On-chip preparation of nanoscale contrast agents towards high-resolution ultrasound imaging

Micron-sized lipid-stabilised bubbles of heavy gas have been utilised as contrast agents for diagnostic ultrasound (US) imaging for many years. Typically bubbles between 1 and 8 μm in diameter are produced to enhance imaging in US by scattering sound waves more efficiently than surrounding tissue. A...

Full description

Saved in:
Bibliographic Details
Published inLab on a chip Vol. 16; no. 4; pp. 679 - 687
Main Authors Peyman, Sally A, McLaughlan, James R, Abou-Saleh, Radwa H, Marston, Gemma, Johnson, Benjamin R. G, Freear, Steven, Coletta, P. Louise, Markham, Alexander F, Evans, Stephen D
Format Journal Article
LanguageEnglish
Published England 01.01.2016
Subjects
Online AccessGet full text

Cover

Loading…
Abstract Micron-sized lipid-stabilised bubbles of heavy gas have been utilised as contrast agents for diagnostic ultrasound (US) imaging for many years. Typically bubbles between 1 and 8 μm in diameter are produced to enhance imaging in US by scattering sound waves more efficiently than surrounding tissue. A potential area of interest for Contrast Enhanced Ultrasound (CEUS) are bubbles with diameters <1 μm or 'nanobubbles.' As bubble diameter decreases, ultrasonic resonant frequency increases, which could lead to an improvement in resolution for high-frequency imaging applications when using nanobubbles. In addition, current US contrast agents are limited by their size to the vasculature in vivo . However, molecular-targeted nanobubbles could penetrate into the extra-vascular space of cancerous tissue providing contrast in regions inaccessible to traditional microbubbles. This paper reports a new microfluidic method for the generation of sub-micron sized lipid stabilised particles containing perfluorocarbon (PFC). The nanoparticles are produced in a unique atomisation-like flow regime at high production rates, in excess of 10 6 particles per s and at high concentration, typically >10 11 particles per mL. The average particle diameter appears to be around 100-200 nm. These particles, suspected of being a mix of liquid and gaseous C 4 F 10 due to Laplace pressure, then phase convert into nanometer sized bubbles on the application of US. In vitro ultrasound characterisation from these nanoparticle populations showed strong backscattering compared to aqueous filled liposomes of a similar size. The nanoparticles were stable upon injection and gave excellent contrast enhancement when used for in vivo imaging, compared to microbubbles with an equivalent shell composition. We present the first on-chip atomisation-like production of phase-change contrast agents at high concentrations towards high-resolution contrast imaging for diagnostic ultrasound.
AbstractList Micron-sized lipid-stabilised bubbles of heavy gas have been utilised as contrast agents for diagnostic ultrasound (US) imaging for many years. Typically bubbles between 1 and 8 μm in diameter are produced to enhance imaging in US by scattering sound waves more efficiently than surrounding tissue. A potential area of interest for Contrast Enhanced Ultrasound (CEUS) are bubbles with diameters <1 μm or 'nanobubbles.' As bubble diameter decreases, ultrasonic resonant frequency increases, which could lead to an improvement in resolution for high-frequency imaging applications when using nanobubbles. In addition, current US contrast agents are limited by their size to the vasculature in vivo. However, molecular-targeted nanobubbles could penetrate into the extra-vascular space of cancerous tissue providing contrast in regions inaccessible to traditional microbubbles. This paper reports a new microfluidic method for the generation of sub-micron sized lipid stabilised particles containing perfluorocarbon (PFC). The nanoparticles are produced in a unique atomisation-like flow regime at high production rates, in excess of 10(6) particles per s and at high concentration, typically >10(11) particles per mL. The average particle diameter appears to be around 100-200 nm. These particles, suspected of being a mix of liquid and gaseous C4F10 due to Laplace pressure, then phase convert into nanometer sized bubbles on the application of US. In vitro ultrasound characterisation from these nanoparticle populations showed strong backscattering compared to aqueous filled liposomes of a similar size. The nanoparticles were stable upon injection and gave excellent contrast enhancement when used for in vivo imaging, compared to microbubbles with an equivalent shell composition.
Micron-sized lipid-stabilised bubbles of heavy gas have been utilised as contrast agents for diagnostic ultrasound (US) imaging for many years. Typically bubbles between 1 and 8 mu m in diameter are produced to enhance imaging in US by scattering sound waves more efficiently than surrounding tissue. A potential area of interest for Contrast Enhanced Ultrasound (CEUS) are bubbles with diameters <1 mu m or 'nanobubbles.' As bubble diameter decreases, ultrasonic resonant frequency increases, which could lead to an improvement in resolution for high-frequency imaging applications when using nanobubbles. In addition, current US contrast agents are limited by their size to the vasculature in vivo. However, molecular-targeted nanobubbles could penetrate into the extra-vascular space of cancerous tissue providing contrast in regions inaccessible to traditional microbubbles. This paper reports a new microfluidic method for the generation of sub-micron sized lipid stabilised particles containing perfluorocarbon (PFC). The nanoparticles are produced in a unique atomisation-like flow regime at high production rates, in excess of 10 super(6) particles per s and at high concentration, typically >10 super(11) particles per mL. The average particle diameter appears to be around 100-200 nm. These particles, suspected of being a mix of liquid and gaseous C sub(4)F sub(10) due to Laplace pressure, then phase convert into nanometer sized bubbles on the application of US. In vitro ultrasound characterisation from these nanoparticle populations showed strong backscattering compared to aqueous filled liposomes of a similar size. The nanoparticles were stable upon injection and gave excellent contrast enhancement when used for in vivo imaging, compared to microbubbles with an equivalent shell composition.
Micron-sized lipid-stabilised bubbles of heavy gas have been utilised as contrast agents for diagnostic ultrasound (US) imaging for many years. Typically bubbles between 1 and 8 μm in diameter are produced to enhance imaging in US by scattering sound waves more efficiently than surrounding tissue. A potential area of interest for Contrast Enhanced Ultrasound (CEUS) are bubbles with diameters <1 μm or ‘nanobubbles.’ As bubble diameter decreases, ultrasonic resonant frequency increases, which could lead to an improvement in resolution for high-frequency imaging applications when using nanobubbles. In addition, current US contrast agents are limited by their size to the vasculature in vivo . However, molecular-targeted nanobubbles could penetrate into the extra-vascular space of cancerous tissue providing contrast in regions inaccessible to traditional microbubbles. This paper reports a new microfluidic method for the generation of sub-micron sized lipid stabilised particles containing perfluorocarbon (PFC). The nanoparticles are produced in a unique atomisation-like flow regime at high production rates, in excess of 10 6 particles per s and at high concentration, typically >10 11 particles per mL. The average particle diameter appears to be around 100–200 nm. These particles, suspected of being a mix of liquid and gaseous C 4 F 10 due to Laplace pressure, then phase convert into nanometer sized bubbles on the application of US. In vitro ultrasound characterisation from these nanoparticle populations showed strong backscattering compared to aqueous filled liposomes of a similar size. The nanoparticles were stable upon injection and gave excellent contrast enhancement when used for in vivo imaging, compared to microbubbles with an equivalent shell composition.
Micron-sized lipid-stabilised bubbles of heavy gas have been utilised as contrast agents for diagnostic ultrasound (US) imaging for many years. Typically bubbles between 1 and 8 μm in diameter are produced to enhance imaging in US by scattering sound waves more efficiently than surrounding tissue. A potential area of interest for Contrast Enhanced Ultrasound (CEUS) are bubbles with diameters <1 μm or 'nanobubbles.' As bubble diameter decreases, ultrasonic resonant frequency increases, which could lead to an improvement in resolution for high-frequency imaging applications when using nanobubbles. In addition, current US contrast agents are limited by their size to the vasculature in vivo . However, molecular-targeted nanobubbles could penetrate into the extra-vascular space of cancerous tissue providing contrast in regions inaccessible to traditional microbubbles. This paper reports a new microfluidic method for the generation of sub-micron sized lipid stabilised particles containing perfluorocarbon (PFC). The nanoparticles are produced in a unique atomisation-like flow regime at high production rates, in excess of 10 6 particles per s and at high concentration, typically >10 11 particles per mL. The average particle diameter appears to be around 100-200 nm. These particles, suspected of being a mix of liquid and gaseous C 4 F 10 due to Laplace pressure, then phase convert into nanometer sized bubbles on the application of US. In vitro ultrasound characterisation from these nanoparticle populations showed strong backscattering compared to aqueous filled liposomes of a similar size. The nanoparticles were stable upon injection and gave excellent contrast enhancement when used for in vivo imaging, compared to microbubbles with an equivalent shell composition. We present the first on-chip atomisation-like production of phase-change contrast agents at high concentrations towards high-resolution contrast imaging for diagnostic ultrasound.
Author Peyman, Sally A
Coletta, P. Louise
Freear, Steven
Evans, Stephen D
McLaughlan, James R
Johnson, Benjamin R. G
Marston, Gemma
Markham, Alexander F
Abou-Saleh, Radwa H
AuthorAffiliation University of Leeds
School of Electronic and Electrical Engineering
School of Physics and Astronomy
Mansoura University
Leeds Institute for Molecular Medicine
St James's Hospital
Faculty of Science
Department of Physics
AuthorAffiliation_xml – sequence: 0
  name: Mansoura University
– sequence: 0
  name: Department of Physics
– sequence: 0
  name: School of Physics and Astronomy
– sequence: 0
  name: School of Electronic and Electrical Engineering
– sequence: 0
  name: Leeds Institute for Molecular Medicine
– sequence: 0
  name: University of Leeds
– sequence: 0
  name: St James's Hospital
– sequence: 0
  name: Faculty of Science
Author_xml – sequence: 1
  givenname: Sally A
  surname: Peyman
  fullname: Peyman, Sally A
– sequence: 2
  givenname: James R
  surname: McLaughlan
  fullname: McLaughlan, James R
– sequence: 3
  givenname: Radwa H
  surname: Abou-Saleh
  fullname: Abou-Saleh, Radwa H
– sequence: 4
  givenname: Gemma
  surname: Marston
  fullname: Marston, Gemma
– sequence: 5
  givenname: Benjamin R. G
  surname: Johnson
  fullname: Johnson, Benjamin R. G
– sequence: 6
  givenname: Steven
  surname: Freear
  fullname: Freear, Steven
– sequence: 7
  givenname: P. Louise
  surname: Coletta
  fullname: Coletta, P. Louise
– sequence: 8
  givenname: Alexander F
  surname: Markham
  fullname: Markham, Alexander F
– sequence: 9
  givenname: Stephen D
  surname: Evans
  fullname: Evans, Stephen D
BackLink https://www.ncbi.nlm.nih.gov/pubmed/26689151$$D View this record in MEDLINE/PubMed
BookMark eNqFkctLxDAQxoOsuA-9eFdyFKGaNE2THJfiCxb2oicPJU3S3Uo3qUmL-N-bfbgehYEZ-H4zzHwzBSPrrAHgEqM7jIi4V7RVCBORyRMwwRkjCcJcjI61YGMwDeEDIUyznJ-BcZrnXGCKJ-B9aRO1bjrYedNJL_vGWehqaKV1QcnWQOVs72XooVwZ2wfYuy_pdYDrZrVOvAmuHXZNQ7vF3GA1bDZy1djVOTitZRvMxSHPwNvjw2vxnCyWTy_FfJEoinmfVIwRzThhXGskkUhJnhtdVbJWFKW1FMjkGaaKUi1iZFGUKhcVrlDF6hSTGbjZz-28-xxM6MtNE5RpW2mNG0KJOULRiZTz_1HGEcVxARHR2z2qvAvBm7rsfDzMf5cYlVvfy4Iuip3v8whfH-YO1cboI_prdASu9oAP6qj-PY78APwUimI
CitedBy_id crossref_primary_10_1039_C9CS00839J
crossref_primary_10_1109_TUFFC_2021_3055141
crossref_primary_10_1038_micronano_2017_87
crossref_primary_10_1016_j_jcis_2023_08_173
crossref_primary_10_1016_j_ultras_2020_106245
crossref_primary_10_1002_idm2_12050
crossref_primary_10_1021_acs_langmuir_8b01163
crossref_primary_10_1039_C6SM00956E
crossref_primary_10_1039_D3SM00380A
crossref_primary_10_1039_D0CS00384K
crossref_primary_10_1177_1536012118778216
crossref_primary_10_1021_acs_jpcb_0c02279
crossref_primary_10_1016_j_colsurfb_2019_04_062
crossref_primary_10_3390_mi9080404
crossref_primary_10_1039_C8SM01949E
crossref_primary_10_1016_j_ultrasmedbio_2018_07_026
crossref_primary_10_1016_j_heliyon_2019_e01907
crossref_primary_10_1021_acs_chemrev_1c00632
crossref_primary_10_1021_acs_iecr_1c04046
crossref_primary_10_1016_j_jcis_2023_09_066
crossref_primary_10_1039_D1CP01279G
crossref_primary_10_1016_j_ultsonch_2024_106809
crossref_primary_10_1039_C7RE00082K
crossref_primary_10_1039_C8NR07769J
crossref_primary_10_1063_5_0040213
crossref_primary_10_1039_D0NR03332D
crossref_primary_10_1021_acsami_7b19755
crossref_primary_10_1039_C7LC00295E
crossref_primary_10_1039_D0RA08727K
crossref_primary_10_1063_1_5089717
crossref_primary_10_1016_j_colsurfa_2022_130169
crossref_primary_10_1021_acsami_0c07022
crossref_primary_10_1002_smll_202100345
crossref_primary_10_1039_C7SM00128B
crossref_primary_10_1016_j_ultsonch_2023_106438
crossref_primary_10_1109_TUFFC_2016_2640342
crossref_primary_10_1126_sciadv_aaz0094
crossref_primary_10_1016_j_cocis_2021_101456
crossref_primary_10_3390_mi14030638
crossref_primary_10_1016_j_ultrasmedbio_2016_09_011
crossref_primary_10_1021_acs_iecr_1c01233
crossref_primary_10_1039_D1RA04890B
crossref_primary_10_3389_fphy_2021_654374
crossref_primary_10_1155_2017_6141734
crossref_primary_10_1038_s41598_018_24713_4
crossref_primary_10_1039_C7LC00056A
crossref_primary_10_1063_5_0032140
crossref_primary_10_1016_j_addr_2024_115200
crossref_primary_10_1021_acs_langmuir_1c00973
crossref_primary_10_1021_acs_langmuir_2c02303
crossref_primary_10_3390_ph17060755
crossref_primary_10_1039_C6LC01049K
Cites_doi 10.1016/j.addr.2014.03.003
10.1021/la703065v
10.1121/1.1901757
10.1039/b701481n
10.1016/j.ijpharm.2009.09.027
10.1016/j.biomaterials.2014.02.036
10.1016/j.biomaterials.2010.06.031
10.1021/la2011259
10.1039/c0lc00731e
10.1016/S0927-7757(97)00033-2
10.1097/00004424-200011000-00003
10.2147/IJN.S30912
10.1016/j.ultrasmedbio.2013.10.010
10.1016/j.ultrasmedbio.2008.12.017
10.1016/j.ultras.2013.10.010
10.1016/j.ces.2009.10.003
10.1021/la062097u
10.1016/j.chemosphere.2011.05.054
10.1016/j.ultrasmedbio.2007.12.011
10.1016/j.jconrel.2010.02.012
10.1016/j.ultrasmedbio.2012.11.017
10.1016/j.ejrad.2006.06.022
10.1002/smll.200902164
10.1016/j.ultrasmedbio.2014.10.020
10.7150/thno.4846
10.1136/bmj.322.7296.1222
10.1016/j.urolonc.2013.01.006
10.1016/j.colsurfa.2013.01.056
10.1016/0301-5629(91)90125-G
10.1016/j.ultrasmedbio.2005.08.009
10.1016/j.cocis.2011.01.010
10.1179/175889709X446507
10.1016/S0301-9322(97)00003-7
10.1016/j.ultrasmedbio.2011.05.021
10.2174/138161212800099883
10.1002/smll.200800591
10.1016/j.colsurfa.2010.03.005
10.1016/j.ultrasmedbio.2011.08.012
10.1016/j.ultrasmedbio.2010.08.012
10.1109/TUFFC.2013.2850
10.1016/j.ultrasmedbio.2013.05.007
10.1021/la304093t
10.1016/j.ultrasmedbio.2013.08.015
10.1039/c2lc40634a
10.1016/j.amjsurg.2011.10.024
10.1016/j.ultrasmedbio.2013.05.016
ContentType Journal Article
DBID CGR
CUY
CVF
ECM
EIF
NPM
AAYXX
CITATION
7QO
8FD
FR3
P64
7SP
7TB
7U5
L7M
DOI 10.1039/c5lc01394a
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
CrossRef
Biotechnology Research Abstracts
Technology Research Database
Engineering Research Database
Biotechnology and BioEngineering Abstracts
Electronics & Communications Abstracts
Mechanical & Transportation Engineering Abstracts
Solid State and Superconductivity Abstracts
Advanced Technologies Database with Aerospace
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
CrossRef
Engineering Research Database
Biotechnology Research Abstracts
Technology Research Database
Biotechnology and BioEngineering Abstracts
Solid State and Superconductivity Abstracts
Mechanical & Transportation Engineering Abstracts
Advanced Technologies Database with Aerospace
Electronics & Communications Abstracts
DatabaseTitleList MEDLINE
Engineering Research Database
CrossRef

Solid State and Superconductivity Abstracts
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Engineering
Chemistry
Biology
EISSN 1473-0189
EndPage 687
ExternalDocumentID 10_1039_C5LC01394A
26689151
c5lc01394a
Genre Research Support, Non-U.S. Gov't
Journal Article
GrantInformation_xml – fundername: Medical Research Council
  grantid: MC_PC_13066
– fundername: Medical Research Council
  grantid: MR/L01629X/1
GroupedDBID ---
-JG
0-7
0R~
29L
4.4
5GY
705
70~
7~J
AAEMU
AAIWI
AAJAE
AAMEH
AANOJ
AAWGC
AAXHV
AAXPP
ABASK
ABDVN
ABEMK
ABJNI
ABPDG
ABRYZ
ABXOH
ACGFS
ACIWK
ACLDK
ADMRA
ADSRN
AEFDR
AENEX
AENGV
AESAV
AETIL
AFLYV
AFOGI
AFVBQ
AGEGJ
AGKEF
AGRSR
AGSTE
AHGCF
ALMA_UNASSIGNED_HOLDINGS
ANBJS
ANUXI
APEMP
ASKNT
AUDPV
BLAPV
BSQNT
C6K
CS3
DU5
EBS
ECGLT
EE0
EF-
EJD
F5P
GGIMP
GNO
H13
HZ~
H~N
IDZ
J3I
L-8
M4U
N9A
O9-
R7B
RAOCF
RCNCU
RNS
ROL
RPMJG
RRA
RRC
RSCEA
SKA
SLH
VH6
CGR
CUY
CVF
ECM
EIF
NPM
0UZ
0VX
1TJ
53G
71~
AAYXX
ACHDF
ACMRT
AFFNX
AHGXI
ANLMG
BBWZM
CAG
CITATION
COF
EEHRC
FEDTE
HVGLF
IDY
J3G
J3H
NDZJH
R56
RCLXC
7QO
8FD
FR3
P64
7SP
7TB
7U5
L7M
ID FETCH-LOGICAL-c518t-b773d78378dd0a092366edbbafc502fa90e6415c55d95d946edac69b1b0b7f213
ISSN 1473-0197
IngestDate Sat Aug 17 01:20:37 EDT 2024
Fri Aug 16 23:28:22 EDT 2024
Fri Dec 06 04:08:27 EST 2024
Sat Sep 28 08:27:44 EDT 2024
Tue Dec 17 21:00:04 EST 2024
IsDoiOpenAccess false
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 4
Language English
LinkModel OpenURL
MergedId FETCHMERGED-LOGICAL-c518t-b773d78378dd0a092366edbbafc502fa90e6415c55d95d946edac69b1b0b7f213
Notes vs.
Electronic supplementary information (ESI) available: Supporting information S1: video of a bubble sample in a viewing chamber showing microbubbles rising to the top and underneath a population of smaller bubbles moving with Brownian motion. Supporting information S2: high speed imaging of the microspray regime (100 000 000 fps) showing the velocity of the microspray was still too high to capture single bubble formation. Supporting information S3: effect of lipid concentration on microspray particle size and concentration. S4: expansion ratio model used to calculate the predicted increase in nanoparticle diameter on the increase of temperature in Fig. 4a from
ref. 42
Supporting information S5: comparison of lipid solution only passing through tubes of the set-up compared to lipid solution going through the microfluidic device. S6: plot to show change in resonant frequency
observations in Fig. 7, TIC curves for microbubble only and nanobubble only. See DOI
in vivo
10.1039/c5lc01394a
bubble diameter. S7: time
intensity curves to support
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ORCID 0000-0001-7858-4155
0000-0002-1600-5100
OpenAccessLink https://pubs.rsc.org/en/content/articlepdf/2016/lc/c5lc01394a
PMID 26689151
PQID 1780513669
PQPubID 23462
PageCount 9
ParticipantIDs crossref_primary_10_1039_C5LC01394A
pubmed_primary_26689151
rsc_primary_c5lc01394a
proquest_miscellaneous_1780513669
proquest_miscellaneous_1800473288
PublicationCentury 2000
PublicationDate 2016-01-01
PublicationDateYYYYMMDD 2016-01-01
PublicationDate_xml – month: 01
  year: 2016
  text: 2016-01-01
  day: 01
PublicationDecade 2010
PublicationPlace England
PublicationPlace_xml – name: England
PublicationTitle Lab on a chip
PublicationTitleAlternate Lab Chip
PublicationYear 2016
References Peyman (C5LC01394A-(cit34)/*[position()=1]) 2012; 12
Needles (C5LC01394A-(cit43)/*[position()=1]) 2008; 34
Maennicke (C5LC01394A-(cit35)/*[position()=1]) 2014; 40
Wang (C5LC01394A-(cit16)/*[position()=1]) 2010; 384
Gorce (C5LC01394A-(cit38)/*[position()=1]) 2000; 35
Abou-Saleh (C5LC01394A-(cit2)/*[position()=1]) 2013; 29
Xing (C5LC01394A-(cit13)/*[position()=1]) 2010
Choi (C5LC01394A-(cit48)/*[position()=1]) 2014; 54
Wang (C5LC01394A-(cit22)/*[position()=1]) 2011; 27
Talu (C5LC01394A-(cit32)/*[position()=1]) 2008; 24
Evans (C5LC01394A-(cit42)/*[position()=1]) 2006; 22
Sun (C5LC01394A-(cit46)/*[position()=1]) 2014; 40
Castro-Hernandez (C5LC01394A-(cit29)/*[position()=1]) 2011; 11
Ruckenstein (C5LC01394A-(cit37)/*[position()=1]) 2013; 423
Zhang (C5LC01394A-(cit17)/*[position()=1]) 2014; 35
McLaughlan (C5LC01394A-(cit45)/*[position()=1]) 2013
Zimmerman (C5LC01394A-(cit8)/*[position()=1]) 2011; 16
Mamou (C5LC01394A-(cit47)/*[position()=1]) 2009; 35
Tong (C5LC01394A-(cit15)/*[position()=1]) 2013; 39
Agarwal (C5LC01394A-(cit9)/*[position()=1]) 2011; 84
Cosgrove (C5LC01394A-(cit1)/*[position()=1]) 2006; 60
Pavlovich (C5LC01394A-(cit36)/*[position()=1]) 2014; 32
Sheeran (C5LC01394A-(cit25)/*[position()=1]) 2013; 39
Sheeran (C5LC01394A-(cit27)/*[position()=1]) 2011; 37
Needles (C5LC01394A-(cit44)/*[position()=1]) 2010; 36
Ushikubo (C5LC01394A-(cit10)/*[position()=1]) 2010; 361
Martz (C5LC01394A-(cit33)/*[position()=1]) 2011; 37
Blomley (C5LC01394A-(cit7)/*[position()=1]) 2001; 322
Sheeran (C5LC01394A-(cit23)/*[position()=1]) 2012; 18
Chen (C5LC01394A-(cit41)/*[position()=1]) 1997; 23
Sirsi (C5LC01394A-(cit3)/*[position()=1]) 2009; 1
Ohgaki (C5LC01394A-(cit11)/*[position()=1]) 2010; 65
Hettiarachchi (C5LC01394A-(cit31)/*[position()=1]) 2007; 7
Alzaraa (C5LC01394A-(cit4)/*[position()=1]) 2012; 204
McLaughlan (C5LC01394A-(cit5)/*[position()=1]) 2013; 60
Anderson (C5LC01394A-(cit21)/*[position()=1]) 2010; 144
Sheeran (C5LC01394A-(cit26)/*[position()=1]) 2015; 41
Kooiman (C5LC01394A-(cit6)/*[position()=1]) 2014; 72
Cavalli (C5LC01394A-(cit18)/*[position()=1]) 2012; 7
Wheatley (C5LC01394A-(cit19)/*[position()=1]) 2006; 32
Hashimoto (C5LC01394A-(cit28)/*[position()=1]) 2010; 6
Matsunaga (C5LC01394A-(cit24)/*[position()=1]) 2012; 2
Wagner (C5LC01394A-(cit20)/*[position()=1]) 2010; 31
Ljunggren (C5LC01394A-(cit12)/*[position()=1]) 1997; 129
Apfel (C5LC01394A-(cit39)/*[position()=1]) 1991; 17
Wu (C5LC01394A-(cit14)/*[position()=1]) 2013; 39
Hashimoto (C5LC01394A-(cit30)/*[position()=1]) 2008; 4
Church (C5LC01394A-(cit40)/*[position()=1]) 2005; 6
References_xml – volume: 72
  start-page: 28
  year: 2014
  ident: C5LC01394A-(cit6)/*[position()=1]
  publication-title: Adv. Drug Delivery Rev.
  doi: 10.1016/j.addr.2014.03.003
  contributor:
    fullname: Kooiman
– volume: 24
  start-page: 1745
  year: 2008
  ident: C5LC01394A-(cit32)/*[position()=1]
  publication-title: Langmuir
  doi: 10.1021/la703065v
  contributor:
    fullname: Talu
– volume: 6
  start-page: 162
  year: 2005
  ident: C5LC01394A-(cit40)/*[position()=1]
  publication-title: Acoust. Res. Lett. Online
  doi: 10.1121/1.1901757
  contributor:
    fullname: Church
– volume: 7
  start-page: 463
  year: 2007
  ident: C5LC01394A-(cit31)/*[position()=1]
  publication-title: Lab Chip
  doi: 10.1039/b701481n
  contributor:
    fullname: Hettiarachchi
– volume: 384
  start-page: 148
  year: 2010
  ident: C5LC01394A-(cit16)/*[position()=1]
  publication-title: Int. J. Pharm.
  doi: 10.1016/j.ijpharm.2009.09.027
  contributor:
    fullname: Wang
– volume: 35
  start-page: 5148
  year: 2014
  ident: C5LC01394A-(cit17)/*[position()=1]
  publication-title: Biomaterials
  doi: 10.1016/j.biomaterials.2014.02.036
  contributor:
    fullname: Zhang
– volume: 31
  start-page: 7567
  year: 2010
  ident: C5LC01394A-(cit20)/*[position()=1]
  publication-title: Biomaterials
  doi: 10.1016/j.biomaterials.2010.06.031
  contributor:
    fullname: Wagner
– volume: 27
  start-page: 6971
  year: 2011
  ident: C5LC01394A-(cit22)/*[position()=1]
  publication-title: Langmuir
  doi: 10.1021/la2011259
  contributor:
    fullname: Wang
– volume: 11
  start-page: 2023
  year: 2011
  ident: C5LC01394A-(cit29)/*[position()=1]
  publication-title: Lab Chip
  doi: 10.1039/c0lc00731e
  contributor:
    fullname: Castro-Hernandez
– volume: 129
  start-page: 151
  year: 1997
  ident: C5LC01394A-(cit12)/*[position()=1]
  publication-title: Colloids Surf., A
  doi: 10.1016/S0927-7757(97)00033-2
  contributor:
    fullname: Ljunggren
– volume: 35
  start-page: 661
  year: 2000
  ident: C5LC01394A-(cit38)/*[position()=1]
  publication-title: Invest. Radiol.
  doi: 10.1097/00004424-200011000-00003
  contributor:
    fullname: Gorce
– volume: 7
  start-page: 3309
  year: 2012
  ident: C5LC01394A-(cit18)/*[position()=1]
  publication-title: Int. J. Nanomed.
  doi: 10.2147/IJN.S30912
  contributor:
    fullname: Cavalli
– volume: 40
  start-page: 541
  year: 2014
  ident: C5LC01394A-(cit46)/*[position()=1]
  publication-title: Ultrasound Med. Biol.
  doi: 10.1016/j.ultrasmedbio.2013.10.010
  contributor:
    fullname: Sun
– start-page: 21
  year: 2010
  ident: C5LC01394A-(cit13)/*[position()=1]
  publication-title: Nanotechnology
  contributor:
    fullname: Xing
– volume: 35
  start-page: 1198
  year: 2009
  ident: C5LC01394A-(cit47)/*[position()=1]
  publication-title: Ultrasound Med. Biol.
  doi: 10.1016/j.ultrasmedbio.2008.12.017
  contributor:
    fullname: Mamou
– volume: 54
  start-page: 754
  year: 2014
  ident: C5LC01394A-(cit48)/*[position()=1]
  publication-title: Ultrasonics
  doi: 10.1016/j.ultras.2013.10.010
  contributor:
    fullname: Choi
– volume: 65
  start-page: 1296
  year: 2010
  ident: C5LC01394A-(cit11)/*[position()=1]
  publication-title: Chem. Eng. Sci.
  doi: 10.1016/j.ces.2009.10.003
  contributor:
    fullname: Ohgaki
– volume: 22
  start-page: 9538
  year: 2006
  ident: C5LC01394A-(cit42)/*[position()=1]
  publication-title: Langmuir
  doi: 10.1021/la062097u
  contributor:
    fullname: Evans
– volume: 84
  start-page: 1175
  year: 2011
  ident: C5LC01394A-(cit9)/*[position()=1]
  publication-title: Chemosphere
  doi: 10.1016/j.chemosphere.2011.05.054
  contributor:
    fullname: Agarwal
– start-page: 1493
  year: 2013
  ident: C5LC01394A-(cit45)/*[position()=1]
  publication-title: IEEE Int. Ultrason. Symp.
  contributor:
    fullname: McLaughlan
– volume: 34
  start-page: 1139
  year: 2008
  ident: C5LC01394A-(cit43)/*[position()=1]
  publication-title: Ultrasound Med. Biol.
  doi: 10.1016/j.ultrasmedbio.2007.12.011
  contributor:
    fullname: Needles
– volume: 144
  start-page: 151
  year: 2010
  ident: C5LC01394A-(cit21)/*[position()=1]
  publication-title: J. Controlled Release
  doi: 10.1016/j.jconrel.2010.02.012
  contributor:
    fullname: Anderson
– volume: 39
  start-page: 893
  year: 2013
  ident: C5LC01394A-(cit25)/*[position()=1]
  publication-title: Ultrasound Med. Biol.
  doi: 10.1016/j.ultrasmedbio.2012.11.017
  contributor:
    fullname: Sheeran
– volume: 60
  start-page: 324
  year: 2006
  ident: C5LC01394A-(cit1)/*[position()=1]
  publication-title: Eur. J. Radiol.
  doi: 10.1016/j.ejrad.2006.06.022
  contributor:
    fullname: Cosgrove
– volume: 6
  start-page: 1051
  year: 2010
  ident: C5LC01394A-(cit28)/*[position()=1]
  publication-title: Small
  doi: 10.1002/smll.200902164
  contributor:
    fullname: Hashimoto
– volume: 41
  start-page: 814
  year: 2015
  ident: C5LC01394A-(cit26)/*[position()=1]
  publication-title: Ultrasound Med. Biol.
  doi: 10.1016/j.ultrasmedbio.2014.10.020
  contributor:
    fullname: Sheeran
– volume: 2
  start-page: 1185
  year: 2012
  ident: C5LC01394A-(cit24)/*[position()=1]
  publication-title: Theranostics
  doi: 10.7150/thno.4846
  contributor:
    fullname: Matsunaga
– volume: 322
  start-page: 1222
  year: 2001
  ident: C5LC01394A-(cit7)/*[position()=1]
  publication-title: Br. Med. J.
  doi: 10.1136/bmj.322.7296.1222
  contributor:
    fullname: Blomley
– volume: 32
  start-page: 34.e27
  year: 2014
  ident: C5LC01394A-(cit36)/*[position()=1]
  publication-title: Urol. Oncol.
  doi: 10.1016/j.urolonc.2013.01.006
  contributor:
    fullname: Pavlovich
– volume: 423
  start-page: 112
  year: 2013
  ident: C5LC01394A-(cit37)/*[position()=1]
  publication-title: Colloids Surf., A
  doi: 10.1016/j.colsurfa.2013.01.056
  contributor:
    fullname: Ruckenstein
– volume: 17
  start-page: 179
  year: 1991
  ident: C5LC01394A-(cit39)/*[position()=1]
  publication-title: Ultrasound Med. Biol.
  doi: 10.1016/0301-5629(91)90125-G
  contributor:
    fullname: Apfel
– volume: 32
  start-page: 83
  year: 2006
  ident: C5LC01394A-(cit19)/*[position()=1]
  publication-title: Ultrasound Med. Biol.
  doi: 10.1016/j.ultrasmedbio.2005.08.009
  contributor:
    fullname: Wheatley
– volume: 16
  start-page: 350
  year: 2011
  ident: C5LC01394A-(cit8)/*[position()=1]
  publication-title: Curr. Opin. Colloid Interface Sci.
  doi: 10.1016/j.cocis.2011.01.010
  contributor:
    fullname: Zimmerman
– volume: 1
  start-page: 3
  year: 2009
  ident: C5LC01394A-(cit3)/*[position()=1]
  publication-title: Bubble Sci., Eng., Technol.
  doi: 10.1179/175889709X446507
  contributor:
    fullname: Sirsi
– volume: 23
  start-page: 699
  year: 1997
  ident: C5LC01394A-(cit41)/*[position()=1]
  publication-title: Int. J. Multiphase Flow
  doi: 10.1016/S0301-9322(97)00003-7
  contributor:
    fullname: Chen
– volume: 37
  start-page: 1518
  year: 2011
  ident: C5LC01394A-(cit27)/*[position()=1]
  publication-title: Ultrasound Med. Biol.
  doi: 10.1016/j.ultrasmedbio.2011.05.021
  contributor:
    fullname: Sheeran
– volume: 18
  start-page: 2152
  year: 2012
  ident: C5LC01394A-(cit23)/*[position()=1]
  publication-title: Curr. Pharm. Des.
  doi: 10.2174/138161212800099883
  contributor:
    fullname: Sheeran
– volume: 4
  start-page: 1795
  year: 2008
  ident: C5LC01394A-(cit30)/*[position()=1]
  publication-title: Small
  doi: 10.1002/smll.200800591
  contributor:
    fullname: Hashimoto
– volume: 361
  start-page: 31
  year: 2010
  ident: C5LC01394A-(cit10)/*[position()=1]
  publication-title: Colloids Surf., A
  doi: 10.1016/j.colsurfa.2010.03.005
  contributor:
    fullname: Ushikubo
– volume: 37
  start-page: 1952
  year: 2011
  ident: C5LC01394A-(cit33)/*[position()=1]
  publication-title: Ultrasound Med. Biol.
  doi: 10.1016/j.ultrasmedbio.2011.08.012
  contributor:
    fullname: Martz
– volume: 36
  start-page: 2097
  year: 2010
  ident: C5LC01394A-(cit44)/*[position()=1]
  publication-title: Ultrasound Med. Biol.
  doi: 10.1016/j.ultrasmedbio.2010.08.012
  contributor:
    fullname: Needles
– volume: 60
  start-page: 2511
  year: 2013
  ident: C5LC01394A-(cit5)/*[position()=1]
  publication-title: IEEE Trans. Ultrason. Ferroelectr. Freq. Control.
  doi: 10.1109/TUFFC.2013.2850
  contributor:
    fullname: McLaughlan
– volume: 39
  start-page: 2137
  year: 2013
  ident: C5LC01394A-(cit14)/*[position()=1]
  publication-title: Ultrasound Med. Biol.
  doi: 10.1016/j.ultrasmedbio.2013.05.007
  contributor:
    fullname: Wu
– volume: 29
  start-page: 4096
  year: 2013
  ident: C5LC01394A-(cit2)/*[position()=1]
  publication-title: Langmuir
  doi: 10.1021/la304093t
  contributor:
    fullname: Abou-Saleh
– volume: 40
  start-page: 244
  year: 2014
  ident: C5LC01394A-(cit35)/*[position()=1]
  publication-title: Ultrasound Med. Biol.
  doi: 10.1016/j.ultrasmedbio.2013.08.015
  contributor:
    fullname: Maennicke
– volume: 12
  start-page: 4544
  year: 2012
  ident: C5LC01394A-(cit34)/*[position()=1]
  publication-title: Lab Chip
  doi: 10.1039/c2lc40634a
  contributor:
    fullname: Peyman
– volume: 204
  start-page: 355
  year: 2012
  ident: C5LC01394A-(cit4)/*[position()=1]
  publication-title: Am. J. Surg.
  doi: 10.1016/j.amjsurg.2011.10.024
  contributor:
    fullname: Alzaraa
– volume: 39
  start-page: 2147
  year: 2013
  ident: C5LC01394A-(cit15)/*[position()=1]
  publication-title: Ultrasound Med. Biol.
  doi: 10.1016/j.ultrasmedbio.2013.05.016
  contributor:
    fullname: Tong
SSID ssj0015468
Score 2.4725788
Snippet Micron-sized lipid-stabilised bubbles of heavy gas have been utilised as contrast agents for diagnostic ultrasound (US) imaging for many years. Typically...
SourceID proquest
crossref
pubmed
rsc
SourceType Aggregation Database
Index Database
Publisher
StartPage 679
SubjectTerms Animals
Aorta - diagnostic imaging
Bubbles
Contrast agents
Contrast Media - chemistry
Drug Stability
Fluorocarbons - chemistry
Imaging
Lab-On-A-Chip Devices
Lipids - chemistry
Mice
Microfluidics
Nanoparticles
Nanostructure
Particle Size
Resonant frequencies
Signal-To-Noise Ratio
Ultrasonography - instrumentation
Ultrasonography - methods
Ultrasound
Title On-chip preparation of nanoscale contrast agents towards high-resolution ultrasound imaging
URI https://www.ncbi.nlm.nih.gov/pubmed/26689151
https://search.proquest.com/docview/1780513669
https://search.proquest.com/docview/1800473288
Volume 16
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3dixMxEA-1h6gPotXT-kVE35bt7Veym8dSTqpUhaMHBz6UZJM9hb1taXeR-uo_7mST_fAqcgplKclmN838mvwyM5lB6K3IaEgJUW4smXSjhEWukJK5ntJWroBwUrv8f_xE5-fRhwtyMRj87HktVaWYpD_-eK7kf6QKZSBXfUr2HyTbPhQK4DvIF64gYbjeSMafCzfVzlabrTIhvA35K3ix3sHYW0d0visdflmfZCtrJ9mdo4MUu7DRtr1zqlzfpjMsOd-u6rxFfdK64ELbFLg--b3p5tJ9ozzleb53ppNOxbfg1eXX3NTWbrjOWVur7UwuNFG1PueMy-_cmXdtuWWjWlt_ZdcMq5Tw-0oJM49GsXbTMq63E9UvMxmD2smX9kAW9WZSanLM2EWZmlX5YL73Qh0udUYWM01lozZiahdU-9pi17og1sb3kK26trfQkY6mGA3R0fR0-X7RGqNIZE5UNr-piXIbspOu9e-85mCzAtRl26SUqanL8gG6b_cceGoA9BANVDFCt00W0v0I3Zk1Sf9G6F4vPuUj9MUCDPcAhtcZbgGGG4BhAzBsAYavAQx3AMMWYI_R-bvT5Wzu2mwcbkr8pHRFHIcy1vkHpPS4BxsDSpUUgmcp8YKMM09RYIMpIZLBJ4JKnlImfOGJOAv88BgNi3WhniIcERKrNKMiAzKbBSLRYRWTRNLME5JzOUZvmrFcbUzQldWhvMbodTPMKxglbejihVpXu5WvE3X40D_2l3sSHSg1DJJkjJ4YGbXvAtKaMKDCY3QMQmuLU5Kn9av5sxt18Dm62_03XqBhua3US6CwpXhlIfYLqYub2A
link.rule.ids 314,780,784,27924,27925
linkProvider Royal Society of Chemistry
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=On-chip+preparation+of+nanoscale+contrast+agents+towards+high-resolution+ultrasound+imaging&rft.jtitle=Lab+on+a+chip&rft.au=Peyman%2C+Sally+A.&rft.au=McLaughlan%2C+James+R.&rft.au=Abou-Saleh%2C+Radwa+H.&rft.au=Marston%2C+Gemma&rft.date=2016-01-01&rft.issn=1473-0197&rft.eissn=1473-0189&rft.volume=16&rft.issue=4&rft.spage=679&rft.epage=687&rft_id=info:doi/10.1039%2FC5LC01394A&rft.externalDBID=n%2Fa&rft.externalDocID=10_1039_C5LC01394A
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1473-0197&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1473-0197&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1473-0197&client=summon