Frederic Zenhausern

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• Zenhausern, F. (2019). Development of biomechanically tunable plant-based scaffolds to study cell-substrate interactions. Biomaterials.
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  Jerome Lacombe, Ashlee Harris, Ryan Zenhausern, Sophia Karsunky and Frederic Zenhausern, Development of biomechanically tunable plant-based scaffolds to study cell-substrate interactions, Biomaterials, in review
• Zenhausern, F. (2019). Molecular profiling of innate immune response mechanisms in ventilator-associated pneumonia. Journal of Infectious Diseases.
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  Khyatiben V. Pathak, Marissa Saltzman-McGilvrey, Krystine Garcia-Mansfield, Karen Lewendoski, Emmanuel Menashi, Charles Hu, Frederic Zenhausern and Patrick Pirrotte, Molecular profiling of innate immune response mechanisms in ventilator-associated pneumonia, Journal of Infectious Diseases, in review.
• Devadhasan, J. P., Gu, J., Chen, P., Smith, S. D., Thomas, B., Gates-hollingsworth, M. A., Hau, D., Pandit, S. G., Aucoin, D. P., & Zenhausern, F. (2021). Critical Comparison between Large and Mini Vertical Flow Immunoassay Platforms for Yersinia Pestis Detection.. Analytical chemistry, 93(27), 9337-9344. doi:10.1021/acs.analchem.0c05278
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  Yersinia pestis is a Gram-negative bacterium that is the causative agent of plague and is widely recognized as a potential biological weapon. Due to the high fatality rate of plague when diagnosis is delayed, the development of rapid, sensitive, specific, and cost-effective methods is needed for its diagnosis. The Y. pestis low calcium response V (LcrV) protein has been identified as a potential microbial biomarker for the diagnosis of plague. In this paper, we present a highly sensitive, paper-based, vertical flow immunoassay (VFI) prototype for the detection of LcrV and the diagnosis of plague. An antigen-capture assay using monoclonal antibodies is employed to capture and detect the LcrV protein, using a colorimetric approach. In addition, the effect of miniaturizing the VFI device is explored based on two different sizes of VFI platforms, denoted as "large VFI" and "mini VFI." Also, a comparative analysis is performed between the VFI platform and a lateral flow immunoassay (LFI) platform to exhibit the improved assay sensitivity suitable for point-of-care (POC) diagnostics. The analytical sensitivity or limit of detection (LOD) in the mini VFI is approximately 0.025 ng/mL, that is, 10 times better than that of the large VFI platform or 80 times over a standard lateral flow configuration. The low LOD of the LcrV VFI appears to be highly suitable for testing clinical samples and potentially diagnosing plague at earlier time points. In addition, optimization of the gold nanoparticle (AuNP) concentration, nanomaterial plasmonic properties, and flow velocity analysis could improve the performance of the VFI. Furthermore, we developed automated image analysis software that shows potential for integrating the diagnostic system into a smartphone. These methods and findings demonstrate that the VFI platform is a highly sensitive device for detecting the LcrV and potentially many other biomarkers.
• Gu, J., Duane, B., Repin, M., Brenner, D. J., & Zenhausern, F. (2021). Transportation container for pre-processing cytogenetic assays in radiation accidents.. Scientific reports, 11(1), 10398. doi:10.1038/s41598-021-89832-x
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  We report a shipping container that enables a disruptive logistics for cytogenetic biodosimetry for radiation countermeasures through pre-processing cell culture during transportation. The container showed precise temperature control (< 0.01 °C) with uniform sample temperature (< 0.1 °C) to meet the biodosimetry assay requirements. Using an existing insulated shipping box and long shelf life alkaline batteries makes it ideal for national stockpile. Dose curve of cytogenetic biodosimetry assay using the shipping container showed clear dose response and high linear correlation with the control dose curve using a laboratory incubator (Pearson's correlation coefficient: 0.992). The container's ability of pre-processing biological samples during transportation could have a significant impact on radiation countermeasure, as well as potential impacts in other applications such as biobanking, novel molecular or cell-based assays or therapies.
• Zenhausern, F. (2019). Development of an integrated fingerprick blood self-collection device for radiation countermeasure. PlosOne. doi:https://doi.org/10.1371/journal.pone.0222951
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  Jian Gu, Alan Norquist, Jianing Yang, Carla Brooks, Jerome Lacombe, Mikhail Repin, David J. Brenner, Sally Amundson and Frederic Zenhausern, Development of an integrated fingerprick blood self-collection device for radiation countermeasure, PLoS ONE, 14(10): e0222951. https://doi.org/10.1371/journal.pone.0222951
• Zenhausern, F. (2019). Fabric Phase Sorptive Extraction: A metabolomic pre-processing approach for ionizing radiation injury assessment,. Journal of Proteome Research. doi:doi.org/10.1021/acs.jproteome.9b00142
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  Alexandra Taraboletti, Maryam Goudarzi, Abuzar Kabir, Bo-Hyun Moon, Evagelia Laiakis, Jerome Lacombe, Pelagie Ake, Sueoka Shoichiro, David Brenner, Albert Fornace and Frederic Zenhausern, Fabric Phase Sorptive Extraction: A metabolomic pre-processing approach for ionizing radiation injury assessment, Journal of Proteome Research, doi.org/10.1021/acs.jproteome.9b00142; (front cover).
• Zenhausern, F. (2019). Paper-based Vertical Flow Immunoassay (VFI) for detection of bio-threat pathogens. Talanta, (2019), 191, 81-88., 191, 81-88. doi:https://doi.org/10.1016/j.talanta.2018.08.043
• Zenhausern, F. (2019). Withanolide D enhances radiosensitivity of human cancer cells by inhibiting DNA damage non-homologous end joining repair pathway. Frontiers in Oncology. doi:doi.org/10.3389/fonc.2019.01468
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  Jerome Lacombe, Titouan Cretignier, Laetitia Meli, E. M. Kithsiri Wijeratne, Jean-Luc Veuthey, Muriel Cuendet, A. A. Leslie Gunatilaka and Frederic Zenhausern, Withanolide D enhances radiosensitivity of human cancer cells by inhibiting DNA damage non-homologous end joining repair pathway, Frontiers in Oncology: Radiation Oncology, 9:1468, doi.org/10.3389/fonc.2019.01468.
• Chou, C. F., & Zenhausern, F. (2018). Electrodeless dielectrophoresis for micro total analysis systems. IEEE engineering in medicine and biology magazine : the quarterly magazine of the Engineering in Medicine & Biology Society, 22(6), 62-7.
• Lacombe, J., & Zenhausern, F. (2017). Emergence of miR-34a in radiation therapy. Critical reviews in oncology/hematology, 109, 69-78.
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  Expressions of many microRNAs (miRNAs) in response to ionizing radiation (IR) have already been investigated and some of them seem to play an important role in the tumor radioresistance, normal tissue radiotoxicity or as predictive biomarkers to radiation. miR-34a is an emerging miRNA in recent radiobiology studies. Here, we review this miR-34 family member by detailing its different roles in radiation response and we will discuss about the role that it can play in radiation treatment. Thus, we will show that IR regulates miR-34a by increasing its expression. We will also highlight different biological processes involved in cellular response to IR and regulated by miR-34a in order to demonstrate the role it can play in tumor radio-response or normal tissue radiotoxicity as a radiosensitizer or radioprotector. miR-34a is poised to assert itself as an important player in radiobiology and should become more and more important in radiation therapy management.
• Lacombe, J., Brooks, C., Hu, C., Menashi, E., Korn, R., Yang, F., & Zenhausern, F. (2017). Analysis of Saliva Gene Expression during Head and Neck Cancer Radiotherapy: A Pilot Study. Radiation research, 188(1), 75-81.
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  Saliva, a biological fluid, is a promising candidate for novel approaches to prognosis, clinical diagnosis, monitoring and management of patients with both oral and systemic diseases. However, to date, saliva has not been widely investigated as a biomarker for radiation exposure. Since white blood cells are also present in saliva, it should theoretically be possible to investigate the transcriptional biomarkers of radiation exposure classically studied in whole blood. Therefore, we collected whole blood and saliva samples from eight head and neck cancer patients before the start of radiation treatment, at mid-treatment and after treatment. We then used a panel of five genes: BAX, BBC3, CDKN1A, DDB2 and MDM2, designated for assessing radiation dose in whole blood to evaluate gene expression changes that can occur during radiotherapy. The results revealed that the expression of the five genes did not change in whole blood. However, in saliva, CDKN1A and DDB2 were significantly overexpressed at the end, compared to the start, of radiotherapy, and MDM2 was significantly underexpressed between mid-treatment and at the end of treatment. Interestingly, CDKN1A and DDB2 expressions also showed an increasing monotonic relationship with total radiation dose received during radiotherapy. To our knowledge, these results show for the first time the ability to detect gene expression changes in saliva after head and neck cancer radiotherapy, and pave the way for further promising studies validating saliva as a minimally invasive means of biofluid collection to directly measure radiation dose escalation during treatment.
• Lacombe, J., Phillips, S. L., & Zenhausern, F. (2016). Microfluidics as a new tool in radiation biology. Cancer letters, 371(2), 292-300.
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  Ionizing radiations interact with molecules at the cellular and molecular levels leading to several biochemical modifications that may be responsible for biological effects on tissue or whole organisms. The study of these changes is difficult because of the complexity of the biological response(s) to radiations and the lack of reliable models able to mimic the whole molecular phenomenon and different communications between the various cell networks, from the cell activation to the macroscopic effect at the tissue or organismal level. Microfluidics, the science and technology of systems that can handle small amounts of fluids in confined and controlled environment, has been an emerging field for several years. Some microfluidic devices, even at early stages of development, may already help radiobiological research by proposing new approaches to study cellular, tissue and total-body behavior upon irradiation. These devices may also be used in clinical biodosimetry since microfluidic technology is frequently developed for integrating complex bioassay chemistries into automated user-friendly, reproducible and sensitive analyses. In this review, we discuss the use, numerous advantages, and possible future of microfluidic technology in the field of radiobiology. We will also examine the disadvantages and required improvements for microfluidics to be fully practical in radiation research and to become an enabling tool for radiobiologists and radiation oncologists.
• Shah, P., Fritz, J. V., Glaab, E., Desai, M. S., Greenhalgh, K., Frachet, A., Niegowska, M., Estes, M., Jäger, C., Seguin-Devaux, C., Zenhausern, F., & Wilmes, P. (2016). A microfluidics-based in vitro model of the gastrointestinal human-microbe interface. Nature communications, 7, 11535.
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  Changes in the human gastrointestinal microbiome are associated with several diseases. To infer causality, experiments in representative models are essential, but widely used animal models exhibit limitations. Here we present a modular, microfluidics-based model (HuMiX, human-microbial crosstalk), which allows co-culture of human and microbial cells under conditions representative of the gastrointestinal human-microbe interface. We demonstrate the ability of HuMiX to recapitulate in vivo transcriptional, metabolic and immunological responses in human intestinal epithelial cells following their co-culture with the commensal Lactobacillus rhamnosus GG (LGG) grown under anaerobic conditions. In addition, we show that the co-culture of human epithelial cells with the obligate anaerobe Bacteroides caccae and LGG results in a transcriptional response, which is distinct from that of a co-culture solely comprising LGG. HuMiX facilitates investigations of host-microbe molecular interactions and provides insights into a range of fundamental research questions linking the gastrointestinal microbiome to human health and disease.
• Zenhausern, F., Dong, G., & Gu, J. (2016). Wearable nanotechnology biosensor research and development and its applications in sports. Ti Yu Shi You.
• Brengues, M., Gu, J., & Zenhausern, F. (2015). Microfluidic module for blood cell separation for gene expression radiobiological assays. Radiation protection dosimetry, 166(1-4), 306-10.
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  Advances in molecular techniques have improved discovery of biomarkers associated with radiation exposure. Gene expression techniques have been demonstrated as effective tools for biodosimetry, and different assay platforms with different chemistries are now available. One of the main challenges is to integrate the sample preparation processing of these assays into microfluidic platforms to be fully automated for point-of-care medical countermeasures in the case of a radiological event. Most of these assays follow the same workflow processing that comprises first the collection of blood samples followed by cellular and molecular sample preparation. The sample preparation is based on the specific reagents of the assay system and depends also on the different subsets of cells population and the type of biomarkers of interest. In this article, the authors present a module for isolation of white blood cells from peripheral blood as a prerequisite for automation of gene expression assays on a microfluidic cartridge. For each sample condition, the gene expression platform can be adapted to suit the requirements of the selected assay chemistry.
• Chase, D., Goulder, A., Zenhausern, F., Monk, B., & Herbst-Kralovetz, M. (2015). The vaginal and gastrointestinal microbiomes in gynecologic cancers: a review of applications in etiology, symptoms and treatment. Gynecologic oncology, 138(1), 190-200.
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  The human microbiome is the collection of microorganisms in the body that exist in a mutualistic relationship with the host. Recent studies indicate that perturbations in the microbiome may be implicated in a number of diseases, including cancer. More specifically, changes in the gut and vaginal microbiomes may be associated with a variety of gynecologic cancers, including cervical cancer, uterine cancer, and ovarian cancer. Current research and gaps in knowledge regarding the association between the gut and vaginal microbiomes and the development, progression, and treatment of gynecologic cancers are reviewed here. In addition, the potential use of probiotics to manage symptoms of these gynecologic cancers is discussed. A better understanding of how the microbiome composition is altered at these sites and its interaction with the host may aid in prevention, optimization of current therapies, development of new therapeutic agents and/or dosing regimens, and possibly limit the side effects associated with cancer treatment.
• Brengues, M., Liu, D., Korn, R., & Zenhausern, F. (2014). Method for validating radiobiological samples using a linear accelerator. EPJ techniques and instrumentation, 1(1).
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  There is an immediate need for rapid triage of the population in case of a large scale exposure to ionizing radiation. Knowing the dose absorbed by the body will allow clinicians to administer medical treatment for the best chance of recovery for the victim. In addition, today's radiotherapy treatment could benefit from additional information regarding the patient's sensitivity to radiation before starting the treatment. As of today, there is no system in place to respond to this demand. This paper will describe specific procedures to mimic the effects of human exposure to ionizing radiation creating the tools for optimization of administered radiation dosimetry for radiotherapy and/or to estimate the doses of radiation received accidentally during a radiation event that could pose a danger to the public. In order to obtain irradiated biological samples to study ionizing radiation absorbed by the body, we performedirradiation of human blood samples using the linear accelerator (LINAC). The LINAC was implemented and calibrated for irradiating human whole blood samples. To test the calibration, a 2 Gy test run was successfully performed on a tube filled with water with an accuracy of 3% in dose distribution. To validate our technique the blood samples wereirradiated and the results were analyzed using a gene expression assay to follow the effect of the ionizing irradiation by characterizing dose responsive biomarkers from radiobiological assays. The response of 5 genes was monitored resulting in expression increase with the dose of radiation received. The blood samples treated with the LINAC can provide effective irradiated blood samples suitable for molecular profiling to validate radiobiological measurements via the gene-expression based biodosimetry tools.
• Hurth, C., Yang, J., Barrett, M., Brooks, C., Nordquist, A., Smith, S., & Zenhausern, F. (2014). A miniature quantitative PCR device for directly monitoring a sample processing on a microfluidic rapid DNA system. Biomedical microdevices, 16(6), 905-14.
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  We report a microfluidic device and measurement method to perform real-time PCR (or qPCR) in a miniaturized configuration for on-chip implementation using reaction volumes of less than 20 μL. The qPCR bioreactor is designed as a module to be embedded in an automated sample-in/profile-out system for rapid DNA biometrics or human identification. The PCR mixture is excited with a 505 nm diode-pumped solid-state laser (DPSSL) and the fluorescence build-up is measured using optical fibers directly embedded to the sidewalls of the microfluidic qPCR bioreactor. We discuss manufacturing and operating parameters necessary to adjust the internal surface conditions and temperature profiles of the bioreactor and to optimize the yield and quality of the PCR reaction for the amplification of 62 bp hTERT intron fragments using the commercial Quantifiler® kit (Life Technologies, Carlsbad, CA) commonly accepted for genotyping analysis. We designed a microfluidic device suitable for continuously processing a specimen by efficiently mixing the reagents from the kit to a set volume of DNA template on chip. Our approach relies on a calibration curve for the specific device using control DNA. We successfully applied this method to determine the concentration of genomic DNA extracted from a buccal swab on separate microfluidic devices which are operated upstream the qPCR device and perform buccal swab lysis and buccal DNA extraction. A precise correlation between the amount determined on chip and that obtained using a commercial cycler is demonstrated.
• Rosenstein, B. S., West, C. M., Bentzen, S. M., Alsner, J., Andreassen, C. N., Azria, D., Barnett, G. C., Baumann, M., Burnet, N., Chang-Claude, J., Chuang, E. Y., Coles, C. E., Dekker, A., De Ruyck, K., De Ruysscher, D., Drumea, K., Dunning, A. M., Easton, D., Eeles, R., , Fachal, L., et al. (2014). Radiogenomics: radiobiology enters the era of big data and team science. International journal of radiation oncology, biology, physics, 89(4), 709-13.
• Yang, J., Brooks, C., Estes, M. D., Hurth, C. M., & Zenhausern, F. (2014). An integratable microfluidic cartridge for forensic swab samples lysis. Forensic science international. Genetics, 8(1), 147-58.
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  Fully automated rapid forensic DNA analysis requires integrating several multistep processes onto a single microfluidic platform, including substrate lysis, extraction of DNA from the released lysate solution, multiplexed PCR amplification of STR loci, separation of PCR products by capillary electrophoresis, and analysis for allelic peak calling. Over the past several years, most of the rapid DNA analysis systems developed started with the reference swab sample lysate and involved an off-chip lysis of collected substrates. As a result of advancement in technology and chemistry, addition of a microfluidic module for swab sample lysis has been achieved in a few of the rapid DNA analysis systems. However, recent reports on integrated rapid DNA analysis systems with swab-in and answer-out capability lack any quantitative and qualitative characterization of the swab-in sample lysis module, which is important for downstream forensic sample processing. Maximal collection and subsequent recovery of the biological material from the crime scene is one of the first and critical steps in forensic DNA technology. Herein we present the design, fabrication and characterization of an integratable swab lysis cartridge module and the test results obtained from different types of commonly used forensic swab samples, including buccal, saliva, and blood swab samples, demonstrating the compatibility with different downstream DNA extraction chemistries. This swab lysis cartridge module is easy to operate, compatible with both forensic and microfluidic requirements, and ready to be integrated with our existing automated rapid forensic DNA analysis system. Following the characterization of the swab lysis module, an integrated run from buccal swab sample-in to the microchip CE electropherogram-out was demonstrated on the integrated prototype instrument. Therefore, in this study, we demonstrate that this swab lysis cartridge module is: (1) functionally, comparable with routine benchtop lysis, (2) compatible with various types of swab samples and chemistries, and (3) integratable to achieve a micro total analysis system (μTAS) for rapid DNA analysis.
• Estes, M. D., Hurth, C., Barrett, M., & Zenhausern, F. (2013). A tuneable array of unique steady-state microfluidic gradients. Physical chemistry chemical physics : PCCP, 15(31), 12805-14.
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  We report an on-chip gradient generator that has been designed, modelled, fabricated, and characterized to facilitate temporal tuning of several unique gradients in parallel for multiple applications. This design allows for steady state programming of the intensities across multiple orders of magnitude while producing exponential, linear, and logarithmic gradient profiles. The magnitude of the gradients is controlled through regulating the ratio of the two on-chip flow inlets without the need for valves or other active mixers. On-chip binding of biotin by a fluorescent streptavidin complex creates a diffusive barrier that regulates access to the gradient inlets, providing a second orthogonal mechanism for regulating the microgradient intensities. The device is also characterized using an on-chip enzymatic reaction to produce an array of tuneable product concentrations within the various microchannels.
• Zenhausern, F., Estes, M. D., Yang, J., Duane, B., Smith, S., Brooks, C., Nordquist, A., & Zenhausern, F. -. (2012). Optimization of multiplexed PCR on an integrated microfluidic forensic platform for rapid DNA analysis. The Analyst, 137(23).
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  This study reports the design, prototyping, and assay development of multiplexed polymerase chain reaction (PCR) on a plastic microfluidic device. Amplification of 17 DNA loci is carried out directly on-chip as part of a system for continuous workflow processing from sample preparation (SP) to capillary electrophoresis (CE). For enhanced performance of on-chip PCR amplification, improved control systems have been developed making use of customized Peltier assemblies, valve actuators, software, and amplification chemistry protocols. Multiple enhancements to the microfluidic chip design have been enacted to improve the reliability of sample delivery through the various on-chip modules. This work has been enabled by the encapsulation of PCR reagents into a solid phase material through an optimized Solid Phase Encapsulating Assay Mix (SPEAM) bead-based hydrogel fabrication process. SPEAM bead technology is reliably coupled with precise microfluidic metering and dispensing for efficient amplification and subsequent DNA short tandem repeat (STR) fragment analysis. This provides a means of on-chip reagent storage suitable for microfluidic automation, with the long shelf-life necessary for point-of-care (POC) or field deployable applications. This paper reports the first high quality 17-plex forensic STR amplification from a reference sample in a microfluidic chip with preloaded solid phase reagents, that is designed for integration with up and downstream processing.
• Zenhausern, F., Hurth, C., Gu, J., Aboud, M., Estes, M. D., Nordquist, A. R., McCord, B., & Zenhausern, F. -. (2012). Direct loading of polymer matrices in plastic microchips for rapid DNA analysis: a comparative study. Electrophoresis, 33(16).
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  We report the design and performance validation of microfluidic separation technologies for human identification using a disposable plastic device suitable for integration into an automated rapid DNA analysis system. A fabrication process for a 15-cm long hot-embossed plastic microfluidic devices with a smooth semielliptical cross section out of cyclic olefin copolymer is presented. We propose a mixed polymer solution of 95% w/v hydroxyethylcellulose and 5% w/v polyvinylpyrrolidone for a final polymer concentration of 2.5 or 3.0% to be used as coating and sieving matrix for DNA separation. This formulation allows preparing the microchip without pretreatment in a single-loading step and provides high-resolution separation (≈1.2 bp for fragments
• Hopwood, A. J., Hurth, C., Yang, J., Cai, Z., Moran, N., Lee-Edghill, J. G., Nordquist, A., Lenigk, R., Estes, M. D., Haley, J. P., McAlister, C. R., Chen, X., Brooks, C., Smith, S., Elliott, K., Koumi, P., Zenhausern, F., & Tully, G. (2010). Integrated microfluidic system for rapid forensic DNA analysis: sample collection to DNA profile. Analytical chemistry, 82(16), 6991-9.
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  We demonstrate a conduit for the delivery of a step change in the DNA analysis process: A fully integrated instrument for the analysis of multiplex short tandem repeat DNA profiles from reference buccal samples is described and is suitable for the processing of such samples within a forensic environment such as a police custody suite or booking office. The instrument is loaded with a DNA processing cartridge which incorporates on-board pumps and valves which direct the delivery of sample and reagents to the various reaction chambers to allow DNA purification, amplification of the DNA by PCR, and collection of the amplified product for delivery to an integral CE chip. The fluorescently labeled product is separated using micro capillary electrophoresis with a resolution of 1.2 base pairs (bp) allowing laser induced fluorescence-based detection of the amplified short tandem repeat fragments and subsequent analysis of data to produce a DNA profile which is compatible with the data format of the UK DNA database. The entire process from taking the sample from a suspect, to database compatible DNA profile production can currently be achieved in less than 4 h. By integrating such an instrument and microfluidic cartridge with the forensic process, we believe it will be possible in the near future to process a DNA sample taken from an individual in police custody and compare the profile with the DNA profiles held on a DNA Database in as little as 3 h.
• Shinde, S. M., Orozco, C., Brengues, M., Lenigk, R., Montgomery, D. C., & Zenhausern, F. (2010). Optimization of a Microfluidic Mixing Process for Gene Expression-Based Bio-dosimetry. Quality engineering, 23(1), 59-70.
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  In recent decades advances in radiation imaging and radiation therapy have led to a dramatic increase in the number of people exposed to radiation. Consequently, there is a clear need for personalized biodosimetry diagnostics in order to monitor the dose of radiation received and adapt it to each patient depending on their sensitivity to radiation exposure (Hall E.J. and Brenner D. J., 2008). Similarly, after a large-scale radiological event such as a dirty bomb attack, there will be a major need to assess, within a few days the radiation doses received by tens of thousands of individuals. Current high throughput devices can handle only a few hundred individuals per day. Hence there is a great need for a very fast self-contained non-invasive biodosimetric device based on a rapid blood test.This paper presents a case study where regression methods and designed experiments are used to arrive at the optimal settings for various factors that impact the kinetics in a biodosimetric device. We use ridge regression to initially identify a set of potentially important variables in the mixing process which is one of the critical sub systems of the device. This was followed by a series of designed experiments to arrive at the optimal setting of the significant microfluidic cartridge and piezoelectric disk (PZT) (D. Sadler, F. Zenhausern, U.S. Patent 6,986,601; Lee, S. Y., Ko, B., Yang, W., 2005) related factors. This statistical approach has been utilized to study the microfluidic mixing to mix water and dye mixtures of 70 μl volume. The outcome of the statistical design, experimentation and analysis was then exploited for optimizing the design, fabrication and assembly of the microfluidic devices. As a result of the experiments that were performed, the system was fine tuned and the mixing time was reduced from 5.5 minutes to 2 minutes.
• Zenhausern, F., Brengues, M., Paap, B., Bittner, M., Amundson, S., Seligmann, B., Korn, R., Lenigk, R., & Zenhausern, F. -. (2010). Biodosimetry on small blood volume using gene expression assay. Health physics, 98(2).
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  This paper reports the development of a biodosimetry device suitable for rapidly measuring expression levels of a low-density gene set that can define radiation exposure, dose and injury in a public health emergency. The platform comprises a set of 14 genes selected on the basis of their abundance and differential expression level in response to radiation from an expression profiling series measuring 41,000 transcripts. Gene expression is analyzed through direct signal amplification using a quantitative Nuclease Protection Assay (qNPA). This assay can be configured as either a high-throughput microplate assay or as a handheld detection device for individual point-of-care assays. Recently, we were able to successfully develop the qNPA platform to measure gene expression levels directly from human whole blood samples. The assay can be performed with volumes as small as 30 microL of whole blood, which is compatible with collection from a fingerstick. We analyzed in vitro irradiated blood samples with qNPA. The results revealed statistically significant discrimination between irradiated and non-irradiated samples. These results indicate that the qNPA platform combined with a gene profile based on a small number of genes is a valid test to measure biological radiation exposure. The scalability characteristics of the assay make it appropriate for population triage. This biodosimetry platform could also be used for personalized monitoring of radiotherapy treatments received by patients.
• Zenhausern, F., Hurth, C., Smith, S. D., Nordquist, A. R., Lenigk, R., Duane, B., Nguyen, D., Surve, A., Hopwood, A. J., Estes, M. D., Yang, J., Cai, Z., Chen, X., Lee-Edghill, J. G., Moran, N., Elliott, K., Tully, G., & Zenhausern, F. -. (2010). An automated instrument for human STR identification: design, characterization, and experimental validation. Electrophoresis, 31(21).
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  The microfluidic integration of an entire DNA analysis workflow on a fully integrated miniaturized instrument is reported using lab-on-a-chip automation to perform DNA fingerprinting compatible with CODIS standard relevant to the forensic community. The instrument aims to improve the cost, duration, and ease of use to perform a "sample-to-profile" analysis with no need for human intervention. The present publication describes the operation of the three major components of the system: the electronic control components, the microfluidic cartridge and CE microchip, and the optical excitation/detection module. Experimental details are given to characterize the level of performance, stability, reliability, accuracy, and sensitivity of the prototype system. A typical temperature profile from a PCR amplification process and an electropherogram of a commercial size standard (GeneScan 500™, Applied Biosystems) separation are shown to assess the relevance of the instrument to forensic applications. Finally, we present a profile from an automated integrated run where lysed cells from a buccal swab were introduced in the system and no further human intervention was required to complete the analysis.
• Gu, J., Xiao, X., Takulapalli, B. R., Morrison, M. E., Zhang, P., & Zenhausern, F. (2008). A New Approach to Fabricating High-density Nanoarrays by Nanocontact Printing. Journal of vacuum science & technology. B, Microelectronics and nanometer structures : processing, measurement, and phenomena : an official journal of the American Vacuum Society, 26(6), 1860-1865.
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  We introduce a new scheme of nanocontact printing that fabricates nanoarrays using stamps generated by ultraviolet nanoimprint lithography. Array patterns can be generated by this printing technique in a high-density (number of features per unit area) fashion with a feature size as low as 30 nm and period of 100 nm. Sub-500 nm alignment accuracy for multilayer printing has been obtained using a traditional contact mask aligner. We also demonstrate that we can image a nanoarray labeled by streptavidin by atomic force microscope (AFM).
• Gu, J., Gupta, R., Chou, C. F., Wei, Q., & Zenhausern, F. (2007). A simple polysilsesquioxane sealing of nanofluidic channels below 10 nm at room temperature. Lab on a chip, 7(9), 1198-201.
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  We present a simple sealing method to fabricate nanofluidic channels, where plasma treated polysilsesquioxane (PSQ) thin film on a rigid support is used to bond to a hydrophilic glass surface permanently at room temperature. This method shows precise dimension control below 10 nm with easy experimental setup. Using this method, one dimensional confined shallow nanochannels with a depth as small as 8 nm and an aspect ratio of

Presentations

• Aponte-Pieras, J., Yang, J., Hu, C., Ghai, M. B., Celaya, M. P., Marsh, S., Zenhausern, F., & Wassef, W. (2024, May). A novel study of the microbiome in chronic pancreatitis using molecular fingerprinting of pancreas fluid. Digestive Disease Week (DDW). Washington DC.
• Zenhausern, F., Turner, H., Amundson, S., Summers, A. J., Khanishayan, A., & Lacombe, J. (2023, September).

  Development of a point-of-care bioassay to detect radiation dosimetry blood biomarkers

  . 17th International Congress for Radiation Research. Montreal, Quebec, Canada.

Poster Presentations

• Zenhausern, F., Gu, J., Lacombe, J., Khanishayan, A., Devadhasan, J. P., & Summers, A. J. (2023, October). Gold Nanostar-Based Vertical Flow Immunoassay for Detection of Biothreat Agents. BMES Annual Meeting. Seattle, WA.