TY - JOUR A1 - Steglich, P. A1 - Rabus, D. G. A1 - Sada, C. A1 - Paul, Martin A1 - Weller, Michael G. A1 - Mai, C. A1 - Mai, A. T1 - Silicon Photonic Micro-Ring Resonators for Chemical and Biological Sensing: A Tutorial N2 - Silicon photonic micro-ring resonators (MRR) developed on the silicon-on-insulator (SOI) platform, owing to their high sensitivity and small footprint, show great potential for many chemical and biological sensing applications such as label-free detection in environmental monitoring, biomedical engineering, and food analysis. In this tutorial,we provide the theoretical background and give design guidelines for SOI-based MRR as well as examples of surface functionalization procedures for label-free detection of molecules. After introducing the advantages and perspectives of MRR, fundamentals of MRR are described in detail, followed by an introduction to the fabrication methods, which are based on a complementary metal-oxide semiconductor (CMOS) technology. Optimization of MRR for chemical and biological sensing is provided, with special emphasis on the optimization of waveguide geometry. At this point, the difference between chemical bulk sensing and label-free surface sensing is explained, and definitions like waveguide sensitivity, ring sensitivity, overall sensitivity as well as the limit of detection (LoD) of MRR are introduced. Further, we show and explain chemical bulk sensing of sodium chloride (NaCl) in water and provide a recipe for label-free surface sensing. KW - Biosensors KW - Biophotonics KW - Chemosensor KW - Biosensor KW - Microresonator KW - Nanophotonics KW - Optical sensors KW - Photonic sensors KW - Optoelectronic KW - Ring resonator KW - Silicon photonics KW - Miniaturization KW - Lab-on-a-chip KW - Lab-on-chip KW - Waveguide KW - Surface chemistry KW - Silanization KW - Glutaraldehyde KW - Affinity immobilization KW - Antibody KW - Oriented immobilization KW - Real-time measurement PY - 2022 DO - https://doi.org/10.1109/JSEN.2021.3119547 SN - 1530-437X VL - 22 IS - 11 SP - 10089 EP - 10105 PB - IEEE AN - OPUS4-55147 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Steglich, P. A1 - Bondarenko, S. A1 - Mai, C. A1 - Paul, Martin A1 - Weller, Michael G. A1 - Mai, A. T1 - CMOS-Compatible Silicon Photonic Sensor for Refractive Index Sensing Using Local Back-Side Release N2 - Silicon photonic sensors are promising candidates for lab-on-a-chip solutions with versatile applications and scalable production prospects using complementary metal-oxide semiconductor (CMOS) fabrication methods. However, the widespread use has been hindered because the sensing area adjoins optical and electrical components making packaging and sensor handling challenging. In this work, a local back-side release of the photonic sensor is employed, enabling a separation of the sensing area from the rest of the chip. This approach allows preserving the compatibility of photonic integrated circuits in the front-end of line and metal interconnects in the back-end of line. The sensor is based on a micro-ring resonator and is fabricated on wafer-level using a CMOS technology. We revealed a ring resonator sensitivity for homogeneous sensing of 106 nm/RIU. KW - Photonic biosensor KW - Lab-on-a-chip KW - Ring resonator KW - Resonance wavelength shift KW - PIC technology KW - Back-side integration PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-517139 DO - https://doi.org/10.1109/LPT.2020.3019114 VL - 32 IS - 19 SP - 1241 EP - 1244 PB - IEEE AN - OPUS4-51713 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Paul, Martin T1 - Development of a biosensor for the online detection of explosives N2 - An affinity column, which removed up to 99 % of high affinity Anti-TNT antibody at high antibody concentrations, was manufactured based on a monolithic glass core and a trinitroaniline-BSA conjugate. To detect the label Dy654 in the nM range an epi-fluorescence microscope setup with a CMOS camera was established to serve as online fluorescence detector with multiplexing capabilities. T2 - ANAKON 2019 CY - Münster, Germany DA - 25.03.2019 KW - Online fluorescence KW - Trinitro KW - Affinty KW - Antibody PY - 2019 AN - OPUS4-47745 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Paul, Martin T1 - Fast Detection of TNT at ppt Level by an Immunofluorometric Biosensor N2 - The mechanism of this system is based on kinetic competition. This biosensor consists of a monolithic glass column with a vast excess of immobilized hapten, which traps the fluorescently labeled antibody as long as no explosive is present. If the explosive 2,4,6-trinitrotoluene (TNT) is introduced some binding sites of the antibody will be blocked, which leads to an immediate breakthrough of the labeled protein. The fluorescence is detected by highly sensitive laser-induced fluorescence with a conventional CMOS camera. The system achieved limits of detection of approx.1 pM (1 ppt) of the fluorescent label and around 100 pM (20 ppt) of TNT. The total assay time is less than 8 minutes. A cross-reactivity test with 5000 pM solutions of pentaerythritol tetranitrate (PETN), 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) showed no cross reactivity. T2 - Doktorandenseminar 2020 des Arbeitskreis-Prozessanalytik CY - Online meeting DA - 21.09.2020 KW - TNT KW - Explosive KW - Antibody KW - Fluorescence KW - Biosensor KW - Affinity PY - 2020 AN - OPUS4-51314 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Paul, Martin T1 - Real time multichannel biomarker detection using photonic integrated circuits on ultra compact CMOS chips N2 - This work presents the real-time, multichannel detection of the biomolecule Neutravidine using photonic integrated circuits on ultra-compact monolithic CMOS chips. The development focuses on implementing bioassays directly on CMOS platforms, enabling highly integrated and scalable biosensing. The presentation will cover key aspects including microfluidic integration, data analysis, surface functionalization, and chip packaging. T2 - World Biosensor Congress CY - Lisbon, Portugal DA - 18.05.2025 KW - Chips KW - Photonics KW - Biosensor KW - Realtime PY - 2025 AN - OPUS4-63777 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Tannenberg, Robert A1 - Paul, Martin A1 - Röder, Bettina A1 - Gande, S. L. A1 - Sreeramulu, S. A1 - Saxena, K. A1 - Richter, C. A1 - Schwalbe, H. A1 - Swart, C. A1 - Weller, Michael G. T1 - Chemiluminescence biosensor for the determination of cardiac troponin I (cTnI) N2 - Cardiac troponin I (cTnI) is a crucial biomarker for diagnosing cardiac vascular diseases, including acute myocardial infarction (AMI). This study presents a proof-of-concept chemiluminescence-based immunosensor for rapid and accurate measurement of cTnI, with the potential for online monitoring. The immunosensor incorporates a flow cell design and a sensitive complementary metal-oxide-semiconductor (CMOS) camera for optical readout. A microfluidic setup was established to enable selective and quasi-online determination of cTnI within ten minutes. The sensor was tested with recombinant cTnI in phosphate buffer, demonstrating measurements in the concentration range of 2–25 µg/L, with a limit of detection (LoD) of 0.6 µg/L (23 pmol/L) achieved using the optimized system. The immunosensor exhibited high selectivity, as no cross-reactivity was observed with other recombinant proteins such as cTnT and cTnC at a concentration of 16 µg/L. Measurements with diluted blood plasma and serum yielded an LoD of 60 µg/L (2.4 nmol/L) and 70 µg/L (2.9 nmol/L), respectively. This biosensor offers a promising approach for the rapid and sensitive detection of cTnI, contributing to the diagnosis and management of acute myocardial infarction and other cardiac vascular diseases. N2 - Das kardiale Troponin I (cTnI) ist ein wichtiger Biomarker für die Diagnose von Herz-Kreislauf-Erkrankungen, einschließlich des akuten Myokardinfarkts (AMI). In dieser Studie wird ein auf Chemilumineszenz basierender Immunsensor für die schnelle und genaue Messung von cTnI vorgestellt, der das Potenzial für eine Online-Überwachung hat. Der Immunsensor besteht aus einer Durchflusszelle und einer empfindlichen CMOS-Kamera (Complementary Metal-Oxide-Semiconductor) zur optischen Detektion. Es wurde ein mikrofluidischer Aufbau entwickelt, der eine selektive und quasi Online-Bestimmung von cTnI innerhalb von zehn Minuten ermöglicht. Der Sensor wurde mit rekombinantem cTnI in Phosphatpuffer getestet und zeigte einen Messbereich von 2-25 µg/L, wobei mit dem optimierten System eine Nachweisgrenze (LoD) von 0,6 µg/L (23 pmol/L) erreicht wurde. Der Immunsensor zeigte eine hohe Selektivität, da keine Kreuzreaktivität mit anderen rekombinanten Proteinen wie cTnT und cTnC bei einer Konzentration von 16 µg/L beobachtet wurde. Messungen mit verdünntem Blutplasma und Serum ergaben einen LoD von 60 µg/L (2,4 nmol/L) bzw. 70 µg/L (2,9 nmol/L). Dieser Biosensor bietet einen vielversprechenden Ansatz für den schnellen und empfindlichen Nachweis von cTnI, der zur Diagnose und Behandlung des akuten Myokardinfarkts und anderer kardialer Gefäßerkrankungen beitragen kann. KW - Acute myocardial infarction KW - Heart attack KW - Emergency KW - Diagnosis KW - Cardiac troponin KW - Biomarker KW - Immunosensor KW - Biosensor KW - Chemiluminescence KW - Luminol KW - Peroxidase KW - Monoclonal antibodies KW - Flow injection immunoassay KW - Immunometric assay KW - Immunometric biosensor KW - Microfluidic system KW - Monolithic column KW - Online biosensor PY - 2023 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-575471 DO - https://doi.org/10.3390/bios13040455 SN - 2079-6374 VL - 13 IS - 4 SP - 1 EP - 20 PB - MDPI CY - Basel AN - OPUS4-57547 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Paul, Martin A1 - Weller, Michael G. T1 - Antibody screening by microarray technology - Direct identification of selective high-affinity clones N2 - The primary screening of hybridoma cells is a time-critical and laborious step during the development of monoclonal antibodies. Often, critical errors occur in this phase, which supports the notion that the generation of monoclonal antibodies with hybridoma technology is difficult to control and hence, a risky venture. We think that it is crucial to improve the screening process to eliminate most of the critical deficits of the conventional approach. With this new microarray-based procedure, several advances could be achieved: Selectivity for excellent binders, high-throughput, reproducible signals, avoidance of misleading avidity (multivalency) effects, and performance of simultaneous competition experiments. The latter can also be used to select clones of desired cross-reactivity properties. In this paper, a model system with two excellent clones against carbamazepine, two weak clones, and blank supernatant containing fetal bovine serum was designed to examine the effectiveness of the new system. The excellent clones could be detected largely independent of the immunoglobulin G (IgG) concentration, which is usually unknown during the clone screening since the determination and subsequent adjustment of the antibody concentration are not feasible in most cases. Furthermore, in this approach, the enrichment, isolation, and purification of IgG for characterization is not necessary. Raw cell culture supernatant can be used directly, even when fetal calf serum (FCS) or other complex media is used. In addition, an improved method for the oriented antibody-immobilization on epoxy-silanized slides is presented. Based on the results of this model system with simulated hybridoma supernatants, we conclude that this approach should be preferable to most other protocols leading to many false positives, causing expensive and lengthy elimination steps to weed out the poor clones. KW - ELISA KW - Immunoassay KW - Microarray KW - Lab-on-a-chip KW - Miniaturization KW - Aautomatisation KW - HTS KW - High-throughput KW - Screening KW - Fluorescence KW - Label KW - Hybridoma KW - Inhibition PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-503361 DO - https://doi.org/10.3390/antib9010001 SN - 2073-4468 VL - 9 IS - 1 SP - 1 EP - 16 PB - MDPI CY - Basel AN - OPUS4-50336 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Tannenberg, Robert A1 - Paul, Martin A1 - Fünning, Tabea A1 - Schuhmann, Christoph A1 - Weller, Michael G. A1 - Steglich, Patrick T1 - Multichannel real-time detection of biomarkers with highly miniaturized photonic microchips N2 - The development of novel photonic integrated microchips (PIC) is a promising approach to allow for the convenient detection of key biomarkers in complex matrices through multichannel real-time analysis in a highly compact package. This study reports the successful development and application of a backside released CMOS chip designed for the multichannel real-time detection of biomarkers. Operating at the C-band at approx. 1550 nm, the microchip features three dedicated detection sensors in addition to a reference sensor, enabling simultaneous analysis of multiple biomarkers. The compact and highly miniaturized design of this microchip, with a footprint of just 1 mm², positions it as promising candidate for point-of-care diagnostics and personalized medicine applications. This technology opens a path to transform biomarker detection across various medical fields, offering rapid, reliable, and cost-effective diagnostic solutions. In conclusion, the presented multichannel photonic microchips signify a substantial leap forward in real-time biomarker detection, providing a highly capable platform for future research and clinical applications. T2 - SPIE Optics + Optoelectronics 2025 CY - Prague, Czech Republic DA - 07.04.2025 KW - Photonic integrated circuit KW - Ring resonator KW - Real-time detection KW - Multiplexing KW - Semiconductor KW - CMOS KW - C-reactive protein KW - CRP KW - Biomarker PY - 2025 SN - 978-1-5106-8850-6 DO - https://doi.org/10.1117/12.3056453 VL - 13527 SP - 1 EP - 6 PB - SPIE CY - Prague, Czech Republic AN - OPUS4-63478 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Paul, Martin T1 - High sensitivity online detection of Trinitrotoluene (TNT) N2 - The antibody A.1.1.1 was labeled and found to be very sensitive and highly selective for TNT. A novel monolithic affinity column was coated with a Trinitroaniline (TNA)-BSA affinity conjugate and a custom laser induced fluorescence detector were built to allow for continuous and sensitive detection. The affinity column combined with the high sensitivity detector resulted in a limit of detection of approx. 100 pM TNT or 20 ppt TNT for offline detection and was able to detect picogram amounts within three minutes. T2 - SALSA Make and Measure 2020 CY - Online meeting DA - 15.10.2020 KW - Biosensor KW - Explosive KW - Antibody KW - Online KW - Fluorescence PY - 2020 AN - OPUS4-51529 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Steglich, Patrick A1 - Paul, Martin A1 - Mai, C. A1 - Böhme, A. A1 - Bondarenko, S. A1 - Weller, Michael G. A1 - Mai, A. T1 - A monolithically integrated microfluidic channel in a silicon-based photonic-integrated-circuit technology for biochemical sensing N2 - In this work, a cost-effective optofluidic system is proposed and preliminary experimental results are presented. A microfluidic channel monolithically integrated into a photonic integrated circuit technology is used in conjunction with a cyclic olefin copolymer (COC) substrate to provide fluidic in- and output ports. We report on initial experimental results as well as on the simple and cost-effective fabrication of this optofluidic system by means of micro-milling. KW - Biosensors KW - Biophotonics KW - Optical sensors KW - Photonic sensors KW - Ring resonators KW - Silicon photonics KW - Lab-on-a-chip KW - Microfluidics KW - Chip KW - Biochip PY - 2021 DO - https://doi.org/10.1117/12.2588791 VL - 11772 SP - 1 EP - 5 PB - SPIE AN - OPUS4-53559 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Steglich, P. A1 - Mai, C. A1 - Bondarenko, S. A1 - Paul, Martin A1 - Weller, Michael G. A1 - Schrader, S. A1 - Mai, A. T1 - BioPIC - Integration of Biosensors based on Photonic Integrated Circuits by Local-Backside Etching N2 - Silicon photonic sensors are promising candidates for lab-on-a-chip solutions with versatile applications and scalable production prospects using complementary metal-oxide semiconductor (CMOS) fabrication methods. However, the widespread use has been hindered because the sensing area adjoins optical and electrical components making packaging and sensor handling challenging. In this work, a local back-side release of the photonic sensor is employed, enabling a separation of the sensing area from the rest of the chip. This approach allows preserving the compatibility of photonic integrated circuits in the front-end of line and metal interconnects in the back-end of line. T2 - ATTRACT online Conference CY - Online meeting DA - 22.09.2020 KW - Silicon Photonics KW - Photonic Sensor KW - Photonic Integrated Circuits KW - Point-Of-Care-Diagnostics KW - CMOS KW - Microfluidics KW - Lab-on-a-chip KW - Ring resonator PY - 2020 UR - https://attract-eu.com/showroom/project/integration-of-biosensors-based-on-photonic-integrated-circuits-by-local-backside-etching-biopic/ SP - 1 EP - 5 AN - OPUS4-51735 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Paul, Martin T1 - Multichannel biomarker detection using photonic integrated circuits on ultra compact CMOS chips N2 - This work presents the development of a real-time, multichannel detector for biomolecules based on photonic integrated circuits with super-compact CMOS chips. The presentation focuses on using micro-ring-resonators for bioassays, enabling highly integrated and scalable biosensing-solutions. The talk also covers major challenges like including microfluidic integration, data analysis, custom surface functionalization, and chip packaging. T2 - Photonics Week 2025 CY - Berlin, Germany DA - 08.10.2025 KW - CMOS KW - Photonics KW - Biosensor KW - Immunoassay KW - Realtime PY - 2025 AN - OPUS4-64585 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -