Device for treating living cells in a given medium

The invention concerns a device for assisting living cell treatment in a given medium, characterised in that is comprises means ( 20 - 1 ) for generating an electric field ( 21 ) with substantially planar and parallel equipotential surfaces ( 22 ) and means ( 20 - 2 ) for applying said electric field ( 21 ) to at least part of the living cells, said means including at least two sets ( 23, 24 ) of electrode means capable of penetrating into the given medium up to the level of the living cells to be treated and means ( 25 ) for applying at least one electrical pulse between the two sets ( 23, 24 ) of electrode means. The invention is particularly advantageous for electrochemotheraphy of cancer tumours or the like, and also in laboratory for treating cell culture, liposomes and the like.

Although the three FIGS. 2 to 4 represent different embodiments of the device according to the invention, the same reference numerals therein denote the same components, irrespective of the representation of these components and irrespective of the figure on which they are represented. The Applicant also wishes to point out that FIGS. 2 to 4 represent different embodiments of the subject according to the invention, but that other embodiments which satisfy the definition of this invention can exist. It is also pointed out that when, according to the definition of the invention, the subject of the invention comprises “at least one” component having a given function, the embodiment described can comprise several of these components. It is also pointed out that, although the embodiment of the subject according to the invention as illustrated comprises several components of identical function and although, in the description, it is not specified that the subject according to this invention should necessarily comprise a particular number of these components, the subject of the invention may be defined as comprising “at least one” of these components. It is first pointed out that the description below refers only to the three FIGS. 2 to 4 , since FIG. 1 relates to the prior art cited in the preamble and has been described and commented upon hereinabove. FIGS. 2 to 4 represent, in a schematic form, a device for assisting in treating living cells in a given medium. By way of non-limiting example, in the following description, the living cells to be treated will be those of a cancer tumour located in the flesh of a patient who in this case constitutes the given medium, but it is clearly understood that the invention is not limited to this application alone. This device comprises means 20 - 1 for creating an electric field 21 having substantially planar and parallel equipotential surfaces 22 , and means 20 - 2 for applying this electric field 21 to at least part of the tumour ( FIG. 2 ), so as to obtain a uniform electric field in the tumour. In one preferred embodiment, the means 20 - 1 for creating an electric field 21 having substantially planar and parallel equipotential surfaces 22 and the means 20 - 2 for applying this electric field 21 to at least part of the tumour comprise at least two sets 23 , 24 of electrode means which are capable of penetrating into the flesh of the patient up to the level of the part of tumour, and means 25 for applying an electric tension between the two sets 23 , 24 of electrode means. It is clearly specified that “electric tension” means any electrical signal defined in volts or amperes, which is direct, alternating or in the form of pulses of any shape or duration. Advantageously, each set 23 , 24 of electrode means which are capable of penetrating into the flesh of the patient up to the level of the part of tumour to be treated consists of a support 52 ( FIG. 4 ) made of an electrically insulating material, a plurality of needles 26 made of an electrically conductive material, each needle comprising a pointed end 34 , and means 27 for mounting each needle 26 onto the support 52 such that they are parallel to each other and in the same plane 28 , 29 . Furthermore, the two planes 28 , 29 in which are arranged the two pluralities of needles 26 corresponding respectively to the two sets 23 , 24 are substantially parallel and the needles of the same set 23 , 24 are located at equal distance to each other. It is quite clear that, in one practical embodiment, the support 52 is the same for the two sets of needles 23 , 24 . Also in a practical embodiment, the device will comprise a plurality of pairs of sets of needles 23 , 24 . In the embodiment illustrated in FIG. 3 , it comprises 12 needles 26 which constitute eleven pairs of sets of needles 23 , 24 referenced I to XI, but only one support 52 for all the needles. To facilitate the present description, the portion of device consisting of the support 52 and all the needles solidly attached to this support will be referred to hereinbelow by the term “applicator” denoted by the reference 50 . Depending on the shape and size of the tumour to be treated, the needles 26 of the applicator 50 can have substantially the same length or different lengths. In one advantageous embodiment illustrated in FIG. 4 , the means 27 for mounting each needle 26 onto the support 52 comprise a seating 30 comprising a hollow open housing, 31 . This seating is mounted, for example by plugging, in a hole 35 made in the support 52 and the means 27 also comprise a socket 32 which is solidly attached to the needle 26 at its end 33 which is opposite the pointed end 34 . The socket 32 constitutes the male part of a male-female connection which is complementary to the female part consisting of the hollow housing 31 . Needless to say, for an industrially advantageous embodiment and for good performance of the needles on the support 52 , this male-female connection is advantageously of the conical type. In order to be able to apply an electric tension to the needle more easily, the seating 30 and the socket 32 are made of an electrically conductive material, and one end of the seating emerges from the support 52 and can constitute an electrical connector capable of receiving an electrical conductor such as those defined below bearing the reference numeral 46 in FIGS. 2 and 3 . In addition, each seating 30 is arranged in the corresponding hole 35 such that the entry 36 of the hollow housing 31 is recessed relative to the entry 37 of the hole 35 facing the pointed end 34 of the needle. In this way, the electrical path between two proximal sockets ( FIG. 4 ) belonging respectively to two sets of a pair 23 , 24 is fairly large. This configuration avoids short circuits between these two sockets, even when they are subjected to high electrical potential differences, for example of the order of 600 volts in the case of the treatments mentioned in the preamble to the present description. When the means 27 for mounting each needle 26 on the support 52 are made up as described above, the device also advantageously comprises means for automatically releasing the sockets 32 , and thus the needles 26 , from the hollow housings 31 , in order, for example, to spare somebody who has to handle the applicator from accidentally injecting themselves when the treatment is complete. These means have not been illustrated since they can be of any type, for example consisting of plates mounted slideably relative to each other such that, when they are placed in a given position, they are capable of exerting traction forces between the seatings 30 and the sockets 32 fitted with the needles 26 , in order to detach the two parts of the fitting, and so that they can then free the sockets to allow the needles to fall into a container without them having to be handled by the person administering the treatment. The process can be performed as follows to place the needles of the applicator 50 on the support 52 . The needles are prearranged in a matrix on an auxiliary support, in relative positions identical to those of the hollow housings 31 on the support 52 and covered with a protective envelope. The sockets 32 are then plugged into the seatings 30 , after which the envelope protecting the needles is removed. As regards the means 25 for applying an electric tension between the two sets 23 , 24 of electrode means 26 according to the embodiment illustrated in FIG. 2 , they comprise an electrical power source 40 whose two outputs 41 are connected, by means of conductors 46 , to the electrodes 26 of the two sets 23 , 24 , respectively. When the device comprises a plurality of needles allowing the production of more than two sets of electrodes, 23 , 24 , as in the embodiment according to FIG. 3 , the means 25 for applying an electric tension to the needles comprise an electrical power source 40 comprising electrical power supply outputs 41 and a commutator 42 which can be controlled using a control input 47 , for example an electronic commutator which is well known per se. This commutator 42 is controlled, for example, by means of a computer or the like which can also control the electrical power supply 40 in order to synchronize the control of the commutator and the emission of the pulses by this source. The electrical power source 40 is, for example, of the type described in the French patent cited in the preamble. The commutator comprises supply inputs 43 and outputs 44 , the latter advantageously being at least equal in number to the number of seatings 30 in the applicator 50 , means 45 for connecting the outputs 41 of the electrical power source 40 to the supply inputs 43 of the commutator 42 , and means 46 such as conductive wires for connecting each output 44 of the commutator to a seating 30 . It is thus possible to control the commutator 42 in order successively to produce the pairs of sets of needles “I” to “XI”and, each time that a pair is produced, to control the electrical power source 40 such that it emits a predetermined electrical pulse. Incidentally, it is clearly understood that the seatings 30 , the sockets 32 and the needles 26 can comprise a central channel passing through them in order to convey medicinal substances into the part of the given medium to be treated. The device according to the invention unquestionably has advantages over the devices of the prior art, more particularly over the device described in the document cited in the preamble. Firstly, it is found that, with the device according to the invention, the treatment requires the emission of a considerably smaller number of pulses than that which is required with the device of the prior art. If it is considered, for example, that the device according to the invention and the one according to the prior art comprise the same number of needles, for example 12 as illustrated in FIG. 3 , the treatment of the part of tumour in which these 12 needles are implanted requires the application of at least 21 pulses with the device of the prior art, whereas no more than 11 pulses are required with the device according to the invention, and it is theoretically possible to treat the entire volume delimited by the 12 needles with only the two pairs of sets of needles I and VI. It should also be mentioned that, as explained in the preamble, with the device of the prior art there nevertheless remains uncertainty regarding the quality of the treatment of the prismatic volumes defined, such as the volume bearing the reference numeral 9 in FIG. 1 . With the device according to the invention, there is no risk of there being an untreated zone in the part of tumour in which the needles are implanted. In the device according to the invention, it is found that the needles are arranged in two ways relative to each other, in a “square” for the pairs of sets I, VI, IX, X and XI, and in “staggered rows” for the pairs II, III, IV, V, VII and VIII, but they delimit a rectangular parallelepipedal treatment volume, thus making it possible to treat the entire tumour by stepwise movement of the applicator 50 without it being necessary, during the new implantation of the needles, to recover a part of the previous volume treated, as in the case of the treatment with the device of the prior art to treat the zones bearing the reference numeral 13 in FIG. 1 . The device according to the invention thus allows faster treatments than that of the prior art and with better efficacy, and thus in conclusion less inconvenient and traumatizing treatments for the patients.