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Integrated microoptical system for continuous fluorescence monitoring of microtissues
KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.ORCID iD: 0009-0007-6016-3708
KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.ORCID iD: 0000-0002-9144-0065
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. (Herland Lab)ORCID iD: 0000-0001-8433-2181
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2025 (English)In: Microsystems & Nanoengineering, E-ISSN 2055-7434, Vol. 11, no 1, article id 213Article in journal (Refereed) Published
Abstract [en]

Microphysiological systems (MPS) are advanced in vitro platforms engineered to replicate in vivo conditions for studying human biology, disease mechanisms, and drug responses with greater physiological relevance. Fluorescence sensing is widely used as a functional readout in MPS due to its high sensitivity, selectivity, and stability. However, conventional fluorescence sensing systems often rely on bulky instrumentation with limited integration, which restricts continuous in situ monitoring, scalable high-throughput analysis, and spatially resolved investigation in multi-organ-on-a-chip models. To address these limitations, we present a highly miniaturized, fully integrated optical system with a 1 mm² footprint, enabling continuous in situ fluorescence monitoring of three-dimensional microtissues in close proximity. The system integrates microscale illumination and sensing units for fluorescence excitation and selective detection, an optical element for guided light propagation, and a microcage for mechanical confinement of microtissues. To demonstrate its capabilities, we integrated the miniaturized optical system with an MPS-relevant platform to monitor fluorescence signals in transgenic mouse pancreatic islets expressing genetically encoded calcium indicators. The integrated platform enables real-time, continuous monitoring of islet responses to potassium chloride stimulation and tracking of calcium oscillations for over two hours, providing valuable information about the functional status of the pancreatic islets. Our work enhances the analytical capabilities of MPS through the integration of miniaturized on-chip quantitative assessment tools, enabling precise, in situ, and continuous monitoring of biological activities in close proximity.

Place, publisher, year, edition, pages
Springer Nature , 2025. Vol. 11, no 1, article id 213
National Category
Engineering and Technology Other Nanotechnology Atom and Molecular Physics and Optics
Identifiers
URN: urn:nbn:se:kth:diva-373124DOI: 10.1038/s41378-025-01073-4PubMedID: 41224775Scopus ID: 2-s2.0-105021471430OAI: oai:DiVA.org:kth-373124DiVA, id: diva2:2015070
Note

QC 20251121

Available from: 2025-11-20 Created: 2025-11-20 Last updated: 2026-01-23Bibliographically approved
In thesis
1. Integrated Microsystems for Fluorescence Sensing and Ultrasonic Energy Harvesting in Biomedical Applications
Open this publication in new window or tab >>Integrated Microsystems for Fluorescence Sensing and Ultrasonic Energy Harvesting in Biomedical Applications
2026 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Advances in miniaturized biomedical microsystems, ranging from in vitro microphysiological systems (MPS) to implantable devices, are enabling new modes of continuous, autonomous preclinical studies. This thesis presents a set of interconnected research contributions on millimeter-scale fluorescence-sensing and ultrasonic energy-harvesting microsystems, collectively advancing the development of integrated and miniaturized biomedical instrumentation.

The first part introduces an integrated microoptical system for fluorescence sensing in MPS, incorporating custom micro-optics and miniaturized excitation and detection units with tailored optical filters. This platform enables real-time, continuous fluorescence monitoring of microtissues under physiologically relevant conditions, strengthening the analytical capabilities of MPS for long-duration studies of drug delivery and cellular behavior.

The second part translates these sensing concepts to fully implantable microsystems capable of autonomous, long-term in vivo fluorescence recording. A compact 5 × 5 × 5 mm³ implant integrates a miniaturized optical module and low-power electronics to track fluorescence dynamics within living tissue. Validated across phantom, in vitro, ex vivo, and in vivo studies, the system demonstrates two-week continuous tracking of tumor-associated fluorescence, establishing its suitability for preclinical studies.

The final part focuses on ultrasonic energy harvesting to enable the autonomous operation of implantable devices. A MEMS-based piezoelectric ultrasonic energy harvester (PUEH) fabricated using a low-temperature bonding process allows integration of high-performance bulk PZT-5H, demonstrating the potential of MEMS architectures for efficient ultrasonic power transfer. An integrated energy-harvesting node, also in a 5 × 5 × 5 mm³ form factor, combines the MEMS-based PUEH with power management and storage to support autonomous operation of millimetric implants.

Together, these contributions advance miniaturized fluorescence sensing and ultrasonic energy transfer, enabling versatile microsystems for biomedical applications.

Abstract [sv]

Framsteg inom miniatyriserade biomedicinska mikrosystem, allt från in vitro-mikrofysiologiska system (MPS) till implanterbara enheter, möjliggör nya former av kontinuerliga, autonoma prekliniska studier. Denna avhandling presenterar en uppsättning sammankopplade forskningsbidrag om millimeterskaliga fluorescensavkännande och ultraljudsenergiupptagnings-mikrosystem, som tillsammans främjar utvecklingen av integrerade och miniatyriserade biomedicinska instrument.

Den första delen introducerar ett integrerat mikrooptiskt system för fluorescensavkänning i MPS, som innehåller anpassad mikrooptik och miniatyriserade excitations- och detektionsenheter med skräddarsydda optiska filter. Denna plattform möjliggör kontinuerlig fluorescensövervakning i realtid av mikrovävnader under fysiologiskt relevanta förhållanden, vilket stärker MPS analytiska kapacitet för långvariga studier av läkemedelsleverans och cellulärt beteende. Den andra delen översätter dessa avkänningskoncept till helt implanterbara mikrosystem som kan utföra autonom, långsiktig in vivo-fluorescensregistrering. Ett kompakt 5 × 5 × 5 mm³-implantat integrerar en miniatyriserad optisk modul och lågeffektselektronik för att spåra fluorescensdynamik i levande vävnad. Systemet har validerats i fantom-, in vitro-, ex vivo- och in vivo-studier och demonstrerar två veckors kontinuerlig övervakning av tumörassocierad fluorescens, vilket fastställer dess lämplighet för prekliniska studier. Den sista delen fokuserar på ultraljudsenergiupp-samling för att möjliggöra autonom implantatdrift. En MEMS-baserad piezoelektrisk ultraljudsenergiuppsamlingsenhet (PUEH) tillverkad med en lågtemperaturbindningsprocess möjliggör integration av högpresterande bulk-PZT-5H, vilket demonstrerar potentialen hos MEMS-arkitekturer för effektiv ultraljudsenergiöverföring. En integrerad energiuppsamlingsnod, också i en formfaktor på 5 × 5 × 5 mm³, kombinerar MEMS PUEH med energihantering och lagring för att stödja autonom drift av millimetriska implantat.

Tillsammans främjar dessa bidrag miniatyriserad fluorescensavkänning och ultraljudsenergiöverföring, vilket möjliggör mångsidiga mikrosystem för biomedicinska tillämpningar.

Place, publisher, year, edition, pages
Stockholm, Sweden: KTH Royal Institute of Technology, 2026. p. ix, 73
Series
TRITA-EECS-AVL ; 2026:11
Keywords
Integrated Microsystems, Fluorescence Sensing, Ultrasonic Energy Harvesting, Integrerade mikrosystem, fluorescensavkänning, ultraljudsenergiinsamling
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Research subject
Electrical Engineering
Identifiers
urn:nbn:se:kth:diva-375879 (URN)978-91-8106-517-6 (ISBN)
Public defence
2026-02-20, https://kth-se.zoom.us/j/63767237845, Q2, Room B218, Malvinas väg 10, Stockholm, 13:00 (English)
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Supervisors
Note

QC 20260127

Available from: 2026-01-27 Created: 2026-01-23 Last updated: 2026-02-09Bibliographically approved

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Tian, XuKavand, HanieJessika, JessikaStemme, Göranvan der Wijngaart, WouterHerland, AnnaRoxhed, Niclas

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