Abstract
Analysis of physiological parameters using small model organisms is an attractive approach in pre-clinical drug discovery when studying effects of new drugs or existing drug combinations. Larval zebrafish (Danio rerio) is a small vertebrate model organism that recently emerged as an innovative experimental system for non-invasive and real-time analysis of physiological parameters such as cardiovascular activity. In this work, we demonstrate a new chip-enabled approach to perform non-invasive imaging micro-echocardiography (iμEC) on immobilized larval stages of zebrafish. The iμEC is a new assay for quantification of the temporal cardiac patterns based on analysis of video stream from a high-resolution camera. The chip-based system utilized hydrodynamic trapping principles to actively capture and immobilize individual larvae using a low-pressure suction for real-time iμEC analysis. The system coupled together with an integrated interface provided a new capability to rapidly assess pharmacologically-induced perturbation in cardiac function by real-time and non-invasive monitoring of zebrafish larvae. We demonstrated the application of the technology for proof-of-concept assessment of model cardio-active compounds delivered using continuous micro-perfusion. The optical transparency of larval stages and micro-hydrodynamic immobilization allowed for visualization of cardiac activity after drug treatment in real-time. Results obtained using micro-perfusion also enabled studies on rapid drug withdrawal that are difficult to achieve using existing protocols such as imaging in microtiter plates. This work demonstrates iμEC as a new technique for cardiological experiments utilizing zebrafish models.
| Original language | English |
|---|---|
| Pages (from-to) | 1131-1141 |
| Number of pages | 11 |
| Journal | Sensors and Actuators B: Chemical |
| Volume | 256 |
| DOIs | |
| Publication status | Published - 1 Mar 2018 |
Keywords
- Cardiology
- Heart
- Lab-on-a-Chip
- Microfluidics
- Toxicity
- Zebrafish
Cite this
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Lab-on-a-Chip imaging micro-echocardiography (iμEC) for rapid assessment of cardiovascular activity in zebrafish larvae. / Fuad, Nurul Mohd; Kaslin, Jan; Wlodkowic, Donald.
In: Sensors and Actuators B: Chemical, Vol. 256, 01.03.2018, p. 1131-1141.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Lab-on-a-Chip imaging micro-echocardiography (iμEC) for rapid assessment of cardiovascular activity in zebrafish larvae
AU - Fuad, Nurul Mohd
AU - Kaslin, Jan
AU - Wlodkowic, Donald
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Analysis of physiological parameters using small model organisms is an attractive approach in pre-clinical drug discovery when studying effects of new drugs or existing drug combinations. Larval zebrafish (Danio rerio) is a small vertebrate model organism that recently emerged as an innovative experimental system for non-invasive and real-time analysis of physiological parameters such as cardiovascular activity. In this work, we demonstrate a new chip-enabled approach to perform non-invasive imaging micro-echocardiography (iμEC) on immobilized larval stages of zebrafish. The iμEC is a new assay for quantification of the temporal cardiac patterns based on analysis of video stream from a high-resolution camera. The chip-based system utilized hydrodynamic trapping principles to actively capture and immobilize individual larvae using a low-pressure suction for real-time iμEC analysis. The system coupled together with an integrated interface provided a new capability to rapidly assess pharmacologically-induced perturbation in cardiac function by real-time and non-invasive monitoring of zebrafish larvae. We demonstrated the application of the technology for proof-of-concept assessment of model cardio-active compounds delivered using continuous micro-perfusion. The optical transparency of larval stages and micro-hydrodynamic immobilization allowed for visualization of cardiac activity after drug treatment in real-time. Results obtained using micro-perfusion also enabled studies on rapid drug withdrawal that are difficult to achieve using existing protocols such as imaging in microtiter plates. This work demonstrates iμEC as a new technique for cardiological experiments utilizing zebrafish models.
AB - Analysis of physiological parameters using small model organisms is an attractive approach in pre-clinical drug discovery when studying effects of new drugs or existing drug combinations. Larval zebrafish (Danio rerio) is a small vertebrate model organism that recently emerged as an innovative experimental system for non-invasive and real-time analysis of physiological parameters such as cardiovascular activity. In this work, we demonstrate a new chip-enabled approach to perform non-invasive imaging micro-echocardiography (iμEC) on immobilized larval stages of zebrafish. The iμEC is a new assay for quantification of the temporal cardiac patterns based on analysis of video stream from a high-resolution camera. The chip-based system utilized hydrodynamic trapping principles to actively capture and immobilize individual larvae using a low-pressure suction for real-time iμEC analysis. The system coupled together with an integrated interface provided a new capability to rapidly assess pharmacologically-induced perturbation in cardiac function by real-time and non-invasive monitoring of zebrafish larvae. We demonstrated the application of the technology for proof-of-concept assessment of model cardio-active compounds delivered using continuous micro-perfusion. The optical transparency of larval stages and micro-hydrodynamic immobilization allowed for visualization of cardiac activity after drug treatment in real-time. Results obtained using micro-perfusion also enabled studies on rapid drug withdrawal that are difficult to achieve using existing protocols such as imaging in microtiter plates. This work demonstrates iμEC as a new technique for cardiological experiments utilizing zebrafish models.
KW - Cardiology
KW - Heart
KW - Lab-on-a-Chip
KW - Microfluidics
KW - Toxicity
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=85031406394&partnerID=8YFLogxK
U2 - 10.1016/j.snb.2017.10.050
DO - 10.1016/j.snb.2017.10.050
M3 - Article
VL - 256
SP - 1131
EP - 1141
JO - Sensors and Actuators B: Chemical
JF - Sensors and Actuators B: Chemical
SN - 0925-4005
ER -