Monmouth Jct., NJ, United States
Monmouth Jct., NJ, United States

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Grant
Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 659.19K | Year: 2015

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project will be to provide researchers and educators a powerful device to monitor biochemical reactions and physical conditions inside living cells in real time. The probe, which is microscopic in size and powered by incoming light, will be inserted into living cells and will report parameters such as pH and concentration of selected molecules via radio transmissions to a nearby receiver. The transmission will contain both the identity of each cell and the parameter(s) being recorded-hence it will be possible to monitor many cells simultaneously. The ?radio p-Chip? will greatly advance the science of probing cell physiology and create a new area in basic and applied research by providing scientists the ability to study localized functions within living cells. As such, it will be a powerful new tool for advancing knowledge in the fields of mechanisms of disease, drug discovery, and control of biochemical functions, metabolism and other areas. The radio p-Chip and receivers are projected to be low enough in cost that they will also become scientific tools for students to study cell physiology and thus become incorporated into educational curricula. The proposed project will result in a system that will, for the first time in history, allow scientists to monitor conditions in a living cell with a device that will not interfere with normal functions including movement. The system will be based the current p-Chip, the world?s smallest microtransponder that continuously emits a radio signal with an identification number (ID) when illuminated with light. The p-Chip is used today to tag, track and authenticate a wide variety of objects. In order to realize the radio p-Chip, the current version of the chip will be shrunk by a factor of 10, and a variety of sensors will be added to its surface. Once complete, the radio p-Chip will be able to alternately transmit its ID and sensor value continuously to a nearby receiver. The receiver will process the signal for further use by the operator. In parallel, a series of tools will be developed to reliably implant the chips into living cells. In order to accomplish the goals of the project, PharmaSeq will combine leading edge technologies in semiconductor device design and fabrication, advanced sensor technology, digital and analogue electronics, optics and software.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 998.41K | Year: 2014

Not Available


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: | Award Amount: 149.99K | Year: 2013

This Small Business Innovation Research (SBIR) Phase I project aims at developing a Radio p-Chip, the first microchip with a sensor that can be injected into live cells, and transmit information from within without a physical connection. The design combines elements of laser light-activation of the p-Chip, a novel device that transmits the chips serial number via radio signals, with enhancements to monitor events by adding a sensor. The target dimensions for the Radio p-Chip are suitable for investigations of large cells. The on-board sensor will gather information about real-time physiological conditions in the cell and transmit it along with the serial number identifying the cell itself. The information will be transmitted to a reading station that will collect data related to the identity of the cell, as well as the reported conditions from the sensor. The main goals of the Phase I project are to 1) design, build and test the fully functional prototype of the Radio p-Chip; 2) implant the device into a living mammalian cell and demonstrate its function; and 3) build and test components of a future version of the chip. The device envisioned is one part of a system incorporating, in addition to the chip, a custom-designed receiver and antenna system, the stimulus apparatus, devices to implant the chip into cells, and associated firmware and application software.

The broader impact/commercial potential of this project will be felt in a wide variety of applications, including the readout of key physiological characteristics, ID-tagging of individual cells and tracking their history, tagging embryos, flow cytometry and process monitoring. All research to date with living cells relies upon indirect or intrusive methods that almost always effect what is being measured. The Radio p-Chip will be superior in both performance and cost and will have a wide commercial impact. The development of a Radio p-Chip will provide a powerful new tool for cell biology and in particular for the in vivo studying of a wide variety of human diseases and have implications for drug discovery and in vitro diagnostics.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: SMALL BUSINESS PHASE II | Award Amount: 796.99K | Year: 2014

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project will be to provide researchers and educators a powerful device to monitor biochemical reactions and physical conditions inside living cells in real time. The probe, which is microscopic in size and powered by incoming light, will be inserted into living cells and will report parameters such as pH and concentration of selected molecules via radio transmissions to a nearby receiver. The transmission will contain both the identity of each cell and the parameter(s) being recorded-hence it will be possible to monitor many cells simultaneously. The ?radio p-Chip? will greatly advance the science of probing cell physiology and create a new area in basic and applied research by providing scientists the ability to study localized functions within living cells. As such, it will be a powerful new tool for advancing knowledge in the fields of mechanisms of disease, drug discovery, and control of biochemical functions, metabolism and other areas. The radio p-Chip and receivers are projected to be low enough in cost that they will also become scientific tools for students to study cell physiology and thus become incorporated into educational curricula.

The proposed project will result in a system that will, for the first time in history, allow scientists to monitor conditions in a living cell with a device that will not interfere with normal functions including movement. The system will be based the current p-Chip, the world?s smallest microtransponder that continuously emits a radio signal with an identification number (ID) when illuminated with light. The p-Chip is used today to tag, track and authenticate a wide variety of objects. In order to realize the radio p-Chip, the current version of the chip will be shrunk by a factor of 10, and a variety of sensors will be added to its surface. Once complete, the radio p-Chip will be able to alternately transmit its ID and sensor value continuously to a nearby receiver. The receiver will process the signal for further use by the operator. In parallel, a series of tools will be developed to reliably implant the chips into living cells. In order to accomplish the goals of the project, PharmaSeq will combine leading edge technologies in semiconductor device design and fabrication, advanced sensor technology, digital and analogue electronics, optics and software.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 224.97K | Year: 2015

DESCRIPTION provided by applicant The main goal of this project is to demonstrate the feasibility of combining novel cancer testing using F rster resonance energy transfer FRET with an emerging platform for clinical diagnostics The intent is to develop an assay capable of detecting and monitoring bladder cancer BlCa using a urine sample The assay targets a family of matrix metalloproteinases MMPs and hyaluronidase HA ase The presence and relative distribution of these enzyme markers is strongly correlated with progression of BlCa The principle of the assay involves the preparation of immobilized peptide substrates that are dual labeled with fluorescent dyes and the determination of the rate at which they are cleaved by MMPs or HA ase present in a patient sample This will be done by measuring the extent of FRET between the two fluorescent moieties linked through the target substrates for each respective MMPs or HA ase In order to differentiate between sequences each substrate will be immobilized on different p Chips which are ultra small integrated circuits with unique serial numbers Invented by PharmaSeq Inc each p Chipandapos s distinctive identification number ID is transmitted to an analyzer when the p Chip is illuminated with laser light The association of a specific substrate with an ID allows construction of a p Chip mounted database in which the identity of a target can be determined by the ID of the p Chip on which it resides Multiple p Chips carrying different substrates for different enzymes can be mixed together in a single assay andquot multiplexingandquot Results are derived by sequentially measuring the fluorescence and obtaining the ID of each p Chip in the assay This is accomplished by passing the p Chips through a flow based reader andquot Simuplexandquot also manufactured by PharmaSeq Sensitivity of the assay can be increased using modified p Chips onto which a silver nanoparticle film has been deposited prior to peptide dye conjugation The benefit of the proposed work is the creation of a highly sensitive multiplex enzymatic assay capable of simultaneously detecting low concentrations of several enzyme biomarkers that are indicative of cancer The research plan involves an evaluation of the suitability of the silver nanoparticle film prepared on the p Chip for maximum fluorescence enhancement and the application of the selected silver nanoparticle configuration toward enhanced detection of metastasis markers for bladder cancer We will use the capability of the PharmaSeq Simuplex flow reader to simultaneously excite and detect fluorescence at two wavelengths suited for two dyes Cy and Cy and evaluate the FRET ratio changes resulting from the release of a target fragment in the substrate cleaving process Our final goal is to take advantage of the metal fluorophore interactions and develop a highly sensitive assay on the p Chip platform to simultaneously detect the activity of MMP MMP as well as HA ase in the urine of bladder cancer patients being monitored for disease progression PUBLIC HEALTH RELEVANCE Tumor markers which can be found in the blood urine or tissues are produced by malignant cells and or by host tissues in response to invasion i e tumor associated inflammatory cells and then released into the bloodstream In the current project we propose to develop a non invasive ultra sensitive enzyme based test for three metastasis biomarkers in the urine of bladder cancer patients Procedures developed during this project have the potential to provide rapid and reliable quantitative diagnostic information that will allow diagnosis and monitoring of bladder cancer and will help guide the selection of proper medical therapies leading to an improvement of the health outcomes for affected patients


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 286.08K | Year: 2015

DESCRIPTION provided by applicant The purpose of the present project is to develop and validate a new method for synthesizing large number of DNA fragments oligodeoxynucleotides The method which is called andquot sequence directed DNA synthesisandquot involves the use of small electronic circuits andquot p Chipsandquot each of which transmits a unique ID number via RF when illuminated with laser light In a massively parallel format oligonucleotides are synthesized using p Chips as the solid phase The p Chip ID provides the ability to associate a given DNA sequence with that particular p Chip as synthesis proceeds A key part of the system is a high speed instrument the sorter that reads the ID of each p Chip and then sorts p Chips into the appropriate reaction vessel based on the p Chip ID thus the specific DNA sequence The system when completed will be able to generate synthetic DNA fragments in very short times and at costs that are much lower than current methods The work plan for the project is to initially in Phase I demonstrate the ability to synthesize DNA on currently available mm p Chips and to show feasibility of sorting Following this in Phase II will shift to a new p Chip design each of which is one thousandth the volume of the mm p Chip The main goals will be to build the sorter for these ultra small chips and to formulate a working method for large scale sequence directed combinatorial DNA synthesis We will also demonstrate applicability of the method by synthesizing a large number of oligonucleotides on p Chips and creating a kb long gene fragment We will obtain the DNA sequence error rate upon cloning and identify the best methods for gene assembly and construction of long segments of chromosomes The prospect of rapidly producing DNA at low prices has profound implications in a number of fields related to synthetic genomics where new tools are needed This includes the design of modified genes for enzymes energy production vaccine designs and many other applications PUBLIC HEALTH RELEVANCE Synthetic genomics is projected to be a rapidly developing field in molecular genetics PharmaSeqandapos s sequence directed DNA synthesis will offer a powerful tool for scientists to design and build many variants of genes and larger genomic fragments at costs that are far lower than those today The ability to economically design new DNA based products using PharmaSeqandapos s sorting technology will accelerate research in diagnostics drug discovery and applied chemistry and provide innovative products


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.17M | Year: 2012

DESCRIPTION (provided by applicant): The purpose of the present project is to develop and validate the use of ultra-small RFID chips to tag and track tissue cassettes and glass slides that are used in histopathology laboratories. The system is based on thePharmaSeq laser light-activated microtransponder, also known as p-Chip . The chip's major advantages are its small size (500 m x 500 m x 100 m), unitary design, inertness, ease of use and very low cost. The system consists of the p-Chip-tagged glassslides and tissue cassettes, a stationary reader, a portable reader for trays with slides, and associated software that allows integration with common database software. The main goals of the project are to: 1) develop semi-automated methods of attachingp-Chips to slides and cassettes, 2) build advanced prototypes of the ID reader (wand) and improve key features, such as the form factors for reading each type of container, 3) improve the design of the p-Chip to increase the read range and refine methods of their post-fabrication processing, and 4) conduct extensive pilot test studies with outside collaborators to validate the system. The ID readers will have a modified optical system and will feature wireless communication between the reader and a workstation or central computer. The adoption of the system will improve reliability for tagging and tracking tissue samples. PUBLIC HEALTH RELEVANCE: Pathology specimens play an important role in research and medical practice, and are analyzed and storedin increasingly large quantities. The new PharmaSeq RFID tracking system has the potential to greatly improving the reliability of maintaining the providence for large numbers of samples using a new type of electronic identification system. Medical studies, including cancer research, clinical investigations, in vitr diagnostics and drug discovery fields will all benefit.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 357.53K | Year: 2015

DESCRIPTION provided by applicant The purpose of the present project is to develop and validate a new method for synthesizing large number of DNA fragments oligodeoxynucleotides The method which is called andquot sequence directed DNA synthesisandquot involves the use of small electronic circuits andquot p Chipsandquot each of which transmits a unique ID number via RF when illuminated with laser light In a massively parallel format oligonucleotides are synthesized using p Chips as the solid phase The p Chip ID provides the ability to associate a given DNA sequence with that particular p Chip as synthesis proceeds A key part of the system is a high speed instrument the sorter that reads the ID of each p Chip and then sorts p Chips into the appropriate reaction vessel based on the p Chip ID thus the specific DNA sequence The system when completed will be able to generate synthetic DNA fragments in very short times and at costs that are much lower than current methods The work plan for the project is to initially in Phase I demonstrate the ability to synthesize DNA on currently available mm p Chips and to show feasibility of sorting Following this in Phase II will shift to a new p Chip design each of which is one thousandth the volume of the mm p Chip The main goals will be to build the sorter for these ultra small chips and to formulate a working method for large scale sequence directed combinatorial DNA synthesis We will also demonstrate applicability of the method by synthesizing a large number of oligonucleotides on p Chips and creating a kb long gene fragment We will obtain the DNA sequence error rate upon cloning and identify the best methods for gene assembly and construction of long segments of chromosomes The prospect of rapidly producing DNA at low prices has profound implications in a number of fields related to synthetic genomics where new tools are needed This includes the design of modified genes for enzymes energy production vaccine designs and many other applications PUBLIC HEALTH RELEVANCE Synthetic genomics is projected to be a rapidly developing field in molecular genetics PharmaSeqandapos s sequence directed DNA synthesis will offer a powerful tool for scientists to design and build many variants of genes and larger genomic fragments at costs that are far lower than those today The ability to economically design new DNA based products using PharmaSeqandapos s sorting technology will accelerate research in diagnostics drug discovery and applied chemistry and provide innovative products


Patent
PharmaSeq, Inc. | Date: 2016-06-16

Provided among other things is an indexed library on one or more solid phase supports of a substantial representation of all theoretical peptide combinations having a certain length of 3 to 5 amino acids, or a combination thereof, and being formed with a certain collection of amino acids that numbers as follows: the peptides spaced apart from the supports sufficiently such that one or more of the peptides binds an antibody composition substantially more strongly than others


Provided is a method of synthesis comprising: (I) providing separate reaction sequences to TABs; (II) utilizing reaction vessels configured to react a separate combinatorial building block with a moiety on a surface of a TAB; and (III) operating one or more TAB sorters comprising a TAB reader, a sorting tree comprising valves or switches and sorting nodes, and a monitor configured to detect TAB location, wherein the operating comprises serially conducting: (a) reacting distinct combinatorial building blocks in the reaction chambers with surfaces of TABs distributed in the reaction chambers; (b) operating a controller to operate the TAB sorters to segregate the TABs to allocations appropriate for the next assigned reaction, the operating including recycling TABs with ambiguous identity back through the sorter; and (c) repeating steps (a) and (b) as needed to complete 30% or more of the assigned sequences.

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