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Simple and Minimally Invasive SID Devices for Native Mass Spectrometry.

ABSTRACT: We describe a set of simple devices for surface-induced dissociation of proteins and protein complexes on three instrument platforms. All of the devices use a novel yet simple split lens geometry that is minimally invasive (requiring a few millimeters along the ion path axis) and is easier to operate than prior generations of devices. The split lens is designed to be small enough to replace the entrance lens of a Bruker FT-ICR collision cell, the dynamic range enhancement (DRE) lens of a Waters Q-IM-TOF, or the exit lens of a transfer multipole of a Thermo Scientific Extended Mass Range (EMR) Orbitrap. Despite the decrease in size and reduction in number of electrodes to 3 (from 10 to 12 in Gen 1 and ?6 in Gen 2), we show sensitivity improvement in a variety of cases across all platforms while also maintaining SID capabilities across a wide mass and energy range. The coupling of SID, high resolution, and ion mobility is demonstrated for a variety of protein complexes of varying topologies.

SUBMITTER: Snyder DT

PROVIDER: S-EPMC7438310 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Simple and Minimally Invasive SID Devices for Native Mass Spectrometry.

Snyder Dalton T DT Panczyk Erin M EM Somogyi Arpad A Kaplan Desmond A DA Wysocki Vicki V

Analytical chemistry 20200807 16

We describe a set of simple devices for surface-induced dissociation of proteins and protein complexes on three instrument platforms. All of the devices use a novel yet simple split lens geometry that is minimally invasive (requiring a few millimeters along the ion path axis) and is easier to operate than prior generations of devices. The split lens is designed to be small enough to replace the entrance lens of a Bruker FT-ICR collision cell, the dynamic range enhancement (DRE) lens of a Waters ...[more]

PMID: 32700898

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Project description:BACKGROUND:Transanal minimally invasive surgery (TAMIS) is deployed for organ preservation in early rectal cancer and significant rectal polyps. Rapid evaporative ionisation mass spectrometry (REIMS) provides biochemical tissue analysis, which could be applied intraoperatively to give real-time tissue feedback to the surgeon and decrease the risk of an involved margin. However, the accuracy and feasibility of this approach have not been established. METHODS:In this prospective observational study, patients undergoing resection of rectal adenomas or carcinomas were recruited. An electrosurgical handpiece analysed tissues ex vivo using diathermy, with the aerosol aspirated into a Xevo G2-S ToF mass spectrometer. The relative abundance of lipids underwent predictive statistical modelling and leave-one-patient-out cross-validation. The outcomes of interest were the ability of REIMS to differentiate normal, adenomatous and cancerous tissue, or any disease subtype from normal. REIMS was coupled with TAMIS for in vivo sampling, assessing the accuracy of tissue recognition and distinguishing bowel wall layers. RESULTS:Forty-seven patients were included, yielding 266 spectra (121 normal, 109 tumour and 36 adenoma). REIMS differentiates normal, adenomatous and cancerous rectal tissues with 86.8% accuracy, and normal and adenomatous tissue with 92.4% accuracy and 91.4% accuracy when differentiating disease from normal. We have performed the first five in-man mass spectrometry augmented TAMIS (MS-TAMIS). In real time, MS-TAMIS can differentiate rectal mucosa and submucosa based on their relative abundance of triglycerides and glycerophospholipids. The ex vivo accuracy distinguishing diseased and normal tissues is maintained in vivo at 90%, with negative predictive value of 95%. The system identified a deep and lateral involved tumour margin during TAMIS. CONCLUSIONS:REIMS distinguishes rectal tissue types based on underlying lipid biology, and this can be translated in vivo by coupling it to TAMIS. There is a role for this technology in improving the efficacy of resection of early rectal cancers.

Project description:SIGNIFICANCE:Noncompliance is a problem affecting glaucoma patients. Approaches to improve adherence include the use of drug-delivery systems and safer forms of surgery. Minimally invasive glaucoma surgery (MIGS) has reduced complications, particularly in combination with cataract surgery, and with its good intraocular pressure (IOP) reduction may reduce or eliminate glaucoma medications.Glaucoma is a progressive disease and a leading cause of irreversible blindness. Elevated IOP is the most important risk factor, but effective medical management is dependent on patient adherence. This review summarizes the adherence problem in glaucoma and the efforts, including MIGS, to provide effective IOP control that is not dependent on patient compliance.The current understanding of patient adherence to pharmacological treatment of glaucoma is discussed including the challenges facing glaucoma patients. Historical approaches to providing IOP control in a sustained and reliable way are presented culminating in a review of the burgeoning use of MIGS devices.It is estimated that, in the United States, 27% of prescriptions written, across all medications, are not filled or are filled but not taken. For ocular hypotensive medications, even when filled, a large percentage (which varies widely by study) are not instilled as prescribed. To address this problem, methods for sustained drug delivery have been and continue to be developed, as well as surgical and laser approaches. Most recently, MIGS devices have gained popularity because of the ease of implantation during cataract surgery, favorable safety profile, and the possibility for effective and long-lasting IOP lowering, as well as the reduction or elimination of need for IOP-lowering medication.Poor adherence to treatment is relatively common among glaucoma patients and is associated with progression of disease. Recommending MIGS implantation during cataract surgery may offer optometrists a valuable treatment option in managing glaucoma patients, particularly where good adherence is in doubt.

Dataset Information

Simple and Minimally Invasive SID Devices for Native Mass Spectrometry.

Publications

Simple and Minimally Invasive SID Devices for Native Mass Spectrometry.

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