A Single Quadrupole Compact Mass Spectrometer Enabling Early Stage Synthetic Optimization of Verubecestat (MK-8931)

We investigated the fusion of high-speed liquid droplets as a way to record the kinetics of liquid-phase chemical reactions on the order of microseconds. Two streams of micrometer-size droplets collide with one another. The droplets that fused (13 μm in diameter) at the intersection of the two streams entered the heated capillary inlet of a mass spectrometer. The mass spectrum was recorded as a function of the distance x between the mass spectrometer inlet and the droplet fusion center. Fused droplet trajectories were imaged with a high-speed camera, revealing that the droplet fusion occurred approximately within a 500-μm radius from the droplet fusion center and both the size and the speed of the fused droplets remained relatively constant as they traveled from the droplet fusion center to the mass spectrometer inlet. Evidence is presented that the reaction effectively stops upon entering the heated inlet of the mass spectrometer. Thus, the reaction time was proportional to x and could be measured and manipulated by controlling the distance x. Kinetic studies were carried out in fused water droplets for acid-induced unfolding of cytochrome c and hydrogen–deuterium exchange in bradykinin. The kinetics of the former revealed the slowing of the unfolding rates at the early stage of the reaction within 50 μs. The hydrogen–deuterium exchange revealed the existence of two distinct populations with fast and slow exchange rates. These studies demonstrated the power of this technique to detect reaction intermediates in fused liquid droplets with microsecond temporal resolution.

Download Full-text

Real-time monitoring of exhaled volatiles using atmospheric pressure chemical ionization on a compact mass spectrometer

Bioanalysis ◽

10.4155/bio-2016-0045 ◽

2016 ◽

Vol 8 (13) ◽

pp. 1325-1336 ◽

Cited By ~ 18

Author(s):

Liam M Heaney ◽

Dorota M Ruszkiewicz ◽

Kayleigh L Arthur ◽

Andria Hadjithekli ◽

Clive Aldcroft ◽

...

Keyword(s):

Real Time ◽

Mass Spectrometer ◽

Atmospheric Pressure ◽

Chemical Ionization ◽

Atmospheric Pressure Chemical Ionization ◽

Real Time Monitoring ◽

Compact Mass ◽

Pressure Chemical Ionization ◽

Pressure Chemical

Download Full-text

Analysis Of Volatile Organic Compounds In Exhaled Air With A Novel Compact Mass Spectrometer (Smart-Nose®)

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a5572 ◽

2011 ◽

Author(s):

Olaf Holz ◽

Thierry Zesiger ◽

Bianca Lavae-Mokhtari ◽

Sven Schuchardt ◽

Norbert Krug ◽

...

Keyword(s):

Volatile Organic Compounds ◽

Organic Compounds ◽

Mass Spectrometer ◽

Compact Mass ◽

Volatile Organic ◽

Exhaled Air

Download Full-text

Alterations in the number of motoneurons containing immunoreactive calcitonin gene-related peptide(CGRP)& choline acetyltransferase(ChAT) in the cervical spinal cord of the wobbler mouse during the development of the motoneuron disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141226 ◽

1995 ◽

Vol 53 ◽

pp. 970-971

Author(s):

L. Vacca-Galloway ◽

Y.Q. Zhang ◽

P. Bose ◽

S.H. Zhang

Keyword(s):

Spinal Cord ◽

Early Stage ◽

Cervical Spinal Cord ◽

Wild Type Mouse ◽

Reflex Response ◽

Mouse Strains ◽

Behavioral Tests ◽

Wobbler Mouse ◽

Stage 4 ◽

Stage 1

The Wobbler mouse (wr) has been studied as a model for inherited human motoneuron diseases (MNDs). Using behavioral tests for forelimb power, walking, climbing, and the “clasp-like reflex” response, the progress of the MND can be categorized into early (Stage 1, age 21 days) and late (Stage 4, age 3 months) stages. Age-and sex-matched normal phenotype littermates (NFR/wr) were used as controls (Stage 0), as well as mice from two related wild-type mouse strains: NFR/N and a C57BI/6N. Using behavioral tests, we also detected pre-symptomatic Wobblers at postnatal ages 7 and 14 days. The mice were anesthetized and perfusion-fixed for immunocytochemical (ICC) of CGRP and ChAT in the spinal cord (C3 to C5).Using computerized morphomety (Vidas, Zeiss), the numbers of IR-CGRP labelled motoneurons were significantly lower in 14 day old Wobbler specimens compared with the controls (Fig. 1). The same trend was observed at 21 days (Stage 1) and 3 months (Stage 4). The IR-CGRP-containing motoneurons in the Wobbler specimens declined progressively with age.

Download Full-text