@article{SteppertSteppertBollingeretal.2020,
  author    = {Steppert, Claus and Steppert, Isabel and Bollinger, Thomas and Sterlacci, William},
  title     = {Rapid non-invasive detection of Influenza-A-infection by multicapillary column coupled ion mobility spectrometry},
  series = {Journal of breath research : volatiles for medical diagnosis ; official journal of the International Association for Breath Research (IABR) and the International Society for Breath Odor Research (ISBOR)},
  volume    = {15},
  journal   = {Journal of breath research : volatiles for medical diagnosis ; official journal of the International Association for Breath Research (IABR) and the International Society for Breath Odor Research (ISBOR)},
  number    = {1},
  publisher = {IOP Publ. Ltd.},
  address   = {Bristol},
  issn      = {1752-7163},
  doi       = {10.1088/1752-7163/abb762},
  pages     = {5},
  year      = {2020},
  abstract  = {Infectious pathogens are a global issue. Global air travel offers an easy and fast opportunity not only for people but also for infectious diseases to spread around the world within a few days. Also, large public events facilitate increasing infection numbers. Therefore, rapid on-site screening for infected people is urgently needed. Due to the small size and easy handling, ion mobility spectrometry coupled with a multicapillary column (MCC-IMS) is a very promising, sensitive method for the on-site identification of infectious pathogens based on scents, representing volatile organic compounds (VOCs). The purpose of this study was to prospectively assess whether identification of Influenza-A-infection based on VOCs by MCC-IMS is possible in breath. Nasal breath was investigated in 24 consecutive persons with and without Influenza-A-infection by MCC-IMS. In 14 Influenza-A-infected patients, infection was proven by PCR of nasopharyngeal swabs. Four healthy staff members and six patients with negative PCR result served as controls. For picking up relevant VOCs in MCC-IMS spectra, software based on cluster analysis followed by multivariate statistical analysis was applied. With only four VOCs canonical discriminant analysis was able to distinguish Influenza-A-infected patients from those not infected with 100\% sensitivity and 100\% specificity. This present proof-of-concept-study yields encouraging results showing a rapid diagnosis of viral infections in nasal breath within 5 min by MCC-IMS. The next step is to validate the results with a greater number of patients with Influenza-A-infection as well as other viral diseases, especially COVID-19. Registration number at ClinicalTrials.gov NCT04282135.},
  language  = {en}
}
@article{SteppertSteppertSterlaccietal.2021,
  author    = {Steppert, Claus and Steppert, Isabel and Sterlacci, William and Bollinger, Thomas},
  title     = {Rapid detection of SARS-CoV-2 infection by multicapillary column coupled ion mobility spectrometry (MCC-IMS) of breath},
  series = {Journal of breath research : volatiles for medical diagnosis ; official journal of the International Association for Breath Research (IABR) and the International Society for Breath Odor Research (ISBOR)},
  volume    = {15},
  journal   = {Journal of breath research : volatiles for medical diagnosis ; official journal of the International Association for Breath Research (IABR) and the International Society for Breath Odor Research (ISBOR)},
  number    = {2},
  publisher = {IOP Publ. Ltd.},
  address   = {Bristol},
  issn      = {1752-7163},
  doi       = {10.1088/1752-7163/abe5ca},
  pages     = {8},
  year      = {2021},
  abstract  = {There is an urgent need for screening of patients with a communicable viral disease to cut infection chains. Recently, we demonstrated that ion mobility spectrometry coupled with a multicapillary column (MCC-IMS) is able to identify influenza-A infections in patients' breath. With a decreasing influenza epidemic and upcoming SARS-CoV-2 infections we proceeded further and analyzed patients with suspected SARS-CoV-2 infections. In this study, the nasal breath of 75 patients (34 male, 41 female, aged 64.4 +/- 15.4 years) was investigated by MCC-IMS for viral infections. Fourteen were positively diagnosed with influenza-A infection and sixteen with SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) of nasopharyngeal swabs. In one patient RT-PCR was highly suspicious of SARS-CoV-2 but initially inconclusive. The remaining 44 patients served as controls. Breath fingerprints for specific infections were assessed by a combination of cluster analysis and multivariate statistics. There were no significant differences in gender or age according to the groups. In the cross validation of the discriminant analysis 72 of the 74 clearly defined patients could be correctly classified to the respective group. Even the inconclusive patient could be mapped to the SARS-CoV-2 group by applying the discrimination functions. Conclusion: SARS-CoV-2 infection and influenza-A infection can be detected with the help of MCC-IMS in breath in this pilot study. As this method provides a fast non-invasive diagnosis it should be further developed in a larger cohort for screening of communicable viral diseases. A validation study is ongoing during the second wave of COVID-19. Trial registration: ClinicalTrial.gov, NCT04282135 Registered 20 February 2020-Retrospectively registered,},
  language  = {en}
}
@phdthesis{Steppert2022,
  author    = {Steppert, Isabel},
  title     = {Entwicklung einer nichtinvasiven Diagnostikmethode zum Nachweis von Infektionserregern},
  doi       = {10.25932/publishup-57544},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-575441},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XIV, 101, LVIII},
  year      = {2022},
  abstract  = {Die aktuelle COVID-19-Pandemie zeigt deutlich, wie sich Infektionskrankheiten weltweit verbreiten k{\"o}nnen. Neben Viruserkrankungen breiten sich auch multiresistente bakterielle Erreger weltweit aus. Dementsprechend besteht ein hoher Bedarf, durch fr{\"u}hzeitige Erkennung Erkrankte zu finden und Infektionswege zu unterbrechen. Herk{\"o}mmliche kulturelle Verfahren ben{\"o}tigen minimalinvasive bzw. invasive Proben und dauern f{\"u}r Screeningmaßnahmen zu lange. Deshalb werden schnelle, nichtinvasive Verfahren ben{\"o}tigt. Im klassischen Griechenland verließen sich die {\"A}rzte unter anderem auf ihren Geruchssinn, um Infektionen und andere Krankheiten zu differenzieren. Diese charakteristischen Ger{\"u}che sind fl{\"u}chtige organische Substanzen (VOC), die im Rahmen des Metabolismus eines Organismus entstehen. Tiere, die einen besseren Geruchssinn haben, werden trainiert, bestimmte Krankheitserreger am Geruch zu unterscheiden. Allerdings ist der Einsatz von Tieren im klinischen Alltag nicht praktikabel. Es bietet sich an, auf technischem Weg diese VOCs zu analysieren. Ein technisches Verfahren, diese VOCs zu unterscheiden, ist die Ionenmobilit{\"a}tsspektrometrie gekoppelt mit einer multikapillaren Gaschromatographies{\"a}ule (MCC-IMS). Hier zeigte sich, dass es sich bei dem Verfahren um eine schnelle, sensitive und verl{\"a}ssliche Methode handelt. Es ist bekannt, dass verschiedene Bakterien aufgrund des Metabolismus unterschiedliche VOCs und damit eigene spezifische Ger{\"u}che produzieren. Im ersten Schritt dieser Arbeit konnte gezeigt werden, dass die verschiedenen Bakterien in-vitro nach einer kurzen Inkubationszeitzeit von 90 Minuten anhand der VOCs differenziert werden k{\"o}nnen. Hier konnte analog zur Diagnose in biochemischen Testreihen eine hierarchische Klassifikation der Bakterien erfolgen. Im Gegensatz zu Bakterien haben Viren keinen eigenen Stoffwechsel. Ob virusinfizierte Zellen andere VOCs als nicht-infizierte Zellen freisetzen, wurde an Zellkulturen {\"u}berpr{\"u}ft. Hier konnte gezeigt werden, dass sich die Fingerprints der VOCs in Zellkulturen infizierter Zellen mit Respiratorischen Synzytial-Viren (RSV) von nicht-infizierten Zellen unterscheiden. Virusinfektionen im intakten Organismus unterscheiden sich von den Zellkulturen dadurch, dass hier neben Ver{\"a}nderungen im Zellstoffwechsel auch durch Abwehrmechanismen VOCs freigesetzt werden k{\"o}nnen. Zur {\"U}berpr{\"u}fung, inwiefern sich Infektionen im intakten Organismus ebenfalls anhand VOCs unterscheiden lassen, wurde bei Patienten mit und ohne Nachweis einer Influenza A Infektion als auch bei Patienten mit Verdacht auf SARS-CoV-2 (Schweres-akutes-Atemwegssyndrom-Coronavirus Typ 2) Infektion die Atemluft untersucht. Sowohl Influenza-infizierte als auch SARS-CoV-2 infizierte Patienten konnten untereinander und von nicht-infizierten Patienten mittels MCC-IMS Analyse der Atemluft unterschieden werden. Zusammenfassend erbringt die MCC-IMS ermutigende Resultate in der schnellen nichtinvasiven Erkennung von Infektionen sowohl in vitro als auch in vivo.},
  language  = {de}
}
@article{SteppertSchoenfelderSchultzetal.2021,
  author    = {Steppert, Isabel and Sch{\"o}nfelder, Jessy and Schultz, Carolyn and Kuhlmeier, Dirk},
  title     = {Rapid in vitro differentiation of bacteria by ion mobility spectrometry},
  series = {Applied Microbiology and Biotechnology},
  volume    = {105},
  journal   = {Applied Microbiology and Biotechnology},
  number    = {10},
  publisher = {Springer},
  address   = {New York},
  issn      = {0175-7598},
  doi       = {10.1007/s00253-021-11315-w},
  pages     = {4297 -- 4307},
  year      = {2021},
  abstract  = {Rapid screening of infected people plays a crucial role in interrupting infection chains. However, the current methods for identification of bacteria are very tedious and labor intense. Fast on-site screening for pathogens based on volatile organic compounds (VOCs) by ion mobility spectrometry (IMS) could help to differentiate between healthy and potentially infected subjects. As a first step towards this, the feasibility of differentiating between seven different bacteria including resistant strains was assessed using IMS coupled to multicapillary columns (MCC-IMS). The headspace above bacterial cultures was directly drawn and analyzed by MCC-IMS after 90 min of incubation. A cluster analysis software and statistical methods were applied to select discriminative VOC clusters. As a result, 63 VOC clusters were identified, enabling the differentiation between all investigated bacterial strains using canonical discriminant analysis. These 63 clusters were reduced to 7 discriminative VOC clusters by constructing a hierarchical classification tree. Using this tree, all bacteria including resistant strains could be classified with an AUC of 1.0 by receiver-operating characteristic analysis. In conclusion, MCC-IMS is able to differentiate the tested bacterial species, even the non-resistant and their corresponding resistant strains, based on VOC patterns after 90 min of cultivation. Although this result is very promising, in vivo studies need to be performed to investigate if this technology is able to also classify clinical samples. With a short analysis time of 5 min, MCC-IMS is quite attractive for a rapid screening for possible infections in various locations from hospitals to airports. Key Points center dot Differentiation of bacteria by MCC-IMS is shown after 90-min cultivation. center dot Non-resistant and resistant strains can be distinguished. center dot Classification of bacteria is possible based on metabolic features.},
  language  = {en}
}