. The fluctuations provide a previously unreported mechanism for enhancing the displacement of a second, capillary trapped, immiscible phase.

Fluorescence detection methods for microfluidic droplet platforms.

The development of microfluidic platforms for performing chemistry and biology has in large part been driven by a range of potential benefits that accompany system miniaturisation. Advantages include the ability to efficiently process nano- to femoto- liter volumes of sample, facile integration of functional components, an intrinsic predisposition towards large-scale multiplexing, enhanced analytical throughput, improved control and reduced instrumental footprints. In recent years much interest has focussed on the development of droplet-based (or segmented flow) microfluidic systems and their potential as platforms in high-throughput experimentation. Here water-in-oil emulsions are made to spontaneously form in microfluidic channels as a result of capillary instabilities between the two immiscible phases. Importantly, microdroplets of precisely defined volumes and compositions can be generated at frequencies of several kHz. Furthermore, by encapsulating reagents of interest within isolated compartments separated by a continuous immiscible phase, both sample cross-talk and dispersion (diffusion- and Taylor-based) can be eliminated, which leads to minimal cross-contamination and the ability to time analytical processes with great accuracy. Additionally, since there is no contact between the contents of the droplets and the channel walls (which are wetted by the continuous phase) absorption and loss of reagents on the channel walls is prevented. Once droplets of this kind have been generated and processed, it is necessary to extract the required analytical information. In this respect the detection method of choice should be rapid, provide high-sensitivity and low limits of detection, be applicable to a range of molecular species, be non-destructive and be able to be integrated with microfluidic devices in a facile manner. To address this need we have developed a suite of experimental tools and protocols that enable the extraction of large amounts of photophysical information from small-volume environments, and are applicable to the analysis of a wide range of physical, chemical and biological parameters. Herein two examples of these methods are presented and applied to the detection of single cells and the mapping of mixing processes inside picoliter-volume droplets. We report the entire experimental process including microfluidic chip fabrication, the optical setup and the process of droplet generation and detection.

Pathologic findings in prophylactic oophorectomy specimens in high-risk women.

OBJECTIVE: To ascertain the frequency of significant pathologic alterations in prophylactic oophorectomy specimens in high-risk women referred to a tertiary care center. METHODS: Surgical cases for prophylactic oophorectomy referred to a gynecologic oncology clinic from November 1996 to January 2001 were reviewed. Serial sections of entirely submitted tubes and ovaries were procured and reviewed by a pathologist with expertise in gynecologic malignancies. All patients had undergone genetic counseling and either underwent mutational analysis of BRCA1 and BRCA2 genes or had family history suggestive for ovarian and breast cancer susceptibility. RESULTS: Thirty women with either a documented deleterious BRCA1 or BRCA2 mutation or a suggestive family history underwent prophylactic oophorectomy during the study period. Seventy-three percent of women had undergone genetic testing. Of those, 63.5% harbored a BRCA1 mutation, 13.5% were BRCA2 carriers, and the remaining 23% tested negative. Five of the 30 women (17%) were found to have clinically occult malignancy. Four of the five were diagnosed only on histologic review. A single patient had grossly apparent primary peritoneal carcinoma at the time of laparoscopy. Three patients were found to have primary fallopian tube malignancy, two with in situ papillary serous carcinoma, and one with early invasive disease. Each of the fallopian tube neoplasms measured less than 1 cm. The final patient was diagnosed with an ovarian adenofibroma with a focus of low malignant potential neoplasm and clear cell features. Three of the five were known BRCA1 mutation carriers, one had a documented BRCA2 mutation, and one has not yet been tested. CONCLUSIONS: The high rate of occult malignancy detected in this series suggests that this finding in women at heightened risk for ovarian cancer is relatively common. Further, clinically occult tumors were not limited to ovarian origin, and the majority of cases harbored malignant foci less than 1 cm in greatest dimension that were not recognized at the time of surgery. These findings support the recommendations that in this high-risk population (1) the fallopian tubes and ovaries should be submitted entirely and be evaluated by a pathologist with expertise in gynecologic malignancies in serial sections; (2) laparoscopy and laparotomy are the surgical modalities of choice to allow inspection of the peritoneal surfaces at time of prophylactic oophorectomy and collect fluid for cytologic evaluation; (3) despite the rarity of fallopian tube carcinoma in the general population, BRCA1 and BRCA2 mutation carriers may be at increased risk for tubal cancers.