Leland Stanford Junior University

Affymetrix, Inc.

Intevac, Inc.

Brion Technologies, Inc.

R Fabian Pease

Glenn H McGall

Richard P Rava

Martin J Goldberg

Lubert Stryer

James L Winkler

Virginia W Goss

Stephen P A Fodor

Ronald W Davis

Stephen P Fodor

Michael Nicholas Mindrinos

Stefanie S Jeffrey

Ashley Ann Powell

Mark A McCord

Jun Ye

Yu Long Cao

Nadim I Maluf

Kenneth A Costello

AmirAli Talasaz

Thomas Kailath

Aaron W Baum

AmirAli Hajhossein Talasaz

Amir A Ghazanfarian

Xun Chen

Weidong Liu

James E Schneider

Described here is an automated robotic device that isolates circulating tumor cells (CTCs) or other biological structures with extremely high purity. The device uses powerful magnetic rods covered in removable plastic sleeves. These rods sweep through blood samples, capturing, e.g., cancer cells labeled with antibodies linked to magnetically responsive particles such as superparamagnetic beads. Upon completion of the capturing protocol, the magnetic rods undergo several rounds of washing, thereby removing all contaminating blood cells. The captured target cells are released into a final capture solution by removing the magnetic rods from the sleeves. Additionally, cells captured by this device show no reduced viability when cultured after capture. Cells are captured in a state suitable for genetic analysis. Also disclosed are methods for single cell analysis. Being robotic allows the device to be operated with high throughput.

Apparatus for magnetic separation of cells

Methods and apparatus for magnetic separation of cells

There are many inventions described and illustrated herein. In one aspect, the present invention is directed to a technique of, and system for inspecting integrated circuits, including, for example, patterns projected, provided or formed on a wafer using photomasks, or patterns on the photomask itself. The inspection system and technique of this aspect includes first identifying, determining and/or detecting areas and/or patterns that are potentially defective by removing, filtering and/or eliminating from a set of potential defects any and/or all typical, regular or normal patterns. The identification, determination and/or detection of potential defects may be performed relatively quickly by a rapidly executing algorithm. In this way, a first or 'coarse' analysis is performed rapidly and some, many, all or substantially all of the regular, normal or typical patterns are eliminated from further analysis. Thereafter, a second more detailed analysis is performed. This second analysis focuses on the set of potential defects that were identified, determined and/or detected during the first analysis of the photomask or wafer (i.e., the 'coarse' analysis). The second analysis may be considerably a more detailed or a &#x201c;fine&#x201d; analysis relative to the first or &#x201c;coarse&#x201d; analysis. Indeed, in one embodiment, the second analysis may implement a more computational intensive process, without sacrificing throughput, since only a small portion of the photomask or wafer is inspected in the second analysis. In this way, the detailed analysis of the defect candidates may identify (i) all or substantially all of the actual defects and/or (ii) only the actual defects from the potential defects identified during the first analysis.

System and method for detecting integrated circuit pattern defects

A method and apparatus for selectively applying a print material onto a substrate for the synthesis of an array of oligonucleotides at selected regions of a substrate. The print material includes a barrier material, a monomer sequence, a nucleoside, a deprotection agent, a carrier material, among other materials. The method and apparatus also relies upon standard DMT based chemistry, and a vapor phase deprotection agent such as solid TCA and the like.

Printing oligonucleotide arrays

Printing molecular library arrays

Systems, methods and computer program products detect a position of a new alignment mark on a substrate by producing an alignment signal model from sample alignment signals and fitting the new alignment signal to the alignment signal model. The alignment signal model may be produced from the multiple sample alignment signals using singular value decomposition, based on subspace decomposition of the alignment signals. By producing an alignment signal model from multiple sample alignment signals, asymmetries in the sample alignment marks and/or in the coatings that are fabricated on the sample alignment marks, may be taken into account when detecting the position of a new alignment mark.

Systems, methods and computer program products for detecting the

An electron source includes a negative electron affinity photocathode on a light-transmissive substrate and a light beam generator for directing a light beam through the substrate at the photocathode for exciting electrons into the conduction band. The photocathode has at least one active area for emission of electrons with dimensions of less than about two micrometers. The electron source further includes electron optics for forming the electrons into an electron beam and a vacuum enclosure for maintaining the photocathode at high vacuum. The photocathode is patterned to define emission areas. A patterned mask may be located on the emission surface of the active layer, may be buried within the active layer or may be located between the active layer and the substrate.

Electron sources utilizing patterned negative electron affinity

Printing oligonucleotide arrays using deprotection agents solely in the

An electron beam system provides low aberration, 10 nm resolution at 100 eV landing energy. The system comprises a lens unit �46! having a built-in semiconductor junction detector �58!. The detector surrounds the sample-side of a focusing electrode �48! just upstream from a retarding electrode �50! which is positioned less than a millimeter from the sample �34!. Because the detector is within a few millimeters of the sample, it provides efficient detection of secondary electrons from the sample. The retarding electrode decreases the energies of the primary beam �22! from 10 keV to less than 100 eV, reduces distortions due to sample surface topography, and serves to accelerate secondary electrons back toward the detector, further improving detection efficiency.

Low voltage electron beam system

Printing molecular library arrays using deprotection agents solely in

Thin film masks with precisely located and positioned features are manufactured using a methodology herein called quantum lithography. A thin film layer, such as a chromium film, is deposited on a substrate such as quartz glass. Then, a set of precisely located dividing lines is defined in the thin film layer. The dividing lines are spaced in accordance with a predefined coordinate system and intersect so as to define tiles between the dividing lines. An electron beam pattern generator may be used to generate a large number of identical masks having a thin film with precisely located dividing lines. These masks will each be customized by subsequent processing steps. Each such mask is customized by selectively identifying a subset of the tiles and removing the selected subset of tiles to form a mask pattern in the thin film layer. The resulting pattern has very precisely located edges because the edges correspond to dividing lines formed using a precision patterning system, such an electron beam pattern generator. However, the actual light blocking pattern of the mask can be defined using a much lower accuracy pattern generator. An alternate embodiment of the invention uses a quantized additive process. A set of precisely located boundary lines are formed on a substrate to form a generic mask. The generic mask is customized by removing a subset of the boundary lines, and then selectively depositing a masking material inside the closed regions defined by the remaining boundary lines.

Quantum lithography mask and fabrication method

Growing community of inventors

Stanford, CA, United States of America

R Fabian Pease