University of California

Affymetrix, Inc.

Peter C Simpson

Richard A Mathies

Adam T Woolley

Charles A Emrich

Brian Paegel

Lester Hutt

Stephen J Williams

Sample component separation apparatus and methods are described. An exemplary sample component separation apparatus includes a separation channel having a turn portion configured to reduce band-broadening caused by passage of a sample through the turn portion. To reduce band broadening caused by passage of a sample through a turn portion, the turn portion may be constructed and arranged to have a sample transport characteristic that is different from the corresponding sample transport characteristic of a substantially straight portion of the separation channel. For example, the turn portion may be configured with an effective channel width that is smaller than the effective channel widths of the substantially straight portion of the separation channel. The actual channel width of the turn portion may be smaller than the channel widths of the substantially straight portion; the effective channel width of the turn portion may be reduced by placing one or more sample transport barriers or constrictions in the turn portion of the channel. Alternatively, the sample velocity through the turn portion may be controlled so as to reduce band broadening. For example, sample transport barriers may be disposed in the turn portion so that sample components of a given band travel through the turn portion at substantially the same effective rate, whereby the band orientation remains substantially aligned along radial directions characteristic of the turn portion. Other a sample transport characteristics, such as electrical resistance or fluid flow resistance, of the turn portion may be adapted to reduce band broadening caused by passage of the sample through the turn portion.

Apparatus and methods for high resolution separation of sample components on microfabricated channel devices

A capillary array electrophoresis (CAE) micro-plate with an array of separation channels connected to an array of sample reservoirs on the plate. The sample reservoirs are organized into one or more sample injectors. One or more waste reservoirs are provided to collect wastes from reservoirs in each of the sample injectors. Additionally, a cathode reservoir is also multiplexed with one or more separation channels. To complete the electrical path, an anode reservoir which is common to some or all separation channels is also provided on the micro-plate. Moreover, the channel layout keeps the distance from the anode to each of the cathodes approximately constant.

Microfabricated capillary array electrophoresis device and method

A microfabricated liquid sample loading system comprising a first plate having an array of microfabricated holes passing therethrough; a second plate positioned against the first plate, the second plate having an array of microfabricated holes passing therethrough; and a plurality of microfabricated channels disposed on a surface of at least one of the first or second plates, the microfabricated channels connecting the array of microfabricated holes in the first plate with the array of microfabricated holes in the second plate.

Microfabricated liquid sample loading system

A fully integrated monolithic small volume PCR-CE device in glass, or the like materials, is fabricated using thin film metal heaters and thermocouples to thermally cycle sub-microliter PCR volumes. Successful amplification of a PCR fragment is demonstrated on a PCR-CE chip. The process utilizes a linear polyacrylamide surface coating coupled with addition of BSA to the amplification buffer was necessary to obtain amplification efficiencies comparable to a positive control. The micro-reactor reduced significantly the time required for amplification and the reaction volume was in the sub-microlitre regime. Likewise addressed are the known problems connected with reliable microfabrication of metal coatings and the insulating layers required to shield these layers from the PCR reaction mix, and the longstanding unresolved issue of exposed metal regions in the PCR-CE chip resulting in electrolysis of water and bubble formation whenever a voltage is applied. The instant teachings employ external heaters and thermocouples and, as such, have alleviated many of these problems. Heaters and thermocouples may still be thin film deposited after chip bonding allowing for easy scale-up to multichannel devices. In addition, direct deposition of these chip components insures good thermal contact with the PCR reactor.

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Oakland, CA, United States of America

Peter C Simpson