Holger Becker

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Papers by Holger Becker

Development of a versatile lab-on-a-chip enzyme assay platform for pathogen detection in CBRNE scenarios

Proceedings of SPIE, May 29, 2013

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Universal lab-on-a-chip system for cell counting and cell density measurements in human and veterinary diagnostics applications

We have developed a chip-based universal platform for cell counting and cell density measurements... more

Integrated microfluidic system with automatic sampling for permanent molecular and antigen-based detection of CBRNE-related pathogens

Proceedings of SPIE, Mar 5, 2015

The continuous monitoring of the environment for lethal pathogens is a central task in the field ... more The continuous monitoring of the environment for lethal pathogens is a central task in the field of biothreat detection. Typical scenarios involve air-sampling in locations such as public transport systems or large public events and a subsequent analysis of the samples by a portable instrument. Lab-on-a-chip technologies are one of the promising technological candidates for such a system. We have developed an integrated microfluidic system with automatic sampling for the detection of CBRNE-related pathogens. The chip contains a two-pronged analysis strategy, on the one hand an immunological track using antibodies immobilized on a frit and a subsequent photometric detection, on the other hand a molecular biology approach using continuous-flow PCR with a fluorescence end-point detection. The cartridge contains two-component molded rotary valve to allow active fluid control and switching between channels. The accompanying instrument contains all elements for fluidic and valve actuation, thermal control, as well as the two detection modalities. Reagents are stored in dedicated reagent packs which are connected directly to the cartridge. With this system, we have been able to demonstrate the detection of a variety of pathogen species.

Lab-on-a-chip PCR in continuous flow: an ultrafast analytical tool for B-agents

Proceedings of SPIE, May 1, 2009

ABSTRACT

Lab-on-a-Chip based device for an optical detection of immobilized cells for food analytics

Biomedical Engineering / Biomedizinische Technik, 2012

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Methods and instruments for continuous-flow PCR on a chip

Microfluidics, BioMEMS, and Medical Microsystems V, 2007

format_quoteMiniaturized PCR devices address thermal mass challenges, significantly speeding up the PCR process compared to conventional setups.format_quote

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Sensor enhanced microfluidic devices for cell based assays and organs on chip

SPIE Proceedings, 2015

ABSTRACT

Lab-on-a-chip enabled HLA diagnostic: combined sample preparation and real time PCR for HLA-B57 diagnosis

Advances in Global Health through Sensing Technologies 2015, 2015

The diverse human HLA (human leukocyte antigen) system is responsible for antigen presentation an... more The diverse human HLA (human leukocyte antigen) system is responsible for antigen presentation and recognition. It is essential for the immune system to maintain a stable defense line, but also is also involved in autoimmunity as well as metabolic disease. HLA-haplotype (HLA-B27), for instance, is associated with inflammatory diseases such as Bechterew's disease. The administration of the HIV drug Abacavir in combination with another HLA-haplotype (HLAB57) is associated with severe hypersensitivity reactions. Accordingly, the HLA status has to be monitored for diagnosis or prior to start of therapy. Along this line, a miniaturized microfluidic platform has been developed allowing performing the complete analytical process from “sample-in” to “answer-out” in a point-of-care environment. The main steps of the analytical cascade inside the integrated system are blood cell lysis and DNA isolation, DNA purification, real-time PCR and quantitative monitoring of the rise of a fluorescent signal appearing during the PCR based sequence amplification. All bio-analytical steps were intended to be performed inside one chip and will be actuated, controlled and monitored by a matching device. This report will show that all required processes are established and tested and all device components work well and interact with the functional modules on the chips in a harmonized fashion.

<title>Portable integrated capillary-electrophoresis system using disposable polymer chips with capacitively coupled contactless conductivity detection for on-site analysis of foodstuff</title>

Sensing for Agriculture and Food Quality and Safety, 2009

We present a compact portable chip-based capillary electrophoresis system that employs capacitive... more We present a compact portable chip-based capillary electrophoresis system that employs capacitively coupled contactless conductivity detection (C4D) operating at 4 MHz as an alternative detection method compared to the commonly used optical detection based on laser-induced fluorescence. Emphasis was put on system integration and industrial manufacturing technologies for the system. Therefore, the disposable chip for this system is fabricated out

Microfluidic system for the identification of bacterial pathogens causing urinary tract infections

SPIE Proceedings, 2015

Urinary tract infections (UTIs) are among the most common bacterial infections and pose a signifi... more Urinary tract infections (UTIs) are among the most common bacterial infections and pose a significant healthcare burden. The growing trend in antibiotic resistance makes it mandatory to develop diagnostic kits which allow not only the determination of a pathogen but also the antibiotic resistances. We have developed a microfluidic cartridge which takes a direct urine sample, extracts the DNA, performs an amplification using batch-PCR and flows the sample over a microarray which is printed into a microchannel for fluorescence detection. The cartridge is injection-molded out of COP and contains a set of two-component injection-molded rotary valves to switch between input and to isolate the PCR chamber during thermocycling. The hybridization probes were spotted directly onto a functionalized section of the outlet microchannel. We have been able to successfully perform PCR of E.coli in urine in this chip and perform a fluorescence detection of PCR products. An upgraded design of the cartridge contains the buffers and reagents in blisters stored on the chip.

format_quoteDeveloped microfluidic device identifies bacterial types from urine samples without prior concentration steps, requiring only 2 µl urine.format_quote

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Portable CE system with contactless conductivity detection in an injection molded polymer chip for on-site food analysis

SPIE Proceedings, 2008

We present a compact portable chip-based capillary electrophoresis system that employs capacitive... more We present a compact portable chip-based capillary electrophoresis system that employs capacitively coupled contactless conductivity detection (C 4 D) operating at 4 MHz as an alternative detection method compared to the commonly used optical detection employing laser-induced fluorescence. The disposable chip for this system is fabricated out of PMMA using injection molding; the electrodes are screen-printed or thin-film electrodes. The system allows the measurement of small ions like Li, Na, K typically present in foodstuff like milk and mineral water as well as acids in wine.

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From microfluidic modules to an integrated Lab-on-a-chip system for the detection ofFrancisella tularensis

Smart Biomedical and Physiological Sensor Technology X, 2013

Lab-on-a-chip (LoC) systems translating the whole process of pathogen analysis to an integrated, ... more Lab-on-a-chip (LoC) systems translating the whole process of pathogen analysis to an integrated, miniaturized, and automatically functioning microfluidic platform are generally expected to be very promising future diagnostic approaches. The development of such a LoC system for the detection of bacterial pathogens applied to the example pathogen Francisella tularensis is described in this report. To allow functional testing of the whole process cascade before final device integration, various bio-analytical steps such as cell lysis, DNA extraction and purification, continuous-flow PCR and analyte detection have been adapted to unique functional microfluidic modules. As a successive step, positively tested modules for pathogen detection have been successfully assembled to an integrated chip. Moreover, technical solutions for a smooth interaction between sample input from the outer world as well as microfluidic chip and chip driving instrument have been developed. In conclusion, a full repertoire of analytical tools have been developed and successfully tested in the concerted manner of a functionally integrated microfluidic device representing a tool for future diagnostic approaches.

Development of a versatile lab-on-a-chip enzyme assay platform for pathogen detection in CBRNE scenarios

SPIE Proceedings, 2013

ABSTRACT

<title>Lab-on-a-chip PCR in continuous flow: an ultrafast analytical tool for B-agents</title>

Chemical, Biological, Radiological, Nuclear, and Explosives (CBRNE) Sensing X, 2009

ABSTRACT

Lab-on-a-chip PCR: real time PCR in miniaturized format for HLA diagnostics

Smart Biomedical and Physiological Sensor Technology XI, 2014

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<title>A sample-in result-out lab-on-a-chip device: from prototype to mass fabrication</title>

Microfluidics, BioMEMS, and Medical Microsystems IX, 2011

In this paper we demonstrate the development of an integrated lab-on-a-chip system for the point-... more In this paper we demonstrate the development of an integrated lab-on-a-chip system for the point-of-care diagnostics of Coeliac disease. A two-step approach is used, using two different microfluidic chips with identical footprint and functional landscape, one for the analysis of the genetic predisposition using human leukocyte antigen typing, the second for a serology assay. Emphasis has been put on using

A lab-on-a-chip system for the development of complex assays using modular microfluidic components

SPIE Proceedings, 2012

ABSTRACT

Lab-on-a-chip platforms from sample preparation via continuous-flow PCR to an ultrafast detection of B-agents

Smart Biomedical and Physiological Sensor Technology IX, 2012

ABSTRACT

<title>Hybrid microfluidic systems: combining a polymer microfluidic toolbox with biosensors</title>

Microfluidics, BioMEMS, and Medical Microsystems V, 2007

In this paper we present polymer based microfluidic chips which contain functional elements (elec... more In this paper we present polymer based microfluidic chips which contain functional elements (electrodes, biosensors) made out of a different material (metals, silicon, organic semiconductors). These hybrid microfluidic devices allow the integration of additional functionality other than the simple manipulation of liquids in the chip and have been developed as a reaction to the increasing requirement for functional integration in microfluidics.

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A microfluidic platform with integrated arrays for immunologic assays for biological pathogen detection

Chemical, Biological, Radiological, Nuclear, and Explosives (CBRNE) Sensing XV, 2014

ABSTRACT The ability to integrate complete assays on a microfluidic chip helps to greatly simplif... more ABSTRACT The ability to integrate complete assays on a microfluidic chip helps to greatly simplify instrument requirements and allows the use of lab-on-a-chip technology in the field. A core application for such field-portable systems is the detection of pathogens in a CBRN scenario such as permanent monitoring of airborne pathogens, e.g. in subway stations or hospitals etc. An immunological assay was chosen as method for the pathogen identification. The conceptual approach was its realization as a lab-on-a-chip system, enabling an easy handling of the sample in an automated manner. The immunological detection takes place on an antibody array directly implemented in the microfluidic network. Different immobilization strategies will be presented showing the performance of the system. Central elements of the disposable microfluidic device like fluidic interface, turning valves, liquid introduction and waste storage, as well as the architecture of measurement and control fluidic network, will be introduced. Overall process times of about 30 minutes were achieved and assays for the detection of Francisella tularensis and Yersinia pestis are presented. An important feature of the integrated lab-on-a-chip approach is that all waste liquids remain on-chip and contamination risks can be avoided.

Holger Becker

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