| During the past decade, lab-on-a-chip integration, design flexibility and detection speed have become life-sciences research instrumentation's key needs, as improved technologies have enabled biomedical breakthroughs. Surface-Plasmon-Resonance (SPR) technology is the standard for measurement of molecular interactions. Limited sensitivity and speed, bulk complexity and cost have prevented its adoption in medical diagnostics. Our development of a robust, miniaturized surface-plasmon sensor which integrates easily into microfluidic structures has overcome many of these obstacles. 1-3;Our 2-mum2 microcavity surface-plasmon-resonance sensor (MSPRS) is a million times smaller than current SPR sensors (e.g., Biacore's sensor is ∼ 1 mm2) so it requires tiny sample volumes (∼ 5 mul). Manufacturing the sensors is inexpensive and their integration with microfluidics allows complex sample manipulation. The MSPRS is the subject of PCT/US2006/047959 and WO/2007/075444 patent filings.;In parallel, we have developed microfluidic devices for analyzing complex biological phenomena. The very accurate microfluidic sample injection, flow and gradient control we developed require tiny amounts of analyte, allowing the study of mouse-sperm chemotaxis in response to chemicals extracted from female genital organs, showing that ovary extracts at dilutions of 10 -3 to 10-5 induce sperm chemotaxis and validating the hypothesis that sperm can respond to extract components signaling the presence of an egg.4, 5;We have developed novel micro-structures to generate well-defined linear and non-linear spatial and temporal chemical gradients. The devices are ∼ 1.6 mm x 0.5 mm, about 10 times smaller than prior pyramidal designs, allowing fast switching (2.6 sec) between gradients with varying slopes and offsets and different compositions, e.g., for cell-migration studies.6 Our compact microfluidic design for generating spatial and temporal gradients is the subject of PCT/US2008/076868 and WO/2009/039283 patent filings. |
