Abstract:
An actuator for arrangement in contact with a biological solvent includes a housing with a wall which is permeable to the solvent and not permeable to a first solute and which contains micro-organisms for transforming a second solute into the first solute. The actuator further includes a deformable chamber connected to the housing which can increase in volume due to the solvent entering the housing by osmosis. An engine may make use of the actuator.

Description:
This application is the national stage application under 35 U.S.C. § 371 of the International Application No. PCT/FR03/00592 and claims the benefit of French Application No. 02/02558, filed Feb. 28, 2002 and Int&#39;l Application No. PCT/FR03/00592, filed Feb. 4, 2003, the entire disclosures of which are incorporated herein by reference in their entireties. 
     BACKGROUND OF THE INVENTION 
     The present invention relates to devices usable as an actuator or a motor which are simple to form, which use low-cost fuel, and which emit little or no waste. 
     Further, the present invention relates to devices usable as an actuator or a motor capable of operating inside of a biological medium such as the human body or an animal body. 
     Such actuators or such motors find applications in the medical field, for example, to palliate the deficiency of a natural muscle. The muscles that can be replaced or assisted, temporarily or definitively, are, for example, the heart muscle, the respiratory muscles, the sphincter, and non-striated or striated muscles, in particular, skeletal muscles. 
     Such actuators and such motors also find applications in fields other than the medical field. In particular, such a motor may be used in all the fields where a small waste generation is an important factor in the motor selection. It may be, for example, the automobile field where the polluting waste generated by the motor used to drive the vehicle wheels is desired to be reduced as much as possible. 
     Still unpublished French patent application FR0109526 assigned to the applicant describes an osmotic actuator intended to be plunged into a biological medium and comprising a deformable enclosure having a semi-permeable membrane, said enclosure containing an osmotically active solute. 
     SUMMARY OF THE INVENTION 
     The present invention aims at providing an osmotic actuator and motor that can operate over a long time and the operation of which can be controlled with more accuracy. 
     More specifically, the present invention provides an actuator intended to be arranged to contact a biological solvent, comprising an enclosure having a wall permeable to the solvent and non-permeable to a first solute and containing microorganisms capable of transforming a second solute into the first solute; and a deformable chamber connected to the enclosure that can see its volume increase under the action of the solvent penetrating into the enclosure by osmosis. 
     According to an embodiment of the present invention, the enclosure comprises a bundle of hollow fibers colonized by the microorganisms. 
     According to an embodiment of the present invention, the enclosure has a wall permeable to the second solute. 
     According to an embodiment of the present invention, the enclosure has a wall non-permeable to the second solute, the microorganisms being capable of transforming a number of particles of the second solute into a higher number of particles of the first solute. 
     The present invention also provides a motor comprising an actuator such as described hereabove, in which the chamber comprises a return means which opposes to the volume increase of the chamber and a controllable means for decreasing the osmotic pressure in the chamber. 
     According to an embodiment of the present invention, the motor further comprises a secondary enclosure having a portion permeable to the solvent and non-permeable to the particles of the first and second solutes, and containing microorganisms capable of transforming a number of particles of the second solute into a smaller number of particles of the first solute, said secondary enclosure being connected to the chamber by a valve. 
     According to an embodiment of the present invention, the enclosure is arranged in a deformable envelope containing the solvent and the first solute, the means for decreasing the osmotic pressure in the chamber being a valve capable of permitting communication between the chamber and the envelope. 
     According to an embodiment of the present invention, the envelope comprises microorganisms capable of transforming a number of particles of the second solute into a smaller number of particles of the first solute. 
     According to an embodiment of the present invention, the motor comprises a means for permitting communication between the envelope and a source for supplying substances necessary to the metabolism of the microorganisms. 
     According to an embodiment of the present invention, the communication means comprises a bundle of hollow fibers crossing the envelope and in which a fluid containing said substances can circulate. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
       The foregoing and other objects, features, and advantages of the present invention will be discussed in detail in the following non-limiting description of specific embodiments in connection with the accompanying drawings, among which: 
         FIGS. 1A and 1B  show two steps of the operation of a first embodiment of a motor according to the present invention; 
         FIGS. 2A and 2B  show two steps of the operation of a variation of the first embodiment of the motor according to the present invention; 
         FIGS. 3A to 3C  show three steps of the operation of a second embodiment of the motor according to the present invention; and 
         FIGS. 4A to 4D  show four steps of the operation of a third embodiment of the motor according to the present invention. 
     
    
    
     DETAILED DESCRIPTION 
     In  FIGS. 1A and 1B , an osmotic motor  10  according to the present invention comprises an enclosure  12  formed by a bundle of hollow fibers with a semi-permeable wall  14 , for example, of the type used for dialysis operations. The wall of fibers  14  has a cut-off threshold on the order of 200 Daltons, that is, it lets through particles having a molar mass substantially smaller than 200 Daltons, that is, than 200 g/mol. Each fiber has, for example a diameter on the order of 200 μm. Fiber bundle  14  is maintained at a first end by a first junction ring  16 , for example, via a gluing area  18 . Ring  16  comprises an opening  20  closed by a plug  21 . The second end of the fiber bundle  14  is maintained by a second junction ring  22 , for example, via a gluing area  24 . A membrane  25 , having a cut-off threshold on the order of 1000 Daltons, closes second ring  22 . 
     Enclosure  12  is attached at the level of second junction ring  22 , to an end of a cylindrical body  28  in which a mobile piston  30  can slide. Mobile piston  30  and the cylindrical body define an expansion chamber  31 . A return means  32 , for example, a spring, exerts on piston  30  a tensile load tending to bring it back to an idle position. Cylindrical body  28  comprises an outlet valve  34  communicating with the outside of motor  10 . 
     A population of bacterial, vegetal, or animal cells, which are capable of fabricating an osmotically-active substance X is arranged within fibers  14 . The cut-off threshold of fibers  14  is set to prevent passing of substance X, while the cut-off threshold of membrane  25  is set to enable passing of substance X, but to block the cells. In the present example, substance X is di-hexose and the cells may consist of  E. Coli  cells genetically engineered to produce the di-hexose. Various genetic engineering means enable having a genetically-engineered cell fabricate di-hexose and export it outside of the cell. 
     In an initial phase, to arrange the genetically-engineered cells inside of fibers  14 , enclosure  12  may be placed alone in an osmotically neutral ambient medium and a culture liquid containing the genetically engineered cells may be slowly circulated inside of fiber bundle  14 , via opening  20 . The cut-off thresholds of membrane  25  and of the wall of fibers  14  are sufficiently low to retain the cells within fibers  14 . The ambient medium comprises a solvent in which are dissolved the nutritive substances essential to the cell metabolism, among which glucose (having a molar mass of approximately 180 Daltons) and oxygen. The cut-off threshold of fibers  14  is determined to let through from the ambient medium to the cells the nutritive substances and to let through, into the ambient medium, the waste generated by the cell metabolism. The genetically-engineered cells can thus colonize the inside of fibers  14 . The cells are for example treated to deposit and adhere on the internal wall of fibers  14  in the form of a monolayer. When the colonization has been performed, opening  20  is closed by plug  21 . 
     The cells may further be treated to obtain properties favorizing the long-term operation of the motor. It may be desired to obtain “immortalized” cells to favor the long-term operation of the device. It may also be desired to obtain cells exhibiting a “contact inhibition” to put the entire cell population in a harmonious state enabling, in particular, a good circulation of the nutritive and catabolic substances. 
     An operating cycle of motor  10  develops as follows. 
     In normal operation, motor  10  is placed in an ambient medium comprising a solvent in which are dissolved the nutritive substances essential to the cell metabolism, in particular glucose. 
       FIG. 1A  shows motor  10  at the beginning of a cycle. Piston  30  is in its idle position, the volume of expansion chamber  31  being minimum and outlet valve  34  is closed. The genetically-engineered cells produce, from the glucose, di-hexose molecules, which tends to increase the osmotic pressure within fiber bundle  14 . The solvent of the ambient medium penetrates into fibers  14  and into expansion chamber  31 , thus displacing piston  30 . The displacement of piston  30  extends spring  32 , enabling storage of mechanical power. 
     In  FIG. 1B , expansion chamber  31  is shown in maximum expansion. Outlet valve  34  then opens. The pressure inside of expansion chamber  31  equalizes with the pressure of the ambient medium. Spring  32  brings piston  30  back to its idle position by evacuating, through outlet valve  34 , the solvent from expansion chamber  31  into the ambient medium. The mechanical power stored in spring  32  is then recuperated. Valve  34  is finally closed, thus ending the motor stroke. 
     Piston  32  may be connected to an external element to which mechanical power is desired to be transmitted. 
     According to the first embodiment, expansion chamber  31  is formed of a cylindrical body in which a piston slides. According to the desired use of motor  10  according to the present invention, expansion chamber  31  may be formed differently. 
       FIGS. 2A and 2B  show another alternative structure of expansion chamber  31  of motor  10  of the first embodiment. According to this variation, expansion chamber  31  corresponds to the space defined between an inner envelope  36  and an outer envelope  37  as in an air chamber. Inner envelope  36  is deformable and extensible and surrounds a deformable body  38 . Outer envelope  37  is flexible and inextensible. It closes back on inner envelope  36  and is connected to junction ring  22  of enclosure  12 . Outlet valve  34  is arranged on junction ring  22 . As an example, in a medical application of osmotic motor  10  according to the present invention, deformable body  38  may be the human heart and the envelopes may define flange-shaped expansion chambers  31  surrounding the heart. 
     A cycle of motor  10  according to this variation of the first embodiment is the following. 
       FIG. 2A  shows motor  10  at the beginning of a cycle. The volume of expansion chamber  31  is minimum, deformable body  38  being in maximum expansion, which may correspond to a heart in diastole. Outlet valve  34  is then closed. The genetically-engineered cells generate di-hexose, which causes, by osmosis, the introduction of solvent into expansion chamber  31 . Inner envelope  36  deforms and compresses deformable body  38 . 
     In  FIG. 2B , deformable body  38  is compressed to a maximum, which may correspond to a heart in systole. On opening of outlet valve  34 , the solvent leaves expansion chamber  31 , enabling expansion of deformable body  38 , which ends the cycle. 
     According to another variation of the present invention, expansion chamber is formed of a resilient envelope enclosing the fibers which are arranged, for example, in a spiral, the two junction rings being tight. When the cells produce the osmotically-active substance, the fibers tend to straighten and deform the resilient envelope. An outlet valve is provided at the level of a junction ring. At the valve opening, the pressure within the fibers decreases and the envelope tends to recover its initial shape. 
     According to another variation of the present invention, the enclosure may be connected to the expansion chamber by a flexible duct. This enables advantageously arranging the enclosure in a ambient medium favorable for the solvent and glucose supply, and placing the expansion chamber at a location where mechanical power is desired to be available. In the case of a medical application, the enclosure could be arranged in an adipose tissue, or on the vascular system. In this last case, the fibers may be arranged to form a hollow tube, leaving at its center a cylindrical space enabling circulation of a fluid such as blood. The junction rings may be O-shaped and placed against the wall of a heart vessel. One of the O-shaped junction rings communicates with the expansion chamber by the flexible duct which perforates the blood vessel. 
       FIGS. 3A to 3C  show a second embodiment of an osmotic motor according to the present invention. Motor  40  comprises the components of the motor of the first embodiment and the reference numerals associated therewith are kept. 
     Motor  40  comprises a first enclosure  12  of the previously-described type and a second enclosure  42 . Second enclosure  42  comprises a second fiber bundle  44  maintained at its ends by junction rings  45 ,  46  by means of gluing areas  47 ,  48 . Second enclosure  42  is attached on cylindrical body  28  at the level of valve  34 , by junction ring  45  which comprises a membrane  49  separating expansion chamber  31  from second fibers  44 . Second enclosure  42  communicates, at the level of ring  46  via a membrane  52 , with a tight deformable vessel  54 . 
     First fiber bundle  14  is colonized by a first population P 1  of genetically-engineered cells producing a substance X (for example, lactose) from a substance Y (for example, di-lactose) so that, from an elementary particle of substance Y, more than one elementary particle of substance X is produced. Second fiber bundle  44  is colonized by a second pollution P 2  of genetically-engineered cells producing substance Y from substance X so that, to produce an elementary particle of substance Y, more than one elementary particle of substance X is used. 
     The walls of fiber bundles  14 ,  44  have a cut-off threshold smaller than the molar mass of substances X and Y. As an example, the cut-off threshold is on the order of 200 Daltons since substance X is lactose and substance Y is di-lactose. Membranes  25 ,  49 , and  52  have cut-off thresholds greater than 1000 Daltons, to let through substances X and Y and maintain the genetically-engineered cells in respective fiber bundles  14 ,  44 . 
     In normal operation, motor  40  is placed in an ambient medium comprising a solvent in which are dissolved the nutritive substances essential to the cell metabolism, in particular, glucose. The operating cycle of osmotic motor  40  according to the present invention is the following. 
       FIG. 3A  shows motor  40  at the beginning of the cycle. Valve  34  is closed. The concentrations in substance X are identical in vessel  54  and expansion chamber  31 , as well the concentrations in substance Y, and in glucose. In first fiber bundle  14 , population P 1  produces substance X, which increases the osmotic pressure in expansion chamber  31 . The solvent of the ambient medium penetrates into first fiber bundle  14 , then into expansion chamber  31 , thus displacing piston  30  and storing mechanical power by the stretching of spring  32 . Meanwhile, in second fiber bundle  44 , population P 2  produces substance Y, which decreases the osmotic pressure in vessel  54 . Vessel  54  sees its volume decrease, without creating effective work since nothing opposes this decrease. 
       FIG. 3B  shows motor  10  at the end of the previously-described step, expansion chamber  31  having a maximum volume. 
     Valve  34  then opens. The concentrations in substance X and in substance Y balance in fiber bundles  14 ,  44 , expansion chamber  31 , and vessel  54 . Similarly, the osmotic pressures balance in the different compartments. Piston  30  thus moves under the action of spring  32  down to the position shown in  FIG. 3C . Further, vessel  54  expands by filling up with liquid, the work necessary to expand vessel  54  being negligible as compared to that provided by spring  32 , the pressures in the ambient medium being low as compared to those present in expansion chamber  31 . Valve  34  is then closed, which ends the cycle. 
     In the second embodiment, the walls of fibers  14 ,  44  only let through the solvent of the ambient medium as well as the substances involved in the metabolism of the genetically-engineered cells, especially glucose, oxygen, or carbon dioxide. 
     The second embodiment is particularly advantageous since the exchanges between motor  40  and the ambient medium are reduced with respect to the first embodiment. Indeed, in the first embodiment, the osmotically-active substance, di-hexose, is produced from glucose present in the ambient medium. Further, at the end of a motor cycle, outlet valve  34  is open and most of the di-hexose produced by the cells is released into the ambient medium. In the case of a medical application, the produced di-hexose is released into the human body, which may be a problem. In the second embodiment, there actually is a glucose consumption by the cells, but only for their normal metabolism, that is, in a much smaller proportion than that of the first embodiment. 
     According to a variation of the second embodiment, substance X may be glucose and substance Y may be lactose. The cut-off threshold of the membranes of fibers  14 ,  44  then is set to a threshold smaller than that of glucose, for example, 100 Daltons. The glucose necessary to the cell metabolism thus cannot cross these membranes. Vessel  54  then comprises a means for putting it in communication with the ambient medium. It may be, for example, a valve associated with a membrane having a cut-off threshold at 200 Daltons. The valve is for example open for a short time period when the vessel is at a minimum volume. This enables glucose molecules of the ambient medium to penetrate into the vessel. The glucose molecules will enable compensating for the losses linked to the cell metabolism. 
       FIGS. 4A to 4D  show a third embodiment of osmotic motor  60  according to the present invention. Motor  60  comprises the components of motor  10  of the first embodiment and the reference numerals associated therewith are kept. 
     Enclosure  12  is arranged in a tight deformable envelope  61  which closes back on junction ring  22  and outlet valve  34 . The enclosure is filled with a biological liquid. A second bundle of fibers  62  is arranged in envelope  61 . Envelope  61  may be arranged in a perforated rigid carter  64  to avoid hindering the deformations of envelope  61 . Fiber bundle  62  is maintained at its ends by junction rings  66 ,  68 , for example, by gluing areas  70 ,  72 . Junction rings  66 ,  68  cross envelope  61  and are attached on rigid carter  64 . They each comprise a valve  74 ,  76  permitting communication between the internal space of fibers  62  and the outside of the carter  64 . 
     First fiber bundle  14  is colonized by a first population P 1  of genetically-engineered cells producing a substance X (for example, di-hexose) from a substance Y (for example, quadri-hexose) so that from an elementary Y particle, more than one elementary X particle is produced. A second population P 2  of genetically-engineered cells, arranged inside of envelope  61 , is capable of producing substance Y from substance X so that, to produce an elementary particle of substance Y, more than one elementary particle of substance X is used. Second population P 2  of cells may be deposited on the external walls of fibers  62 . 
     The membranes of fiber bundles  14 ,  62  have a cut-off threshold greater than the molar mass of glucose but smaller than the molar mass of substances X and Y. As an example, the cut-off threshold is on the order of 200 Daltons when substance X is a di-hexose, and substance Y a quadri-hexose. 
     Rigid carter  64  may be arranged in a biological medium so that a biological fluid can flow into second fiber bundle  62  when valves  74 ,  76  are open. Fluid supply and outlet ducts may also be directly connected at the level of junction rings  66 ,  68 . The cut-off threshold, for example, of 100 Daltons, of the membrane of fiber bundle  62  enables passing of the substance necessary to the metabolism of cell populations P 1 , P 2 . 
     An operating cycle of motor  60  according to the third embodiment is the following. 
       FIG. 4A  shows motor  60  at the beginning of a cycle. Valves  34 ,  74 ,  76  are closed. Envelope  61  is at its maximum volume. All the compartments contain a solvent where substance X and Y are in solution. First population P 1  of cells starts producing substance X, which increases the osmotic pressure in bundle  14  and expansion chamber  31 . Second population P 2  starts producing substance Y, thus reducing the osmotic pressure inside of envelope  61 . The liquid exchanges occur, the liquid flowing towards first fiber bundle  14  and, from there, to expansion chamber  31 , causing the displacement of piston  30 . The piston is in an ascending phase. 
       FIG. 4B  shows motor  60  at the end of the previously-described step. The concentration in substance Y is minimum in first fiber bundle  14  and maximum inside of envelope  61 . Conversely, the concentration in substance X is maximum in first fiber bundle  14  and minimum in envelope  61 . The different compartments have a reduced oxygen concentration as compared to the beginning of the cycle and a carbon dioxide concentration greater than that of the beginning of the cycle. 
     In  FIG. 4C , valves  74 ,  76  are opened to permit communication between second fiber bundle  62  and a fluid external to rigid carter  64 . The gas concentrations then balance in all the compartments. Similarly, the glucose concentrations balance between envelope  61  and the external fluid without for the piston position to vary. 
     Valves  74 ,  76  are then closed and outlet chamber  34  is opened, which permits direct communication between expansion chamber  31  and envelope  61 . The pressure in expansion chamber  31  drops and return spring brings piston  30  back to its initial position evacuating the solvent from expansion chamber  31  to envelope  61 . The piston is said to be in a descending phase. First fiber bundle  14  is thus put in communication with the inside of envelope  61 . The concentrations in substance X and Y equalize between the two compartments. 
       FIG. 4D  shows motor  60  at the end of the descending phase of piston  30 . Valve  64  is then closed, which ends the cycle. 
     A variation of the fourth embodiment of the osmotic motor may be used as a motor for driving the wheels of an automobile vehicle. According to this variation, the spring is suppressed and the piston is connected, for example, by a rod to a wheel drive shaft similarly to the connection between a piston of a thermal motor and the crankshaft. The driving power corresponds to the ascending phase of the piston, that is, to the expansion phase of the expansion chamber. In descending phase, when the volume of the expansion chamber decreases, the piston encounters but a small resistance, corresponding to the passing of the solvent through the outlet valve of the expansion chamber. Advantageously, at least two osmotic motors may be arranged in parallel to drive the drive shaft so that the expansion chambers of the motors work in opposition, one being in expansion phase while the other is in contraction phase. 
     Such a motor may further be used to recover power on braking of the vehicle. In this case, it comprises an additional valve, called the supply valve, arranged between the first fiber bundle and the expansion chamber. Upon operation of the motor to drive the wheels, the supply valve is opened so that the motor operates as described previously. 
     In the case of a braking, when the piston is in ascending phase, the supply valve is closed and the outlet valve is open so that the expansion chamber fills up with liquid with no significant effort. A large part of the liquid contained in the deformable envelope passes into the expansion chamber without for the concentrations in the various compartments to vary. The supply valve is then opened and the outlet valve is closed. When the piston goes down under the action of the drive shaft driven by the wheels, the liquid contained in the expansion chamber is chased through the fiber bundle and reaches the envelope. The work thus generated enables both slowing down the vehicle and varying the concentrations of substance X and Y. Indeed, the osmolarity of the first fiber bundle increases as the osmolarity in the deformable envelope decreases. 
     Thereby, when the motor operates again as a wheel drive motor, the supply valve being open, the motor cycle is resumed with a greater efficiency. Indeed, the concentration differences between compartments will create a pressure difference due to which the cycle will be completed faster. 
     Of course, the present invention is likely to have various alterations, modifications, and improvements which will readily occur to those skilled in the art. In particular, for the second and third embodiments of the motor, the expansion chamber may be formed according to the described variations of the first embodiment. 
     Further, each enclosure  12 ,  42 ,  62  may be formed other than by a fiber bundle. It may have any shape enabling a good exchange of the solutes and of the solvent on either side of the enclosure wall and easing the colonization of the enclosure by a population of genetically-engineered cells. 
     Moreover, each valve  34 ,  74 ,  76  may exhibit any known structure type. The openings and closings of each valve may for example be controlled by a device external to the motor, synchronously or not, or be automatically triggered by the very structure of the valve when the pressure in a compartment of the motor exceeds a determined value.