The State University of New York

Vera Gorfinkel

Mikhail Gouzman

Serge Luryi

Boris Gorbovitski

Luryi Serge

Georgiy Gudkov

Dmytro Gudkov

Andriy Tsupryk

Evgeni A Kabotyanski

Dmitri N Gavrilov

Bradley S Carlson

Michael Gorbovitski

Marina Tcherevishnik

Ivan Tovkach

Dmitriy Gavrilov

A true random number generator including a light source configured to produce randomly distributed photons, a plurality of detection channels configured to receive the randomly distributed photons produced by the light source, each detection channel including a photon sensor configured to detect a receipt of at least one photon during successive integration time-periods and generate an output signal by assigning a value for each integration time-period based on whether at least one photon was received during each integration time-period, a signal conditioning unit configured to condition the output signal of each of the plurality of detection channels and generate a conditioned output signal for each of the plurality of detection channels, and a signal processing unit configured to combine the conditioned output signals and generate a true random number based on the combination of the conditioned output signals.

Quantum true random number generator

The present application provides methods and devices for absolute quantification of polymerase chain reaction target nucleic acids. In particular, the methods and devices of the present application provide for splitting a nucleic acid sample to be analyzed into small, isolated volumes, conducting the method of polymerase chain reaction (PCR) on said volumes, detecting PCR amplification products, analyzing said detected PCR amplification products, performing absolute quantification of the PCR target and presenting said quantification results.

Absolute PCR quantification

This invention discloses a highly efficient method, system and apparatus for nucleic acid analysis, including sequencing (both automated re-sequencing and de-novo sequencing). The system is capable of sequencing DNA sizes ranging from fragments to mammalian size genomes having mouse draft quality at a much reduced cost. The system comprises a massive parallel capillary electrophoretic separation using two-dimensional monolith multi-capillary arrays (2D-MMCA). Sequence identification can be performed using fluorescent or otherwise labeled dideoxynucleotide-terminated DNA extension product generated by gel matrix-, or beads-, or substrate tethered-, or otherwise immobilized colonies of single template molecules. Cost reduction is a significant advantage over currently known methods because of: (i) using massively parallel sub-nanoliter volume reactions; and (ii) employing 2D-MMCAs that increase the throughput of the CE separation and detection by at least two orders of magnitude compared to the commercial high-throughput DNA machines.

Massively parallel 2-dimensional capillary electrophoresis

A fiberized single photon sensitive spectrometer based on a 32-channel PMT sensor is highly sensitive with broad detection dynamic range. The spectrometer enables accurate and high speed detection, identification and analysis of biological samples labeled with multiple fluorescent markers, such as compositions of multi-color fluorescence signals or radiation emitted by multiple fluorescence dyes. A fiberized optical input of the spectrometer allows an easy and efficient coupling to any measurement system based on fiber collection of the analyzed fluorescence. The spectrometer provides highly accurate DNA sequencing. A 32 channel PMT single photon detector has a detection dynamic range of more than 20 bits and has a frame rate of about 3300 frames per second. The dynamic range of the detector's pixels reaches 10photocounts per second.

Single photon spectrometer

The invention relates to devices that contain linear channels having optically transparent substances for focusing light. In some embodiments, the invention relates to improved nucleic acid sequencing methods using devices disclosed herein. In other embodiments, the invention relates to the arrangement of materials in and around capillary tubes with refractive indexes that maximize the number of channels useful for fluorescent detection of compositions after capillary electrophoresis.

Light focusing in linear channel arrays

The present invention relates to microfluidic systems having components with specially designed and fabricated areas of enhanced and/or reduced capillarity (flow guides). The methods and devices of the present invention permit the bubble-less dispensing and mixing of small volumes of different liquids for subsequent incubation and/or detection of products of various biological reactions. Thus present invention is well-suited to applications such as polymerase chain reaction and capillary electrophoresis.

Method and device for manipulating liquids in microfluidic systems

The present invention is directed to a system and method for cross-talk cancellation for multi-lane fluorescence detectors. The invention may be implemented in accordance with a variety of systems, including systems for multi-capillary electrophoresis. The present invention is based on a special calibration procedure for determination of a channel cross-talk matrix and enables an accurate separation of the fluorescence emitted from individual capillary lanes. The proposed method for cross-talk calibration and removal is very useful for design and development of multi-lane single photon counting detection systems.

System and method for cross-talk cancellation in a multilane fluorescence detector

In analyzing radiation from a communication link, single-photon counting can be used to advantage especially at low levels of radiation energy, e.g. in the detection of optical radiation. Preferred detection techniques include methods in which (i) received optical radiation is intensity-modulated in accordance with a preselected code, (ii) wherein it is the optical radiation which is intensity-modulated with the preselected code, and (iii) wherein the radiation modulated with a preselected code is received. For registration of the signals received by a sensing element of a single-photon detector, time of arrival is recorded, optionally in conjunction with registration of time intervals. Advantageously, in the interest of minimizing the number of pulses missed due to close temporal spacing of pulses, D-triggers can be included in counting circuitry.

Method and apparatus for detecting radiation

In analyzing radiation from a sample, single-quanta counting can be used to advantage especially at low levels of radiation energy, e.g. in the detection of fluorescent radiation. Preferred detection techniques include methods in which (i) fluorescence-stimulating radiation is intensity-modulated in accordance with a preselected code, (ii) wherein it is the fluorescent radiation which is intensity-modulated with the preselected code, and (iii) wherein modulation with a preselected code is applied to a sample to influence a property which functionally affects emitted fluorescent radiation. For registration of the signals from a sensing element of a single-photon detector, time of arrival is recorded, optionally in conjunction with registration of time intervals. Advantageously, in the interest of minimizing the number of pulses missed due to close temporal spacing of pulses, D-triggers can be included in counting circuitry.

The development of the network structure and the basic modules of an automated 4-color DNA sequencing apparatus comprising more than one thousand capillary electrophoresis lanes is disclosed. The basic modules represent small 32-lane units based on multicolor excitation of fluorescent labels and single-photon detection. The individual units operate asynchronously, controlled by a network computer. Excitation of fluorescence is done with low-power illumination via a fiber-optic network.

Method and apparatus for DNA sequencing

A novel method of spatial compression of a DNA sample inside the capillary for the gel capillary electrophoresis and an article for operating the method are disclosed. In this method, after the electrokinetic injection, the sample is compressed using the reverse electric field. A special DNA barrier material is used to contain the sample in the capillary. We expect that this Electro Static Compression (ESC) can increase the DNA concentration in the capillary by orders of magnitude. In the proposed method and article the injection and compression of the DNA sample are followed by subsequent electrophoretic separation in any kind of sequencing container (for instance glass capillary). The use of the ESC method will allow the increase of the length and the quality of the read, as well as reduction of the DNA consumption. ESC method will also permit the use of low power illumination sources including miniature and inexpensive light emitting diodes (LED) instead of the Ar-ion laser for exciting fluorescent labels in 4-color DNA sequencing.

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Stony Brook, NY, United States of America

Vera Gorfinkel