IROS2019国际学术会议论文集 2203

Characterizing Nanoparticle Swarms with Tuneable Concentrations for Enhanced Imaging Contrast Jiangfan Yu1 Qianqian Wang1 Mengzhi Li1 Chao Liu2 Lidai Wang2 Tiantian Xu3 and Li Zhang1 4 5 Abstract Microrobots capable of performing targeted de livery are promising for biomedical applications Due to the restriction of their small size and volume however the real time in vivo imaging strategy for microrobots meets limitations at the current stage Performing swarm actuation and control may be a promising candidate to increase the contrast of the imaging feedback signal Herein we use paramagnetic nanoparticles as tiny agents to systematically investigate the relationship between the imaging intensity and the areal concentration of the nanoparticles using three different bio imaging approaches Magnetic actuation strategies are applied to effectively tune the nanoparticle concentration via spread and gathering processes Three imaging modalities are applied including fl uorescent imaging FI ultrasound imaging UI and photoacoustic imaging PAI for tracking the nanoparticles The results of spreading and vortex like swarm generation gathering are fi rst validated using optical microscope and then the processes are performed under the monitoring of FI UI and PAI respectively The change of the imaging intensity with the particle areal concentration is analysed This work supports that forming a high concentrated swarm enhances the intensity of feedback signals with multiple imaging methods Index Terms microrobotic swarm magnetic actuation fl u orescent imaging ultrasound imaging photoacoustic imaging Untetheredmagneticmicrorobotsarepromisingfor biomedical applications due to the harmless magnetic fi eld driven actuation strategy and their good controlibilities 1 8 To realise different kinds of tasks various microrobots actuated by external magnetic fi elds have been reported For instance helical swimmers such as artifi cial bacterial fl agella ABF can swim in low Reynolds fl uids with corkscrew mo tions 9 Tumbling nanowires actuated by rotating magnetic fi elds is also capable of performing on demand navigation 10 Other microrobots such as micro nanoparticles 11 12 bacteria 13 and U shaped microrobots with slots for cargos 14 also well demonstrated their capability of per forming robotic tasks at the microscale e g targeted delivery 1 J Yu Q Wang and L Zhang are with the Department of Me chanical and Automation Engineering of The Chinese University of Hong Kong CUHK Shatin NT Hong Kong SAR China E mails lizhang mae cuhk edu hk 2 Department of Biomedical Engineering City University of Hong Kong 83 Tat Chee Ave Kowloon Hong Kong SAR China 3 Guangdong Provincial Key Laboratory of Robotics and Intelligent System Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen China 4 Chow Yuk Ho Technology Centre of Innovative Medicine The Chinese University of Hong Kong CUHK Shatin NT Hong Kong SAR China 5 T Stone Robotics Institute The Chinese University of Hong Kong CUHK Shatin NT Hong Kong SAR China Current address Shanghai Nuclear Engineering Research a magnetic force exerted by the other chains and an inward force provided by the major vortex These three forces are dynamically balanced and the resultant force serves as the centrifugal force leading the chain to rotate about the centre of the swarm As a result by applying rotating magnetic fi elds a high concentrated vortex like particle swarm can be formed In this process a proper combination of magnetic fi eld strength and rotating frequency is required If the fi eld strength is larger or rotating frequency is lower the particles tend to form long chains which may cause the fl uidic fi eld irregular and the vortices cannot be successfully merged In contrast with lower fi eld strength or higher rotating frequency shorter particle chains will form In this case more smaller and weaker vortices will be formed and it will be diffi cult to fi nally form one major swarm II EXPERIMENTALSETUP ANDNANOPARTICLES A Experimental setups The experimental validations are conducted in an 3 axis Helmholtz electromagnetic coils setup The control signals t 0 st 26 s t 100 st 0 s a b Fig 4 The experimental results of a the swarm generation and b the spreading of nanoparticle clusters under optical microscope The dashed blue circles and the red circles indicate the original and fi nal coverage areas of the nanoparticles respectively The scale bar is 800 m are generated by a Sensoray 826 card and then the current is amplifi ed to generate magnetic fi elds in the working space The sequence of the dynamic fi eld is given by the control PC An inverted fl uorescence microscope Model Ti S Nikon Instruments Inc with a fl uorescence illuminator Model C HGFI Nikon Instruments Inc is for the fl uorescence imaging of the nanoparticles An ultrasound system Tera son t3200 Teratech Corporation USA is integrated to the magnetic actuation system for the ultrasound imaging of the nanoparticles A linear array transducer 15L4 Teratech Corporation USA with bandwidth 15 4 MHz is applied A homemade photoacoustic imaging setup is used for the third type of imaging The imaging frame rates of FI and UI are 10 Hz and 30 Hz respectively The control updating rate is 1 kHz One drop of nanoparticle solution 8 L is added into the tank and then the diffused particles are fi rstly gathered onto the bottom of the tank by applying a magnetic fi eld gradient Then the nanoparticle clusters are put into the workspace of the electromagnetic setup for further magnetic actuations The nanoparticles used for the demonstrations with optical imaging UI and PAI have an average diameter of 100 nm as shown in Figure 3 Meanwhile the nanoparticles used for FI have an average diameter of 20 nm B Synthesis of the fl uorescent nanoparticles The fabrication method of the nanoparticles has been reported 37 and then the SiO2coated magnetite particles are synthesised 38 The prepared magnetite nanoparticles solution 4mg mL and 1 mL NH4OH 28 are mixed with 150 mL ethanol Afterwards 1 mL tetraethyl orthosilicate TEOS is dropped into the solution with continuous stirring for 45 min Then rhodamine B 50mg is added to the solution to be incorporated into the SiO2matrix under rapid stirring for 48 h The magnetic fl uorescent particles are prepared after the washing using ethanol and DI water III EXPERIMENTALVALIDATIONS A Swarm generation and spreading of nanoparticle chains The results of swarm generation from suspended nanopar ticle chains are shown in Figure 4 a Using 6 Hz rotating magnetic fi elds 7 mT the nanoparticle clusters fi rstly rotate about their own centres due to the applied magnetic torque Gradually a relative high concentration region is formed and fi nally a swarm consists of most of the particle chains with a clear contour is formed at t 100 s The initial and fi nal areas are highlighted by the blue dashed and red circles respec tively At the fi nal stage there are still some nanoparticles not being assembled into the major swarm Due to the small sizes of each nanoparticle diameter 100 nm the particle particle magnetic interactions are not strong enough to maintain a long chain during rotation and the induced vortices are weak Therefore the fl uidic interactions induced between vortices are not strong enough to attract distant nanoparticles into the major swarm After the generation of the swarm the particle concentration of the swarm core is increased more than 300 The spreading process of the particle clusters are also conducted and the experimental results are shown in Figure 4 b The nanoparticle cluster is spread and simultaneously disassembled into short pieces The initial and fi nal coverage areas of the particles are highlighted by the blue dashed curves and the red ellipse The increased coverage area indicates the signifi cant decrease of the areal concentration of nanoparticles In our following experiments the nanoparticles we used are paramagnetic and after the absence of external magnetic fi elds the nanoparticles only retain an ignorable magnetisation Therefore the proposed actuation strategies have good robustness and repeatability B Imaging One of the major drawback of applying a single mi crorobot for biomedical applications is the weak imaging feedback due to its small size and volumn A promising solution to tackle this issue is to generate high concentrated microrobotic swarms which may enhance the imaging contrast Hereby we use three imaging methods that are promising for tracking microrobots in vivo i e fl uorescence imaging ultrasound imaging and photoacoustic imaging In this section the same volume of nanoparticle suspension is applied in the experiments for the imaging 1 Fluorescence imaging The synthesis process of the fl uorescent nanoparticles is shown in Figure 5 a Section IIIB The fl uorescence imaging of the swarm generation and spreading of the nanoparticles are demonstrated in Figure 5 b and d respectively In Figure 5 b at fi rst the nanopar ticles are suspended in DI water and the fl uorescent imaging has a weak imaging feedback due to the low concentration Then the nanoparticles are gathered using a magnetic fi eld gradient into a relatively smaller region t 6 s and a rotating magnetic fi eld is applied for swarm generation 10 16 s At the fi nal stage one major swarm with multiple sub swarms are generated The fi nal pattern is not an ideal circle because the diameter of the fl uorescent nanoparticles 1 8 6 while the intensity gradually increases to 30 Then the dynamic magnetic fi eld is applied for spreading the concentrated nanoparticles and the fl uorescence images are shown in Figure 5 d During the process the area of the swarm is enlarged while the fl uorescence intensity of the nanoparticle swarm becomes lower as shown in Figure 5 e From t 0 s to t 16 s the area of the swarm spreads from 0 42 mm2to 0 74 mm2 which indicates that the concentration of the nanoparticles decreases by 43 2 and the intensity decreases by 36 during the process During this short period the photobleaching effect is negligible Therefore the particle concentration signifi cantly infl uences the fl uorescence intensity and by forming a microrobotic swarm the concentration can be raised which thus enhance the fl uorescent imaging feedback 2 Ultrasound imaging The ultrasound imaging is then applied for low concentrated nanoparticle clusters and high concentrated nanoparticle swarms and the results are shown in Figure 6 a and b In Figure 6 a the suspended nanopar ticles are gathered into a swarm using rotating magnetic fi elds and the real time ultrasound imaging are performed At fi rst the imaging feedback signal of the nanoparticle clusters are weak as shown in the region circled by the white dotted line at t 0 s Then the contrast of the nanoparticles gradually increases and at t 400 s the particle swarm can be clearly observed as an elliptical shape Meanwhile the reversible process i e the spreading of nanoparticle clusters is conducted and the results are presented in Figure 6 b The contrast of the images after t 50 s decreases signifi cantly compared with that of the initial image The intensity colour map of the fi nal stage of the gathering process t 400 s Figure 6 a and the spreading process t 200 s Figure 6 b is shown in Figure 6 c and Figure 6 d respectively In order to guarantee the accuracy of the calculated imaging a b c d e f Swarm Suspened Spread Fig 7 Photoacoustic imaging of the nanoparticle swarms with different concentrations i e a suspended state b spreading state and c swarm state and the concentrations are 0 7 g mm2 4 3 g mm2and 40 5 g mm2 respectively The colour bar indicates the intensity of the imaging feedback The imaging enhancement of forming a swarm is signifi cant The scale bar is 1 mm The colour map for b d and f are the same intensity we use a similar strategy for imaging processing as that aforementioned in FI and the average intensity is calculated from the selected regions After the swarm is generated the intensity of the core part is signifi cantly higher than the other region of the image In contrast the intensity of the spread nanoparticle clusters is much lower than the swarm case and in a large area the range of the intensity is similar The quantitative relationships between the particle coverage areas and imaging intensity during swarm generation and spreading processes are presented in Figure 6 e and f respectively The imaging intensity increases with the gathering of nanoparticle and decreases with the spreading process Therefore forming a swarm from suspended nanoparticle clusters can enhance the ultrasound imaging contrast 3 Photoacoustic imaging PAI The photoacoustic im ages for nanoparticles with different concentrations are shown in Figure 7 In Figure 7 a the particle suspension is dropped into the tank fi lled with DI water and the tank is put statically for some time in order to wait for the particles sinking onto the bottom of the tank The coverage area of the particles is relatively large 100 mm2 which leads to a low particle concentration 0 7 g mm2 In this case the imaging feedback is very weak and most of the nanoparticles are not suffi ciently clear or even invisible Then the most of the particles are attracted into a cluster using a magnetic fi eld gradient and the spreading process is conducted In the spread state the particle swarm using PAI is demonstrated in Figure 7 b Compared with Figure 7 a the signal is stronger and the contour of the swarm becomes Intensity range 6000 90009000 1200012000 18000 Percentage of signal points 0 20 40 60 80 100 Suspended Spread Swarm Fig 8 The statistical data of imaging feedback intensity The entire images are statistically analysed by calculating the numbers of pixels with the corresponding intensity range The percentages of the signal points on the photoacoustic images in different intensity range are presented The bars show the relationship between the results with different particle concentra tions in the same intensity range while the curves indicate the the percentage difference among the intensity ranges with the same concentration The error bars indicate the standard deviation obtained from three trials clear Finally a concentrated elliptical swarm pattern is formed using rotating magnetic fi elds Much concentrated and stronger signals are emitted as shown in Figure 7 c the particle swarm is shown by the bright yellow ellipsoidal region The statistical data of the feedback intensity using PAI is shown in Figure 8 The blue green and yellow bars indicate the results of the suspended state spread state and swarm state respectively When the nanoparticles are in suspended state Figure 7 a the percentage of signal points in the low intensity range is very high 95 In the middle and high ranges of intensity the image of the suspended particles have very few signal points When the particles are gathered into the spread state Figure 7 c the percentage of signal points gradually decrease with the raising of the intensity range as shown by the green curve In this case the percentage in the middle and high intensity ranges reaches approximately 45 which are signifi cantly higher compared with the results in the suspended state After the nanoparticle swarm is generated almost half of the signal points are located in high intensity range and another 30 points are in the middle range Therefore based on the data it can be concluded that the strength of the PAI imaging feedback can be signifi cantly enhanced by performing the generation of the microrobotic swarm IV CONCLUSION In this work we use paramagnetic nanoparticles as agents to quantitatively investigate the relationship between the imaging contrast and the areal concentration of the nanopar ticles FI UI and PAI are applied for observing the nanopar ticles with different areal concentrations which are tuned by two swarm actuation strategies i e spreading and vortex like swarm generation processes Using all the three imag ing modalities the nanoparticles with lower concentration have relatively weak imaging feedback contrast while the high concentrated swarm signifi cantly increases the imaging contrast This work provides signifi cance for a better un derstanding of the potential applications using microrobotic swarms ACKNOWLEDGMENT The authors would like to thank K Yuan for the syn thesis of spherical paramagnetic nanoparticles The research work is fi nancially support by the the General Research Fund GRF with Project No 14209514 14203715 and 14218516 from the Research Grants Council RGC of Hong Kong the ITF projects with Project No ITS 231 15 ITS 440 17FP and MRP 036 18X funded by the HKSAR Innovation and Technology Commission ITC the funding support from the CUHK T Stone Robotics Institute the joint Research Fund U1713201 between the National Natural Science Foundation of China NSFC and Shenzhen the NSFC for Young Scholar with the Project No 61703392 the Science Technology and Innovation Committee of Shenzhen Municipality SZSTI for the Fundamental Research and Discipline Layout project No JCYJ20170413152640731 the National Natural Science Foundation of China NSFC 81627805 61805102 Research Grants Council of the Hong Kong Special Administrative Region 21205016 11215817 11101618 and Shenzhen Basic Research Project JCYJ20160329150236426 JCYJ20170413140519030 REFERENCES 1 M Sitti H Ceylan W Hu J Giltinan M Turan S Yim and E Diller Biomedical applications of untethered mobile milli microrobots Proceedings of the IEEE vol 103 no 2 pp 205 224 2015 2 L Zhang J J Abbott L Dong B E Kratochvil D Bell and B J Nelson Artifi cial bacterial fl agella Fabrication and magnetic control Applied Physics Letters vol 94 no 6 p 064107 2009 3 L Zhang T Petit Y Lu B E Kratochvil K E Peyer R Pei J Lou and B J Nelson Controlled propulsion and cargo transport of rotating nickel nanowires near a patterned solid surface ACS nano vol 4 no 10 pp 6228 6234 2