Time-of-flight mass spectrometry-most notably matrix-assisted laser-desorption-ionization time-of-flight (MALDI-TOF) spectrometry-is an important class of techniques for the study of proteins and other biomolecules. Although these techniques provide excellent performance for masses up to about 20,000 daltons, there has been limited success in achieving good mass resolution at higher masses. This is because the sensitivity of the microchannel plate (MCP) detectors used in most systems decreases rapidly with increasing particle mass, limiting the utility of MCP detectors for very large masses. It has recently been proposed that cryogenic particle detectors may provide a solution to these difficulties. Cryogenic detectors measure the thermal energy deposited by the particle impact, and thus have a sensitivity that is largely independent of particle mass. Recent experiments have demonstrated the sensitivity of cryogenic particle detectors to single biomolecules, a quantum efficiency several orders of magnitude larger than the MCP detectors, and sensitivity to masses as large as 750,000 daltons. Here we present results demonstrating an order of magnitude better energy resolution than previous measurements, allowing direct determination of particle charge state during acceleration. Although application of these detectors to practical mass spectrometry will require further development of the detectors and cryogenics, these detectors can be used to elucidate the performance-limiting processes that occur in such systems.

Macromolecules with masses up to 50 kDa have been detected with a cryogenic particle detector in a MALDI time-of-flight biopolymer mass spectrometer. The cryogenic particle detector was a Sn/Sn-ox/Sn tunnel junction operated at a temperature of 0.4 K. A calibration with 6 keV single photons inferred that the delayed detector pulses corresponded to the absorption of the kinetic energy of a single macromolecule. Time-of-flight spectra of lysozyme proteins are presented. The mass resolution is 100 Da at 14 300 Da. The energy sensitive detection mechanism suggests that cryogenic particle detectors have a high and mass independent detection efficiency for macromolecules.

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Experimental results from equimolar PEG and protein standards samples are presented from a MALDI-TOF mass spectrometer equipped with both ionizing detectors and the novel single molecule sensitive cryodetectors. The data are consistent with a model hypothesis suggesting that the observed decrease in signal strength in conventional ionizing detector MALDI-TOF mass spectrometers can be explained by the exponentially decreasing quantum efficiency of ionizing detectors. Cryodetectors, in contrast, have a mass independent detection efficiency of 100% on impact and provide additional information on the molecule state owing to the calorimetric nature of the detection mechanism.

Background: Temporary mechanical circulatory support (MCS) devices provide hemodynamic assistance for shock refractory to pharmacological treatment. Most registries have focused on single devices or specific etiologies of shock, limiting data regarding overall practice patterns with temporary MCS in cardiac intensive care units. Methods: The CCCTN (Critical Care Cardiology Trials Network) is a multicenter network of tertiary CICUs in North America. Between September 2017 and September 2018, each center (n=16) contributed a 2-month snapshot of consecutive medical CICU admissions. Results: Of the 270 admissions using temporary MCS, 33% had acute myocardial infarction-related cardiogenic shock (CS), 31% had CS not related to acute myocardial infarction, 11% had mixed shock, and 22% had an indication other than shock. Among all 585 admissions with CS or mixed shock, 34% used temporary MCS during the CICU stay with substantial variation between centers (range: 17%–50%). The most common temporary MCS devices were intraaortic balloon pumps (72%), Impella (17%), and veno-arterial extracorporeal membrane oxygenation (11%), although intraaortic balloon pump use also varied between centers (range: 40%–100%). Patients managed with intraaortic balloon pump versus other forms of MCS (advanced MCS) had lower Sequential Organ Failure Assessment scores and less severe metabolic derangements. Illness severity was similar at high- versus low-MCS utilizing centers and at centers with more advanced MCS use. Conclusions: There is wide variation in the use of temporary MCS among patients with shock in tertiary CICUs. While hospital-level variation in temporary MCS device selection is not explained by differences in illness severity, patient-level variation appears to be related, at least in part, to illness severity.