Workshop 6
Recent Advances in CMOS Cellular and Molecular Biosensors
Organizer : Hua Wang (ETH Zurich)
Organizer : Drew Hall (UC San Diego)
Over the past two decades, we have seen remarkable advancements in the use of CMOS integrated circuits (ICs) to develop integrated biosensors and bioelectronics. Modern CMOS IC technologies provide unmatched device performance, high integration density, and advanced computational capabilities, driving continuous innovation in integrated bioelectronics at the circuit level. Simultaneously, increasing investments in CMOS-compatible post-processing technologies have significantly broadened the functionalities of CMOS bioelectronics. As a result, CMOS biosensors are experiencing rapid growth and finding applications in diverse areas, including neural interfaces, gas sensors, and intelligent sensor arrays that directly interact with cells and molecules. This workshop aims to showcase recent advancements in CMOS-based cellular and molecular sensors and foster discussions on the future technology directions of this dynamic field.
About Organizers
Organizer:Hua Wang is a Full Professor and the Chair of Electronics at D-ITET of ETH Z?rich. He is also the Institute Deputy Head of the Integrated Systems Laboratory (IIS). Prior to that, he was a Tenured Associate Professor at the School of ECE at Georgia Institute of Technology, USA. He worked at Intel Corporation and Skyworks Solutions from 2010 to 2011. He received his M.S. and Ph.D. degrees in electrical engineering from the California Institute of Technology, Pasadena, in 2007 and 2009, respectively.
Dr. Wang is interested in analog, mixed-signal, RF, and mm-Wave integrated circuits and hybrid systems for communication, sensing, and bioelectronics. He is an IEEE Fellow. He has authored or co-authored over 250 peer-reviewed journal and conference papers.
Co-Organizer: Drew A. Hall is a Full Professor at the Department of Electrical and Computer Engineering at the University of California at San Diego (UCSD). Prior to joining UCSD, he was a Research Scientist in the Integrated Biosensors Laboratory at Intel Corporation. He received the B.S. degree in computer engineering with honors from the University of Nevada, Las Vegas in 2005, and the M.S. and Ph.D. degrees in electrical engineering from Stanford University in 2008 and 2012, respectively.
His research interests include bioelectronics, biosensors, analog circuit design, medical electronics, and sensor interfaces. Dr. Hall is a Tau Beta Pi Fellow. He has served as an Associate Editor of the IEEE TRANSACTIONS ON BIOMEDICAL INTEGRATED CIRCUITS since 2015, a member of the CICC Technical Program Committee from 2017-2024, a member of the ISSCC Technical Program Committee since 2020, and an Associate Editor of the IEEE Solid-State Circuits Letters from 2021 to 2024.
- 1. Multi-Modal CMOS Biosensing and Actuation: Advancing Cellular and Molecular Diagnostics, Hua Wang, ETH Zurich
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Abstract
This workshop presentation introduces the state-of-the-art multi-modal CMOS biosensing and actuating platforms for multi-parametric cellular and molecular analysis. Featuring arrays with up to 21,952 multimodal pixels at single-cell and subcellular resolution, these systems integrate multiple sensing modalities?impedance tomography, pH sensing, electrochemical detection, and ion-selective imaging?and actuation functions such as dielectrophoresis and current stimulation.|Validated with human and mouse progenitor cells, as well as SARS-CoV-2 RNA, these CMOS multi-modal bio-sensing/actuation platforms enable high-throughput characterization of cellular behavior, drug responses, and ion channel activity. Innovations like in-pixel biosensing/actuation circuits, antifouling surfaces, and robust current-to-digital conversion ensure biocompatibility, scalability, and environmental noise resistance.|Participants will explore applications in organ-on-chip systems, personalized diagnostics, and molecular disease modeling, gaining insights into how these technologies will potentially advance biophysical and biochemical analyses at unparalleled resolution and throughput.
- 2. A Scalable CMOS Molecular Electronics Chip for Single-Molecule Biosensing, Drew Hall, UC San Diego
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Abstract This work reports the first CMOS molecular electronics chip, where the primary sensing element is a single molecule “molecular wire” consisting of a ?100 GΩ, 25 nm long alpha-helical peptide integrated into a current monitoring circuit. The engineered peptide contains a central conjugation site for attachment of various probe molecules, such as DNA, proteins, enzymes, or antibodies, which program the biosensor to detect interactions with a specific target molecule. The current through the molecular wire under a dc applied voltage is monitored with millisecond temporal resolution. The detected signals are millisecond-scale, picoampere current pulses generated by each transient probe-target molecular interaction. Implemented in a 0.18 ?m CMOS technology, 16k sensors are arrayed with a 20 ?m pitch and read out at a 1 kHz frame rate. The resulting biosensor chip provides direct, real-time observation of the single-molecule interaction kinetics, unlike classical biosensors that measure ensemble averages of such events. This molecular electronics chip provides a platform for putting molecular biosensing “on-chip” to bring the power of semiconductor chips to diverse applications in biological research, diagnostics, sequencing, proteomics, drug discovery, and environmental monitoring.
- 3. Advancing Neuroscience with CMOS Neuroelectronic Interfaces, Donhee Ham, Harvard University
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Abstract Understanding the brain's computational power requires advanced tool platforms capable of capturing large-scale neuronal dynamics with intracellular precision. This workshop presentation introduces a revolutionary CMOS neuroelectronic interface (CNEI) with 4,096 recording and stimulation sites, combining nanoscale platinum-black electrodes and CMOS technology. The CNEI enables stable intracellular recording of subthreshold potentials, ion-channel currents, and network-wide synaptic connections, achieving unmatched throughput for functional connectome mapping.
We will explore the CNEI’s advantages over existing techniques?such as microelectrode arrays, planar patch-clamp systems, and optical electrophysiology?demonstrating its capacity for high-throughput neuronal network analysis and drug screening. Additionally, we discuss its transformative role in neuromorphic engineering, proposing a "copy-and-paste" strategy to transfer synaptic connectivity maps to silicon-based platforms, paving the way for brain-inspired computational systems.
The talk will end with exploring this cutting-edge interface to bridge neuroscience and technology, unlocking new possibilities in understanding and replicating the brain’s intelligence. - 4. A 376μW per-channel, Drift-tolerant Translocation Recording Frontend with Event Detection for Nanopore Sensor Arrays, Chris Van Hoof, IMEC
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Abstract This paper presents a multi-channel readout chip for high throughput single molecule sensing with solidstate nanopores. The readout IC achieves 1 MHz BW to capture the fast translocation signals coming from such nanopores. Since molecule translocation events are typically sparse in time, the ASIC features a novel analog event detection circuit to detect which pores have molecules passing through them and only records from those pores. A 16-channel prototype readout IC implemented in??CMOS is demonstrated which can be connected to commercial nanopores. The recording frontend is only??channel and consumes??channel. Both electrical characterization and actual single-molecule sensing with commercial nanopores are demonstrated.
- 5. Ingestible capsule for detecting labile inflammatory biomarkers in situ, Rabia Tugce Yazicigil, Boston University
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Abstract Transient molecules in the gastrointestinal (GI) tract, such as nitric oxide and hydrogen sulfide, are key signals and mediators of inflammatory bowel disease (IBD). Because these molecules are extremely short-lived in the body, they are difficult to detect. To track these reactive molecules in the GI tract, we have developed a miniaturized device that integrates genetically-engineered probiotic biosensors with a custom-designed photodetector and readout chip. Leveraging the molecular specificity of living sensors, we genetically encoded bacteria to respond to IBD-associated molecules by luminescing. Low-power electronic readout circuits (nanowatt power) integrated into the device convert the light from just 1 μL of bacterial culture into a wireless signal. We demonstrate biosensor monitoring in the GI tract of small and large animal models and integration of all components into a sub-1.4 cm3?ingestible form factor capable of supporting wireless communication. The wireless detection of short-lived, disease-associated molecules could support earlier diagnosis of disease than is currently possible, more accurate tracking of disease progression, and more timely communication between patient and their care team supporting remote personalized care.