The performance, field utility, and low cost of lateral flow assays (LFAs) have driven a tremendous shift in global health care practices by enabling diagnostic testing in previously unserved settings. This success has motivated the continued improvement of LFAs through increasingly sophisticated materials and reagents. However, our mechanistic understanding of the underlying processes that drive the informed design of these systems has not received commensurate attention. Here, we review the principles underpinning LFAs and the historical evolution of theory to predict their performance. As this theory is integrated into computational models and becomes testable, the criteria for quantifying performance and validating predictive power are critical. The integration of computational design with LFA development offers a promising and coherent framework to choose from an increasing number of novel materials, techniques, and reagents to deliver the low-cost, high-fidelity assays of the future.
A practical asymmetric synthesis of (S)
4-ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione (1), a versatile intermediate
for the synthesis of camptothecin analogs, was
developed. Commercially available citrazinic acid is converted in
four steps into the 2-chloro-6-methoxypyridine 5. An ortho-directed metalation followed
by reaction with a formamide produces
an aldehyde with the required 2,3,4,6-substituted pyridine
(6) with high regioselectivity. After
refunctionalization of the aldehyde, the chloropyridine is converted
into an ester by a facile
palladium-mediated carbonylation reaction. Wittig reaction and
racemic osmylation produce the
diol 16 which is resolved by an efficient lipase resolution
to an ee > 99%, and a one-pot recycle of
the unwanted diol enantiomer was developed. A series of
high-yielding oxidation and deprotection
steps convert (S)-16 into the pyridone
25, which is then converted into 1 with an ee >
99.6%.
We investigated alternatives to whole blood for blood feeding of mosquitoes with a focus on improved stability and compatibility with mass rearing programs. In contrast to whole blood, an artificial blood diet of ATP-supplemented plasma was effective in maintaining mosquito populations and was compatible with storage for extended periods refrigerated, frozen, and as a lyophilized powder. The plasma ATP diet supported rearing of both Anopheles and Aedes mosquitoes. It was also effective in rearing Wolbachia-infected Aedes mosquitoes, suggesting compatibility with vector control efforts.
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