Extending the Golay Equation for Coupling a Gas Chromatograph to a Drift Tube IMS

When it comes to analyzing complex mixtures with highly sensitive ion mobility spectrometers (IMS), a pre-separation of these mixtures is often required due to chemical cross sensitivities and limitations in IMS resolving power. In most cases, gas chromatographic (GC) pre-separation is used. In contrast to typical GC detectors, such as flame ionization detectors or photo ionization detectors, an IMS can add significant dead volume to the system due to its ionization chamber. This dead volume causes memory effects and peak broadening affecting the performance of the chromatographic pre-separation. Therefore, a new but simple model has been developed to estimate the effect of additional detector dead volume and to obtain the optimal operating parameters. This model considers both geometric parameters, such as column length and column diameter, and operating parameters, such as flow rate and temperature of the gas chromatograph and IMS. In addition, the effects induced by the compressibility of the mobile phase were taken into account. In comparison to the commonly used Golay equation our model predicts increased plate heights at low and medium linear velocities. Our model has been experimentally verified using an ultra-high sensitive IMS detector in combination with capillary columns of different lengths and diameters. A UV lamp has been used for ionization due to its good linearity. The columns have been held in isotherm conditions and, additionally, they have been operated with purified air as mobile phase. For each capillary under investigation, a series of measurements with different linear drift velocities has been performed. From these experimental data, the vast difference in plate heights at low linear velocities compared to the expected values from the Golay equation can be confirmed. Despite the simplicity of our model, the predictions are in good accordance with the measurements. Thus, the GC-IMS operating parameters can be easily optimized with respect to maximum gas chromatic pre-separation

Burden of illness of Pompe disease in patients only receiving supportive care

Background: Pompe disease is an orphan disease for which enzyme replacement therapy (ERT) recently became available. This study aims to estimate all relevant aspects of burden of illness-societal costs, use of home care and informal care, productivity losses, and losses in health-related quality of life (HRQoL)-for adult Pompe patients only receiving supportive care. Methods: We collected data on all relevant aspects of burden of illness via a questionnaire. We applied a societal perspective in calculating costs. The EQ-5D was used to estimate HRQoL. Results: Eighty adult patients (87% of the total Dutch adult Pompe population) completed a questionnaire. Disease severity ranged from mild to severe. Total annual costs were estimated at €22,475 (range €0-169,539) per adult Pompe patient. Patients on average received 8 h of home care and 19 h of informal care per week. Eighty-five percent of the patients received informal care from one or more caregivers; 40% had stopped working due to their disease; another 20% had reduced their working hours. HRQoL for Pompe patients who only received supportive care was estimated at 0.72, 17% lower than the Dutch population at large. Conclusions: Adult Pompe disease is associated with a considerable burden of illness at both the societal and patient levels. The disease leads to substantial costs and dependency on medical devices, home care, and informal care, and has a high impact on the patient's social network. In addition, patients are limited in their ability to work and have significantly reduced HRQoL

A Simple Analytical Model for Predicting the Detectable Ion Current in Ion Mobility Spectrometry Using Corona Discharge Ionization Sources

Corona discharge ionization sources are often used in ion mobility spectrometers (IMS) when a non-radioactive ion source with high ion currents is required. Typically, the corona discharge is followed by a reaction region where analyte ions are formed from the reactant ions. In this work, we present a simple yet sufficiently accurate model for predicting the ion current available at the end of this reaction region when operating at reduced pressure as in High Kinetic Energy Ion Mobility Spectrometers (HiKE-IMS) or most IMS-MS instruments. It yields excellent qualitative agreement with measurement results and is even able to calculate the ion current within an error of 15%. Additional interesting findings of this model are the ion current at the end of the reaction region being independent from the ion current generated by the corona discharge and the ion current in High Kinetic Energy Ion Mobility Spectrometers (HiKE-IMS) growing quadratically when scaling down the length of the reaction region. The final publication is available at Springer via https://doi.org/10.1007/s13361-018-1970-6

High-Resolution High Kinetic Energy Ion Mobility Spectrometer Based on a Low-Discrimination Tristate Ion Shutter

High kinetic energy ion mobility spectrometry (HiKE-IMS) allows for sensitive trace gas analysis within seconds, mitigating many disadvantages of standard ion mobility spectrometers through operation at reduced pressure and high electric field strengths. However, these advantages usually come at the cost of reduced resolving power, ranging from a maximum of 75 down to 50 at a reduced field strength of 120 Td for the original device. In this work, we present an extended theory for HiKE-IMS resolving power and a novel tristate ion shutter principle able to achieve initial ion packet widths of 1 μs without significant mobility discrimination. Such an ultrashort injection time allows for improving the resolving power of the HiKE-IMS to 140 for a wide range of reduced electric field strengths. With this resolving power, separating all ion species generated from a mixture of benzene, toluene, and xylene is possible. Furthermore, a resolving power of 140 is sufficient to partially separate isotopologues under high electric field strengths

High-Resolution High Kinetic Energy Ion Mobility Spectrometer Based on a Low-Discrimination Tristate Ion Shutter

High kinetic energy ion mobility spectrometry (HiKE-IMS) allows for sensitive trace gas analysis within seconds, mitigating many disadvantages of standard ion mobility spectrometers through operation at reduced pressure and high electric field strengths. However, these advantages usually come at the cost of reduced resolving power, ranging from a maximum of 75 down to 50 at a reduced field strength of 120 Td for the original device. In this work, we present an extended theory for HiKE-IMS resolving power and a novel tristate ion shutter principle able to achieve initial ion packet widths of 1 μs without significant mobility discrimination. Such an ultrashort injection time allows for improving the resolving power of the HiKE-IMS to 140 for a wide range of reduced electric field strengths. With this resolving power, separating all ion species generated from a mixture of benzene, toluene, and xylene is possible. Furthermore, a resolving power of 140 is sufficient to partially separate isotopologues under high electric field strengths

High-Resolution High Kinetic Energy Ion Mobility Spectrometer Based on a Low-Discrimination Tristate Ion Shutter

High kinetic energy ion mobility spectrometry (HiKE-IMS) allows for sensitive trace gas analysis within seconds, mitigating many disadvantages of standard ion mobility spectrometers through operation at reduced pressure and high electric field strengths. However, these advantages usually come at the cost of reduced resolving power, ranging from a maximum of 75 down to 50 at a reduced field strength of 120 Td for the original device. In this work, we present an extended theory for HiKE-IMS resolving power and a novel tristate ion shutter principle able to achieve initial ion packet widths of 1 μs without significant mobility discrimination. Such an ultrashort injection time allows for improving the resolving power of the HiKE-IMS to 140 for a wide range of reduced electric field strengths. With this resolving power, separating all ion species generated from a mixture of benzene, toluene, and xylene is possible. Furthermore, a resolving power of 140 is sufficient to partially separate isotopologues under high electric field strengths

Tentative clinical diagnosis of Lujan-Fryns syndrome-A conglomeration of different genetic entities?

The clinical diagnosis of Lujan-Fryns syndrome (LFS) comprises X-linked intellectual disability (XLID) with marfanoid habitus, distinct combination of minor facial anomalies and nasal speech. However the definition of syndrome was significantly broadened since the original report and implies ID with marfanoid habitus. Mutations of three genes (MED12, UPF3B, and ZDHHC9) have been reported in "broadly defined" LFS. We examined these genes in 28 individuals with a tentative clinical diagnosis of LFS but we did not identify any causative mutation. By molecular karyotyping we detected other disorders, i.e., Phelan-McDermid syndrome and 16p11.2 microduplication, each in one patient. One affected individual was carrier of a different recurrent duplication on 16p11.2 that has been reported several times to the DECIPHER and ISCA databases in individuals with autism, intellectual disability (ID), and developmental delay. It may represent a new duplication syndrome. We also identified previously unreported de novo duplication on chromosome 12p13.31 which we considered to be disease-causing. X-exome sequencing of four individuals revealed private or non-recurrent mutations in NKAP and LAS1L in one patient each. While LFS is defined as a form of XLID, there seem to be various conditions that have rather similar phenotypes. Therefore, the combination of ID and marfanoid habitus in a male patient is not sufficient for the diagnosis of LFS. We suggest that the diagnosis of LFS in patients with ID and marfanoid habitus should be made only in presence of specific facial features, nasal speech and obvious X-linked segregation of the disorder or an unambiguously pathogenic mutation in the MED12. © 2015 Wiley Periodicals, Inc.status: publishe

Identification of three novel plasminogen (PLG) gene mutations in a series of 23 patients with low PLG activity

Inherited severe hypoplasminogenaemia is a multisystemic disorder leading to deficient extravascular fibrinolysis.As a clinical consequence wound healing capacity of mucous membranes is markedly impaired leading to ligneous conjunctivitis and several other manifestations. Here we report the molecular genetic and clinical findings on 23 new cases with severe hypoplasminogenaemia. Homozygous or compound-heterozygous mutations in the plasminogen (PLG) gene were found in 16 of 23 patients (70%), three of which were novel mutations reported here for the first time (C166Y, Y264S, IVS10-7T/G). Compared to 79 previously published cases, clinical manifestations of the current group of patients showed higher percentages of ligneous periodontitis, congenital hydrocephalus, and involvement of the female genital tract. In contrast, involvement of the gastrointestinal or urogenital tract was not observed in any of the cases. Patients originated to a large extent (61%) from Turkey and the Middle East, and showed a comparably frequent occurrence of consanguinity of affected families and a greater female to male ratio than was derived from previous reports in the literature. Individual treatment of ligneous conjunctivitis included topical plasminogen or heparin eye drops, topical or systemic fresh frozen plasma, and surgical removal of ligneous pseudomembranes, mostly with modest or transient efficacy. In conclusion, the present study underscores the broad range of clinical manifestations in PLG-deficient patients with a trend to regional differences. Transmission of genetic and clinical data to the recently established Plasminogen Deficiency Registry should help to determine the prevalence of the disease and to develop more efficient treatment strategies