A multi-channel and multi-color bio-separation detection method and apparatus in which a single detector is coupled to a plurality of radiation sources, in a one detector/many radiation sources configuration. Each radiation source directs radiation at a detection zone of a single separation channel, and a single detector is applied to detect light emissions from the detection zones associated with several radiation sources. The radiation sources are activated to direct radiation at the detection zone in a predetermined sequence and further in a cyclic manner, with the detector output synchronized to the radiation sources by a controller. Bio-separation may be conducted simultaneously in all the channels in parallel, with detection time-staggered and/or time multiplexed with respect to the light sources. In one embodiment, low cost light emitting diodes may be used as radiation sources. In another aspect, the detection scheme is configured for radiation induced fluorescence detection in an capillary electrophoresis instrument.
CROSS-REFERENCE
This application is a continuation-in-part and claims the priority of the following: (a) U.S. Provisional Patent Application No. 60/348,034, filed Oct. 19, 2001; (b) U.S. patent application Ser. No. 10/060,052, filed Jan. 28, 2002; and (c) U.S. patent application Ser. No. 10/059,993, filed Jan. 28, 2002. These applications are fully incorporated by reference as if fully set forth herein.
A particle detector has a chamber defining a pathway that a target particle follows between an entry and an exit point, a solid-state energy source such as an LED, and a re-emission sensor. The energy source imparts energy to the particle between the two points, and the sensor includes an arcuate or multi-planar lens to focus energy re-emitted by the particle. The particle is identifiable by its re-emitted energy spectrum. A scanner re-directs the beam from a single energy source to track the particle between the entry and exit points. Alternatively, the energy source is a plurality of source elements that each scan the particle at a single position. Another embodiment is a chipscale detector system wherein energy source elements are disposed on a source layer, sensor elements are disposed on a sensor layer, and one or more target particles to be detected are retained on a capture layer disposed therebetween.
An apparatus and method for detecting particles. A flow tube is surrounded by eight off-axis ellipsoidal mirrors all having a common first focus coincident with a portion of the flow tube and each having a distinct second focus. In one embodiment, sources of radiation are arranged coincident with exit ports in the mirrors that are also coincident with the respective distinct second foci. These radiation sources are momentarily energized in sequence (or simultaneously), causing light to illuminate a corresponding ellipsoidal mirror. This light strikes the common first focus within a portion of the flow tube. Any particles within the first focus will then scatter the light, and depending upon the source wavelength and the particle, may also provide some amount of fluorescence. This energy is captured by detectors and analyzed to determine the type, size and quantity of particles at the first focus.
A bio-separation system using an efficient, compact, portable, interchangeable, reusable, recyclable, multi-channel cartridge, has integrated pre-aligned optics and an integrated reagent reservoir. The cartridge supports, for example, multiple capillaries for CE separation. An integrated reservoir containing a separation support medium (e.g., a gel buffer) is common to all capillaries. The chemistry of the medium and the characteristics of the capillaries (e.g., capillary size, coating and length) are defined for each cartridge. Different cartridges can be easily interchanged in the bio-separation system to suit the particular sample based separation. The reservoir is coupled to an air pressure pump that pressurizes the gel reservoir to purge and fill the capillaries with buffer as the separation support medium. In another aspect of the present invention, optics requiring fine alignment with respect to the detection zones (such as fiber optics for directing incident radiation and/or radiation emissions) are integrated into the cartridge.
A bio-separation instrument using a multi-segment cartridge. The cartridge includes a plurality of efficient, compact, portable, interchangeable, reusable, recyclable, modular, multi-channel segments. Each segment supports multiple capillaries for CE separation. Each segment has an integrated reservoir containing a buffer/gel common to all the capillaries. Air pressure can be supplied to the reservoir through the periphery of each segment. Each segment has an integrated LED array board directly coupled to capillaries for providing excitation light. Optical fibers of a fiber bundle are individually guided through the periphery of each segment to the capillaries for emission collection. The fiber bundle delivers emissions to a detector that can read the emissions in a time-staggered multiplexed scheme. Each segment includes electrodes electrically coupled to a voltage source through the periphery of the segment for effecting CE separation. Providing each segment with pneumatic and voltage connections on the periphery and direct coupling LED's allow the segments to easily stack together for integration into the instrument.
