Analytical biochemistry system with robotically carried bioarray

Abstract

An analytical biochemistry system featuring a substrate with reactants immobilized thereon at fixed, known locations, a holder supporting the substrate and a manipulator for transporting the holder to a fixed sample and to an inspection station. The reactants are binding agents for a target biomolecule in a sample which forms a bound substance having a detectable characteristic. The holder may be a standard pipettor, optionally carried by a robot arm or hand as the manipulator to contact the sample for detection of the presence of target biomolecules within the sample. In one embodiment, the holder is a pipette tip within which the substrate is housed, or it may be a pipette adapter which bears the substrate and fits within the sample wells of a standard microtiter plate.

Description

[0001] This application is a continuation of U.S. patent application Ser. No. 11 / 073,288 filed on Mar. 4, 2005 which is a continuation of U.S. patent application Ser. No. 10 / 200,720 filed on Jul. 22, 2002, which is a divisional application of U.S. patent application Ser. No. 08 / 586,116 filed Jan. 16, 1996 now U.S. Pat. No. 6,660,233. All these application are incorporated by reference in their entirety for all purposes.TECHNICAL FIELD [0002] This invention relates to a system and methods for detecting the presence of target biomolecules within samples with robotic assistance for a sample holder carrying an array of reactants. BACKGROUND ART [0003] Assays for the detection of target biomolecules within a sample, especially of multiple target biomolecules within a sample, are often performed by applying a volume of the sample to a test slide, membrane, or other substrate having immobilized reactants which may interact with the target or targets to form detectable complexes. These immo...

AI Technical Summary

Benefits of technology

[0013] Another example of a useful holder is a pipette adapter resembling a truncated pipette tip and having a bracket or a flat surface or supporting the substrate. The pipette adapter may be placed directly into a sample, such as in a well of a microtiter plate or in a vial, in order to provide contact of the holder and the sample. The pipette adapter and accompanying substrate are then removed from the sample to a detector station. The various holders of the present invention may be adaptations of standard pipetting tools. The holders also are designed to require minimal sample volumes and to allow optical inspection of the substrate with minimal interference by the holder.

[0016] Prior to probing, intermediary steps to enhance visualization or realization of complementation, such as treatment with development chemicals, fluorescent dyes, etc. may be desired. Optical inspection of the substrate within the pipette tip is possible by use of an optical surface on the pipette tip. Optical inspection on the pipette adapter is unencumbered. A manipulator in the form of a robotic arm gripping the pipette tip or pipette adapter type of substrate holder may place the bioarray in contact with the sample, and subsequently transfer the substrate to a detection assembly. Multiple sample transfers are thus eliminated. A computer controlling the robotic arm movement, the incubation times, and providing further analysis or display of detected signals from the substrate is preferred. An automated instrument includes a detection assembly, which in one embodiment includes a laser source providing an excitation beam to impinge upon the active sites of the substrate, a light collector for gathering signals emitted from the substrate, and a detector, such as a photomultiplier tube or CCD array. Alternatively, it may have multiple detection assemblies, depending on the requirements of the sample and the substrate chemistries. Relative movement of an excitation beam and the Bioarray may be provided by the robotic arm holding the substrate or by scanning optics, such as a galvo mirror, within the excitation path of the detection assembly. A substrate intended for use in the present invention may be an oligonucleotide array, a peptide array, or an immunochemical array, among others, and may be created on a separate member, such as a small slide, and affixed to the holder, or it may be created directly on the holder. Creation of the bioarray may be via biopolymer synthesis on a solid phase member or deposition of reactants, e.g. by movable nozzles, such as the type used for ink jet printing, or by some other method. The reactants may be affixed to the member via specific or non-specific covalent linkages, physical adsorption, or some other form of adhesion. The interaction or complexing of the target biomolecules and the immobilized reactants may be by affinity linkages, ionic linkages, adsorption, or some other reasonably secure manner. The present invention provides a simple, highly adaptable method and apparatus for quickly and easily assessing samples for the presence of biomolecules.

Problems solved by technology

These pipette tips are limited in their sample throughput because they house only a single ligand reagent and thus preclude the detection of multiple analytes within a sample.

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