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Lanlan NIE, Dawei LIU, He CHENG, Feng ZHAO, Xinpei LU. The state-of-the-art of atmospheric pressure plasma for transdermal drug delivery[J]. Plasma Science and Technology, 2024, 26(4): 043001. DOI: 10.1088/2058-6272/ad1044
Citation: Lanlan NIE, Dawei LIU, He CHENG, Feng ZHAO, Xinpei LU. The state-of-the-art of atmospheric pressure plasma for transdermal drug delivery[J]. Plasma Science and Technology, 2024, 26(4): 043001. DOI: 10.1088/2058-6272/ad1044

The state-of-the-art of atmospheric pressure plasma for transdermal drug delivery

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  • Plasma-enhanced transdermal drug delivery (TDD) presents advantages over traditional methods, including painless application, minimal skin damage, and rapid recovery of permeability. To harness its clinical potential, factors related to plasma’s unique properties, such as reactive species and electric fields, must be carefully considered.This review provides a concise summary of conventional TDD methods and subsequently offers a comprehensive examination of the current state-of-the-art in plasma-enhanced TDD. This includes an analysis of the impact of plasma on HaCaT human keratinocyte cells, ex vivo/in vivo studies, and clinical research on plasma-assisted TDD. Moreover, the review explores the effects of plasma on skin physical characteristics such as microhole formation, transepidermal water loss (TEWL), molecular structure of the stratum corneum (SC), and skin resistance. Additionally, it discusses the involvement of various reactive agents in plasma-enhanced TDD, encompassing electric fields, charged particles, UV/VUV radiation, heat, and reactive species. Lastly, the review briefly addresses the temporal behavior of the skin after plasma treatment, safety considerations, and potential risks associated with plasma-enhanced TDD.

  • Comprehensive Research Facility for Fusion Technology (CRAFT) is one of national large science and technology infrastructures of China, which aims to explore and master the key technologies, standards and methods for the construction and operation of future fusion reactors (especially for the China Fusion Engineering Test Reactor, CFETR). CRAFT program is divided into two research systems (for the superconducting magnet and the divertor, respectively) and includes 20 test facilities or prototypes totally. Neutral beam injection (NBI) is an effective auxiliary heating method for magnetically confined plasma, which can inject energic deuterium (or its isotopes) atomic beam into the fusion device and deliver the kinetic energy and momentum to the plasma. NBI has made great contributions in the milestones of fusion development [18] and is still promising in future fusion reactors for not only plasma heating but also current drive, plasma rotation, burning control, and so on [914]. Hence, the research on NBI technology is included in the CRAFT program.

    As the size of the fusion device enlarges, the required injecting beam energy also increases to attain the core plasma heating and current drive (e.g., 125 keV for JET [15], 500 keV for JT-60SA [16], 1000 keV for ITER [17]). For the beam energy is larger than 150 keV, the negative ion source based NBI (NNBI) system is more practical than the positive ion source based NBI (PNBI) system, because the neutralization efficiency of negative ion beam can stay above 55% but that is below 30% for positive ion beam [18]. However, according to the research and operation experiences of the only two routine NNBI systems for JT-60U tokamak [19] and LHD heliotron [20] respectively, the NNBI system is more complex and challenging than the PNBI system in views of the negative ion production, negative ion extraction and acceleration, multiply higher acceleration voltage, multiply larger beam size, negative ion neutralization, residual ion removal, and so on. Moreover, the demanded operating parameters of future NNBI system are much higher than the achievements worldwide.

    CRAFT NNBI facility, also called CRANE (Comprehensive Research Facility for NNBI Experiment), formally started construction in 2019 and planned to be completed in 2025. The aim of the CRAFT NNBI facility is to explore and master the key technologies for future CFETR NBI system [21, 22]. An acceptance mark for the construction completion of CRAFT NNBI facility is to attain a hydrogen neutral beam with the particle energy of 200–400 keV, beam power of > 2 MW, and pulse duration of > 100 s.

    The CRAFT NNBI facility mainly contains two testbeds: HONOR (Hefei Open-facility for Negative-ion Source Research) focuses on the negative ion source research for fusion, CANBE (CFETR Advance Neutral Beam Equipment) is the full-function prototype for the CFETR neutral beam injector. There are other supporting systems, for example, the acceleration voltage power supply, cooling plant, cryogenic plant. The HONOR and CANBE started the first operations in April 2023 and December 2023, respectively.

    This paper mainly reports the design and developments that have been carried out to realize the CRAFT NNBI facility, and highlights the experimental results made in their first operations.

    The layout of the whole CRAFT NNBI facility is shown in figure 1. HONOR and CANBE are designed to be operated individually. So there are independent control systems, high voltage (HV) platform or tank, assembly areas for the two testbeds. The electrical power system, cooling water plant and cryogenic plant can also support the simultaneous operation of the two testbeds. Considered the construction cost, the acceleration voltage power supply is shared by HONOR and CANBE. There are several research and development units for NNBI relevant technologies, for example, caesium (Cs) dynamics, laser neutralizer, HV insulation in vacuum.

    Figure  1.  Layout of CRAFT NNBI facility (i.e., CRANE site).

    The negative ion source is the most critical and challenging component in an NNBI system. The technology for the negative ions production, extraction, acceleration and steering is still immature especially in the long-pulse and high-power operation. Intuitively, the required parameters of ITER negative ion source (1000 keV, 40 A and 1 h D beam) have never been reached simultaneously until now. HONOR devotes to tackle the key physics and engineering issues of the large-scale negative ion source for fusion application.

    An overall view of HONOR and the HV platform are shown in figure 2. Due to the potential advantages of low maintenance, simple structure and high stability and repeatability in the long-term operation, radio frequency (RF) driven plasma source is more promising for future NBI system and it has been chosen for the ITER and CFETR NNBI systems [2326]. Two RF generators on the HV platform are used to produce the plasma with the power of 200 kW and the frequency of 1–1.5 MHz for each [27]. Another large power supply on the HV platform is the extraction voltage power supply of 16 kV/80 A for negative ions extraction, which is based on the pulse step modulation (PSM) technology [2830]. There are some small power supplies assembled in a unit on the HV platform: two bias power supplies of 100 V/600 A for changing the plasma potential and suppressing the co-extracted electrons [31, 32]; one magnetic filter power supply of 15 V/6000 A to produce the filter field across the source for lowering the electron temperature and reducing the loss of negative ions [33, 34]; one starter filament power supply including two voltage regulators for the filament current and filament bias respectively. The high-temperature water supply is also placed on the HV platform, which can provide the high-pressure hot water up to 200 °C for optimizing the Cs surface condition and enhancing the negative ion production. Note that, HONOR can only operate at the acceleration voltage up to 200 kV, so the insulating supports and the isolation transformer are designed to insulate against the 200 kV voltage.

    Figure  2.  View of the HONOR testbed at the CRANE site.

    A view of the HONOR in-vessel components is shown in figure 3. The rectangular beamline vacuum vessel is 5 m in length, 4 m in width and 4 m in height [35]. The top plate of the vacuum vessel can be removed for the installation of inner components. The front port of the vacuum vessel is connected to a gate valve with the opening of 2 m in diameter. The major inner components are the beam dump and the cryopumps for the ion beam operation only. The beam dump adopts an ITER heating neutral beam (HNB) like design that consists of two multi-pipe arrays [3638]. There are two cryopumps of cryo-absorption type installed on the two lateral walls. The cryopump is of modular structure, and each unit is designed to have a pumping speed of 500000 L/s with the pumping opening of 2.3 m (height) × 1.0 m (width) [3944]. One cryopump contains 4 units (displayed in figure 3) and another one contains 2 units to make room for beam diagnostics. 4 turbo molecular pumps (with pumping speed of 2200 L/s for each) and 2 units of rotary vane pump and Roots pump are used as the backing pumps.

    Figure  3.  3D model of the HONOR main structure with in-vessel components.

    The most important feature of HONOR is the application of various plasma and beam diagnostic systems. Table 1 lists the diagnostic systems which have been equipped already. By installing a special diagnostic flange in front of the plasma grid (PG) in the negative ion source, the key parameters of the plasma (for example, electron density, electron temperature, Cs density, negative ion density) in the extraction region can be measured and analyzed via different diagnostic techniques. By using the carbon fibre composite (CFC) dump downstream the negative ion source, the multi-beamlet footprints can be measured via the infrared (IR) camera, and then, the multi-beamlet divergences and orbits can be evaluated. The other beam diagnostic techniques (e.g., W-wire dump, visible light camera, secondary electron emission) can give the profile, uniformity, divergence of the whole beam. Hence, the plasma and the beam parameters can be comparably investigated in different designs or operation conditions.

    Table  1.  Diagnostics equipped on the HONOR.
    Plasma diagnostics Objects Beam diagnostics Objects
    Langmuir probe [45] Electron density, electron temperature, plasma potential Carbon dump with
    infra-red camera [47]
    Beamlet divergence,
    beamlet alignment
    Optical emission
    spectroscopy
    Hα, Hβ, Hγ, Cs+, impurities’ line density Tungsten wire dump
    with camera [48]
    Beam uniformity,
    beam divergence
    Cavity ring-down
    spectroscopy [46]
    H line density Doppler shift
    spectroscopy [49]
    Beam energy, beam divergence, stripping loss
    Laser absorption
    spectroscopy
    Cs0 line density Visible light camera Beam uniformity, beam divergence
    Microwave
    interferometer
    Electron line density Secondary electron
    emission [50]
    Beam uniformity,
    beam divergence
    Water flow
    calorimetry [51]
    Power load on grid
     | Show Table
    DownLoad: CSV

    As the CFETR NBI prototype, CANBE can carry out the whole working process of an NNBI injector including the negative ion beam launch, negative ion beam neutralization, residual ions removal, neutral beam transport to the beam dump, except the beam transport in the drift and injection tubes. Significantly, CANBE adopts an electric deflection technique for removal of the powerful residual ions that is the same with the ITER NBI design. CANBE is the first NBI equipment that can test the electric deflection technique ahead of the ITER NBI system and its test facility [5254].

    An overall view of CANBE and the HV tank is shown in figure 4. The components and their design parameters inside the CANBE HV tank are similar to that of HONOR HV platform, including RF generator, extraction voltage power supply, magnetic filter power supply, bias power supply, high-temperature water supply. The difference is that the CANBE HV tank is design to insulate against 400 kV voltage.

    Figure  4.  View of the CANBE testbed at the CRANE site.

    A view of the CANBE in-vessel components is shown in figure 5. There are two vacuum vessels connecting via the gate valve. One vacuum vessel is for negative ion source (5×5×5 m3) and the other one is for beamline (12×4×4 m3). It means that a vacuum insulated negative ion source can be operated inside the vacuum vessel for better insulation and lower stripping loss, like ITER negative ion source [55]. The acceptance beam energy of CRAFT NNBI facility is 200–400 keV, which is no necessary to use a vacuum insulated negative ion source. However, according to the operation experience of the ITER neutral beam test facility SPIDER [5658], several problems arose and powerful negative ion beam was hardly produced during the source operation immersed in the vacuum. So the vacuum vessels for negative ion source are prepared on both HONOR and CANBE for future research on the vacuum insulated negative ion source.

    Figure  5.  3D model of the CANBE main structure with in-vessel components.

    A gas neutralizer with the length of 3 m is used for the neutralization of the negative ion beam [5961]. The neutralizer is divided into two narrow beam channels to reduce the gas inlet for forming optimal gas target. The maximal cross section of each channel is 1.7 m (height) × 0.3 m (width) which can be changed according to different negative ion source.

    An electrical residual ion dump (ERID) is applied to CANBE following the ITER NBI design [62]. Although the previous NBI systems all use the magnetic field to deflect the residual ions onto the dumps, a bending magnet for removing the energic and widespread ions in ITER or CFETR NBI (i.e., 1 MeV D+ or D with a cross section of 0.6 m in width and 1.5–2 m in height) is enormous and uneconomical. Hence, the ERID concept is more realisable. The ERID of CANBE also has two beam channels (0.31 m in width for each) forming by three ion dumps. The middle dump is connected to the positive HV which absorbs the negative ions; the two lateral dumps are grounded which collect the positive ions. Actually, two identical ERIDs have been manufactured, each of which is 1.5 m in length. One can assembly the two modules together to form the 3 m long channels, or just use one module according to the experiments. Thus, ERID can provide with more convenient experimental plan, as the first facilities to test the electric deflection technique.

    The beam dump of CANBE is the same with that of HONOR. The cryopumps are also installed on the two lateral walls in the beamline vacuum vessel of CANBE. Each cryopump comprises 8 units with a total length of 8 m. The positions of each component in the beamline vacuum vessel are shown in figure 6.

    Figure  6.  Positions of the in-vessel components in the CANBE beamline.

    The science and technology of negative ion source is developed step by step in the CRAFT project. Four negative ion sources are being or will be tested, as shown in figure 7: the number of RF driver (and also source size) is increased from one, two, to four with 2×2 arrangement or 1×4 arrangement; the accelerator is upgraded from single-stage acceleration of 50 kV, single-stage acceleration of 200 kV, to two-stage acceleration of 400 kV working in air or vacuum. Therefore, the major key issues for future CFETR negative ion source about the multi-driver, large-area, high-current, multi-acceleration and vacuum immersed operation are included in the development progress of those four CRAFT negative ion sources.

    Figure  7.  R&D progress of negative ion source in the framework of CRAFT project.

    The single-driver negative ion source has been put into operation since 2022 on a previous testbed HUNTER and successfully achieved the repeatable long-pulse (> 100 s) extractions of negative ions (H) with an available current density (> 150 A/m2) [6366]. The single-driver negative ion source is used to understand and optimize the physical issues on RF plasma discharge and power transfer, plasma transport in magnetic field, Cs dynamics and conditioning, plasma characteristics near the PG [6774]. The dual-driver negative ion source is the first source operating on the CRAFT NNBI facility and its experimental results are discussed in section 3. Both of the quad-driver negative ion sources are being manufactured, as shown in figure 8 [7577]. The 2×2 driver source will work in air and can take the ITER half-size source ELISE as reference [7880], thus it deems to be easier to reach. Besides studying the operation in vacuum, the 1×4 driver source with large aspect ratio is more favourable to the beam neutralization, although its non-uniformity of plasma or beam is probably more difficult to deal with.

    Figure  8.  (a) Assembly of 2×2 driver plasma source, (b) assembly of 1×4 driver plasma source.

    A whole system commissioning was carried out in the first operation of the CRAFT NNBI facility, to test and debug the problems when all the sub-systems working together. By using the acceleration voltage power supply, both of HONOR HV platform and CANBE HV tank could hold a high voltage of 200 kV for 100 s.

    Until now, both of 2-unit and 4-unit cryopumps have been installed on the HONOR as design; a full-size cryopump with 8 units has been installed on CANBE, but another one just has 2 units due to the deferred delivery. The cryopump with only 2 units in either HONOR or CANBE vacuum vessel was tested to have a pumping speed of > 100000 L/s, as shown in figure 9. The gas was puffed into from the negative ion source. The pumping speed reduced a bit with the increasing gas inflow.

    Figure  9.  Measurement of pumping speed of the cryopump with 2 units.

    During the commissioning, a high-power and long-pulse RF plasma discharge (140 kW for 110 s) was obtained via the dual-driver negative ion source; a H beam current of ~ 1 A was successfully extracted for 10 s in the volume mode (i.e., without Cs seeding). The design parameters of the dual-driver negative ion source are listed in table 2.

    Table  2.  Key designs of the dual-driver negative ion source.
    Items Design values
    RF power140 kW
    RF frequency1 MHz (±5% adjustable)
    RF driverΦ 24 cm, 16 cm (height)
    Expansion chamber90 (length) × 50 (width) × 20 (depth) cm3
    PG apertureΦ 14 mm, 6×16×4
    Extraction voltage−8 kV
    Acceleration voltage50/200 kV
    Ion current15 A (~ 255 A/m2)
    Pulse duration> 100 s
     | Show Table
    DownLoad: CSV

    The dual-driver negative ion source of CRAFT is based on the design and experimental results of the single-driver negative ion source. In order to demonstrate the physical designs and operation methods for a RF driven negative ion source, the dual-driver negative ion source is required to replicate the results of single-driver source that is long-pulse negative ions extraction. Hence, the dual-driver negative ion source was equipped with a 50 keV accelerator at first [81]. The experiments were carried out with the 2-unit cryopump only in the HONOR.

    A long-pulse extraction of H has been achieved repeatably and the typical waveforms are shown in figure 10. The RF coils were connected in series between two drivers and the RF power was 50 kW in this shot. The filling pressure was 0.4 Pa, the bias voltage was 14 V, and the PG current for magnetic filter was 1000 A. The extraction voltage was 5.4 kV, the acceleration voltage was 50 kV. The bias voltage was generally applied 3 s leading the beam extraction pulse. Because the bias voltage was already lower than the floating potential, the bias current should be negative, but the unipolar power supply could not display the negative current. Note that, the floating potential was not measured simultaneously during the beam extraction because it requires the high-voltage isolation. But it was measured during the shots of the plasma only.

    Figure  10.  Typical waveforms of the long-pulse extraction of negative ions.

    Here, the current load on the extraction grid (EG), IEG, was regarded as the co-extracted electron current, because almost all the electrons could be deflected onto the EG [82]; the current output of the acceleration voltage power supply, IACC, was regarded as the extracted H current, although it included part of stripping electrons (assumed to be < 10% of the acceleration current). There were 20 times of breakdown (i.e., the burrs of the acceleration voltage signal, VACC) during the pulse duration of 105 s and the pause before the restart of beam extraction was 200 ms. The breakdowns were all due to the over-current of the high voltage power supply, which were the sparks between two grid electrodes essentially. But the over-current signals were not displayed in the waveforms because the high-speed data acquisition system was not ready [83]. Among them, 17 times were related to the extraction voltage and 3 times were due to the acceleration voltage. Furthermore, the breakdowns were more frequent after 45 s and the reasons were not determined (maybe outgas from the grids by particle bombardment or Cs pollution on the grids). The IEG was gradually increased from 0.8 A to 1.1 A and IACC was increased from 7.3 A (~ 123 A/m2) to 8 A (~ 135 A/m2), which induced an electron-to-ion ratio of < 0.15.

    By increasing the RF power and extraction voltage, a high-current extraction of negative ions was also tested. The typical waveforms are shown in figure 11. The RF power was 97 kW, the filling pressure was 0.4 Pa, the bias voltage was 15 V, and the PG current for magnetic filter was 1100 A. The extraction voltage was 8.0 kV, the acceleration voltage was 47 kV. The IACC was almost constant at 14.7 A (~ 248 A/m2) and IEG was below 6.0 A, which induced an electron-to-ion ratio of < 0.41. There were 9 times of breakdowns during the pulse duration of 30 s and all of them were related to the extraction voltage. Note that, only the room-temperature water was used for the PG in these experiments. For Cs seeding, the temperature of the Cs delivery pipe was constant at a value between 220 °C and 260 °C in general, the temperature of the Cs oven was increased in the step of 10 °C when the electron-to-ion ratio was almost unchanged [84].

    Figure  11.  Typical waveforms of the high-current extraction of negative ions.

    Since the extraction of negative ions has been verified, the dual-driver negative ion source was upgraded with 200 keV accelerator. The major differences were that the acceleration gap was enlarged from 20 mm to 90 mm and the height of main insulator was increased from 100 mm to 400 mm. The target was to achieve a high-energy and high-power negative ion beam. The waveforms of the highest beam power in the first operation of HONOR are shown in figure 12. The RF power was 69 kW, the filling pressure was 0.4 Pa, the bias voltage was 16 V, and the PG current for magnetic filter was 1100 A. The extraction voltage was 5.9 kV, the acceleration voltage was 130 kV. The IACC was constant at 8.9 A and IEG was 5.0 A. There were 2 times of breakdowns during the pulse duration of 10 s, and the pause before restart of beam extraction was changed to 1 s during the high energy operation. Because the breakdown rate was hardly below 0.2 count/s (breakdown rate = number of breakdown / pulse duration), the long-pulse and high-energy acceleration of negative ions was not attempted.

    Figure  12.  Typical waveforms of the high-energy acceleration of negative ions.

    Until the end of the first operation on HONOR (from July 2023 to November 2023), the acceleration voltage of the dual-driver negative ion source was hardly higher than 140 kV even decreasing extracted ion current. Several creepage paths were found on the outside surface of the insulator between PG and EG. But the reason of the limited acceleration voltage was not sure. After upgrading to 200 keV accelerator, the electron-to-ion ratio of the dual-driver negative ion source showed a general increase in different levels of extracted ion current, even with a higher heating temperature for the Cs injection system. The reasons were not determined. But one guess was that the back-streaming ions with higher energy changed the Cs re-distribution or impurities released from the back plate of the source.

    Considered the performance of the dual-driver negative ion source hitting a bottleneck, the first operation of HONOR was closed and the source was installed on CANBE for its first operation. The target was to demonstrate a whole operation process of negative ion based neutral beam injector. The operation value of acceleration voltage was limited to 120 kV to avoid too much breakdowns. The cross section of either beam channel of the neutralizer was changed to 0.6 m × 0.18 m to match the beam profile from the dual-driver negative ion source. However, the structure of ERID was hard to be changed, which caused the width of beam channels of ERID (0.31 m) being larger than that of neutralizer. To ensure the removal of the residual ions, the ERID with 3 m in length was used. As mentioned above, the experiments could be carried out only with a 2-unit cryopump on CANBE. It resulted in the accelerated beam current being hardly higher than ~ 6 A when the ERID was on work, because the HV breakdown on the ERID became frequent.

    The typical waveforms of the neutral beam purification with the ERID are shown in figure 13 (displaying three shots: Nos. 2496, 2498 and 2499). The operation parameters of negative ion source were the same in these three shots. The RF power was 42 kW, the filling pressure was 0.4 Pa, the bias voltage was 25 V, and the PG current for magnetic filter was 2000 A. The extraction voltage was 4.5 kV, the acceleration voltage was 105 kV. The IACC was 3.4 A and IEG was 1.5 A. For No. 2496 and No. 2498, the ERID was off work and on work, respectively. For No. 2498 and No. 2499, the ERID was both on work, but the gas input from the neutralizer was 0 and 100 mL/min, respectively.

    Figure  13.  Typical waveforms of the neutral beam production: shot No. 2496 without ERID on work, shot No. 2498 with ERID on work and without adding gas from neutralizer, and shot No. 2499 with ERID on work and with adding gas from neutralizer of 100 mL/min. The gas inlet rates to negative ion source were all 1750 mL/min.

    The applied voltage to ERID VERID was gradually increased to 4.6 kV to ensure that the residual ions were fully deflected onto the ERID. The judgement was that the power load on the beam dump had little increase when raising the VERID. Generally, the ratio of the power loads on the beam dump (i.e., calorimeter) with and without the removal of residual ions (i.e., with and without the VERID here) was used to evaluate the neutralization efficiency [8588], and then, the average neutralization efficiency was 35.7% without the makeup gas and 43.1% with gas input of 100 mL/min from neutralizer. Note that, the gas input to the negative ion source was constant at 1750 mL/min.

    The ERID current IERID (i.e., the output current of the ERID power supply) was already higher than the IACC, which was the solid evidence of the production of secondary plasma inside the ERID. Because the maximal residual ion beam current could not be higher than the initial ion beam current even if there was no neutralization. Moreover, when adding the gas from the neutralizer (shot No. 2499), the IERID was increased but the neutralization efficiency was higher (i.e., less residual ions) comparing to the shot without gas from neutralizer (shot No. 2498). Therefore, the increased IERID was due to the secondary plasma. Just because of the increased IERID, the breakdowns became frequent when trying to raise the gas inlet rate from neutralizer.

    Although no higher beam energy or beam power and no maximal neutralization efficiency was achieved, the first operation of CANBE (from November 2023 to January 2024) was closed to modify and assemble the large cryopumps.

    This paper gives an overview of the CRAFT NNBI facility, called CRANE, and its two testbeds: HONOR for the negative ion source research and CANBE as the CFETR NBI injector prototype. CRANE also hosts some necessary supporting systems for the testbeds, such as high voltage power supply, cryogenic plant, cooling plant. The most outstanding features of HONOR are the flexible assembly and the various diagnostics for source plasma and beam. The CANBE is designed to have a comparable size and full working process to the CFETR NBI injector, especially the unconfirmed technique of the electrical removal of powerful residual ions.

    The CRANE building construction was started in 2019 and completed in 2021. The component integration and commissioning of HONOR and CANBE were finished in 2022 and 2023, respectively. The power supply, vacuum pumping, diagnostics and control have been implemented and tested. Both of two testbeds have possessed the experimental ability of negative ion beam acceleration.

    The CRAFT dual-driver negative ion source was applied to the first operations of HONOR and CANBE. By using a 50 keV accelerator, the long-pulse and high-current extractions of negative hydrogen ions have been achieved on HONOR, and the typical values were 55.4 keV, 7.3 A (~ 123 A/m2), 105 s and 55.0 keV, 14.7 A (~ 248 A/m2), 30 s, respectively. The results demonstrated the physical design of the dual-driver negative ion source which was transplanted from the CRAFT single-driver negative ion source. By replacing with a 200 keV accelerator, the MW-class negative ion acceleration has been achieved on HONOR, and the typical values were 135.9 keV, 8.9 A (~ 150 A/m2), 8 s. However, the acceleration voltage could not raise above 140 kV.

    By installing dual-driver negative ion source on CANBE, a whole operation process of negative ion production, neutralization and purification has been demonstrated, and the typical values were 109.5 keV, 3.4 A, 8 s with a neutralization efficiency of 43.1%. The electrical removal of powerful residual ions was applied to an NNBI injector for the first time. However, a problem of frequent HV breakdowns on the ERID was exposed when the large cryopump was not fully on work.

    According to the results of the first operation of CRANE and the acceptance target of the project (200–400 keV, 2 MW, 100 s, H0), several tasks will be carried out in the next step. The dual-driver negative ion source needs to resolve the HV breakdown problem on the accelerator and has to attain a long-pulse and MW-class negative ion beam. The Cs pollution, beam optics, stray charged particles could be the causes of the HV breakdown or spark down. In future, we will detect the reason and further improve the beam parameters. Two different quad-driver negative ion sources will be assembled and tested. For HONOR, several diagnostic systems need to support the research on the plasma and beam uniformity in the next campaign. For CANBE, the large cryopumps should be fully on work at first.

  • [1]
    Gantwerker E A and Hom D B 2011 Facial Plast. Surg. Clin. North Am. 19 441 doi: 10.1016/j.fsc.2011.06.009
    [2]
    Hwa C, Bauer E A and Cohen D E 2011 Dermatol. Ther. 24 464 doi: 10.1111/j.1529-8019.2012.01460.x
    [3]
    Goebel A S B et al 2012 Skin Pharmacol. Physiol. 25 281 doi: 10.1159/000341085
    [4]
    Münch S, Wohlrab J and Neubert R H H 2017 Eur. J. Pharm. Biopharm. 119 235 doi: 10.1016/j.ejpb.2017.06.019
    [5]
    Williams A C and Barry B W 1992 Crit. Rev. Ther. Drug Carrier Syst. 9 305
    [6]
    Finnin B C and Morgan T M 1999 J. Pharm. Sci. 88 955 doi: 10.1021/js990154g
    [7]
    Prausnitz M R, Mitragotri S and Langer R 2004 Nat. Rev. Drug Discov. 3 115 doi: 10.1038/nrd1304
    [8]
    Akomeah F et al 2004 Eur. J. Pharm. Sci. 21 337 doi: 10.1016/j.ejps.2003.10.025
    [9]
    Clarys P et al 1998 Eur. J. Pharm. Biopharm. 46 279 doi: 10.1016/S0939-6411(98)00044-7
    [10]
    Brown M B et al 2006 Drug Deliv. 13 175 doi: 10.1080/10717540500455975
    [11]
    Ogiso T et al 1998 Int. J. Pharm. 176 63 doi: 10.1016/S0378-5173(98)00309-3
    [12]
    Klemsdal T O, Gjesdal K and Bredesen J E 1992 Eur. J. Clin. Pharmacol. 43 625 doi: 10.1007/BF02284961
    [13]
    Mitragotri S, Blankschtein D and Langer R 1995 Science 269 850 doi: 10.1126/science.7638603
    [14]
    Mitragotri S and Kost J 2001 Pharm. Res. 18 1151 doi: 10.1023/A:1010979010907
    [15]
    Tachibana K 1992 Pharm. Res. 9 952 doi: 10.1023/A:1015869420159
    [16]
    Mitragotri S and Kost J 2000 Biotechnol. Prog. 16 488 doi: 10.1021/bp000024+
    [17]
    Zorec B et al 2018 Eur. J. Pharm. Biopharm. 127 387 doi: 10.1016/j.ejpb.2018.03.008
    [18]
    Park D et al 2014 Ultrasonics 54 56 doi: 10.1016/j.ultras.2013.07.007
    [19]
    Tezel A and Mitragotri S 2003 Biophys. J. 85 3502 doi: 10.1016/S0006-3495(03)74770-5
    [20]
    Wolloch L and Kost J 2010 J. Control. Release 148 204 doi: 10.1016/j.jconrel.2010.07.106
    [21]
    Tang H et al 2002 Pharm. Res. 19 1160 doi: 10.1023/A:1019898109793
    [22]
    Mitragotri S, Blankschtein D and Langer R 1996 Pharm. Res. 13 411 doi: 10.1023/A:1016096626810
    [23]
    Forbes M M, Steinberg R L and O’Brien W D Jr 2008 Ultrasound Med. Biol. 34 2009 doi: 10.1016/j.ultrasmedbio.2008.05.003
    [24]
    Escobar-Chavez J J et al 2009 J. Pharm. Pharm. Sci. 12 88 doi: 10.18433/J3C30D
    [25]
    Colussi A J, Weavers L K and Hoffmann M R 1998 J. Phys. Chem. A 102 6927 doi: 10.1021/jp980930t
    [26]
    Fan C H et al 2022 Expert Opin. Drug Deliv. 19 8
    [27]
    Bommannan D et al 1992 Pharm. Res. 9 1043 doi: 10.1023/A:1015806528336
    [28]
    Hibst R and Kaufmann R 1991 Lasers Med. Sci. 6 391 doi: 10.1007/BF02042461
    [29]
    Paasch U and Haedersdal M 2011 Expert Rev. Med. Devices 8 67 doi: 10.1586/erd.10.74
    [30]
    Waibel J et al 2009 J. Drugs Dermatol. 8 481
    [31]
    Lee W R et al 2003 J. Invest. Dermatol. 121 1118 doi: 10.1046/j.1523-1747.2003.12537.x
    [32]
    Forster B et al 2010 Exp. Dermatol. 19 806 doi: 10.1111/j.1600-0625.2010.01093.x
    [33]
    Sklar L R et al 2014 Lasers Surg. Med. 46 249 doi: 10.1002/lsm.22227
    [34]
    Arora A et al 2007 Proc. Natl. Acad. Sci. USA 104 4255 doi: 10.1073/pnas.0700182104
    [35]
    Gao Y et al 2022 Medicine 101 26
    [36]
    Wang Y et al 2022 Drug Deliv. Transl. Res. 12 15 doi: 10.1007/s13346-021-00898-6
    [37]
    Liatsopoulou A et al 2023 Int. J. Cosmet. Sci. 45 117 doi: 10.1111/ics.12824
    [38]
    Hasan M, Khatun A and Kogure K 2022 Pharmaceutics 14 525 doi: 10.3390/pharmaceutics14030525
    [39]
    Zhang R et al 2023 Colloids Surf. B: Biointerfaces 226 113302
    [40]
    Guillot A J et al 2023 WIREs Nanomed. Nanobiotechnol. 15 e1884 doi: 10.1002/wnan.1884
    [41]
    Larrañeta E et al 2016 Mater. Sci. Eng. R: Rep. 104 1
    [42]
    Lee K J et al 2020 Int. J. Pharm. 573 118778 doi: 10.1016/j.ijpharm.2019.118778
    [43]
    Neumann E et al 1982 EMBO J. 1 841 doi: 10.1002/j.1460-2075.1982.tb01257.x
    [44]
    Bhonsle S P et al 2015 BioMed. Eng. OnLine 14 S3
    [45]
    Sano M B et al 2018 Phys. Med. Biol. 63 135022 doi: 10.1088/1361-6560/aacb62
    [46]
    Fromm M, Taylor L P and Walbot V 1985 Proc. Natl. Acad. Sci. USA 82 5824 doi: 10.1073/pnas.82.17.5824
    [47]
    Toneguzzo F and Keating A 1986 Proc. Natl. Acad. Sci. USA 83 3496 doi: 10.1073/pnas.83.10.3496
    [48]
    Yarmush M L et al 2014 Annu. Rev. Biomed. Eng. 16 295 doi: 10.1146/annurev-bioeng-071813-104622
    [49]
    Weaver J C 2000 IEEE Trans. Plasma Sci. 28 24 doi: 10.1109/27.842820
    [50]
    Gehl J and Mir L M 1999 Biochem. Biophys. Res. Commun. 261 377 doi: 10.1006/bbrc.1999.1014
    [51]
    Novickij V et al 2022 Frontiers in oncology 12 958128 doi: 10.3389/fonc.2022.958128
    [52]
    Malyško-Ptašinskė V, Staigvila G and Novickij V 2023 Front. Bioeng. Biotechnol. 10 1094968 doi: 10.3389/fbioe.2022.1094968
    [53]
    Schoenbach K H et al 2007 IEEE Trans. Dielect. Electr. Insul. 14 1088 doi: 10.1109/TDEI.2007.4339468
    [54]
    Kotnik T et al 2015 Trends Biotechnol. 33 480 doi: 10.1016/j.tibtech.2015.06.002
    [55]
    Davalos R V, Mir L M and Rubinsky B 2005 Ann. Biomed. Eng. 33 223 doi: 10.1007/s10439-005-8981-8
    [56]
    Golberg A and Yarmush M L 2013 IEEE Trans. Biomed. Eng. 60 707 doi: 10.1109/TBME.2013.2238672
    [57]
    Dunki-Jacobs E M, Philips P and Martin II R C G 2014 J. Am. Coll. Surg. 218 179 doi: 10.1016/j.jamcollsurg.2013.10.013
    [58]
    Wong T W et al 2006 J. Control. Release 110 557 doi: 10.1016/j.jconrel.2005.11.003
    [59]
    Miklavčič D et al 2005 Bioelectrochemistry 65 121 doi: 10.1016/j.bioelechem.2004.07.004
    [60]
    Golberg A and Rubinsky B 2012 Technol. Cancer Res. Treat. 11 189 doi: 10.7785/tcrt.2012.500249
    [61]
    Yao C G et al 2017 IEEE Trans. Biomed. Eng. 64 2924 doi: 10.1109/TBME.2017.2690624
    [62]
    Arena C B et al 2011 BioMed. Eng. OnLine 10 102 doi: 10.1186/1475-925X-10-102
    [63]
    Schoenbach K H et al 2009 IEEE Trans. Dielectr. Electr. Insul. 16 1224 doi: 10.1109/TDEI.2009.5293932
    [64]
    Schoenbach K H, Beebe S J and Buescher E S 2001 Bioelectromagnetics 22 440 doi: 10.1002/bem.71
    [65]
    Steelman et al 2021 J. Biophotonics 14 e202100125 doi: 10.1002/jbio.202100125
    [66]
    Buescher E S and Schoenbach K H 2003 IEEE Trans. Dielectr. Electr. Insul. 10 788 doi: 10.1109/TDEI.2003.1237328
    [67]
    Zhang J et al 2008 Arch. Biochem. Biophys. 471 240 doi: 10.1016/j.abb.2007.12.009
    [68]
    Beebe S J et al 2004 Physiol. Meas. 25 1077 doi: 10.1088/0967-3334/25/4/023
    [69]
    Vernier P T et al 2003 IEEE Trans. Dielectr. Electr. Insul. 10 795 doi: 10.1109/TDEI.2003.1237329
    [70]
    Nuccitelli R et al 2006 Biochem. Biophys. Res. Commun. 343 351 doi: 10.1016/j.bbrc.2006.02.181
    [71]
    Prausnitz M R 1996 J. Control. Release 40 321 doi: 10.1016/0168-3659(95)00199-9
    [72]
    Vanbever R, Leroy M A and Préat V 1998 J. Control. Release 54 243 doi: 10.1016/S0168-3659(97)00146-6
    [73]
    Escobar-Chávez, J J 2009 Journal of clinical pharmacology 49 1262 doi: 10.1177/0091270009344984
    [74]
    Ita K 2016 Pharmaceutics 8 9 doi: 10.3390/pharmaceutics8010009
    [75]
    Pliquett U, Langer R and Weaver J C 1995 Biochim. Biophys. Acta (BBA) – Biomembranes 1239 111
    [76]
    Bose V G 1994 Electrical characterization of electroporation of human stratum corneum MSc Thesis Massachusetts Institute of Technology, Cambridge, USA
    [77]
    Nemanic M K and Elias P M 1980 J. Histochem. Cytochem. 28 573 doi: 10.1177/28.6.7190175
    [78]
    Boddé H E et al 1991 J. Control. Release 15 227 doi: 10.1016/0168-3659(91)90114-S
    [79]
    Grimnes S 1984 Acta Dermato-Venereol. 64 93 doi: 10.2340/00015555649398
    [80]
    Chizmadzhev Y A et al 1995 Biophys. J. 68 749 doi: 10.1016/S0006-3495(95)80250-X
    [81]
    Edwards D A et al 1995 J. Control. Release 34 211 doi: 10.1016/0168-3659(94)00132-E
    [82]
    Prausnitz M R 1996 J. Control. Release 38 205 doi: 10.1016/0168-3659(95)00121-2
    [83]
    Graves D B 2012 J. Phys. D: Appl. Phys. 45 263001
    [84]
    Laroussi M and Leipold F 2004 Int. J. Mass Spectrom. 233 81 doi: 10.1016/j.ijms.2003.11.016
    [85]
    Attri P et al 2015 Sci. Rep. 5 9332 doi: 10.1038/srep09332
    [86]
    Liu F et al 2020 Plasma Sources Sci. Technol. 29 065001 doi: 10.1088/1361-6595/ab8e4d
    [87]
    Cheng H et al 2020 Phys. Plasmas 27 063514 doi: 10.1063/5.0008881
    [88]
    Cheng H et al 2022 Phys. Plasmas 29 063506 doi: 10.1063/5.0089357
    [89]
    Busco G et al 2019 J. Phys. D: Appl. Phys. 52 24LT01
    [90]
    Keidar M 2015 Plasma Sources Sci. Technol. 24 033001 doi: 10.1088/0963-0252/24/3/033001
    [91]
    Leduc M et al 2009 New J. Phys. 11 115021 doi: 10.1088/1367-2630/11/11/115021
    [92]
    von Woedtke T et al 2019 In Vivo 33 1011 doi: 10.21873/invivo.11570
    [93]
    Lietz A M and Kushner M J 2016 J. Phys. D: Appl. Phys. 49 425204
    [94]
    Yusupov M et al 2014 J. Phys. D: Appl. Phys. 47 025205
    [95]
    Guo L et al 2018 Free Radic. Res. 52 783 doi: 10.1080/10715762.2018.1471476
    [96]
    Babaeva N Y and Naidis G V 2018 Trends Biotechnol. 36 603 doi: 10.1016/j.tibtech.2017.06.017
    [97]
    Bruggeman P and Schram D C 2010 Plasma Sources Sci. Technol. 19 045025 doi: 10.1088/0963-0252/19/4/045025
    [98]
    Ostrikov K et al 2016 J. Phys. D: Appl. Phys. 49 304001
    [99]
    Busco G et al 2020 Free Radic. Biol. Med. 161 290 doi: 10.1016/j.freeradbiomed.2020.10.004
    [100]
    Gelker M, Müller-Goymann C C and Viöl W 2018 Clin. Plasma Med. 9 34
    [101]
    Choi J H et al 2014 Arch Dermatol. Res. 306 635 doi: 10.1007/s00403-014-1463-9
    [102]
    Lee H Y et al 2018 J. Phys. D: Appl. Phys. 51 215401
    [103]
    Lee S et al 2021 Appl. Sci. 11 2390 doi: 10.3390/app11052390
    [104]
    Lademann O et al 2011 Laser Phys. Lett. 8 758 doi: 10.1002/lapl.201110055
    [105]
    Shimizu K, Hayashida K and Blajan M 2015 Biointerphases 10 029517 doi: 10.1116/1.4919708
    [106]
    Shimizu K et al 2016 J. Phys. D: Appl. Phys. 49 315201
    [107]
    Kristof J et al 2017 Biointerphases 12 02B402 doi: 10.1116/1.4982826
    [108]
    Gelker M et al 2019 Biochim. Biophys. Acta (BBA) - Gen. Subj. 1863 1513 doi: 10.1016/j.bbagen.2019.05.014
    [109]
    Xin Y et al 2021 J. Cosmet. Dermatol. 20 626 doi: 10.1111/jocd.13581
    [110]
    Lv Y et al 2021 Plasma Process Polym. 18 2000180 doi: 10.1002/ppap.202000180
    [111]
    Lee Y R, Lee S and Kim D G 2019 Biomed. Phys. Eng. Express 5 045027 doi: 10.1088/2057-1976/ab2bad
    [112]
    Szili E J et al 2018 Trends Biotechnol. 36 594 doi: 10.1016/j.tibtech.2017.07.012
    [113]
    Szili E J et al 2015 J. Phys. D: Appl. Phys. 48 202001
    [114]
    Szili E J, Bradley J W and Short R D 2014 J. Phys. D: Appl. Phys. 47 152002
    [115]
    Lademann J et al 2013 Laser Phys. Lett. 10 083001 doi: 10.1088/1612-2011/10/8/083001
    [116]
    Xin Y, Wen X and Jiang X 2021 J. Cosmet. Dermatol. 20 2794 doi: 10.1111/jocd.13983
    [117]
    Shimizu K, Tran A N and Blajan M 2016 Jpn. J. Appl. Phys. 55 07LG01 doi: 10.7567/JJAP.55.07LG01
    [118]
    Kristof J et al 2019 Plasma Sci. Technol. 21 064001 doi: 10.1088/2058-6272/aafde6
    [119]
    Vijayarangan V et al 2018 IEEE Trans. Radiat. Plasma Med. Sci. 2 109 doi: 10.1109/TRPMS.2017.2759322
    [120]
    Wu E et al 2023 Free Radic. Biol. Med. 198 109 doi: 10.1016/j.freeradbiomed.2023.02.011
    [121]
    Babaeva N Y and Kushner M J 2010 J. Phys. D: Appl. Phys. 43 185206
    [122]
    https://uigelz.eecs.umich.edu/Projects/ELECTROPORATION/electroporation.html
    [123]
    Yan D Y et al 2020 ACS Appl. Mater. Interfaces 12 345483
    [124]
    Yan D Y et al 2020 Sci. Rep. 10 11788 doi: 10.1038/s41598-020-68585-z
    [125]
    Wu S et al 2013 J. Appl. Phys. 113 043305 doi: 10.1063/1.4788797
    [126]
    Jurov A et al 2022 Biointerphases 17 021004 doi: 10.1116/6.0001596
    [127]
    Van der Paal J, Fridman G and Bogaerts A 2019 Plasma Process Polym. 16 1900122 doi: 10.1002/ppap.201900122
    [128]
    Kos S et al 2017 PLoS One 12 e0174966 doi: 10.1371/journal.pone.0174966
    [129]
    Weishaupt C and Emmert S 2018 Clin. Plasma Med. 10 16 doi: 10.1016/j.cpme.2018.03.002
    [130]
    Isbary G et al 2013 Clin. Plasma Med. 1 36 doi: 10.1016/j.cpme.2012.10.001
    [131]
    Boehm D and Bourke P 2018 Biol. Chem. 400 3 doi: 10.1515/hsz-2018-0222
    [132]
    Heslin C et al 2021 Front. Phys. 8 613046 doi: 10.3389/fphy.2020.613046
    [133]
    Dai X F, Shen L and Zhang J Y 2023 Trends Biotechnol. 41 15 doi: 10.1016/j.tibtech.2022.07.007
    [134]
    Wu A S et al 2013 J. Surg. Res. 179 e1 doi: 10.1016/j.jss.2012.02.039
    [135]
    Daeschlein G et al 2012 J. Dtsch. Dermatol. Ges. 10 509
    [136]
    Fluhr J W et al 2012 Exp. Dermatol. 21 130 doi: 10.1111/j.1600-0625.2011.01411.x
    [137]
    van der Linde J et al 2017 Plasma Med. 7 383 doi: 10.1615/PlasmaMed.2017019167
    [138]
    Dai X F et al 2020 Cancers 12 3360 doi: 10.3390/cancers12113360
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