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Millimetric Implantable Device for Extended In Vivo Fluorescence Recording
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: 0009-0006-5439-4051
The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institute, Sweden.
The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institute, Sweden.
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2025 (English)In: 2025 23rd International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers), Institute of Electrical and Electronics Engineers (IEEE) , 2025, p. 566-569Conference paper, Published paper (Refereed)
Abstract [en]

In vivo fluorescence sensing devices have recently gained considerable attention owing to their capabilities and potential in advancing biomedical research, clinical diagnostics, and therapeutic applications. In this work, we present a highly miniaturized, fully implantable device capable of excitation, detection, and recording of fluorescence signals, enabling continuous measurements of biological processes in vivo. The device was engineered to be minimally invasive, with a compact 5×5×5mm3 form factor. It incorporates an optical system integrating micro illumination and sensing units with a sub-mm2 footprint, achieving selective detection of fluorescence signals in close proximity. Additionally, the device features low-power on-board electronics and a customized bi-stable magnetic switch for remote activation, resulting in a device lifetime of over a month once the device is powered on. The device successfully recorded the infusion of green fluorescence protein (GFP) solution at a low concentration of 100 μg/mL delivered at a rate of 4 μL/h for a 24-hour period, as well as the diffusion of a 150 μL GFP bolus with a concentration of 200 μg/mL over a 40-hour period, in a tissue-like phantom model made of gelatin. Further, the device was implanted into a living mouse for subcutaneous in vivo GFP recording as a proof of concept, and the fluorescence signal was successfully detected and recorded in the living animal.

Place, publisher, year, edition, pages
Institute of Electrical and Electronics Engineers (IEEE) , 2025. p. 566-569
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
URN: urn:nbn:se:kth:diva-375875DOI: 10.1109/TRANSDUCERS61432.2025.11111316ISI: 001600364100142Scopus ID: 2-s2.0-105030286089OAI: oai:DiVA.org:kth-375875DiVA, id: diva2:2031611
Conference
The 23rd International Conference on Solid-State Sensors, Actuators and Microsystems, Orlando, FL, USA, June 29 - July 3, 2025
Note

QC 20260226

Available from: 2026-01-23 Created: 2026-01-23 Last updated: 2026-02-26Bibliographically 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)
Opponent
Supervisors
Note

QC 20260127

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

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Tian, XuSpyrou, ArgyrisStemme, GöranRoxhed, Niclas

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