The invention provides a process to prepare a complex of adsorption charcoal-GM1 stable at different pH values. This process is based on the suspension method, the formulation example being presented. An analytical method to determine non derivatized GM1 in aqueous solutions using the high efficiency liquid chromatography technique is also object of the present invention.

This invention refers to a process for the preparation of a charcoal-GM1 complex and to an analytical method designed to determine underivatized GM1 in aqueous solutions by high performance liquid chromatography (HPLC).
This complex may be utilized as adjutant in the treatment for cholera, in the sense that it contributes to the neutralization of the correspondent toxin [STOLL et al. Lancet, p.888-891, 1980]. Moreover, in vitro tests demonstrated its potential as antidote for cases of ferrous ions intoxication.
In order to assess the effectiveness of the process for the preparation of the activated charcoal-GM1 complex, a analytical method has been developed in order to determine the GM1 by HPLC, using a new solvent system for the analysis of the ganglioside in the underivatized form.
This isocratic system has made possible the execution of the analysis with some advantages to the methodology as described in the literature.
The process for the attainment of the charcoal-GM1 complex described herein was developed seeking the stability of the product obtained in the conditions of pH as those of gastrointestinal tract, therefore helping in its safety.
The bacterial caused enteric infections, that result in diarrhea, dysentery and enteric fevers, accounts for serious health problems [BLACK., R. E., BROWN, K. H., BECKER, S., ALIM, A.R.M.A., HUQ, I. Am. J. Epidemiol., v. 115, p.315-324, 1982].
Among the most important pathologies of this type, we have cholera, pathology that results from the action of an enterotoxin developed from the Vibrio cholerae 01, a gram-negative bacteria. The production of this toxin takes place as the microorganism successfully couples with the mucous of the proximal portion of the small intestine. [LEVINE, R., KAPER, J. B., BLACK, R. E., CLEMENTS, M. L., Microbiol. Rev., v.47, n.4, p.510-550, 1983].
This toxin presents sub unity A separated from the ring plane formed by 5 minor sub units that are identical (Sub units B). Its molecular weight is of approximately 84,000, and each sub unity B has molecular weight equivalent of 11,000 and the sub unity A is divided into A1 (PM=24,000) and A2 (PM=5,000) [LEVINE, R., KAPER, J. B., BLACK, R. E., CLEMENTS, M. L. Microbiol. Rev., v.47, n.4, p.510-550, 1983].
The B pentamer is connected with GM1 ganglioside in the membrane of the intestinal epithelium cells [SUREWICZ, W. K., LEDDY, J. J., MANTSCH, H. H. Biochemistry, v.29, p.8106-8111, 1990]. The sub unity A is inserted into the cytosol, thereby liberating the A1 fragment that will activate the latent adenylate-cyclase. The result is a rapid increase in the production of the cyclical-AMP [LEVINE, R., KAPER, J. B., BLACK, R. E., CLMENTS, M. L. Microbiol. Rev., v.47, n.4, p.510-550, 1983]. The consequence of these and other factors is an excessive accumulation of salts and water in the intestinal lumen and the death of the cell [FIELD, M., RAO, M. C., CHANG, E. B., N. Engl. J. Med., v.321, p.800-806, 1989].
The ganglioside-GM1 is the specific receptor for the cholera toxin [WU, G., LEDDEN, Anal R.. Biochem., v.173, p.368-375, 1988]. Also known as monosialoganglioside, the GM1 belongs to the class of glicosphingolipids, and is differentiated (together with other gangliosides) from other components of this class by the presence of sialic acid [HADJICONSTANTIONOU, M., NEFF, N. H. J. Neurochem., v.70, n.4, p.1335-1342, 1998].
Its structure, as represented below, shows hydrophobic and hydrophilic regions. The first one consists of ceramide, constituted of sphingosine and stearic acid and the hydrophilic portion is represented by the sialoligosacaridic chain. These features may provide the formation of micelles, and it is believed that the sialic segment may be involved with the reactivity of the ganglioside with the toxin.
In view of its specificity by the cholera toxin, the GM1 could be used for the treatment of the toxinfection by neutralisation of the toxin in the intestinal lumen. This was originally tested with the development of the charcoal-GM1 adsorption complex by STOLL et al. [STOLL et al. Lancet, p.888-891, 1980]. Despite this, it is important to point out that the authors cite the process for obtaining this complex without, however, describing it, neither the protocol for study of stability under which the complex was submitted. There is, therefore, no description of a process for obtaining this complex in the literature, and the above work concentrates on the analysis of the therapeutic benefits made available by this complex to or for the conventional treatment of cholera.
Currently, cholera treatment covers the disinfection by antibiotictherapy, the utilization of vaccines, besides different measures for the relief of the symptoms caused by that infection. In this connection, the use of this complex accounts for an important complement for the therapy that is applied.
Aiming at the safety of the utilization of this compound, it is essential that the process used for its development results in the stability of the same under pH values that are similar to the ones found in the gastrointestinal tract. This is due, particularly to the fact that the incorporation of the GM1 in the membrane of the intestinal cells increases the biological response to the cholera toxin by an increase in the number of receptors [HOLMGREN, J., LONNROTH, J., SVENNERHOLM, L. Proc. Nat. Acad. Sci. USA 72, p.2520-2524, 1975].
For the execution of a process for the preparation of the charcoal-GM1 complex, one should obviously be certain of the quantities and degree of purity of the basic components of that complex; the charcoal and the GM1, separately.
This invention, therefore, also comprises a new method for the determination of the GM1 in aqueous solutions.
The previous technique has used HPLC, by utilizing gradient systems for elution, which at times, would generate limitations concerning the resources made available by the equipment.
Table 1 hereinbelow summarizes the methodologies described in the literature.
It can be verified that the techniques indicated in the table above show times of analysis that vary from 20 minutes to 1 hour and 20 minutes. The proposed method has retention times somewhere around 8 minutes.
In addition, as can be seen from the literature describing the new method, below, this invention provides a method that was isocraticaly developed, i.e., utilizing a single mobile phase (a single composition), with relevant technical advantages.
Activated charcoal is one of the more frequently used adsorbents in medical practice, particularly in toxicology.
The pH is an important factor in its effectiveness [ROIVAS, L., NEUVONEN, P. J., J. Pharm. Sci., v.81, n.9, p.917-919, 1992], and this emphasizes the importance of verifying the behavior of this complex concerning variations of pH values and conditioning of the process for maximum effectiveness in the adsorption of the GM1.
Although the use of activated charcoal can be seen as the conduct of choice for the prevention of absorption of pharmacological agents and toxins [BYERLY, W. G., Am. Pharm., v.NS32, n.7, p.36, 1992], one of the main limitations to its antidotal activity lies in the inefficacy of adsorption of cations, for instance ferrous ions.
Accidental ingestions of preparations that contain iron are common, and this is a serious problem in pediatrics. According to ENGLE et al. [ENGLE, J. P., et al., Drug Intell. Clin. Pharm., v.21, p.153-159, 1987], approximately 2,000 cases of toxicity by iron in children are reported annually, so iron ingestion is one of the most common pediatric ingestion issues. Still according to the author, despite the frequency of poisoning by iron, there is no universally accepted protocol for cases of patients who have ingested toxic quantities of iron.
In this connection, the antidotal potential of the complex obtained by the proposed methodology, as demonstrated through in vitro tests, can account for an important alternative for cases of poisoning by ferrous ions.
The purpose of the invention is to provide a new process for the preparation of a charcoal-GM1 complex, characterized by the fact it comprises stages of:
(a) preparing a diluente solution (A) composed of 0 to 0.9% of sodium chloride, from 0 to 0.03% of monobasic sodium phosphate-2H2O, and 0 to 0.4% of dibasic sodium phosphate-12H2O, dissolved in distilled water;
(b) dissolving, in part of solution (A), sufficient amounts of GM1 that would result in concentrations that range from 0.2 to 4.0% of the ganglioside, with a new solution then obtaining (B);
(c) suspending charcoal activated in the other part solution (A) in the ratio of 1:3 to 1:7 w/v, by initiating and maintaining moderated agitation for a period of 5 to 15 minutes;
(d) slowly adding, under agitation, adequate amounts of solution (B) in order to obtain proportions that vary between 1:100 and 1:10 (GM1:charcoal), the agitation of which is maintained by a period of 10 to 20 minutes;
(e) filtering the suspension, rinsing the complex with the solution (A) and submitting it to a process of drying; and,
(f) passing the dried complex through a 40 xe2x80x9cmeshxe2x80x9d sieve, preparing and placing the product in a hermetically locked recipient.
In a preferred embodiment, this invention is characterized by the fact that:
In stage (a), in diluente solution (A), the concentration of sodium chloride is 0.800%, and that of monobasic sodium phosphate is 0.025%, and that of dibasic sodium phosphate is 0.300%;
In stage (b), in solution (B) the concentration of GM1 in the solution (A) is of 2.000%;
In stage (c), it is suspended the activated charcoal in solution (A) in the ratio of 1:5 w/v, by initiating and maintaining moderated agitation by 15 minutes;
In stage (d), it is added, slowly and under agitation, amounts of solution xe2x80x9cBxe2x80x9d equivalent to the ratio 1:100 (GM1:charcoal), and the agitation should be maintained for 20 minutes; and,
In stage (e) the drying up is carried out at a temperature of 40xc2x0 C. during 24 hours.
The purpose of this invention is also to provide a new analytical method to determine underivatized GM1 in aqueous solutions by HPLC, characterized by the use of isocratic solvent system using a mobile phase made up of potassium chloride/acetonitrile.
In a preferred alternative for this invention method the mobile phase is made up of potassium chloride/acetonitrile of 0.1M (65:35).
Finally, this invention also comprises the study of the potential use of this complex as an antidote in intoxications by ferrous ions based on several tests conducted in vitro.
The GM1 content (solution (B)) was determined by using the HPLC technique, utilizing a Hewlett-Packard chromatographer model HP 1090M series 2, equipped with Rheodyne gauge with xe2x80x9cloopingxe2x80x9d of 250xc2x0 L, and xe2x80x9cDiode Arrayxe2x80x9d detector, coupled to an acquisition system, with control and data impression. The mobile phase was made up of potassium chloride/acetonitrile 0.1M (65/35, v/v) was used a LiChrosorb column NH2HPLC (250 mmxc3x974.6 mmxc3x975 xcexcm). The flow selected was of 1 mL/minute and the wave length for the detection was equivalent to 210 nm. The period for the stabilization of the equipment was 60 minutes, under analytical conditions.
The method was validated and has demonstrated sufficiently acceptable linearity (r=0.9997) in the interval of 1.50 xcexcg and 6.04 xcexcg of GM1, showing replicability with relative standard deviation lower than 0.700% and precision and accuracy varying between 0.230-1.280% and 97.930-103.440%, respectively (assays intra and inter-days).
The limits of detection and quantification were appropriate to the purpose proposed, with values calculated in 0.2518 xcexcg and 0.4689xc2x10.0265 xcexcg of GM1, respectively.
The method developed, using an unusual solvent system for the determination of underivatized GM1, by using the high efficiency liquid chromatography technique, presents several advantages when compared to those presented in literature. Such methods use an elution gradient system and analysis time estimated between 25 and 80 minutes (Table 1), whereas the methodology proposed uses the isocratic system, with time of retention of, approximately, 8 minutes, which simplifies its execution and significantly reduces the analysis cost.
The process which is the object of the present invention comprises the following stages:
Initially, diluente solution (A) was prepared, composed of up to 0.900% of sodium chloride, up to 0.030% monobasic sodium phosphate-2H2O, up to 0.400% dibasic sodium phosphate- 12H2O, and the solution is completed to 100.000% with distilled water.
In this solution (A) GM1 (TRB Pharma) was dissolved, obtaining concentrations varying between 0.200% and 4.000%, which resulted in new solution (B).
In an adequate recipient, activated charcoal was suspended in a solution (A) in the proportion of 1:3-1:7 w/v, starting and maintaining moderated agitation during 5-15 minutes. After this stage, solution xe2x80x9cBxe2x80x9d was slowly added, under agitation. The agitation was maintained by 10-20 minutes.
The suspension was filtered using Whatman(copyright) paper filter 42, washing the complex with, approximately, 25% of the solution (A) volume.
The complex was then submitted to the process of drying (40xc2x0 C./24h) and, when dried, it was passed through a sieve with 40 xe2x80x9cmeshxe2x80x9d and kept in hermetically sealed recipient.
The effectiveness of the process of adsorption of GM1 for the activated charcoal was checked analyzing the content of ganglioside in the filtrate. The amount of GM1 in the filtrate is inversely proportional to the effectiveness of the process.
The absence of GM1 in the filtrate, determinated according to the sensitivity of the above described method, indicates the minimum effectiveness of the complex estimated in 98%.
Stability tests on the complex were carried out at pH levels of 1.3; 7.0 and 8.3. The complex was maintained in a suspension in the respective solutions for 20 minutes and then was filtered through paper. The assays were carried out three times and the absence of GM1 in the filtrates indicate the stability of the complex at such conditions.
A HCl solution was prepared with a pH of 1.2, adding 300 mL of the solution in 4 cubes of the solution device, which was being started using paddles.
The speed used was of 100 rpm and the average temperature was 37xc2x0 C. and, once the balance of the system was established, the complex was added in 3 of the cubes of the device, the fourth cube being reserved for the addition of control charcoal.
The exposition of the complex to the acid medium was maintained, under the experimental conditions, for 20 minutes, and it was subsequently filtrated through paper.
The filtrate was submitted to the detection of GM1. The concentration of GM1 is inversely proportional to the stability of the complex.
The assay was repeated in a alkaline medium (solution of 0.18 M of NaHCO3-pH=8.2) and in distilled and deaerated water.
The absence of GM1 in the filtrates resulting from this test indicates the stability of the complex in the pH values studied, in experimental conditions.
The conditions under which the complex presented best stability were:
The activated charcoal must be suspended in solution A in the proportion of 1:5 w/v, starting and maintaining moderated agitation during 5 minutes. Solution (B) is slowly added, under agitation, according to the proportion adopted (see examples), maintaining the agitation for 20 minutes.
The suspension is filtered, washing the complex with, approximately, 25% of the solution (A) volume used in the process, submitting it to drying (40xc2x0 C./24 hours). The complex should be passed through a 40 xe2x80x9cmeshxe2x80x9d sieve and kept in hermetically sealed recipient.
The following are examples of execution of this process. Such examples are added as illustration, but they do not limit the scope of the present invention.

Process for preparing a charcoal-GM1 complex

TRB Pharma Industria Quimica e Farmaceutica Ltda


A method of producing a photographic image in an imagewise exposed photographic material comprising one or more silver halide emulsion layers comprises

The invention relates to a method of producing a photographic image. More particularly, the invention involves the photographic processing of silver halide materials. It applies particularly to processes which do not include washing stages which remove materials from the imaging layers. It is particularly useful for chromogenic colour development where the developer must not be allowed to remain in the image.
Processing of photographic materials in automatic processing equipment is normally carried out using tanks of solution through which the processed material is passed. The solutions are modified as they carry out the chemical processes. The effects of this modification are compensated for by replenishment of the tanks with replenisher solutions which add chemicals that have been used during processing. Care has to be taken to replenish tank solutions accurately so that the chemical concentrations are maintained at a constant level so that consistent performance can be ensured.
Solution is lost from the tanks when the processed material leaves the tank. Also, replenisher solutions are added to the tanks in larger quantities than are removed with the processed material thus producing liquid effluent. The solution removed from the tank by over-flow and by being carried out by the processed material allows the removal of chemicals introduced by the chemical processes occurring during processing.
Single-use processing systems involving the use of small volumes of solution have been described ( Research Disclosure September 1997 p638 ). These can involve the application of solutions to the surface of materials in a way which results in a uniform amount of solution being applied. The uniform application of developer to the surface of colour negative paper using ink-jet methods has been described in EP A 94201050.5. U.S. Pat. No. 3,869,288 describes the separate application of developer solution components by spraying droplets. U.S. Pat. No. No. 5,200,302 describes a method of processing involving coating developer to produce a film of processing solution of thickness xe2x80x9cat most 20xxe2x80x9d that of the dry gel thickness. Uniform application results in low density areas being treated with the same chemical amounts as maximum density areas. This results in inefficient chemical use and possibly in the production of higher than required density in minimum density areas.
U.S. Pat. No. 5,121,131 describes the use of an ink-jet writer to lay down a solution of bleach in an image-wise manner on a material with a uniform, silver-containing layer to produce an image in silver after the bleaching action of the solution has taken effect.
The use of the image information to control the amount of solution applied so that it is applied in an image-wise manner has also been described in U.S. Pat. No.5,701,541 for high silver papers. Processing involves bleaching and fixing to remove silver and silver halide followed by washing to remove all the soluble chemicals left in the coating including developing agent from the developer solution and the dissolved silver halide.
Removal of any material including developer, which will cause the image to be modified on keeping is necessary and a suitable treatment is therefore required. Removal of chemicals is usually performed by a washing stage involving the use of multiple tanks containing water or stabilising solution. These are often replenished by clean water or solutions added to the last of the sequence of tanks with overflow from the last tank replenishing the previous tank and so on until overflow emerges from the first wash/stabiliser tank. In this way, effluent is reduced but the effluent from the wash stage usually forms the majority of the liquid effluent from the process.
Low silver materials have been described which use small fractions of the amount of silver needed to provide the oxidation of developer resulting from development of the silver halide crystals when that oxidised developer is used to provide the image dye in sufficient amount for high image densities via reaction with colour-forming couplers. These low silver materials are processed in the presence of oxidising agents such as hydrogen peroxide in development amplification processes commonly referred to as Redox Amplification or RX processes. In such processes the developed silver image is used to catalyse in an image-wise manner, the production of oxidised developer and hence image dye. Such materials are appropriate for print production.
These were described in combination with the ink-jet application of developer in EP A 94201050.5. The amounts of silver coated in papers processed with RX solutions can be so low that silver can be left in the images without serious loss of quality.
The amounts of silver can also be sufficiently low to allow the retention of undissolved silver halide though it may be necessary to take steps to prevent the production of photolytic silver as described in U.S. Pat. No. 5,246,822 and U.S. Pat. No. 5,441,853.
U.S. Pat. No. 4,469,780 describes image production without washing by developing silver halide material, intensifying and treating with dilute acid-to-neutral buffer solution. Intensification with hydrogen peroxide or other oxidants is used to produce the image and no bleach or fix stages are present to remove silver or silver halide. The minimum image densities after processing are used as the criteria for the effectiveness of the post-development stages.
Colour developer can be removed by chemical treatment as described in a co-pending simultaneously filed patent application by the present applicant or by lamination with a cover sheet containing carbon as described in PCT GB99/04319. In addition, silver or silver halide can be removed by processes enabled by laminating the imaging material with a cover sheet.
It is very desirable to provide as simple and rapid a process as possible and one which requires a simple processing machine with minimal maintenance and which produces little or no effluent. Single-use processing can be used to avoid replenishment but uniform application of processing solutions results in wastage of chemicals because high levels of developer solution are applied whether image density is required or not. The higher than necessary levels of developer provide not only greater difficulty removing the developer but the excess developer produces higher than desired densities in low density image areas.
Normally, removal of unused developer by washing stages is performed and is effective but this produces liquid effluent. The other methods of extraction or destruction of developer are more limited in capacity. It is desirable to minimise the amount of material used to perform the function of extraction or destruction. When developer is applied uniformly, the amounts needed to be removed from the areas of minimum density (Dmin areas) are high. In particular, if methods such as lamination with carbon or the application of chemical treatments are used, the difficulty of removal is greatest where the largest amounts of developer exist. Further, the areas where this occurs are precisely those areas where the problems caused by any density increase are of greatest impact, namely in Dmin areas.
The use of RX processing can allow the retention of silver and silver halide in the image if coated silver levels are sufficiently low. This greatly simplifies the process cycle. However, the avoidance of stages, after development, used for the purposes of silver and silver halide removal, eliminates the opportunity for removal of developer from the coating during these stages, in particular from the low density areas. The problem of removal of developer components from Dmin areas is therefore more serious when these silver-removal stages are eliminated.
The problem to be solved therefore is to provide a process cycle involving a development stage and a subsequent treatment which produces much less liquid effluent than a multi-tank counter-current wash/stabiliser stage. Preferably, no effluent is produced whilst ensuring that the image is substantially as stable as it would be with a washing stage which produces liquid effluent, typically 200 mls/m2. In particular, this problem should be solved using the minimum amounts of material used for extracting or destroying the developer components which, if left in the image, potentially destabilise the image over time.
The invention provides a method of producing a photographic image in an imagewise exposed photographic material comprising one or more silver halide emulsion layers which method comprises
applying to the material in an imagewise manner a developer solution containing a silver halide developing agent wherein the amount of solution applied depends on the image density to be produced,
removing unreacted developing agent from the material or inactivating unreacted developing agent in the material by means other than immersion of the material in a liquid in a tank.
This invention provides a method for processing photographic material by providing a development stage in which developer is applied to the surface of the processed material in an imagewise manner and developer components harmful to the image over long-term keeping are removed or inactivated without extraction into a volume of solution in a tank e.g. without a wash tank. Unreacted developing agent may be inactivated by chemically converting the developing agent into a form in which it will no longer cause image modification e.g. by degradation. Preferably, the development stage is carried out in a way which produces substantially no liquid effluent from the process or in a way which does not require any treatment or re-use of any effluent which is produced. Unreacted developer components may be extracted or destroyed using either lamination with a separate coated material or by applying chemicals in a coating or spraying process which does not produce liquid effluent.
The photographic material used in the method of the invention may be any black and white or colour silver halide material. In a preferred embodiment, the material is a colour silver halide material e.g. a colour print or film material. In colour photographic materials, dye images can be formed by reaction of oxidised developer with image dye forming couplers. A preferred class of developing agents for chromogenic colour development is the the paraphenylene diamine class of developer agents.
A preferred form of photographic processing is redox amplification also known as development amplification. An advantage of redox amplification is that a low-silver material can be used. Low silver materials typically contain less than 400 mg/m2, preferably less than 200 mg/m2 silver.
With redox amplification, a bleach step may be carried out if required using solution application methods producing no effluent. Preferably, for environmental reasons, the bleaching stage uses an iron-free bleaching agent such as persulphate or peroxide. Alternatively, a process not involving a bleach step may be necessary or possible.
As a further means of simplifying the process, the fixing of the unreacted silver halide or bleached silver and its removal in liquid effluent may be avoided.
During the process cycle the photographic material can be heated to accelerate the process and remove liquid components from the processed material.
A developer solution containing a silver halide developing agent is applied to the material in an imagewise manner wherein the amount of solution applied depends on the image density to be produced.
The solution may be applied by known techniques e.g. the use of an inkjet printing head or similar device.
By adjusting the amount of processing solution in accordance with an image signal recorded on a light-sensitive material, the inkjet printing head can stop feeding the processing solution on a portion of the image not requiring development.
The image signal may either be obtained from a real image e.g. an image on a film or reflection print material by measurement of the optical density of the image by conventional reading means such as an image scanner, or it can be obtained from a digital image such as could be contained in a stored computer file such as a Kodak PhotoCD(trademark) image or a JPEG image. The image signal thus obtained can be used, with a knowledge of the characteristics of the photographic light sensitive material to calculate the amount of image density required in any particular area of the material in order to form the desired image.
By adjusting the amount of processing solution applied to any part of the surface of the photographic material in accordance with the image density required, the application apparatus can apply lower amounts of solution where low image densities are to be produced. If a modified inkjet printer is used, the solution is applied as fine droplets. The printing heads must be capable of reliably applying the chemically corrosive solutions used for photographic processing.
In one preferred embodiment, the removal of the unreacted developer is achieved by releasably laminating the material with a receiver sheet containing an adsorbent for the developing agent in oxidised and unoxidised form, and, after a period of time sufficient for adsorption of the developing agent in the receiver sheet, separating the photographic material and the receiver sheet.
The receiver sheet may comprise a layer of the adsorbent suspended in a suitable binder coated on a support. Suitable supports include those used for photographic materials e.g. polymer such as polyester, and paper. Suitable binders include hydrophilic colloids and other binders used in the preparation of photographic emulsion layers. A more detailed description of suitable binders may be found in Research Disclosure, September 1994, No. 365, Section IIA. A preferred binder is gelatin.
The adsorbent used in the invention may be chosen from any of the known adsorbents of organic compounds. A particularly preferred adsorbent is carbon e.g. activated carbon, especially activated charcoal. Alternative adsorbents include a range of polymeric materials, for example, the polymers obtained by condensation, such as polyesters, polyamides, polyurethanes, polyethers, epoxy resins, amino resins, phenol-aldehyde resins and acrylic polymers, and polymers derived from ethylenically unsatured monomers such as polyolefins, polystyrene, polyvinyl chloride, and polyvinyl acetate.
For dispersion in a binder, the adsorbents are preferably in particulate form. It is also preferred that the adsorbents are porous.
Particular examples of polymeric adsorbents include cross-linked polystyrene beads and polyacrylic resin beads marketed under the name Amberlite XAD(copyright).
Suitable adsorbents include ion-exchange resins.
In addition to containing an adsorbent to remove organic compounds, the receiver sheet preferably contains a substance for solubilising silver halide and/or a substance capable of converting soluble silver into an insoluble form.
The silver, both developed and undeveloped, in the developed photographic material can be rendered soluble before contact with the receiver sheet by including in the developing solution, or another solution in a subsequent processing step, a means of solubilising the silver. Alternatively, a means of solubilising the silver may be incorporated in the receiver sheet. Examples of silver solubilising compounds include chelating agents and silver halide solvents. As silver solvents, thiosulphates, thiocyanates, thioether compounds, thioureas, thioglycoloic acid and sulphites can be used. A specific example is hydroxyethyletrahydrotriazole thione (HTTT). A preferred component is thiosulphate e.g. ammonium thiosulphate. Alternative counter ions such as alkali metal ions e.g. lithium, potassium, sodium, caesium and rubidium may be used.
The silver can be trapped in the receiver sheet by including substances which convert the silver in its soluble form into an insoluble form such as silver metal or an insoluble silver compound.
The receiver sheet may contain reducing means capable of forming metallic silver from solubilised silver halide. Examples of suitable reducing means include a metal more electropositive than silver dispersed in the receiver sheet e.g. particles of magnesium, zinc or aluminium. Alternatively, a salt such as zinc sulphide is used and the silver precipitated as silver sulphide. The receiver sheet may contain nuclei on which silver develops to give a metallic deposit.
Between the development step and lamination step, the method of the invention may include a development-stopping step, a bleach step, a fixing step or any combination of such steps. The receiver sheet may also contain a material to stop the development reaction when the lamination occurs.
As mentioned above, the developer solution may contain fixing agent and the receiver sheet may contain the means for converting the silver in its soluble form into an insoluble form such as silver metal or an insoluble silver compound.
Aqueous solution carried over from the development step or another step prior to lamination may be sufficient for the desired transfer of substances to the receiver sheet to occur. Preferably, the receiver sheet is soaked in an aqueous solution before lamination. In a preferred embodiment, the aqueous solution is acidic.
In another embodiment of the invention, removing unreacted developing agent from the material or inactivating unreacted developing agent in the material is achieved by applying to the surface of the developed material a solution of a sulphite compound that reacts with oxidised developing agent and prevents further development, and
applying to the surface of the developed material a solution of an oxidant that oxidises any remaining developing agent,
wherein said sulphite compound is present in an amount sufficient to react with all the oxidised developing agent.
Preferably, the sulphite compound is a hydrogen sulphite or metabisulphite compound. Examples of suitable compounds include soluble alkali metal, alkaline earth metal or ammonium hydrogen sulphites and metabisulphites e.g. sodium hydrogen sulphite and sodium metabisulfite.
The solution of the sulphite compound may contain the sulphite compound in an amount from 0.02 to 1 mole/1, preferably from 0.15 to 0.5 mole/1.
Preferably, the oxidant is a salt of a peroxy sulphuric acid such as peroxymonosulphuric acid (H2SO5) or peroxydisulphuric acid (H2S2O8). Salts of peroxydisulphuric acid are often simply referred to as persulphates. Examples of suitable compounds include soluble alkali metal, alkaline earth metal or ammonium peroxymonosulphates and persulphates e.g. sodium peroxymonosulphate and sodium persulphate.
The solution of the oxidant may contain the oxidant in an amount from 0.02 to 1 mole/1, preferably from 0.15 to 0.5 mole/1. Preferably, the concentration of the oxidant is less than that of the sulphite compound.
It is preferred that the total amount of the solutions of sulphite and oxidant applied to the surface of the developed material does not exceed 100 ml/m2. A preferred amount is from 20 to 60 ml/m2.
The weight ratio of the solutions of sulphite and oxidant applied to the surface of the developed material may vary from 5:1 to 1:5. Preferably, the solutions are employed in substantially equal amounts.
The solutions of sulphite and oxidant are applied to the material by means other than immersion in a tank. Examples of suitable means include spraying from a fine nozzle, an air brush, an ink jet head or by application with a roller. The roller may or may not have a surface pattern, or a roller covered with an adsorbent material such as felt or sponge may be used. If two separate applications are required it is preferable that the second solution is applied by a non-contact method such as spraying with a nozzle, an air-brush or an ink-jet head.
In a preferred embodiment, the solutions of sulphite and oxidant are applied to the material sequentially. Preferably, the oxidant solution is applied within 20 seconds, more preferably within 10 seconds of application of the sulphite solution.
In an alternative embodiment, the solutions of sulphite and oxidant are applied to the material simultaneously. If the solutions are mixed together before application, it is preferable to apply the mixture within 10 seconds of mixing.
Only very low volumes of sulphite and oxidant solution need be used. Preferably, the volumes of solution used are such that there is substantially no effluent created. A small volume of solution can be accommodated by the swell of the photographic material being treated. Additional solution can be accommodated on the surface of the material without creating effluent. Subsequent drying of the material removes the unwanted water.
The invention provides a process which does not produce liquid effluent but produces high quality images of good image stability. In a number of forms of the invention as described, the process is very simple, and of low maintenance. It can combine these attributes with a low-silver material which is inexpensive to manufacture and which reduces the environmental impact of manufacturing and processing of the material.
The invention has the advantage not only of removing developer but also other materials which can be extracted using lamination or chemical treatment.
The invention may be employed in processing any silver halide photographic material.
The photographic elements can be single colour elements or multicolour elements having a paper or a transparent film base. Multicolour elements contain dye image forming units sensitive to each of the three primary regions of the spectrum. Each unit can be comprised of a single emulsion layer or of multiple emulsion layers sensitive to a given region of the spectrum. The layers of the element, including the various orders as known in the art. In an alternative format, the emulsions sensitive to each of the three primary regions of the spectrum can be disposed as a single segmented layer.
A typical multicolour photographic element comprises a support bearing a cyan dye image-forming unit comprised of at least one red-sensitive silver halide emulsion layer having associated therewith at least one cyan dye-forming coupler, a magenta dye image-forming unit comprising at least one green-sensitive silver halide emulsion layer having associated therewith at least one magenta dye-forming coupler, and a yellow dye image-forming unit comprising at least one blue-sensitive silver halide emulsion layer having associated therewith at least one yellow dye-forming coupler. The element can contain additional layers, such as filter layers, interlayers, overcoat layers and subbing layers.
Suitable materials for use in this invention, can have any of the components described in Research Disclosure Item 36544, September 1994, published by Kenneth Mason Publications, Emsworth, Hants P010 7DQ, United Kingdom.
A description of typical photographic materials may be found in Research Disclosure, September 1997, p. 613, Section I.
Photographic processing steps such as development, bleaching and flxing together with the compositions used in those steps e.g. developing agents are described in, for example, Research Disclosure, September 1994, No.365, Sections XIX and XX and Research Disclosure, September 1997, p. 613, Section XXIII.
A preferred form of photographic processing is redox amplification also known as development amplification. Such processes are well known and details may be found in Research Disclosure, September 1997, p. 629-630, Section XVI.
Redox amplification processes have been described, for example in British Specification Nos. 1,268,126, 1,399,481, 1,403,418 and 1,560,572. In such processes colour materials are developed to produce a silver image (which may contain only small amounts of silver) and then treated with a redox amplifying solution (or a combined developer-amplifier) to form a dye image.
The developer-amplifier solution contains a colour developing agent and an oxidising agent which will oxidise the colour developing agent in the presence of the silver image which acts as a catalyst.
Oxidised colour developer reacts with a colour coupler to form the image dye. The amount of dye formed depends on the time of treatment or the availability of colour coupler and is less dependent on the amount of silver in the image as is the case in conventional colour development processes.
Examples of suitable oxidising agents include peroxy compounds including hydrogen peroxide and compounds which provide hydrogen peroxide, e.g. addition compounds of hydrogen peroxide or persulphates; cobalt (III) complexes including cobalt hexammine complexes; and periodates. Mixtures of such compounds can also be used.
In conventional processing (non-RX) of colour materials, separate bleach and fix baths or a bleach-fix bath which both bleaches silver image and removes all silver from the material may be employed. However, because of the small amounts of silver present in the photographic material used in RX processing, it is possible to leave out the processing stages that bleach and fix because the degradation of the image is minimal.
The invention is further illustrated by way of example as follows.

Method of producing a photographic image


A silicon on insulator (SOI) substrate is converted into a strained SOI substrate by first providing an SOI substrate having a thin silicon layer and an insulator and at least one first epitaxial relaxing layer on the SOI-substrate. Then a defect region is produced in a layer by implantation of SI ions above the silicon layer of the SOI-substrate. Finally the first layer is relaxed by a thermal treatment in an inert atmosphere to simultaneously strain the silicon layer of the SOI-substrate via dislocation mediated strain transfer and to produce the strained silicon layer directly on the insulator.

The rapid advance in nanoelectronics has required increasingly more rapid transistors, especially metal oxide field effect transistors (MOSFETs). A power increase is as a rule obtained with a reduction in the transistor dimensions. This is, however, very expensive and difficult to achieve since the key technologies in chip production, like the lithographic process and the etching process must be replaced by systems capable of greater outputs.
An alternative approach is the use of materials capable of greater outputs. Instead of the usual silicon substrates, increasingly so-called silicon on insulator (SOI) substrates are used. In those cases, beneath a monocrystalline silicon surface a buried silicon oxide (SiO2) layer may be provided with insulating characteristics. Electronic components, especially MOSFETs (metal oxide silicon field effect transistors) have with SOI substrates more rapid switching operations and reduced losses. These substrates are commercially available and are made either by ion implantation of oxygen in silicon and heat treating (the so-called SIMOX process, SIMOX wafer) or by means of bonding of two oxidized wafers and splitting or back etching a part of the second wafer (the so-called Wafer Bond process). The thus made wafer is referred to as a BESOI wafer (bonded and etch back SOI).
It is known also to use strained silicon (strained silicon-germanium alloys (Si—Ge) or silicon-carbon (Si—C) and silicon-germanium-carbon (Si—Ge—C). The use of silicon or Si—Ge, Si—C or Si—Ge—C in certain elastic dislocation states or distorted states, improves the material properties especially with respect to the charge carrier mobility of electrons and holes which are primarily important for electronic components. The use of these and other high value materials enables a performance enhancement of Si based high power electronic components like MOSFETs and MODFETs without the need to reduce the critical structural dimensions of the electronic components. Such elastically strained layer systems enable epitaxial growth on special substrates or on strain-relaxed layers and so-called virtual substrates whose production with reduced defect densities is very expensive and difficult (F. Schaeffler, Semiconductor Sci. Techn. 12 (1997) pages 1515-1549).
The production of monocrystalline layers with substrate materials which are currently available is greatly limited or the quality of the layers grown is reduced. Different crystal structures as well as different lattice parameters between the substrate and the layer material (lattice mismatch) reduce as a rule the ability for monocrystalline growth of layers of the higher quality. When monocrystalline layers are deposited on surfaces or bodies with lattice parameters which are not matched to those of the monocrystalline layer, the monocrystalline layer develops from the beginning in a strained state since its lattice structure differs in this state from that of the substrate. If the deposited layer exceeds a so-called critical layer thickness, the mechanical strain undergoes dislocation formation as it tends toward relief and the lattice structure becomes closer to the original or to that of the substrate. This process is referred to as strain relaxation and in the following as relaxation. At the interface so-called lattice mismatch dislocations (misfit dislocations) can arise and in the relaxed layer are in the form of threading dislocations which run from the surface of the layer to the interface. The misfit dislocations are required for strain relaxation and do not degrade the layers lying thereabove. From a certain lattice mismatch (about >0.5%) the threading dislocation density is so high, however, that such layers maybe unsuitable for electronic components. In general, the threading dislocation density can be somewhat reduced by a temperature treatment. Under the term dislocation density or defect density, the threading dislocation density is to be understood here. Since most of the dislocations either advance through newly grown layers, they may reduce the electrical and optical characteristics of these layers significantly.
Since the silicon-germanium (Si—Ge) material system is thermodynamically a fully miscible system, the compound can be produced in optional concentrations in either silicon or germanium. Silicon and germanium indeed are characterized by the identical crystal structure although they differ with respect to the lattice parameter by about 4%, that is an Si—Ge layer or a pure Ge layer will grow in a strained state on silicon. Carbon can be incorporated into silicon in an amount up to about two atomic % on substitutional lattice sites so as to reduce the lattice parameter.
The state of the art in the production of strained silicon on strain free qualitatively high value silicon-germanium alloy layers on a silicon substrate is the use of the so-called graded layer on which the desired strained layer is deposited in a further step. The graded layer can be a silicon-germanium layer whose germanium concentration increases continuously to the surface until it reaches the desired germanium content continuously or in a stepwise manner. Since, to maintain the layer quality, only an increase in the germanium content of about 10 atomic % per μm is required, such layers depending upon the germanium concentration to be achieved, can be up to 10 micrometer thick. The layer growth of this graded layer is described in (Thin Solid Films, 294 (1997), 3 to 10).
This process gives rise, as a drawback, to excessively high layer roughnesses, to dislocation multiplication and thus to a bundling of threading dislocations which can develop in such manner as to make the electronic components to be made from the layers nonfunctional.
In addition, there can be a tipping or tilting crystallographically of certain regions so that an expensive polishing operation of the layer, for example by means of chemical mechanical polishing techniques is required before strained silicon can be deposited on the thus produced buffer in an additional epitaxial growing step.
Before this second layer deposition in a CVD reactor or in a molecular beam epitaxy apparatus, a special wafer cleaning must also be carried out to insure a monocrystalline growth and to minimize the inclusions of impurities or undesired doping substances. The many process steps, among others, a lengthy deposition process as a consequence of the large layer thicknesses required, expensive polishing, wafer cleaning and two separate epitaxy steps, reduce the output or productivity of the process and limit the quality. The thermal conductivity of such graded layers is so sharply reduced by comparison to silicon that high power electric components rapidly are overheated.
Indeed, from Leitz, et al, Applied Physics Letters, Vol. 79(25) (2001), pages 4246-4248) and Cheng et al (Mat. Res. Soc. Symp., Vol. 686 (2002) A1.5.1-A1.5.6 it is known that a strain relaxed or a strained layer can be transferred to a second wafer with wafer bonding. The disadvantage of this approach is, however, that very many technically difficult steps are required. A strain relaxed layer or also only a single strained surface layer can thus be bonded to an insulating SiO2 layer on the second wafer. Among other things, it is exceptionally problematical to transfer the strained layer by wafer bonding to a second substrate without altering the elastic strain of the layer and in such manner as to avoid the inclusion of impurities. Impurities, for example at the interface of the strained silicon with the SiO2 increase in an undesirable manner the interface state density. Even the smallest impurity level can effect the switching properties of MOSFETs which are formed on the strained silicon in a highly detrimental manner. Precisely with MOSFETs with ultrathin strained silicon the interface state density should be in the range of 1010 cm−2 at the Si/SiO2 interface. Technologically, this can be achieved only with ultrapure interfaces. Whether this wafer bond process can satisfy this requirement has not yet been shown.
From R. Delhouge, P. Meunier-Beillard, M. Caymax, R. Loo, W. Vanderhorst (First Int. SiGe Technology and Device Meeting (ISTDM2003), Jan. 15-17, 2003, Nagoya, Japan, page 115) it is known that thin relaxed Si—Ge layers can be produced by forming in an SiGe layer (for example 170 nanometer Si—Ge with 22 atomic % Ge) a very thin (for example 10 nanometer) Si—C layer with a sufficiently high carbon content. During the heat treatment at elevated temperatures of about 1000° C. carbon precipitates out as a result of supersaturation. In this manner defects are formed which promote the relaxation of an Si—Ge layer.
It is a disadvantage that in this manner no strained layer can be formed on an insulator. The surface roughness makes polishing necessary as a rule. Furthermore, a high temperature is required for the relaxation since the high temperature is made necessary by the precipitation of carbon and thus lower temperatures cannot be used.
From WO1999/038201, a method is known which permits the production of a thin strain-relaxed Si—Ge buffer layer by means of ion implantation and thermal treatment. A drawback of this method is that with it, no strained layer can be directly produced on a substrate. As a consequence, two separate epitaxial deposition and wafer cleaning steps are required.
The object of the invention is thus to provide a simple method of making a strained layer of high quality on a substrate without wafer bonding and/or wafer polishing.
Especially in an advantageous mode, strained silicon should be directly applicable of an SOI wafer over its entire surface or locally and in an optional form. In local application, the planarity between the strained and nonstrained response should be free from any step formation to enable the further processing of electronic components.
It is an object of the invention, further, to provide electronic and/or optoelectronic components which have the above mentioned advantageous layer structures.
The objects of the invention are achieved with a method according to the main claim. The objects are achieved further by a layer structure according to the auxiliary claim. Advantageous modes and features are found in the patent claims which are respectively dependent thereon.
According to the main claim, to produce a strained layer on a substrate, the following steps are carried out:                generating defects in a layer adjoining the layer to be strained,        relaxing at least one of the layers adjoining the strained layer.
For this purpose, the layer structure is subjected to at least one thermal treatment and/or an oxidation so that starting from the defects, dislocations are formed which give rise to a relaxation of one of the layers neighboring the strained layer.
As a consequence, the straining of the layer to be formed as a strained layer is advantageously effected.
Under the term "defect", crystal defects are to be understood, that means atomic and extended defect locations, for example, clusters, bubbles, hollows and the like. Starting from such generated defect regions, dislocations are formed which give rise to a relaxation of a layer neighboring the layer to be formed as the strained layer.
Under "relaxation" an abatement of the elastic strain within a layer is to be understood.
The term "neighboring layer" is to be understood as referring to a layer which may be directly adjacent the layer to form the strained layer or to one or more layers separated therefrom to the extent that the relaxation of dislocations therein gives rise to the strained layer.
The term "substrate" is used in the broadest sense to refer to a layer on which the strained layer can be provided. In the course of the invention, it is possible to provide additional layers on the substrate as well.
On the free surface of the strained layer or the layer to be the strained layer, epitaxially at least one first layer can be applied, whereby this first layer has a different degree of strain than the layer to form the strained layer.
In the first layer, therefore, defects can be generated. The layer structure is subjected to at least one temperature treatment so that starting from the defects, dislocations will be formed which lead to relaxation of the first layer. As a consequence thereof, the layer below which is to be the strained layer is thereby strained.
The defects also can be self generating also in the layer to form the strained layer.
As in the first layer, a graded layer is also to be understood with which, when the graded layer is in the vicinity of the layer to form the strained layer, it has a different degree of strain than the layer to form the strained layer. Thus, in the graded layer a defect region is produced. The layer structure is then subjected to a thermal treatment so that starting from this defect region, dislocations are formed which give rise to a relaxation of the region of the graded layer in the vicinity of the strained layer. As a consequence, the strain will transmit to the bounding layer intended to form the strained layer.
In the course of the method of the invention, the layer intended to form the strained layer is formed into an elastically strained layer. To this end, the layer bounding on the strained layer to be formed relaxes, thereby insuring advantageously a transition of the layer to be strained into the desired strained state. In the case of a graded layer as the first layer, the layer region of the graded layer which bounds upon the strained layer relaxes so that the strained layer is transformed into the desired strained state. The layer disposed upon the layer which is to form the strained layer has a different degree of strain than the layer to form the strained layer itself.
In the course of the method, the deposition of additional layers is possible.
Thus, it is possible to carry out the method with the following steps:                on a layer to form the strained layer on a substrate, at least one first layer of a different lattice structure is deposited and a second layer deposited on the first layer, whereby the first layer has a different degree of strain than the layer to form the strained layer, in the second layer and/or in a further layer a defect region is produced,        the layer structure is subjected to a thermal treatment so that starting from the defect region dislocations are formed which contribute to relaxation of the first layer.
The first relaxing layer borders upon the layer which is intended to form the strained layer and as a consequence, causes that layer to be a strained layer.
When different lattice structures for the layers are described, it is meant that they have a difference in the respective lattice parameters and/or in the crystal structure.
According to the invention, between a layer adapted to form the strained layer and the substrate, a further layer which is also relaxed in the course of the process can also be arranged. In that case, one obtains a relaxed layer on a substrate upon which a layer to form the strained layer is arranged. On the latter, in the further course of the method, a relaxing layer is applied. Upon this relaxing layer can a layer adapted to form a strained layer, be applied. Further layers can then be applied thereto. The relaxing layers have a different degree of strain than the neighboring layers which are to form the strained layer. After relaxation of the layers, the layer adapted to form the strained layer is strained in a method step during the thermal treatment or during the oxidation.
The defect region can also be produced in the substrate. The defect region is so produced that the dislocations give rise to a relaxation of a neighboring layer to the layer adapted to form the strained layer.
Such an epitaxial layer structure or wafer can advantageously be made in a deposition process. It is especially advantageous when the wafer is introduced into the reactor and can be coated without expensive polishing and cleaning operations.
By the choice of the strain of the layer to be applied to the layer adapted to form the strained layer, namely, whether that strain is a tension strain or a compression strain, the resulting strain is selected for the layer adapted to form the strained layer.
So that the relaxation of a strained layer and thus a strain can be applied to the layer to be strained, the layer structure is advantageously subjected to a thermal treatment. It is, however, also conceivable in place of a temperature treatment to use another treatment so that a neighboring layer will be relaxed and the layer is strained.
It is especially advantageous to carry out the relaxation by means of an oxidation with O2 or water vapor [steam]. Instead of a purely thermal treatment to form the relaxed region, an oxidation treatment can be carried out thereafter or, also a combination of oxidation and thermal treatment can be used. In this case, the concentrations of the elements are important for the functionality of the electronic component, can be increased within the layer structure (for example, there can be a Ge enrichment of the Si—Ge).
The substrate is preferably an SOI substrate whose silicon surface is to be strained.
As to the substrate generally, an amorphous layer, of especially an insulator, can also be used. The substrate can, however, equally well be a material with optional electrical characteristics which permits a thermally induced straining of the layer to form the strained layer with the aid of the method according to the invention. In this sense, a crystalline hetero interface with a sufficiently large lattice mismatch (for example 1%) or with different crystal structures is suitable when the layer thickness d3 of the layer to form the strained layer is selected to be sufficiently small (for example 5 to 50 nm) and the substrate sufficiently thick, for example 10 to 100 times the thickness of the to be strained layer. These conditions are fulfilled for example by a monocrystalline SOI substrate, silicon on sapphire.
Also suitable are substrate materials which at the temperatures required for relaxation, become Viscous. For example, silicon dioxide (SiO2) become viscoelastic at temperatures of about 950° C. By means of boron doping SiO can be made viscoelastic already at about 800° C.
In this sense, other temperature resistant glasses are also suitable. Such substrates can be made by wafer bonding, in a manner similar to that for commercial BESOI substrates whereby a thin Si layer is bonded to silicon dioxide. The putative strained layer that is the layer to be transformed into the strained layer, can thus in principle be applied to a suitable optional glass or another appropriate temperature resistant substrate. With corresponding thicknesses of these materials, they can also fulfill the functions of a suitable mechanical support for the layer structure. A certain bendability of the substrate is also desired in conjunction with the development of "flexible electronics".
As materials for the substrate, especially for example Si—C, graphite, diamond, quartz glass, Gd Ga garnet as well as III-V semiconductors III-V nitrides fall within the considerations.
The process according to the invention has a number of advantages.
Advantageously, this process enables the production of a strained layer only through an epitaxial deposition and without expensive and time consuming process steps like wafer bonding and polishing (CMP).
It is also an advantage that commercially available SOI structures, BESOI wafers or SIMOX wafers with a thin silicon surface adapted to form the strained layer can be used as the base. The silicon layer of this wafer is then strained during the process. SIMOX wafers have generally a dislocation density of about 10−5 cm−2, more usually 102-103 cm−2 but show good layer homogeneity and purity as well as economical fabrication.
The method utilizes process steps which have become established in silicon technology. The technology can also be transferred to very large wafers, for example 300 mm wafers.
The defect region can be produced by ion implantation.
In a further development of the invention it is also possible to produce the defect region already with the application of the layers to the putatively strained layer, for example by reducing the temperature, for instance to about 200° C., in a molecular beam epitaxy apparatus during the deposition of the layer or of a graded layer upon the layer to form the strained layer.
In a further advantageous feature of the invention, the defect region can be produced by incorporating an Si—C layer.
In a further features of the invention, for the thermal treatment, as a suitable parameter, a temperature is selected which lies between 550° C. and 1200° C. and especially between 700° C. and 950° C. In this case, starting from a defect region in the first and/or second layer, defects and especially dislocations which can give rise to a relaxation of the first layer are formed as a result of which the putative strained layer can be strained.
By the choice of the straining of the first layer, tension strains or compression strains can be selected and the resulting strain in the putative strained layer can be selected. If the first layer prior to the temperature treatment is under compressive strain, for example, by the selection of Si—Ge as the material for the first layer (with an optional Ge concentration,) then the layer which is to be provided with the strain, for example, comprised of silicon, will have a tensile strain transferred thereto.
Conversely, compression-strained silicon can be produced for example by the use of a first layer under tensile strain and, for example, of Si—C with up to about 1 to 2 atomic % C. The use of ternary alloys like Si—Ge—C and the use of doped Si layers or alloys (B, As, P, Sb, Er, S or others) is also possible.
The thermal treatment can be carried in an inert atmosphere, vacuum or also in an oxidizing environment, for example, in O2 or H2O, or in a nitriding atmosphere, for example, in NH3, or a reducing atmosphere, for example, in forming gas. Very good results are obtained with thermal treatment in nitrogen.
The so produced strained layer can be exposed, for example, by wet chemical removal of the second layer and then at least partially of the first layer. This layer structure serves to allow complex layer structures to be built up. For this purpose, the skilled worker in the art can use all available processing techniques and layering materials depending upon the layer structure to be formed and the particular requirements the layer structure is to satisfy.
As starting structures, as has been noted, basically SOI structures, SIMOX wafers or BESOI structures can be used. In these cases, the layer to be formed into the strained layer, the insulator and the substrate will already be available as the basic structure.
It is, however, possible to apply the layer to form the strained layer initially to an amorphous layer, for example, an insulator forming the amorphous layer and then generate the strain. The insulator can be disposed on a substrate, for example, of silicon or can form the substrate itself. The layer to be strained can advantageously be silicon. The layer to be strained can especially advantageously be formed with a thickness of 1 to 100 nm, especially of 5 to 30 nm. This layer thickness d3 should at least not exceed the critical layer thickness and must be so small that at least a substantial part of the dislocations from the first layer can spread along the glide planes in this layer. This technique depends especially upon the degree of strain in the first layer and its layer thickness d4. The larger the desired strain of the layer the smaller must d3 be. A large layer thickness ratio of d4/d3 appears to be advantageous, especially a layer thickness ratio of d4/d3 of greater than 10.
In an especially advantageous feature of the invention as the first layer upon the layer to form the strained layer should be for example an epitaxial Si—Ge or Si—Ge—C or Si—C layer with a thickness close to the critical thickness. The critical layer thickness defines the maximum layer thickness for this first layer at which a defect free growth is still possible on the nonlattice matched layer to ultimately from the strained layer. At a layer thickness below this critical layer thickness as a rule strongly pseudomorphic that is completely defect free growth will be produced. The critical layer thickness should not be exceeded to the extent that the layer will already be noticeably relaxed.
As an alternative to a layer with constant composition, the graded layer can be used. The composition can rise or fall within the graded layer. In the case of Si—Ge, the concentration can slowly rise or rise in steps or it can commence with an higher germanium concentration or even with pure germanium (Ge) over only several nanometers. If in spite of this a sufficient layer thickness d4 must be maintained without exceeding the critical layer thickness, the Ge concentration can rapidly drop (for example to 25 atomic %). Under this selected condition, the layer thickness can lie at about 80 nanometers. The region with the higher Ge concentration enables high degrees of relaxation in excess of 80%.
A U-concentration profile can also be of advantage to produce a certain Ge concentration of, for example, 20 to 40 atomic % and the greatest possible degree of relaxation of the first layer and thus a high degree of strain in the layer to which the strain is to be transferred.
It is thus advantageous to select a thickness d4 of the first layer which is as large as possible consistent with efficient strain relaxation.
With a constant Ge concentration of 20 atomic % Ge a maximum thickness of about 400 nanometers can be produced. A complex concentration profile is of advantage with higher Ge contents.
In a further feature of the invention, the second epitaxially deposited layer can be made from epitaxial silicon. This layer then serves to form a defect region. The layer thickness d5 of this layer can be optimized for the formation of the defect region. It is not limited by growth criteria. The thickness d5 can thus be freely varied (for example from 0 to 1000 nanometers). Advantageously, a thickness of about 200 to 500 nanometers is used with hydrogen and helium implantation. The thinnest possible layer enables implantation with low energies (for example 10 keV) and thus with a sharper distribution of the implanted ions as is advantageous for the formation of a thin defect region with a constant cost saving.
Optionally, a further layer is also deposited, for example, to avoid surface roughening by blistering after hydrogen or helium implantation upon the second layer. This further layer can be amorphous or a polycrystalline layer. This further layer can be deposited before or after the generation of the defect region, for example, by ion implantation. The layer thickness of this optional layer need be determined only by the implantation parameters.
The materials and techniques of the individual layers given here are given by way of example only and should not be understood to be a limitation of the invention.
In an especially advantageous feature of the invention by arranging a mask on the second or optional further layer, a locally limited defect region is produced. It is especially advantageous in this connection that the layer which is to become the strained layer should have planar regions which may be locally strained and unstrained, that is regions which are strained and unstrained in a plane directly adjacent one another without step formation between them as has been the case with the techniques known in the art.
The defect region or regions can be made especially advantageous by ion implantation using light ions like hydrogen (H+, H2+), helium, fluorine, boron, carbon, nitrogen, sulfur, and so forth, or using ions of the layer material or the substrate materials themselves, and thus for example silicon or germanium in an Si/Si—Ge-heterostructure in such manner that the ions are primarily implanted in the second layer.
It is advantageous to use ions which avoid undesired contamination or doping of the structure. In this case, inert gas ions, for example, Ne, Ar, Kr, etc. are usable.
For hydrogen or helium ions a dose of about 3×1015 to 3.5×1016 cm-2 and especially for helium of 0.4×1016 to 2.5×1016 cm−2 is used. A combination of two implants, for example the first being hydrogen and the second being helium or the first being boron and the second being hydrogen, can be suitable. A boron implantation in combination with hydrogen implantation permits the hydrogen implantation dose to be reduced. In addition, a thermal treatment between the implantation steps can be advantageous to produce nucleation seeds for the defect formation.
The defect region is advantageously formed at a distance of 50 to 500 nm from the layer to be relaxed.
In the case of hydrogen or helium ions, the energy of the ions and the main range of the ions is so selected that they are implanted at a distance d6 from the interface of the first and second layers. This distance d6 lies, for example, in the range of 50 to 300 nm. For heavier ions and/or larger layer thicknesses of the second layer, these limits can also be exceeded.
If there is only one layer with a constant concentration (or a graded layer) applied to the layer to form the strained layer, it is possible for the artisan with few and simple tests to so arrange the defect region that after the thermal treatment the first layer will be relaxed and the layer to be strained will have the requisite strain.
The implantation depth is matched to the layer thickness of the second layer and, where appropriate, also to further optional layers and to the mass of the selected ions.
In an especially advantageous further feature of the invention, the maximum damage will lie within the second layer, especially at a distance d6 from the first layer and not in the first layer itself. This applies especially for ions which give rise to bubble formation or crack formation like, for example, helium, fluorine, neon, argon and so forth.
Advantageously with an Si implantation be comparison to implantation with very light ions like for example hydrogen ions or helium ions, the dose can be significantly reduced, that is by a factor of 10 to 100. This shortens advantageously the implantation duration and increases the wafer output significantly. With the goal of achieving a higher degree of relaxation, it is possible, however, also to carry out defect formation by means of two or more implantations in the first layer and in the second layer independently from one another. An advantageous mode of operation is also to carry out first one or more implantations with different energies, possibly also with different ions in the first layer at reduced doses and to create the defect regions in the second layer with a second implantation. The production of point defects in the first layer to be relaxed gives rise to accelerated diffusion and to more relaxation.
The ion implantation can be carried out over the entire area of the substrate or, by the use of an implantation mask, for example a photo lacquer, at optionally selected location on the wafer.
In a further feature of the invention, the wafer is not tilted at an angle of 7° for the ion implantation as is known from the state of the art. Rather, the wafer is tilted at an angle greater than 7° from the normal, especially to an angle of 30° to 60°.
This makes it possible to produce strained and nonstrained layers one after the other upon the wafer while insuring planarity. This is possible since the subsequent thermal treatment can be carried out with a thermal budget which is so small that nonimplanted regions of the first layer are not relaxed or are scarcely relaxed and so that the layer to form the strained layer is also not changed at these locations.
It is especially advantageous to match the implantation mask to the layout of the electronic component or its insulation regions. Only the regions where for example strained silicon is required for the components are implanted.
Advantageously, the first layer is scarcely damaged or not damaged at all by the implantation which is thus carried out. The optimal dose and energy and ion type does not depend upon the composition and layer thickness of the first layer to be relaxed and thus can be simply optimized when the implantation takes place in the second layer.
After removal of the first layer and optionally the second layer and further optional layers, one obtains the desired strained layer or unstrained regions of this layer at the nonimplanted locations with the same layer thickness, thereby maintaining planarity throughout. Advantageously, the first layer applied thereon at least in the last part of the removal phase is selectively removed by a wet chemical process.
The transition regions between strained and unstrained portions are advantageously configured as insulation regions between the electronic components.
It is especially advantageous when silicon dioxide is selected as the insulation material. In a further feature of the invention instead of an exclusive first layer, i.e. only the first layer on the layer to form the strained layer, a layer system of multiple layers is used.
Upon the strained regions which are produced, further epitaxial layers can be deposited in order, for example, to increase the layer thickness of the strained region or to match the thickness locally of the wafer or to apply new layers, for example, in order to realize more complex electronic or optoelectronic components.
With the method according to the invention, a strained layer can be produced it advantageously has an extremely small surface roughness, usually of less than 1 nm and only a limited defect density of less than 107 cm−2, especially less than 105 cm2.
The limited roughness is especially advantageous for the production of MOSFETs in which a thermal oxide or another dielectric, for example, a high-k dielectric, that is a material with high dielectric constant, must be produced on the strained layer. The surface roughness has an exceptionally sensitive effect on the electrical quality of the dielectric which is the heart of a transistor. The mobility of the charge carries also is determined to a significant extent by the nature of the interface in a very thin layer. The surface roughness of for example strained silicon can be reduced by the growth of a thermal oxide thereon even further. This thus produced oxide can be removed prior to the growth or deposition of the gate dielectric on the strained layer.
The method in a further and especially advantageous feature of the invention offers the potential for a further reduction in the dislocation density in the relaxed and the strained layers.
This can be achieved by the etching of trenches in the coating with a spacing of the order of micrometers, for example, 1 to 100 micrometer or advantageously, by trench etching, matching the electric component structures and subsequent heat treatment at temperatures above 500° C. Threading dislocations in the layer slip to the edge of this region and are thereby healed. These etched trenches can however also be used to produce so-called shallow trench insulation. For this purpose, the trench is filled with insulator material and so separates electronic components from one another electrically.
A further suitable method of reducing the defect density is the application of a counter or oppositely strained layer upon the relaxed first layer after that layer has been partially relaxed by implantation and thermal treatment. For the further relaxation of for example an Si—Ge layer a compression strained layer, for example, a silicon nitride layer (for example 100 nm) is deposited in a PE-CVD reactor. A subsequent thermal treatment, for example, by tempering or heat treating in an inert or reactive atmosphere, produces a higher level of relaxation of the Si—Ge layer and thus a greater level of tension of the Si layer which is to be dimensioned. Simultaneously the dislocation density is reduced. This method can also be applied to previously structured surfaces.
The production of a system on a chip, that is various electronic components with different functions in a single plane is thus advantageously possible within the scope of the invention. As has already been indicated, with the invention strained and nonstrained portions of a layer can be made while insuring the planarity thereof. This enables the production of special electronic components/circuit elements with strained or nonstrained regions of for example silicon. These especially very thin layers can be locally reinforced or amplified by further deposition, for example, also be selective deposition, in order to fabricate for example contacts for the source and drain, so-called raised source and drain source to make power components.
The second layer also, for example, a strained Si—Ge layer, can be used in the nonimplanted regions for the production of special components for example especially advantageously for p-MOSFETs, since these layers depend upon the germanium content and can have especially high hole mobilities which are 2 to 3 times greater than those of silicon.
For the production of, for example, p and n channel MOSFETs, the thus made strained Si layers are advantageously used since the electron mobility and the hole mobility in the tetragonal lattice of the strained silicon is higher by about 100% and to about 30% than that of the unstrained silicon when the lattice strain is greater than 1%. Thus one is not bound to particular transistor types or components. MODFETs, resonant tunnel diodes, photodetectors and quantum cascade lasers can be realized.
In the following, the invention is described in greater detail in connection with examples or embodiments and the accompanying figures. They show:
FIG. 1: a schematically illustrated layer system comprising an SOI substrate 1, 2, 3 and a first epitaxially applied layer 4 and a second epitaxially applied layer 5.
FIG. 2: a schematically illustrated layer system comprising an SOI substrate 1, 2, 3 and a epitaxially applied layer structure with an implantation mask 6 and a defect region 7 in the second layer 5.
FIG. 3: a schematically illustrated layer system comprising an SOI substrate 1, 2, 3 and an epitaxially applied layer structure comprising a further optional protective layer 8.
FIG. 4: a schematically illustrated layer system comprising an SOI substrate 1, 2, 3 with a strained region 9 adjacent a nonstrained region 3 on an insulator layer 2.
FIG. 5: a schematically illustrated layer system with an additional epitaxial layer 10 which is epitaxially applied to the strained and nonstrained regions 9 and 3.
FIG. 6: an alternative schematically illustrated layer structure with three layers 11, 12, 13 applied to the layer 3 to be strained, layer 11 serving as an additional buried layer to be strained or as an etch-stop layer.
FIG. 7: a schematically illustrated layer system with an insulation region 14 (shallow trench insulation) between strained region 9 and unstrained region 3.
FIG. 8: a schematically illustrated layer system as in FIG. 1 with etched trenches 15.
FIG. 9: a schematic illustration of a MOSFET on a strained Si layer with a gate stack and raised source and drain and a silicide contact on an insulator. To the right of the transistor an unstrained silicon layer 3 can be seen and to the left a strained Si—Ge layer 11 on an unstrained Si layer 3.

Method of producing a tensioned layer on a substrate


This relates to restoring recoil or maintaining compression of an emphysematous or otherwise unhealthy lung and includes elastic members which contract or compress the lung tissue. The elastic member is secured to tissue of the lung either inside or outside of the lung to supplement the natural elasticity of the lung or maintain the tissue in a compressed state. The elastic member may include elastic patches, elastic bands, coil springs, covers or a combination of these elements.

1. Field of the Invention
The invention relates to a device and method for restoring lung function, and more particularly, the invention relates to a device and method for restoring the elasticity or recoil of a lung to improve pulmonary function by increasing gas exchange or for restoring the efficiency of the lung by compressing the less useful, diseased portions of the lungs.
2. Brief Description of the Related Art
Chronic obstructive pulmonary diseases (COPD), such as emphysema are steadily increasing in frequency, possibly due to continued smoking, increasing air pollution, and the continued aging of the population. Emphysema patients have reduced lung capacity and efficiency due to the breakdown of lung tissue often caused by smoking. Healthy lung tissue includes a multitude of air passageways leading to tiny air sacks called alveoli throughout the lung which inflate and deflate with air when we breath. The alveoli are small, tightly packed, polyhedral recesses composed of a fibrillated connective tissue and surrounded by a few involuntary muscular and elastic fibers. The thin walls of the alveoli perform gas exchange as we inhale and exhale. The lungs are expanded to draw air into the alveoli by moving the diaphragm downward and moving the chest outward. The air is expelled from the lungs by the natural elasticity or recoil of the lung tissue in combination with the pushing of the diaphragm back up into place by the abdominal contents.
In the lungs of an emphysema patient, the walls between adjacent alveoli within the alveolar sac deteriorate. This wall deterioration is accelerated by the chemicals in smoke which affect the production of mucus in the lungs. Although the breakdown of the walls of the alveoli in the lungs occurs over time even in a healthy patient, this deterioration is greatly accelerated in a smoker causing the smoker""s lungs to have multiple large spaces with few connecting walls instead of the much smaller and more dense alveoli spaces in healthy lung tissue.
In a diseased emphysematous lung many of the walls of alveoli and other lung tissue are deteriorated. Because of the deterioration, the diseased lung has larger open spaces and a larger overall volume than a healthy lung. However, the diseased lung is less efficient as it has less wall tissue to achieve gas exchange.
In addition, deterioration of the lung tissue in an emphysematous lung reduces the amount of elastic fibers within the lung and thus reduces the overall elasticity of the lung. The reduction of the lung""s elasticity permits the chest wall to pull the lung outward more easily and reduces the lung""s ability to contract or recoil to expel air. This inability of the lung tissue to recoil results in a larger residual volume of air remaining in the lungs after exhalation. Consequently, this increased residual gas volume interferes with the ability of the lung to draw in additional gas during inspiration. As a result, a person with advanced COPD can only take short shallow breaths. Accordingly, emphysema patients often have a flattened diaphragm, a barrel chest or enlarged chest, and shoulders which are shrugged upwards. When patients with severe emphysema take in as much air as their chest cavity can accommodate, they still have insufficient gas exchange because their chest is full of non-functional air filling the large cavities in the lungs. This non-functional residual air cannot be expelled from the lungs. As a result, this decreased lung efficiency causes even the most ordinary activities to be extremely difficult causing the patient to lose mobility.
In cases of severe emphysema, lung volume reduction surgery (LVRS) attempts to improve lung efficiency to allow the patient to regain mobility. In lung volume reduction surgery, a diseased portion of an emphysematous lung having alveolar wall deterioration is surgically removed. LVRS is performed by opening the chest cavity, retracting the ribs, stapling off, and removing the more diseased portion of the lung. The removal of the diseased lung tissue allows the remaining healthier tissue to inflate more fully and take greater advantage of the body""s ability to inhale and exhale. Since there is more air and more gas exchange in the healthier portion of the lung, lung efficiency improves.
LVRS addresses the loss in lung efficiency but does not address the loss of the natural lung tissue elasticity in a diseased lung. In addition, LVRS is an extremely invasive procedure having substantial risks of serious post-operative complications, such as pneumothorax, and requires an extended convalescence.
Accordingly, it is desirable to achieve improved lung efficiency for emphysema patients by improving lung elasticity or recoil, or by providing a means to reduce the volume of the diseased portions of the lung through tissue compression.
The present invention relates to a device and method to improve lung efficiency by restoring recoil of an emphysematous or otherwise unhealthy lung. The present invention may also improve lung efficiency by reducing the volume of diseased portions of the lung through compression of lung. Compressing certain portions of lung tissue prevents expansion and over-inflation of this lung tissue which increases the volume within the chest cavity and allows otherwise increased expansion of relatively healthier lung tissue. A device for either restoring recoil or mechanically compressing lung tissue may include at least one elastic member positioned inside or outside of the lung and which is secured to the lung tissue and supplements the natural elasticity of the lung or compresses that portion of lung.
In accordance with one variation of the present invention, a device for restoring lung recoil ability may include a bio-compatible elastic member having at least a first end and a second end, the elastic member having sufficient elasticity which is capable of compressing lung tissue when applied to a lung. The elastic member may also be capable of being stretched by the lung tissue during inhalation. The first end and the second end of the elastic member may be fixed to the lung tissue with the elastic member in a stretched condition to improve the elasticity of a lung.
The variations describe above may also be configured to have an elasticity which, when placed over a compressed lung or a compressed portion of the lung, prevents expansion of the lung tissue during inspiration. Alternatively, the present invention includes a covering which prevents the lung or portions of the lung from significantly expanding in volume during inspiration. These variations may also be configured to mechanically compress the diseased lung tissue as well.

Lung elastic recoil restoring or tissue compressing device and method