Conventional cell trapping methods using microwells with small dimensions (10-20 μm) are useful for examining the instantaneous cell response to reagents; however, such wells have insufficient space for longer duration screening tests that require observation of cell attachment and division. Here we describe a flow method that enables single cell trapping in microwells with dimensions of 50 μm, a size sufficient to allow attachment and division of captured cells. Among various geometries tested, triangular microwells were found to be most efficient for single cell trapping while providing ample space for cells to grow and spread. An important trapping mechanism is the formation of fluid streamlines inside, rather than over, the microwells. A strong flow recirculation occurs in the triangular microwell so that it efficiently catches cells. Once a cell is captured, the cell presence in the microwell changes the flow pattern, thereby preventing trapping of other cells. About 62% of microwells were filled with single cells after a 20 min loading procedure. Human prostate cancer cells (PC3) were used for validation of our system.
To the Editor: The dearth of information on drugs for children led to children being called "therapeutic orphans." In 1975, Wilson determined that 78% of drug labeling had inadequate pediatric information. 1 In 1999, Wilson summarized 25 years of efforts to get pediatric information into labeling and extended his analysis. 2 In the decade after Wilson's review, regulations and legislation have led to more pediatric studies and labeling. 3 We hypothesized that a higher percentage of labeling has information on use in children compared with the analyses by Wilson in 1975 1 and in 1999. 2 Methods. We evaluated labeling in the June 2009 electronic Physicians' Desk Reference 4 (ePDR) using methods established by Wilson 1 in analyzing the 1973 print PDR. Labeling was categorized as adequate if it stated that the drug was approved for pediatric use, had been studied, or had safety, efficacy, or dosing information for all appropriate pediatric populations; and inadequate if labeling lacked data on dosing, safety, or efficacy in at least 1 pediatric subpopulation. Partially labeled was a subgroup of inadequately labeled and defined as adequate labeling for at least 1 but not all appropriate pediatric subpopulations. Labeling in the ePDR was reviewed by 3 people (A.N.S., D.A., W.R.). Differences were reviewed by a fourth person who made final assignments (M.D.M.). The was 0.91. Topicals, nasal sprays and most over-the-counter products were excluded per the methods of Wilson. In products with multiple formulations, only 1 likely to be used in children (ie, oral formulation) was analyzed. Because limitations in the ePDR may lead to an underestimate of pediatric labeling, 2 subanalyses were performed. First we excluded products on the US Food and Drug Administration's (FDA's) list of Products Deemed Not Relevant to Pediatrics. 5 Second, we compared the ePDR list with the FDA's Pediatric Labeling Changes Table (February 1998-June 2009), which reflects only pediatric legislative initiatives and is not comprehensive, to determine whether most new pediatric labeling changes were included in the ePDR. 3 Similar to Wilson, 2 we also assessed the labeling for all new molecular entities (NMEs) approved between 2002 and 2008 6 to determine if the product might be used in pediatrics and the adequacy of the pediatric information.
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