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Bereman M.S.,University of Washington | Hsieh E.J.,University of Washington | Corso T.N.,Corsolutions, Llc | Van Pelt C.K.,Corsolutions, Llc | MacCoss M.J.,University of Washington
Molecular and Cellular Proteomics | Year: 2013

We report the development and characterization of a novel, vendor-neutral ultra-high pressure-compatible (∼10,000 p.s.i.) LC-MS source. This device is the first to make automated connections with user-packed capillary traps, columns, and capillary emitters. The source uses plastic rectangular inserts (referred to here as cartridges) where individual components (i.e. trap, column, or emitter) can be exchanged independent of one another in a plug and play manner. Automated robotic connections are made between the three cartridges using linear translation powered by stepper motors to axially compress each cartridge by applying a well controlled constant compression force to each commercial LC fitting. The user has the versatility to tailor the separation (e.g. the length of the column, type of stationary phase, and mode of separation) to the experimental design of interest in a cost-effective manner. The source is described in detail, and several experiments are performed to evaluate the robustness of both the system and the exchange of the individual trap and emitter cartridges. The standard deviation in the retention time of four targeted peptides from a standard digest interlaced with a soluble Caenorhabditis elegans lysate ranged between 3.1 and 5.3 s over 3 days of analyses. Exchange of the emitter cartridge was found to have an insignificant effect on the abundance of various peptides. In addition, the trap cartridge can be replaced with minimal effects on retention time (<20 s). © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.60M | Year: 2011

DESCRIPTION (provided by applicant): Nano-liquid chromatography is a desirable technique because when coupled with mass spectrometry it can identify many of the components of a very complex proteomic or glycomic sample including subtle chemical variationswithin the sample, and can also obtain quantitative information. The technique is renowned for its high chromatographic resolution, high sensitivity, and small sample size requirement. But the technique remains cumbersome as it suffers from several limitations including system reproducibility issues created by user inabilities in column and/or spray emitter set-up, difficulty making nanofluidic connections, and difficulty troubleshooting system malfunctions. Others have tried to simplify this underutilizedtechnique through primarily chip-based approaches, but have unfortunately compromised the technique's resolution and sensitivity. However, in a Phase I project, CorSolutions developed a robust, reliable, user-friendly nanoLC/ESI device that addresses theselimitations of conventional nanoLC/ESI systems while still maintaining state-of- the-art performance, and is able to operate at elevated UHPLC pressures. These Phase I prototypes are the first plug-and-play nanoLC/ESI devices which do not compromise the high chromatographic resolution and sensitivity for which nanoLC is renowned. But although the technology developed in Phase I offers great improvements over conventional approaches, further developments are required for the technology to reach its large commercialization potential. The goals of the Phase II are to build upon the compression connection, plug-and-play technology developed in Phase I, in order to ready the technology for commercialization. This includes development of a cartridge-based insertfor the column, allowing a column of any length to be wound in a small footprint. This enhancement will allow the overall device dimension to be substantially reduced. Additionally an emitter changer will be added, permitting the device to quickly exchange an emitter, in less than 1 sec, without need for user intervention. A spray sensor and leak sensors will be incorporated into the device with smart software to continuously monitor the sensor read back. The software will be capable of diagnosing systemmalfunctions and attempting automated repair such as an emitter change, greatly simplifying the troubleshooting process. Furthermore the ability to deliver nebulization gas will be incorporated into the device. These enhancements will allow for product commercialization. We see this simple, intuitive product becoming an integral part of biological laboratories, allowing standardization of proteomic and glycomic analyses. And most importantly the product will allow biologists to benefit from the highly informative nanoLC/MS data, enabling scientific breakthroughs and greater understanding of complex biological systems. This significant reduction in complexity of nanoLC will also allow for the technique to infiltrate deeper into the life sciences. PUBLIC HEALTH RELEVANCE: Nano-liquid chromatography mass spectrometry (nanoLC/MS) is a powerful technique for proteomic and glycomic studies which is able to not only identify proteins and glycans from very complex mixtures, but is also able to structurally characterize differences between the components, which is particularly important for post-translational modifications. However, conventional nanoLC/MS is a very difficult technique to perform, requiring a highly skilled user. Therefore this powerful technique, which could enable scientific discoveries and greater understanding of complex biological systems, is alarmingly underutilized. CorSolutions proposes to develop an intuitive, robust, reliable, user-friendly, plug-and-play device, which will address the challenges of conventional nanoLC/MS, dramatically reducing the complexity of the technique and thereby allowing its pervasive use in biological laboratories.


Patent
Corsolutions, Llc | Date: 2013-06-28

The invention allows for the formation of robust, reproducible, non-permanent connections to microchips. The connections are formed using either indexing arms or multiple fitting holder heads which are capable of forming a compression seal to a port located at any position on the surface of the microchip. The sealing force is user-defined and can be tightly controlled with integrated force sensors. In addition, the sealing force is monitored with a force sensor and force compensation mechanism ensuring that the desired force is maintained. The device is compatible with all microchip architectures. Alterations to the microchip surface is avoided as connections are established using instrumentation rather than processing steps. Further, the process is automatable allowing for exchanging microchips and subsequently creating electrical and fluidic connections in an automated fashion. Optionally, the integration of leak sensors to monitor leaks are included.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 267.71K | Year: 2013

DESCRIPTION (provided by applicant): The merging of cell culture and microfluidic technology has resulted in improved in vitro models for toxicity studies, drug development, and biomedical research. The reason for which microfluidic approaches provide a more accurate in vitro model of in vivo effects is because devices can be designed with unique properties to closely mimic the in vivo environment. Specifically the micrometer dimensions in the devices allow for a high surface area to volume ratio, leading to more effective nutrient transfer, and allowing a more in vivo-like cellular environment in terms of cell secretion and signaling. Furthermore there is no turbulence in the microchannels as fluid flow is laminar, allowing the only means of mass transportto be through diffusion, similar to a cell's natural environment. Consequently microfluidic approaches allow for biomolecular gradients to be imitated, and additionally microfluidic devices allow for 3D cell culture. Although much research has been performed in this exciting, emerging area, it nearly exclusively has focused on the microfluidic devices themselves, leaving the means of interfacing the technology with the macro-world largely ignored. As conventional, macro detectors and fluid pumps are proven, established technology, it is desirable for microfluidic approaches to employ these industry standards. And although many acknowledge that development of micro-to-macro interface technology is vital to the future of the field as well as to the commercialsuccess of the technology, alarming little progress has been made. To date the rudimentary technique of gluing tubing to microchips for use in large, cumbersome incubators is the norm. Therefore CorSolutions proposes to develop and evaluate a universal platform, the CorCardio, to interface a wide variety of microfluidic devices to the macro-world. The platform will incorporate technology previously developed at CorSolutions including non-permanent, compression, fluidic interconnects and accurate, pulse-free fluid delivery pumps, with a heated insert design that will offer a simple alternative to an incubator. The proposed platform will be reliable, compatible with all substrate materials, easy to use with little training, flexible for use with chips having varied architectures, chemically compatible, allow for maximum field of view for optical assessment, leak-free over a wide-range of flow rates and backpressures, low cost, and have potential for automation. Thus the user-friendly platform will offer an interconnect solution with the potential of becoming the standard for cells-on-a-chip applications. This platform will allow for cells-on-a- chip applications to become pervasive in toxicology studies, lowering the high attrition rate of drugs in clinical trial while also limiting the number of animals needed for biomedical research. Furthermore the platform will allow for point-of-care applications, where patient-derived cells will permit individualized drug testing, improving therapeutic outcomes. Insummary, the interconnect platform will assist in the commercialization of cells-on-a- chip applications, enabling scientifc breakthroughs and greater understanding of complex biological systems. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Culturing cells in microfluidic devices has led to development of improved in vitro models that are able to more closely mimic in vivo environments than classic cell culture, offering more accurate correlation with in vivo results for toxicology, drug development and biomedical research. However in this emerging area, the focus has been placed on microfabrication of the devices themselves and in contrast, little attention has been placed on the essential need to interface these devices with the established, proven technologies of the macro-world. To meet this need, CorSolutions proposes to develop a flexible, universal platform, capable of interfacing a wide variety of devices with the macro-world, in a user-friendly, robust and reliable manner.


Patent
Corsolutions, Llc | Date: 2012-06-06

The invention provides for fluidic connections to be established between tubes, ports, fluidic components and fluidic devices. The leak-tight connections are formed through controlled, compressive forces and can be used for both low and high pressure applications.


Patent
Corsolutions, Llc | Date: 2014-09-11

A chromatography and fluidic device with connections capable of automated component changing, diagnostic leak and current sensing. The chromatography-electrospray device contains a chromatography column, a pre-column, a spray emitter, or other fluidic component imbedded within one or more inserts. The inserts are robotically placed in receiving hardware, and a plug and play compression fitting connection mechanism makes the fluidic seals in an automated fashion. A plurality of sensors capable of detecting leaks is situated in the device near leak-prone regions. The electrospray emitter has a current sensing electrode in proximity of the electrospray region, capable of detecting the electrospray current. In conjunction with an electronics system, these sensors allow for system and component diagnostics. The diagnostic information may then be used for manual or automated system repair.


Patent
Corsolutions, Llc | Date: 2013-04-08

An apparatus, system and method providing a fluid flow suitable to grow and maintain living cells in the fluid flow are disclosed. The apparatus includes a fluid displacement apparatus capable of providing at least one of positive and negative displacement of the fluid and configured to indirectly displace the fluid, an in-line flow sensor configured to directly measure the fluid flow, and a feed-back control in communication with the fluid displacement apparatus and the in-line flow sensor, wherein the feed-back control is configured to continuously control the fluid flow in response to the flow sensor measurements.


Patent
Corsolutions, Llc | Date: 2014-07-17

A system for the precise metering and delivery of discrete volumes is described. The system is composed of inexpensive components that can be easily assembled, allowing for cost-effective manufacturing of the system. The system can precisely meter and deliver fluids, solids in particulate or powder form, or alternatively it could mix discrete amounts of fluid and solid. Potential applications for the system and microfluidic device include subcutaneous, long-term, automated drug delivery, such as insulin for diabetics.


Trademark
Corsolutions, Llc | Date: 2012-06-22

Scientific apparatus and instruments, namely, fluidic connectors for extending between tubes, microdevices, or tubes-to-microdevices by compression, and parts and fittings therefor, for use in microfluidics, mass spectrometry and liquid chromatography.


Patent
Corsolutions, Llc | Date: 2010-08-25

The invention allows for the formation of robust, reproducible, non-permanent connections to microchips. The connections are formed using either indexing arms or multiple fitting holder heads which are capable of forming a compression seal to a port located at any position on the surface of the microchip. The sealing force is user-defined and can be tightly controlled with integrated force sensors. In addition, the sealing force is monitored with a force sensor and force compensation mechanism ensuring that the desired force is maintained. The device is compatible with all microchip architectures. Alterations to the microchip surface is avoided as connections are established using instrumentation rather than processing steps. Further, the process is automatable allowing for exchanging microchips and subsequently creating electrical and fluidic connections in an automated fashion. Optionally, the integration of leak sensors to monitor leaks are included.

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