-
Journal of Chromatography. A Jan 2009In recent years, liquid-phase microextraction (LPME), a microscale implementation of liquid-liquid extraction, has become a very popular sample pretreatment technique... (Review)
Review
In recent years, liquid-phase microextraction (LPME), a microscale implementation of liquid-liquid extraction, has become a very popular sample pretreatment technique because it combines extraction and enrichment, and is inexpensive, easy to operate and nearly solvent-free. Especially so in hollow fiber-protected LPME, sample cleanup is also effected. Essentially, owing to its high sample-to-extracting solvent volume ratio, LPME can achieve high analyte enrichment. Since its advent, the technique has been widely used, and applied to environmental, pharmaceutical, biological and forensic analyses. This review focuses on developments relating to chemical reactions associated with LPME applications, in contrast to conventional, straightforward extractions in which analytes remain as they are during the extraction process. Chemical reactions brought about during LPME serve to promote the extractability of the analytes (thus expanding the scope of applicability of the technique), facilitate their (analyte) compatibility with the analytical system and/or improve detection sensitivity. The reactions that are usually enabled during LPME include ion-pair extraction (carrier-mediated membrane transport), complexation, chemical (pre-extraction, in situ, and post-extraction) derivatization, phase-transfer catalysis and other "special affinity" reactions. Strategies on chemical reactions in LPME are overviewed in this report.
Topics: Catalysis; Chemical Fractionation; Ions; Microchemistry
PubMed: 18951550
DOI: 10.1016/j.chroma.2008.10.005 -
Mutation Research 2010Microbeam radiation therapy (MRT) uses highly collimated, quasi-parallel arrays of X-ray microbeams of 50-600keV, produced by third generation synchrotron sources, such... (Review)
Review
Microbeam radiation therapy (MRT) uses highly collimated, quasi-parallel arrays of X-ray microbeams of 50-600keV, produced by third generation synchrotron sources, such as the European Synchrotron Radiation Facility (ESRF), in France. The main advantages of highly brilliant synchrotron sources are an extremely high dose rate and very small beam divergence. High dose rates are necessary to deliver therapeutic doses in microscopic volumes, to avoid spreading of the microbeams by cardiosynchronous movement of the tissues. The minimal beam divergence results in the advantage of steeper dose gradients delivered to a tumor target, thus achieving a higher dose deposition in the target volume in fractions of seconds, with a sharper penumbra than that produced in conventional radiotherapy. MRT research over the past 20 years has yielded many results from preclinical trials based on different animal models, including mice, rats, piglets and rabbits. Typically, MRT uses arrays of narrow ( approximately 25-100 microm wide) microplanar beams separated by wider (100-400 microm centre-to-centre) microplanar spaces. The height of these microbeams typically varies from 1 to 100 mm, depending on the target and the desired preselected field size to be irradiated. Peak entrance doses of several hundreds of Gy are surprisingly well tolerated by normal tissues, up to approximately 2 yr after irradiation, and at the same time show a preferential damage of malignant tumor tissues; these effects of MRT have now been extensively studied over nearly two decades. More recently, some biological in vivo effects of synchrotron X-ray beams in the millimeter range (0.68-0.95 mm, centre-to-centre distances 1.2-4 mm), which may differ to some extent from those of microscopic beams, have been followed up to approximately 7 months after irradiation. Comparisons between broad-beam irradiation and MRT indicate a higher tumor control for the same sparing of normal tissue in the latter, even if a substantial fraction of tumor cells are not receiving a radiotoxic level of radiation. The hypothesis of a selective radiovulnerability of the tumor vasculature versus normal blood vessels by MRT, and of the cellular and molecular mechanisms involved remains under investigation. The paper highlights the history of MRT including salient biological findings after microbeam irradiation with emphasis on the vascular components and the tolerance of the central nervous system. Details on experimental and theoretical dosimetry of microbeams, core issues and possible therapeutic applications of MRT are presented.
Topics: Animals; Blood Vessels; Brain; Brain Neoplasms; Dose Fractionation, Radiation; History, 20th Century; History, 21st Century; Humans; Neoplasms; Radiometry; Radiotherapy; Synchrotrons; Technology, Radiologic; X-Rays
PubMed: 20034592
DOI: 10.1016/j.mrrev.2009.12.003 -
Brachytherapy 2017In image-guided adaptive brachytherapy (IGABT), dose distributions are optimized for each fraction. Optimum fractional dose can be constant or adapted to previous... (Comparative Study)
Comparative Study
PURPOSE
In image-guided adaptive brachytherapy (IGABT), dose distributions are optimized for each fraction. Optimum fractional dose can be constant or adapted to previous fractions and a conjecture about the future ones. We evaluate the efficacy of different fraction size schemes, derived from total IGABT dose constraints, against constant per-fraction constraints.
METHODS AND MATERIALS
This retrospective planning study included 20 IGABT patients where four different fractionation schedules were compared based on modern planning recommendations. A total high-risk-clinical target volume D (minimum dose in 90% of the volume) dose aim of 90.0 Gy with constant per-fraction organs at risk (OARs) dose constraint planning (CONST) was compared with conservative and aggressive fractionation compensation (COMP) techniques. COMP allows variations in the per-fraction dose constraints. Dose accumulation was performed through dose summation at a given volume and equivalent uniform dose (EUD) worst-case dose estimates.
RESULTS
No significant differences were identifiable between dose metrics of CONST and COMP in the total patient population. However, a subgroup of patients with alternating dose-limiting OARs had significant benefit from COMP. Median high-risk-clinical target volume dose escalation ranged from 5% to 12%, whereas OAR dose increases were lower and ranged from 3% to 8%. EUD-based planning delivered similar tumor doses, although slightly lower OAR doses. By distributing the treatment aim over an increased number of treatment fractions, median tumor dose could be increased by a further 8% per additional treatment fraction at the same OAR dose levels for both CONST and COMP.
CONCLUSIONS
COMP is effective in patients with alternating dose-limiting OARs and is enhanced using more treatment fractions and EUD constraints.
Topics: Brachytherapy; Dose Fractionation, Radiation; Female; Humans; Organs at Risk; Radiation Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Image-Guided; Retrospective Studies; Uterine Cervical Neoplasms
PubMed: 28185761
DOI: 10.1016/j.brachy.2017.01.002 -
Angewandte Chemie (International Ed. in... Oct 2019Cells can form membraneless organelles by liquid-liquid phase separation. As these organelles are highly dynamic, it is crucial to understand the kinetics of these phase...
Cells can form membraneless organelles by liquid-liquid phase separation. As these organelles are highly dynamic, it is crucial to understand the kinetics of these phase transitions. Here, we use droplet-based microfluidics to mix reagents by chaotic advection and observe nucleation, growth, and coarsening in volumes comparable to cells (pL) and on timescales of seconds. We apply this platform to analyze the dynamics of synthetic organelles formed by the DEAD-box ATPase Dhh1 and RNA, which are associated with the formation of processing bodies in yeast. We show that the timescale of phase separation decreases linearly as the volume of the compartment increases. Moreover, the synthetic organelles coarsen into one single droplet via gravity-induced coalescence, which can be arrested by introducing a hydrogel matrix that mimics the cytoskeleton. This approach is an attractive platform to investigate the dynamics of compartmentalization in artificial cells.
Topics: Artificial Cells; Chemical Fractionation; Kinetics; Microfluidic Analytical Techniques
PubMed: 31334587
DOI: 10.1002/anie.201907278 -
Technology in Cancer Research &... Jan 2019Stereotactic body radiotherapy has been suggested to provide high rates of local control for locally advanced pancreatic cancer. However, the close proximity of highly...
BACKGROUND
Stereotactic body radiotherapy has been suggested to provide high rates of local control for locally advanced pancreatic cancer. However, the close proximity of highly radiosensitive normal tissues usually causes the labor-intensive planning process and may impede further escalation of the prescription dose.
PURPOSE
The present study aims to evaluate the consistency and efficiency of Pinnacle Auto-Planning for pancreas stereotactic body radiotherapy with original prescription and escalated prescription.
METHODS
Twenty-four patients with pancreatic cancer treated with stereotactic body radiotherapy were studied retrospectively. The prescription is 40 Gy over 5 consecutive fractions. Most of patients (n = 21) also had 3 other different dose-level targets (6 Gy/fraction, 5 Gy/fraction, and 4 Gy/fraction). Two types of plans were generated by Pinnacle Auto-Planning with the original prescription (8 Gy/fraction, 6 Gy/fraction, 5 Gy/fraction, and 4 Gy/fraction) and escalated prescription (9 Gy/fraction, 7 Gy/fraction, 6 Gy/fraction, and 5 Gy/fraction), respectively. The same Auto-Planning template, including beam geometry, intensity-modulated radiotherapy objectives and intensity-modulated radiotherapy optimization parameters, were utilized for all the auto-plans in each prescription group. The intensity-modulated radiotherapy objectives do not include any manually created structures. Dosimetric parameters including percentage volume of PTV receiving 100% of the prescription dose, percentage volume of PTV receiving 93% of the prescription dose, and consistency of the dose-volume histograms of the target volumes were assessed. D and D of highly radiosensitive organs were also evaluated.
RESULTS
For all the pancreas stereotactic body radiotherapy plans with the original or escalated prescriptions, auto-plans met institutional dose constraints for critical organs, such as the duodenum, small intestine, and stomach. Furthermore, auto-plans resulted in acceptable planning target volume coverage for all targets with different prescription levels. All the plans were generated in a one-attempt manner, and very little human intervention is necessary to achieve such plan quality.
CONCLUSIONS
Pinnacle Auto-Planning consistently and efficiently generate acceptable treatment plans for multitarget pancreas stereotactic body radiotherapy with or without dose escalation and may play a more important role in treatment planning in the future.
Topics: Automation; Dose Fractionation, Radiation; Humans; Organs at Risk; Pancreatic Neoplasms; Precision Medicine; Radiometry; Radiosurgery; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted
PubMed: 31195891
DOI: 10.1177/1533033819851520 -
Biotechnology and Bioengineering Sep 2004The separation and purification of biomolecules in aqueous media driven by excluded-volume interactions is a well-established concept. In this article we propose a new... (Comparative Study)
Comparative Study
The separation and purification of biomolecules in aqueous media driven by excluded-volume interactions is a well-established concept. In this article we propose a new separations method, based on excluded-volume principles, consisting of an aqueous micellar-gel system (AMGS). Specifically, an outer aqueous phase containing cylindrically shaped micelles of the nonionic surfactant n-decyl tetra (ethylene oxide) (C10E4) is physically separated from an inner aqueous phase defined by the interior volume of gel beads, from which the micelles are completely excluded because of their shape and size. In the AMGS, the concentration of the micelles outside the gel beads is sufficiently high that the volume excluded to a biomolecule in the solution external to the gel beads is much larger than that within the gel beads. Accordingly, when biomolecules are introduced into the AMGS, they partition preferentially into the gel-bead phase, according to their sizes, as a result of the greater effect of the excluded-volume interactions with the C10E4 micelles present in the aqueous phase outside the gel beads. The new AMGS is more versatile and adaptable than the conventional two-phase aqueous C10E4 micellar system because the micelle volume fraction is independent of the temperature and because the effects of entrainment are eliminated. After demonstrating the experimental feasibility of creating the new AMGS, the three proteins myoglobin, ovalbumin, and BSA-FITC, and the enzyme G6PD, were partitioned in the AMGS and their partitioning behavior was found to follow the experimental excluded-volume trends dictated by the interactions of the biomolecules with the C10E4 micelles. Specifically, the measured partition coefficients of the four biomolecules into the micellar phase were found to be less than unity and to decrease with increasing biomolecule size. A theoretical description of the partitioning behavior of the biomolecules in the new AMGS was formulated, based on excluded-volume considerations, and the predicted biomolecule partition coefficients were found to compare favorably with those measured for the four biomolecules studied.
Topics: Chemical Fractionation; Colloids; Complex Mixtures; Computer Simulation; Gels; Micelles; Models, Chemical; Proteins; Ultrafiltration; Water
PubMed: 15329928
DOI: 10.1002/bit.20172 -
In Vivo (Athens, Greece) 2022Stereotactic radiotherapy (SRT) for spine metastases with helical tomotherapy requires a long irradiation time due to the high dose per fraction. Since helical...
BACKGROUND/AIM
Stereotactic radiotherapy (SRT) for spine metastases with helical tomotherapy requires a long irradiation time due to the high dose per fraction. Since helical tomotherapy can neither confirm nor correct the position during irradiation, a plan with a long irradiation time cannot be used in actual clinical practice, given the intra-fractional motion error. To address this problem, we devised a method called REPEAT irradiation.
PATIENTS AND METHODS
REPEtitive pAinTing (REPEAT) irradiation is a method of dividing the irradiation for a given fraction per day into several sessions and performing the irradiation after position correction using mega-voltage computed tomography images for each session. In order to evaluate how REPEAT irradiation changes irradiation time and the dose-volume histogram (DVH), a planning study with helical tomotherapy was conducted using CT images of a patient with lumbar spine metastasis.
RESULTS
In this case, we found that dividing 3 irradiation fractions into 3 sessions per day (i.e., 9 fractions=9 sessions in 3 days) using REPEAT irradiation shortened the irradiation time per session and simultaneously improved dose-volume histogram parameters.
CONCLUSION
Although the optimal number of sessions may differ depending on the patient's condition, the fixing method, the irradiation site, and the calculation parameters, REPEAT irradiation does not require any special equipment and is a simple practical treatment method.
Topics: Dose Fractionation, Radiation; Humans; Radiosurgery; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated
PubMed: 34972730
DOI: 10.21873/invivo.12706 -
Bioanalysis Oct 2010Microfluidic-based systems are ideal for handling small microliter volumes of samples and reagents, but 'real-world' or clinical samples for bioanalysis are often on the...
BACKGROUND
Microfluidic-based systems are ideal for handling small microliter volumes of samples and reagents, but 'real-world' or clinical samples for bioanalysis are often on the milliliter scale. We aimed to develop and validate a large-volume centrifugal or compact disc-based device for blood plasma separation, capable of processing 2 ml undiluted blood samples.
RESULTS
This automated blood sample preparation device was shown to yield high purity plasma in less than half the time of commercial plasma preparation tubes, while enabling integration with downstream analysis and detection steps.
CONCLUSION
This article draws upon a novel large-volume device to further illustrate the challenges in combining microfluidics structures with large-volume samples and the implications for sample-driven microfluidics systems.
Topics: Centrifugation; Chemical Fractionation; Compact Disks; Equipment Design; Humans; Microfluidic Analytical Techniques; Plasma; Reproducibility of Results; Time Factors
PubMed: 21083322
DOI: 10.4155/bio.10.140 -
Medical Physics Feb 2014To evaluate the impact of dose size in single fraction, spatially fractionated (grid) radiotherapy for selectively killing infiltrated melanoma cancer cells of different...
PURPOSE
To evaluate the impact of dose size in single fraction, spatially fractionated (grid) radiotherapy for selectively killing infiltrated melanoma cancer cells of different tumor sizes, using different radiobiological models.
METHODS
A Monte Carlo technique was employed to calculate the 3D dose distribution of a commercially available megavoltage grid collimator in a 6 MV beam. The linear-quadratic (LQ) and modified linear quadratic (MLQ) models were used separately to evaluate the therapeutic outcome of a series of single fraction regimens that employed grid therapy to treat both acute and late responding melanomas of varying sizes. The dose prescription point was at the center of the tumor volume. Dose sizes ranging from 1 to 30 Gy at 100% dose line were modeled. Tumors were either touching the skin surface or having their centers at a depth of 3 cm. The equivalent uniform dose (EUD) to the melanoma cells and the therapeutic ratio (TR) were defined by comparing grid therapy with the traditional open debulking field. The clinical outcomes from recent reports were used to verify the authors' model.
RESULTS
Dose profiles at different depths and 3D dose distributions in a series of 3D melanomas treated with grid therapy were obtained. The EUDs and TRs for all sizes of 3D tumors involved at different doses were derived through the LQ and MLQ models, and a practical equation was derived. The EUD was only one fifth of the prescribed dose. The TR was dependent on the prescribed dose and on the LQ parameters of both the interspersed cancer and normal tissue cells. The results from the LQ model were consistent with those of the MLQ model. At 20 Gy, the EUD and TR by the LQ model were 2.8% higher and 1% lower than by the MLQ, while at 10 Gy, the EUD and TR as defined by the LQ model were only 1.4% higher and 0.8% lower, respectively. The dose volume histograms of grid therapy for a 10 cm tumor showed different dosimetric characteristics from those of conventional radiotherapy. A significant portion of the tumor volume received a very large dose in grid therapy, which ensures significant tumor cell killing in these regions. Conversely, some areas received a relatively small dose, thereby sparing interspersed normal cells and increasing radiation tolerance. The radiobiology modeling results indicated that grid therapy could be useful for treating acutely responding melanomas infiltrating radiosensitive normal tissues. The theoretical model predictions were supported by the clinical outcomes.
CONCLUSIONS
Grid therapy functions by selectively killing infiltrating tumor cells and concomitantly sparing interspersed normal cells. The TR depends on the radiosensitivity of the cell population, dose, tumor size, and location. Because the volumes of very high dose regions are small, the LQ model can be used safely to predict the clinical outcomes of grid therapy. When treating melanomas with a dose of 15 Gy or higher, single fraction grid therapy is clearly advantageous for sparing interspersed normal cells. The existence of a threshold fraction dose, which was found in the authors' theoretical simulations, was confirmed by clinical observations.
Topics: Dose Fractionation, Radiation; Melanoma; Models, Biological; Monte Carlo Method; Tumor Burden
PubMed: 24506618
DOI: 10.1118/1.4862837 -
Seminars in Radiation Oncology Apr 2016Radiation oncologists need reliable estimates of risk for various fractionation schemes for all critical anatomical structures throughout the body, in a clinically... (Review)
Review
Radiation oncologists need reliable estimates of risk for various fractionation schemes for all critical anatomical structures throughout the body, in a clinically convenient format. Reliable estimation theory can become fairly complex, however, and estimates of risk continue to evolve as the literature matures. To navigate through this efficiently, a dose-volume histogram (DVH) Risk Map was created, which provides a comparison of radiation tolerance limits as a function of dose, fractionation, volume, and risk level. The graphical portion of the DVH Risk Map helps clinicians to easily visualize the trends, whereas the tabular portion provides quantitative precision for clinical implementation. The DVH Risk Map for rib tolerance from stereotactic ablative body radiotherapy (SABR) and stereotactic body radiation therapy (SBRT) is used as an example in this overview; the 5% and 50% risk levels for 1-5 fractions for 5 different volumes are given. Other articles throughout this issue of Seminars in Radiation Oncology present analysis of new clinical datasets including the DVH Risk Maps for other anatomical structures throughout the body.
Topics: Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Humans; Radiation Injuries; Radiation Tolerance; Radiosurgery; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Risk
PubMed: 27000504
DOI: 10.1016/j.semradonc.2015.11.005