A process for purifying high molecular weight hyaluronic acid from a biological source, including the steps of adjusting the pH of an aqueous solution containing high molecular weight hyaluronic acid from a biological source to a pH in the range from 1.7 to 3.3 and then diafiltering said aqueous solution at the same pH using a filter having a pore size in the range from 100,000 Daltons nominal molecular cut-off to 0.45 m, and of removing cells from the aqueous solution containing high molecular weight hyaluronic acid from biological source.

The present invention relates to a process for purifying high molecular weight high molecular weight hyaluronic acid or a salt thereof.
Hyaluronic acid is a mucoid polysaccharide of biological origin, which is widely distributed in nature. For example, it is known that hyaluronic acid is present in various animal tissues such as umbilical cord, synovial fluid, vitreous humor, rooster comb and various connective tissues such as skin and cartilage.
Chemically, hyaluronic acid is a member of glycosaminoglycans and it is constituted by alternating and repeating units of D-glucuronic acid and N-acetyl-D-glucosamine, to form a linear chain having a molecular weight up to 13xc3x97106 Daltons.
In the meaning of the present invention, high molecular weight hyaluronic acid is hyaluronic acid having a molecular weight of not less than about 0.5xc3x97106 Daltons.
It is to be noted that the term xe2x80x9chyaluronic acidxe2x80x9d in the present description and claims may mean indifferently hyaluronic acid in its acidic form or in its salt form such as for example sodium hyaluronate, potassium hyaluronate, magnesium hyaluronate, calcium hyaluronate, or others.
Hyaluronic acid, at high molecular weight, is viscous and able to maintain a jelly state, acting as a lubricant, preventing the invasion of bacteria and retaining water.
Due to these properties, hyaluronic acid is able to retain the tonicity and elasticity of the skin.
Pharmaceutical use of hyaluronic acid or of a salt thereof is widely described in the literature.
Since hyaluronic acid is a non-immunogenic substance and has viscoelastic and hydrophilic properties, it is used, since several years, as an eye vitreous or joint fluid replacement or as a supportive medium in ophthalmic surgery, as disclosed for example in U.S. Pat. No. 4,141,973 of Balazs.
In joint fluids, the viscous hyaluronic acid solution serves as a lubricant to provide a protective environment to the cells, and for this reason, it is used in the treatment of inflamed knee joints.
EP-A-0 781 547 of Chemedica S.A. discloses a sodium hyaluronate based ophthalmic formulation for use in eye surgery.
EP-A-0 719 559 of Chemedica S.A. discloses sodium hyaluronate viscous solutions for use as masking fluid in therapeutic photokeratectomy by means of excimer laser.
EP-A-0 875 248 of Chemedica S.A. discloses the use of hyaluronic acid or of one of its pharmaceutically acceptable salts for the preparation of an aqueous solution useful as intra-articular lavage liquid.
EP-A-0 698 388 of Chemedica S.A. discloses an ophthalmic preparation for use as artificial tears containing hyaluronate as a viscosity thickener.
Thanks to its highly hydrophilic nature, hyaluronic acid may also be used in cosmetic products such as lotions and creams.
The pharmaceutical use of hyaluronic acid or of a salt thereof requires a highly pure product.
Hyaluronic acid can be extracted and purified for example from umbilical cords, from rooster combs or from group A and C Streptococci as disclosed for example in U.S. Pat. No. 4,141,973 of Balazs and U.S. Pat. No. 5,559,104 of Romeo et al.
Production of hyaluronic acid by Streptococci was first disclosed by Forrest et al. in 1937, (J. Biol. Chem. 118, 61 (1937)) and later it was demonstrated that hyaluronic acid from animal source is identical to hyaluronic acid from microbial source.
Processes for producing hyaluronic acid from microbial source are based on the property of Streptococci to have hyaluronic acid as the main component of their capsules.
Such microorganisms are able to transform the glucose present in their environment into D-glucuronic acid and N-acetyl-D-glucosamine and to produce hyaluronic acid as a secondary metabolite, to build their protective capsules.
The biosynthesis of hyaluronic acid by Streptococci is disclosed for example in U.S. Pat. No. 4,897,349 of Swann et al.
A number of processes are known for obtaining pharmaceutical grade hyaluronic acid or a sodium salt thereof from microbial sources.
For example, U.S. Pat. No. 4,780,414 of Nimrod et al., U.S. Pat. No. 4,517,295 of Bracke et al., and U.S. Pat. No. 5,563,051 of Ellwood et al. disclose processes for obtaining hyaluronic acid by continuous fermentation of Streptococcus bacteria and then purifying hyaluronic acid thus obtained up to pharmaceutical grade.
However, in all these processes, the purification of hyaluronic acid involves the precipitation of hyaluronic acid from microbial source by using large amounts of organic solvents such as ethanol, acetone, isopropanol, etc.
Some purifying processes are known wherein precipitation of hyaluronic acid from microbial source occurs by means of quatemary ammonium salts (U.S. Pat. No. 4,517,295 of Bracke et al.) or by means of anionic and cationic surfactants (U.S. Pat. No. 5,316,926 of Brown et al.).
However, the described procedures are quite complex and result in high production costs.
Some purifying processes are known wherein hyaluronic acid solution is diafiltered by using a filter having a nominal molecular weight cut-off of 10.000, 20,000 or 30,000 Daltons as disclosed for example in U.S. Pat. No. 5,563,051 of Ellwood et al. and U.S. Pat. No. 4,517,295 of Bracke et al.
However, due to the small nominal molecular weight cut-off used, these diafiltering procedures can be used only to discard small soluble molecules, and the diafiltered hyaluronic acid solution has to be treated by further processing in which various precipitation systems are involved, which render the whole purifying process complex.
An object of the present invention is to obtain a pharmaceutical grade high molecular weight hyaluronic acid or a salt thereof from any biological source, in particular from microbial sources, in high yield, at relatively low cost and preferably without the use of organic solvents or other added substances.
According to the present invention, this object has been achieved by a process for purifying high molecular weight hyaluronic acid from a biological source, characterized by:
a) a step of adjusting the pH of an aqueous solution containing high molecular weight hyaluronic acid from a biological source to a pH in the range from 1.7 to 3.3 and then diafiltering said aqueous solution at the same pH using a filter having a pore size in the range from 100,000 Daltons nominal molecular weight cut-off to 0.45 xcexcm;
b) a step of removing cells from the aqueous solution containing high molecular weight hyaluronic acid from biological source, said step being carried out either before step a) or after step a);
c) a step of sterilization.
Advantageously, by means of a process including a step of diafiltration at a pH in a range of 1.7 to 3.3 and a step of removing cells it is possible to purify high molecular hyaluronic acid so as to obtain in high yield a pharmaceutical grade high molecular weight hyaluronic acid or a salt thereof from any biological source and in particular from a microbial source.
According to step a) of the process of the present invention, hyaluronic acid is diafiltered at a nominal molecular weight cut-off or pore size which allows the returning of the hyaluronic acid and the passing through the filter of all substances contained in the solution or broth.
The process of the present invention may be carried out by using any biological source of hyaluronic acid.
Advantageously, pharmaceutical grade hyaluronic acid may be obtained by the process of the present invention without traces of organic solvents or other added substances, since in the purifying process of the present invention, hyaluronic acid is not precipitated with organic solvents or other substances, but is maintained in aqueous solution during the whole process.
Other objects, characteristics and advantages of the present invention become apparent from the following detailed description.
Hyaluronic acid from any biological source may be purified up to a pharmaceutical grade by the process of the present invention.
For example, the aqueous hyaluronic acid solution containing high molecular weight hyaluronic acid which is firstly treated, either according to step a) of the present invention, or according to step b) of the present invention, may be an aqueous solution containing high molecular weight hyaluronic acid obtained by extraction from umbilical cord, rooster comb or others.
However, in a preferred embodiment of the invention, the aqueous hyaluronic acid solution which is firstly treated, either according to step a), or according to step b), is an aqueous broth containing high molecular weight hyaluronic acid from microbial source.
The microbial source is preferably a Streptococcus species producing high molecular weight hyaluronic acid, and more preferably the microbial source is selected from Streptococcus zooepidemicus, Streptococcus equi and Streptococcus pyogenes.
A broth containing high molecular weight hyaluronic acid may be prepared by any well-known process including fermentation of a Streptococcus culture producing high molecular weight hyaluronic acid in an appropriate aqueous medium and under appropriate conditions. Such processes are disclosed for example in U.S. Pat. No. 4,780,414 of Nimrod et al., U.S. Pat. No. 5,563,051 of Ellwood et al. or U.S. Pat. No. 5,316, 916 of Brown et al.
The process for preparing an aqueous broth containing high containing high molecular weight hyaluronic acid according to the present invention may be the following, by way of example:
At the end of an usual fermentation process, the broth containing hyaluronic acid, having a pH of about 7.4, is harvested and transferred into a tank equipped with automatic temperature control.
The temperature is maintained at a value in the range from 15xc2x0 C. to 25xc2x0 C., preferably, at 20xc2x0 C.
The aqueous hyaluronic acid solution or broth thus obtained may then be treated according to the purifying process of the present invention.
The diafiltration, according to step a) of the present invention, of a solution of hyaluronic acid from a biological source at a pH in the range from 1.7 to 3.3, using a filter having a pore size in the range from a 100,000 Daltons nominal molecular weight cut-off to 0.45 xcexcm, leads to the removal of all proteins and other soluble materials present in the aqueous solution.
It is assumed that when the pH of a hyaluronic acid solution is adjusted in the range from 1.7 to 3.3, a kind of reversible cross-linkage occurs, in which the molecules of hyaluronic acid form a network which may be broken under other pH conditions.
In the range of pH from 1.7 to 3.3, the network is able to be retained by the filter having a pore size in the range from a 100,000 Daltons nominal molecular weight cut-off to 0.45 xcexcm, while proteins and other materials pass through the filter, thereby making it possible to separate hyaluronic acid from any soluble substances contained in the solution.
In step a), the pH of the aqueous solution is preferably adjusted to a value in the range from 2.0 to 2.7 and then this solution is diafiltered at the same pH.
More preferably, in step a), the pH of the aqueous solution is adjusted to a value in the range from 2.3 to 2.7 and then this solution is diafiltered at the same pH.
In step a), the pH is preferably adjusted by means of an HCl aqueous solution.
In a first preferred embodiment of the process of the invention, wherein step b) of removing cells is carried out after diafiltration step a), the pH of the aqueous hyaluronic acid solution or broth obtained from a biological source is first adjusted to a value in the range from 1.7 to 3.3, preferably to 2.5-2.6, preferably with an HCl aqueous solution.
At this pH, the aqueous hyaluronic acid solution or broth is transformed into a very viscoelastic aqueous solution or broth containing high molecular weight hyaluronic acid in a network arrangement.
The aqueous solution or broth containing high molecular weight hyaluronic acid thus obtained is then diafiltered, preferably according to a cross flow diafiltration process, while maintaining the same pH during the whole diafiltration step.
In step a) of the purifying process according to said first preferred embodiment, a filter particularly preferred has a pore size of 0.2 xcexcm.
In said diafiltration step a), the viscoelastic aqueous solution or broth containing high molecular weight hyaluronic acid is pumped into a cross flow filter holder equipped with suitable number of filter cartridges having a pore size in the range from a 100,000 Daltons nominal molecular weight cut-off to a 0.45 xcexcm pore size, preferably a 0.2 xcexcm pore size and pyrogen free distilled water is then added in the tank containing the viscoelastic aqueous solution containing high molecular weight hyaluronic acid, at the same flow rate as the outgoing filtrate, in order to maintain a constant volume.
In step a) of the purifying process according to said first preferred embodiment, the viscoelastic aqueous solution or broth containing high molecular weight hyaluronic acid is preferably diafiltered until the filtrate which is discarded has an optical density (OD) at a wavelength of 280 nm equal to or lower than 0.02. In this case, the optical density of the filtrate at this wavelength should be monitored during the entire diafiltration process.
According to said first preferred embodiment, the step a) of diafiltration is followed by a step b) of removing cells, preferably a step b) of centrifugation in order to remove any cells or proteins still present in the diafiltered solution or broth.
In case of microbial source, the step of centrifugation may comprise for example adjusting the pH of the diafiltered broth to a pH in the range from 3.5 to 5.0, preferably to 4.0, and then centrifuging the diafiltered aqueous broth, thus obtaining a supernatant containing high molecular weight hyaluronic acid.
Preferably, the pH of the diafiltered broth is adjusted by means of an aqueous NaOH solution. However, other basic aqueous solutions could be used.
According to said first preferred embodiment, the step b) of removing cells is followed by a step of sterilization c).
According to a second preferred embodiment of the process of the invention, step b) of removing cells is carried out before diafiltration step a).
In said second preferred embodiment, the step b) of removing cells is preferably a cross flow diafiltration step of removing cells.
In said diafiltration step of removing cells b), the pH of the aqueous hyaluronic acid solution or broth obtained from biological source is first adjusted to 3.5, preferably with an HCl aqueous solution, and then the thus obtained aqueous solution or broth is diafiltered at the same pH using a filter having a pore size of 0.2 xcexcm.
In said diafiltration step b) of removing cells, the aqueous solution or broth containing high molecular weight hyaluronic acid is pumped into a cross flow filter holder equipped with suitable number of filter cartridges having a pore size of 0.2 xcexcm and sterile pyrogen free distilled water is then added in the tank containing the aqueous solution or broth containing high molecular weight hyaluronic acid, at the same flow rate as the outgoing filtrate, in order to maintain a constant volume.
At this pH, the filter having the pore size of 0.2 xcexcm allows the returning of the cells and the passing through the filter of hyaluronic acid.
In step b) of the purifying process according to said second preferred embodiment, the aqueous solution containing high molecular weight hyaluronic acid is preferably diafiltered until 10 equivalent volumes of sterile pyrogen free distilled water was added.
In step a) of said second preferred embodiment, the pH of the aqueous hyaluronic acid solution essentially free of cells obtained in step b) is first adjusted to 1.7 to 3.3, preferably to 2.4, preferably with an HCl aqueous solution.
At this pH, the aqueous hyaluronic acid solution is transformed into a very viscoelastic aqueous solution containing high molecular weight hyaluronic acid in a network arrangement.
The aqueous solution containing high molecular weight hyaluronic acid thus obtained is then diafiltered, preferably according to a cross flow process, while maintaining the same pH during the whole diafiltration step.
In step a) of the purifying process of the present invention according to said second preferred embodiment, a filter particularly preferred has a 300.000 D nominal molecular weight cut-off.
In said diafiltration step a), the viscoelastic aqueous solution containing high molecular weight hyaluronic acid is preferably pumped into a filter holder equipped with suitable number of filter cartridges having a pore size in the range from a 100,000 Daltons nominal molecular weight cut-off to a 0.45 xcexcm pore size, preferably 300.000 D nominal molecular weight cut-off and concentrated, and sterile pyrogen free distilled water is then added in the tank containing the concentrated viscoelastic aqueous solution containing high molecular weight hyaluronic acid, at the same flow rate as the outgoing filtrate, in order to maintain a constant volume.
In step a) of the purifying process of the present invention according to said second preferred embodiment, the viscoelastic aqueous solution containing high molecular weight hyaluronic acid is preferably diafiltered until 15 equivalent volumes of sterile pyrogen free distilled water was added. The filtrate is discarded.
By applying said second preferred embodiment, a centrifugation is advantageously avoided.
According to said second preferred embodiment, the step a) of diafiltration is followed by a step of sterilization c).
The step of sterilization according to the present invention is preferably a filtering sterilization step.
In the present invention, the filtering sterilization may be carried out according to a standard filtering sterilization method.
According to said first preferred embodiment, the filtering sterilization step is carried out by adjusting the pH of the supernatant obtained in the step b) of centrifugation to a value of 7.0 and then filtering the supernatant through a filter having a pore size of 0.2 xcexcm.
According to said second preferred embodiment, the filtering sterilization step is carried out by adjusting the pH of the diafiltered solution containing hyaluronic acid obtained in step a) to a value of 7.0 and then filtering the solution through a filter having a pore size of 0.2 xcexcm.
In these two preferred embodiments, the pH is preferably adjusted by means of an aqueous NaOH solution. However, other basic aqueous solutions could be used.
Then, the sterile solution may be concentrated by using a filter having a 5,000-10,000 Daltons nominal molecular weight cut-off.
After concentration, the sterilized solution may be finally freeze dried to obtain a dry powder of hyaluronic acid or of a salt thereof.
The hyaluronic acid or a salt thereof obtained by the purifying process according to the present invention has a pharmaceutical grade and the yield is about 70-90% by weight with regard to the hyaluronic acid content in the crude solution.
The hyaluronic acid or salt thereof obtained by the purifying process of the present invention is remarkable by the absence of pyrogenicity and inflammatory activity.
The hyaluronic acid or salt thereof obtained by the purifying process of the present invention contains between 90% and 95% by weight of hyaluronic acid consisting of D-glucuronic acid and N-acetyl-D-glucosamine in a ratio of 1:1, from about 3% to 5% by weight of water, less than 0.2% by weight of proteins, less than 0.3% by weight of nucleic acids and less than 0.3% by weight of neutral sugar.
The process of the present invention is very simple and very advantageous from economical and ecological points of view since no other substance than HCl or NaOH are involved.
When the purifying process of the present invention is being used, the hyaluronic acid or salt thereof contains no trace of organic solvents.
The following examples of the process for obtaining pharmaceutical grade high molecular weight hyaluronic acid or a salt thereof according to the present invention are given for illustrative purposes only and are not intended to limit the scope of the invention.

Process for purifying high molecular weight hyaluronic acid


The invention relates to a method for commanding the brakes (F1, F2, F3) of the motors (M1, M2, M3) of a multi-axis robot (R1), comprising:                a robot arm (B) comprising at least two degrees of freedom each associated with an electric motor (M1, M2, M3), a sensor (C1, C2, C3) for measuring movement information, and a brake (F1, F2, F3),        an interfacing unit (4) of the brakes (F1-F3) able to control the supply of electricity to the brakes (F1-F3),        a central processing unit (2),        variable drives (V1, V2, V3) having a torque off function of the motors (M1-M3),        a security system (4, 5),the method comprising the following successive steps:        6a) selecting a motor (M1-M3),        6b) activating an electric braking function using the selected motor (M1-M3),        6c) opening the brake (F1-F3),        6d) comparing the movement information delivered by the sensor (C1-C3) to a threshold,        6e) closing the brake (F1-F3) when the movement information exceeds the threshold.

Field of the Invention
The present invention relates to a method for commanding a multi-axis robot, as well as a robot for implementing such a command method.
Brief Description of the Related Art
It is known to command a multi-axis robot by providing the variable steering drives of its electric motors with command signals generated from a computation unit that determines the trajectory of the robot. The motor of each axis of the robot is equipped with an electromagnetic brake actuated by the computation unit after the controlled stop of the movement on its programmed trajectory, so as to lock the movements of the robot, in order to guarantee the safety of the users and equipment. Once the robot is stopped, the computation unit cuts the motor torque.
It is known from US-A-2002/0084766 to equip the robot with variable drives that control the supply of electricity for the phases of each motor. Each variable drive includes a bridge circuit, which comprises an upper branch equipped with three switchable switches, each connected to a positive bus and to one of the phases of the motor, as well as a lower branch equipped with three additional switchable switches each connected to a negative bus and to one of the phases of the motor.
To allow the emergency stop, the variable drives of US-A-2002/0084766 incorporate a safe torque off function, preventing the switches from switching when it is activated. This function is activated when the command of all of the switches of the two branches of the bridge circuit of a variable drive is neutralized. When a variable drive cuts the power supply of the switches of both branches of the bridge at the same time, this creates a redundancy that makes it possible to improve safety, since the torque will be cut even if a fault occurs resulting in erroneously powering one of the branches of the bridge.
Furthermore, the variable drives make it possible to implement an electric braking function, performed by short-circuiting the phases of the motor that one wishes to brake, i.e., by closing all of the switches of one of the branches of the bridge. The electric braking function is useful to move a moving part of the robot subject to gravity manually in complete safety, since the braking limits the acceleration of the moving part when it is driven downward by its own weight.
When the emergency stop is activated and the user needs to release a brake to move a moving part of the robot, there is then a risk of rapid and uncontrolled movement of that part under the effect of gravity, which is dangerous.
It is necessary to deactivate the torque off function on one of the branches of the bridge to allow activation of the electric braking, so as to reactivate the command switches to close them. This is detrimental to the safety level, since the redundancy introduced by the safe torque off function is then limited, since the switches of one of the branches are no longer neutralized. Standard ISO 10218-1 relative to industrial robots requires a safety level SIL 2 and a redundancy on the emergency stop function. These safety requirements are then no longer met.

Method for commanding a multi-axis robot and robot for implementing such a method


Methods and systems for assessing patient compliance with opioid drug therapy are provided. A liquid chromatography tandem mass spectrometer (LC/MS/MS) can be used to simultaneously detect a set of measurements including an amount of at least ten opioids (and their metabolites) in a body fluids sample from a patient. The set of at least ten opioids can include at least oxymorphone and fentanyl. The amounts of opioids and their metabolites are analyzed. For example, the ratios of opioids and their respective metabolites can be used to determine which opioids a patient has been administered. A report of patient compliance is generated based on the set of measurements.

Promoting pain relief and preventing the abuse of pain medications can be difficult for health professionals to balance. Patients who use drugs of abuse are more likely to abuse pain medications and more likely to divert medication either for financial gain or to fund an addition to legal or illegal drugs. Patients who use drugs of abuse are also at higher risk of combining such use with the legal drugs that are prescribed to them, which puts them at risk for overdoses and accidents. Patients who take legally prescribed controlled medications may also be knowingly or unknowingly combining prescriptions from multiple prescribers, which can put them at risk for overdoses and accidents. The ingestion of multiple opioid/opiates can result in respiratory depression and/or fatal respiratory failure. Moreover, death rates from prescription opioid/opiate use are increasing, and the abuse of prescription opioid/opiate use is also increasing.
However, the interpretation of pain management opioid/opiate toxicology test data is complex. Physicians may lack the time and/or expertise to interpret pain management opioid/opiate toxicology data. In addition, opioid/opiate drug metabolism is complex, and some opioid/opiate drug metabolites are also available as prescription drugs, which makes the source of the opioid/opiate drug difficult to determine.

Methods and systems for analyzing medication levels in a sample


Separators for separating a multi-phase composition include a separator casing defining a chamber and a permeate outlet, at least one hydrocyclone within the separator casing, and at least one ceramic membrane. Each hydrocyclone includes a hydrocyclone inlet, a tapered section downstream of the hydrocyclone inlet, an accepted outlet, and a reject outlet. The ceramic membrane may be disposed within the separator casing and downstream of the accepted outlet of the hydrocyclone or may be disposed within at least a portion of the tapered section of the hydrocyclone. The ceramic membrane includes a retentate side and a permeate side, where the permeate side is in fluid communication with the chamber. Systems and methods for separating a multi-phase composition into a lesser-density fluid, a greater-density fluid, and a medium-density fluid using the separators are also disclosed.

Petroleum drilling, production, and/or refining can produce various mixed phase streams, such as produced water, that contain an aqueous phase, an oleaginous phase, and a solid phase in the form of solid particulates. Produced water is the largest mixed phase stream produced in the oil and gas industry and is produced in estimated amounts of 3:1 produced water to crude oil on a volume basis. The oleaginous phase of produced water and other mixed phase streams may include organic compounds, such as oils, phenolic compounds and other organic and inorganic contaminants. Many of these organic and inorganic contaminants must be removed from the aqueous streams before the water from these aqueous streams can be reused in drilling operations and refining processes or directed to downstream treatment processes. Additionally, solid components of the produced water or other mixed phase stream are also generally removed prior to reuse in drilling and refining operations or treatment in a downstream treatment process.

Systems and methods for separating multi-phase compositions


A SOI device may include a waveguide adapter that couples light between an external light source—e.g., a fiber optic cable or laser—and a silicon waveguide on the silicon surface layer of the SOI device. In one embodiment, the waveguide adapter is embedded into the insulator layer. Doing so may enable the waveguide adapter to be formed before the surface layer components are added onto the SOI device. Accordingly, fabrication techniques that use high-temperatures may be used without harming other components in the SOI device—e.g., the waveguide adapter is formed before heat-sensitive components are added to the silicon surface layer.

SOI optical devices may include an active surface layer that includes waveguides, optical modulators, detectors, CMOS circuitry, metal leads for interfacing with external semiconductor chips, and the like. Transmitting optical signals from and to this active surface layer introduces many challenges. For example, a fiber optic cable may be attached to the SOI optical device and interface with a waveguide on its surface layer; however, the diameter of the one or more modes of the optic cable (e.g., approximately 10 microns for a single-mode cable) may have a much different size than the mode of a sub-micron dimensioned waveguide tasked with routing the optical signal in the SOI device. Accordingly, directly interfacing the fiber optic cable with the sub-micron waveguide may result in low transmission efficiency or high coupling loss.
To facilitate understanding, identical reference numerals have been used, where possible, to designate identical elements that are common to the figures. It is contemplated that elements disclosed in one embodiment may be beneficially utilized on other embodiments without specific recitation.


A die attachment to a support is disclosed. In an embodiment, a semiconductor package includes a support and a die attached to the support by an adhesive on a backside of the die, wherein the die includes a capacitive pressure sensor integrated on a CMOS read-out circuit, and wherein the adhesive covers only a part of the backside of the die.

Pressure sensors, such as microelectromechanical systems (MEMS) sensors, have many applications. These sensors can be used, for example, in automotive, consumer, industrial, medical, and other applications. In MEMS sensors, for example, pressure can be measured via deflection of a membrane caused by an external pressure. Large deflections or temperature differences, however, can induce significant non-linearity in the sensors, which may present challenges in a variety of applications. Accurate and repeatable manufacturing processes of membranes and pressure sensors can allow for more accurate pressure readings over a range of temperatures and pressures.
Although some thermal effects and related stresses are predictable and thus can be included in calibrated devices, the overall stress state of the sensor die may be altered by other influences, such as bending of the carrier on which the sensor is mounted and/or moisture uptake leading to non-uniform swell of the carrier. For an ultra-sensitive pressure sensor, such changes often lead to undesirable sensor output drift.

Attachment of stress sensitive integrated circuit dies


An image forming apparatus includes a housing, a first discharge opening and a second discharge opening, a sheet discharge portion, a restricting member and a sheet discharge tray. The sheet discharge portion is connected at a position below the first discharge opening, and the sheet discharged through the first discharge opening is to be placed thereon. The restricting member stands up on a downstream side of the sheet discharge portion in a discharging direction of the sheet and can come into contact with a downstream end edge of the sheet discharged to the sheet discharge portion in the discharging direction. The sheet discharge tray includes a first fixing portion and a second fixing portion to be fixed to an upper end part of the restricting member and is attachable above the sheet discharge portion, and a sheet discharged through the second discharge opening is to be placed thereon.

The present disclosure relates to an image forming apparatus for forming an image on a sheet and particularly to an image forming apparatus with a sheet discharge portion to which a sheet having an image formed thereon is to be discharged and a sheet discharge tray additionally attached above the sheet discharge portion.
A sheet discharge portion to which a sheet having an image forming process applied thereto is to be discharged is arranged in an image forming apparatus such as a copier, a printer, a facsimile machine or a complex machine having these functions. Particularly, in some image forming apparatuses, the sheet discharge portion is arranged on an upper surface portion of an image forming apparatus main body because of an advantage that discharged sheets are easily taken out. Further, by arranging another sheet discharge tray above and at a predetermined distance from the sheet discharge portion, the sheet discharge portions can be switched according to users.
Conventionally, a technology has been disclosed in which an image reading apparatus is arranged above and at a predetermined distance from an image forming unit and a sheet discharge portion to which a sheet is to be discharged is arranged on an upper surface portion of the image forming unit. A plurality of sheet discharge portions are provided by additionally attaching a sheet discharge tray between the sheet discharge portion and a lower surface portion of the image reading apparatus.
In the above technology, the sheet discharge tray added to the image forming apparatus includes a hook member projecting upward or downward from the sheet discharge tray at one end side in a tray width direction intersecting with an attaching direction of the sheet discharge tray. If projecting upward from the sheet discharge tray, the hook member is attached to the lower surface portion of the image reading apparatus. Further, if projecting downward from the sheet discharge tray, the hook member is mounted in a guide groove formed in the upper surface of the image forming unit.
If the hook member projects upward or downward from one end of the sheet discharge tray additionally attached to the image forming apparatus as described above, it may be broken when the sheet discharge tray is attached. Further, if the hook member projects upward, it is difficult for an operator to confirm a hook mounting portion arranged on the lower surface portion of the image reading apparatus and an attaching operation has taken time in some cases.
The present disclosure was developed to solve the above problem and an object thereof is to provide an image forming apparatus which enables easy attachment of a sheet discharge tray.


The collapsible small vehicle loader apparatus provides for use with an existing receiver hitch, such as those often used on pickups, cars, vans, and other vehicles. Ideally made of aluminum, the apparatus provides for easy, lightweight transport to and engagement with a receiver hitch. While the first ramp downturns may most easily engage a pickup tailgate from above, the apparatus may also be easily fitted to other vehicles that may provide a rest as the tailgate of a pickup does, for the first ramps. After engagement with the transport vehicle, the apparatus may be collapsed and elevated and thereby remain engaged as desired. In loading a small vehicle such as an ATV or golf cart for example, the appropriate pins are disengaged to extend the ramps, and then inserted to hold the ramps in the extended position.

There remain challenges in creating the ideal small vehicle loader. For example, many loaders are cumbersome and difficult to use. Those devices that merely rest upon a pickup bed, for example, are subject to movement as well as difficulty in pickup engagement, disengagement, and device transport. Some small vehicle loading devices are too short and thereby provided too steep of loading and unloading angles. Some loading devices are too long and difficult to use and transport. The present apparatus solves these problems and provides support advantages not heretofore provided.

Collapsible small vehicle loader apparatus


Provided is an inkjet-recording ink composition comprising one or more white pigment(s), one or more polymer dispersant(s), one or more photocurable compound(s), and one or more photoinitiator(s) as its principal components, wherein the polymer dispersant(s) has a sulfonic acid group.

1. Field of the Invention
The present invention relates to an inkjet ink composition, and in particular, to an inkjet ink composition containing a polymeric compound having an acidic group that suppresses sedimentation of white ink and prevents clogging of inkjet nozzles.
2. Description of the Related Art
Essential functionality of white ink is high masking efficiency and tinting strength, because white ink having a lower masking potential, when printed on a colored medium, often results the color of the printed medium appearing through the ink and deterioration in color reproducibility.
Thus, white ink is applied first, and then, other inks of different color are applied thereon. Thus, the amount of white ink used is larger than those of the inks of other colors, and demand for white ink has been constantly growing. Screen printing is often used for application of white ink, but this method has problems in that it is only applicable to printing on flat surfaces and it is difficult to draw fine detail.
On the other hand, inkjet printing ink, which is more convenient and compact than ink in conventional printing methods, and allows printing on three-dimensional media because it is non-contact printing, is becoming more and more popular.
It is possible to overcome the problems of conventional screen printing, and thus, to print images on 3D media and fine detail, by coating with white ink using an inkjet system.
However, the viscosity of the ink used in the inkjet system needs to be low. Accordingly, white inkjet inks have problems of low dispersion stability and easier sedimentation of the pigment. Because the sediment pigment often coagulates, resulting in clogging of inkjet nozzle, blurring of printing image, or uneven printing, there exists an urgent need for a white inkjet ink of low viscosity with superior dispersion stability.
A method of specifying the specific gravity of silica and alumina, and adding an acidic group-containing polymer dispersant was proposed for preparation of white inkjet ink improved in dispersion stability (for example, see Japanese Patent Application Laid-Open (JP-A) No. 2004-59857), but this method is difficult to stabilize and difficult to produce. Thus, white inkjet ink having a favorable dispersion stability is not yet available.


An optical fiber amplifier system is described and comprises a first optical fiber having a doped core with a first gain spectral profile upon being pumped. The first optical fiber is adapted to receive an optical signal from a light source. A second optical fiber has a doped core with a second gain spectral profile upon being pumped. The second optical fiber is optically coupled to the first optical fiber. A continuous wave pump light system is optically coupled to the fibers so as to store energy in the fibers for a subsequent amplification of the optical signal from the light source. An overlapping configuration is provided between the first gain spectral profile and the second gain spectral profile so as to reduce energy depletion in one of the optical fibers from amplification of spontaneous emission generated by another of the optical fibers.

Multi-stages fiber amplifiers typically involve rare-earth doped optical fiber amplifiers optically coupled in series (i.e., cascaded fiber amplifiers). When coupled to a cascaded fiber amplifier system, an optical signal, such as, for example, a pulsed seed laser, can be amplified. A pulsed seed laser refers to a laser having an emission state that periodically changes from an on state (radiation emission) to an off state (no radiation emission). This periodic modulation of the seed laser may be accomplished by switching the power supply of the laser itself, or by using an external switch placed at its output. In the above-referenced design of cascaded fiber amplifiers, when the seed laser is in the on state, its power radiation is amplified at least by two fiber amplifiers. Those fiber amplifiers are usually designed such that the pulse energy is maximized at the device output.
A fiber amplifier is typically made of an optical fiber having a rare-earth doped core. A particular gain spectrum is associated to each type of rare-earth ions (also called dopant). In order to amplify light guided in the fiber core, rare-earth ions have to be in an excited state of energy. This energy is usually provided by the absorption of continuous wave laser pump light guided in the fiber core or cladding.
When the seed laser is in the off state, no signal light is incoming in the first amplifier doped core. Rare-earth ions in the amplifier cascade absorb the continuous wave pump light without amplifying the seed radiation. As a consequence, the potential gain of the amplifiers increases, and so does the energy stored in the fiber amplifiers. When the seed laser is switched on again, part of this stored energy is transferred to the traveling pulse by stimulated emission.
Rare-earth ions in an excited state spontaneously emit a photon within an average time span called the fluorescence lifetime. Even when an amplifier is not seeded by the master oscillator, spontaneously emitted photons are guided in the amplifier core and are amplified by neighboring rare-earth ions still in the excited state. The resulting light guided in the fiber core is called amplified spontaneous emission (ASE). The immediate consequence of ASE is the depletion of available energy in the doped fiber. When many amplifiers are used in series, ASE emitted by one amplifier may act as a seed and furthers depletion of stored energy in the other amplifiers as well.
In U.S. Pat. No. 5,933,271, Waarts et al. propose a solution to reduce the energy depletion in the first amplifier from ASE generated in the second amplifier by using pulsed pumping and synchronization. However, this solution complicates the amplifier configuration compared to continuous wave pumping.

Optical fiber amplifier system and method


The present invention provides fibers and products produced therefrom, including nonwoven webs and adhesive articles. The fibers, which can be multilayer fibers, include a polydiorganosiloxane polyurea copolymer.

Fibers having a diameter of no greater than about 100 microns (.mu.m), and particularly microfibers having a diameter of no greater than about 50 .mu.m, have been developed for a variety of uses and with a variety of properties. They are typically used in the form of nonwoven webs that can be used in the manufacture of face masks and respirators, air filters, vacuum bags, oil and chemical spill sorbents, thermal insulation, first aid dressings, medical wraps, surgical drapes, disposable diapers, wipe materials, and the like. The fibers can be made by a variety of melt processes, including a spunbond process and a melt-blown process.
In a spunbond process, fibers are extruded from a polymer melt stream through multiple banks of spinnerets onto a rapidly moving, porous belt, for example, forming an unbonded web. This unbonded web is then passed through a bonder, typically a thermal bonder, which bonds some of the fibers to neighboring fibers, thereby providing integrity to the web. In a melt-blown process, fibers are extruded from a polymer melt stream through fine orifices using high air velocity attenuation onto a rotating drum, for example, forming an autogenously bonded web. In contrast to a spunbond process, no further processing is necessary.
Fibers formed from either melt process can contain one or more polymers, and can be of one or more layers, which allows for tailoring the properties of the fibers and products produced therefrom. For example, melt-blown multilayer microfibers can be produced by first feeding one or more polymer melt streams to a feedblock, optionally separating at least one of the polymer melt streams into at least two distinct streams, and recombining the melt streams, into a single polymer melt stream of longitudinally distinct layers, which can be of at least two different polymeric materials arranged in an alternating manner. The combined melt stream is then extruded through fine orifices and formed into a highly conformable web of melt-blown microfibers.
Thermoplastic materials, such as thermoplastic elastomers, can be used in the melt processing of fibers, particularly microfibers. Examples of such thermoplastic materials include polyurethanes, polyetheresters, polyamides, polyarene polydiene block copolymers such as those sold under the trade designation KRATON, and blends thereof. It is known that such thermoplastic materials can be either adhesive in nature or can be blended with tackifying resins to increase the adhesiveness of the materials. For example, webs of microfibers made using a melt-blown process from pressure-sensitive adhesives comprising block copolymers, such as styrene/isoprene/styrene block copolymers available under the trade designation KRATON, are disclosed in International Publication No. WO 96/16625 (The Procter & Gamble Company) and U.S. Pat. No. 5,462,538 (Korpman). Also, webs of multilayer microfibers made using a melt-blown process from tackified elastomeric materials, such as KRATON block copolymers, are disclosed in U.S. Pat. Nos. 5,176,952 (Joseph et al.), 5,238,733 (Joseph et al.), and 5,258,220 (Joseph).
Thus, nonwoven webs are known that are formed from melt-processed fibers having a variety of properties, including adhesive and nonadhesive properties. Not all polymeric materials, however, are suitable for use in melt processes used to make such fibers. This is particularly true for materials that are pressure-sensitive adhesives, typically because the extreme conditions used in melt processes can cause significant breakdown of molecular weights of the polymers resulting in low cohesive strength of the fiber. Thus, there is still a need for nonwoven webs of fibers having a variety of properties, particularly pressure-sensitive adhesive properties.

Fibers of polydiorganosiloxane polyurea copolymers


The invention relates to a method and a circuit arrangement for deciding a symbol upon the reception of a signal including or coupled with a quadrature signal pair, wherein the decision is made by means of an analysis of the metric of at least one reception point to at least one nominal point in a complex coordinate space, and the metric is analyzed in the non-Cartesian or not exclusively Cartesian complex coordinate space. The decision is made after the analysis, and during the decision process, a second most probable nominal point and a reliability of the decision are determined.

During most current transmissions of radio, TV and data broadcasts conducted in particular through a cable or through terrestrial radio, data ise transmitted with a complex digital modulation method such as for example QAM (quadrature amplitude modulation). High-order symbol alphabets, for example according to 256-QAM or 1024-QAM, require a very precise adjustment of the reception in a reception device. In addition to Gaussian noise, the main problem is that a phase noise is created during the adjustment of the reception, which is produced by insufficient mixer and transmitter oscillators. Such phase noise causes statistical fluctuations in the system of coordinates of the received signal.
DE 103 44 756 A1 describes a circuit arrangement for symbol decision upon the reception of a signal coupled with a quadrature signal pair. The circuit arrangement is provided with a coordinate converter for conversion of the signal from Cartesian coordinates to non-Cartesian coordinates, a pre-decision device for determination of a minimal distance between a reception point and at least one corresponding nominal point based on the non-Cartesian signal, and a decision device for deciding a symbol based on the distance analysis. A control device in the circuit arrangement performs in this case a procedure for the determination of a symbol upon the reception of a signal which is coupled with a quadrature signal pair, during which the decision is made with an analysis of the distance of at least one reception point to at least one nominal point in the complex coordinate space. A particular characteristic in such a case is the fact that the distance in non-Cartesian or not exclusively Cartesian complex space is analyzed and a decision is then made based on this analysis. This makes it possible to avoid symbol decisions in a raster with boundaries which are optimized according to Gaussian noise. According to this procedure, decision cells are formed which in contrast to quadrants are widened in the phase direction, as one can see from the difference between FIG. 5 and FIG. 6.
FIG. 5 shows the first quadrant having 64[CCB1] QAM with possible symbols or symbol positions, symbol radii and Cartesian decision boundaries. FIG. 6, on the other hand, shows decision boundaries which are widened in the phase direction, as well as possible symbols and symbol radii.
This procedure makes it possible to ensure that a decision will be found not in the Cartesian space, that is to say in the system of I-Q coordinates, but in a system of polar coordinates. While with the Cartesian decision, a distance ΔI2+ΔQ2 between the digitalized input signal and an alphabet signal is minimized, with the decision in the system of polar coordinates is determined a distance a |Δr|+|Δφ, or the distance a Δr2+Δφ2, or a combination thereof.
Also possible is a combination of systems which takes into account both the parameters which are based on the system of polar coordinates and the parameters which are based on the Cartesian system. The factor a indicates in this case the form of the decision process and it can be adjusted according to reception conditions.
While according to the Cartesian decision, the boundaries are predetermined geometrically, in particular based on quadrant cells, and the decision can be easily realized by cutting off the low-order bits, all the distances must be explicitly calculated for the decision in the system of polar coordinates. To keep the expenditure required for this at a low level, preferably only probable symbols or symbol positions are included in the selection, for example only four possible symbols. An auxiliary decider is used for the selection according to the Cartesian decision type. A grid network of the auxiliary decider is illustrated in FIG. 7. Only four symbols in corner points of each quadrant of the auxiliary grid network are selected in order to make a decision, within which the received symbol is located. Other calculation rules are used for the outer regions.
The application of Viterbi decoders is generally known, and is used to correct an error of a trellis-coded information stream in which not all symbols are possible. In this case, after the reception of a sequence of symbols, the distance to several allowed symbols is compared and the most probable symbol sequence is selected, that is to say a symbol sequence which displays the lowest number of errors. The evaluation of the error is more precise when not only so called "hard" errors are taken into consideration, in which each false bit is evaluated as an error, but when also a "soft" error is considered within the framework of a so called soft decision.
Under the term soft error is referenced the distance which the received and digitalized signal had to the selected symbol, as well as the distance to the next most probable symbol.
The object of the present invention is to obtain an improved circuit arrangement and a method for deciding a symbol upon the reception of a signal which is coupled with a quadrature signal pair, provided with a procedure wherein the distance is analyzed in the non-Cartesian or not exclusively Cartesian complex coordinate space in order to obtain additional information about reliability.
This object is achieved with a method for deciding a symbol upon the reception of a signal coupled with a quadrature signal pair which has the characteristics according to embodiments described herein, and with a circuit arrangement for deciding a symbol upon the reception of a signal coupled with a quadrature signal pair having the characteristics according to embodiments describe herein.
A method for deciding a symbol upon the reception of a signal sd coupled with a quadrature signal pair is thus realized so that the decision is made with an analysis of the metric or of the distance of at least one reception point to at least one nominal point in a space of complex coordinates, and the metric in the non-exclusively Cartesian space of complex coordinates is analyzed and the decision is made on this basis, wherein the reliability of the decision is determined during the decision process.
The decision is preferably considered in a polar coordinate space, wherein for the metric, the Euclidean distance between the reception points and the nominal points is used, and/or a sum or the values of the angular projections and radial projections of the metric between the reception point and at least one nominal point are analyzed.
The reliability is preferably determined by taking into consideration the smallest metric between the reception point relative to both a first nominal point and to a second nominal point. The smallest metrics are in each case determined relative to nominal point for the previous symbol. The second nominal point forms preferably a second most probable point for the decision.
The reliability Z can be with advantage determined according to
  Z  =      log    (                            ∑                      A            ∈                          M                                                                                1                                                                                P                                [                          s              =                              α                |                R                                      ]                                                ∑                      A            ∈                          M                                                                                0                                                                                P                                [                          s              =                              α                |                R                                      ]                                )  with the sum of the conditional probability P[s=A|R] that the symbol α was transmitted if the symbol R was received formed over the set M1 of all transmission symbols which represent a sent value "1", and the corresponding formation of sums over the set M0 of all transmission symbols which represent a "0".
The reliability can be determined in a simple manner according to
  Z  =      log              (                        P                                [                          s              =                                                α                                                                                1                                |                R                                      ]                                    P                                [                          s              =                                                α                                                                                0                                |                R                                      ]                              )      with p[s=α1|R] for the probability of a transmission symbol with the transmission value 1 and P[s=α0|R] for the probability of one of the most probable symbols having the transmission value 0.
The reliability Z can be in a particularly preferred version determined according toZ=abs[transmission](A1−A2)/NF=(A2−A1)/NF wherein A1 is the smallest metric for a most likely symbol position, A2 is second smallest metric for a second most probable symbol position, and NF is a normalization factor. The normalization factor is in this case preferably formed with the second smallest metric or the sum of the metrics or a constant.
Accordingly, preferred is a circuit arrangement for deciding a symbol upon the reception of a signal coupled with a quadrature signal part, provided with a coordinate converter for conversion of the signal from the Cartesian coordinates into non-Cartesian coordinates, and a decision device for deciding a symbol based on a distance analysis of a minimal metric between a reception point and two next most probable nominal points for this point, and a determination of the reliability of the decision. The circuit arrangement is used preferably in order to realize the method described above.
On the other hand, a decision that is per se known in a polar coordinate system is obtained with a corresponding decider or decision process at this time as a criterion for a soft decision[CB2]. In this manner, this new type of a decision is thus obtained with additional information for which the next Viterbi code is required.
Advantageous application fields can be found in complex digital modulation methods, such as for example QAM. Similar modulation methods are at this time employed in particular for radio, TV and data services which are transmitted via cable, but also through terrestrial radio.

Method and circuit arrangement for symbol decision upon the reception of a signal including a quadrature signal pair


A method for molding digital storage memory cards such as, for example, multimedia cards (MMC), secure digital cards (SD), and similar small form factor digital memory cards. A PCA subassembly including, for example, a leadframe (TSOP) package for enclosing a flash IC and a (e.g., land grad array) controller package for enclosing a controller IC are mounted on a printed wiring board within a mold cavity. A high melt flow index resin is injected into the mold cavity to form an integral, solid body within which to completely encapsulate the flash IC and controller packages and form a cover over top the flash IC package so as to maintain the required memory card height tolerance. In one embodiment, the resin material is injected downwardly into the mold cavity from locations above the respective rows of leads of the flash IC package. In another embodiment, the resin material is injected laterally into the mold body from locations at opposite sides thereof adjacent the respective rows of leads of the flash IC package.

1. Field of the Invention
This invention relates to a method for molding digital storage memory cards such as, for example, multimedia cards (MMC), secure digital cards (SD), and similar small form factor digital memory cards.
2. Background Art
Thin form factor digital flash memory cards such as secure digital (SD), mini-SD, multimedia cards (MMC), and others contain three major components: an active flash memory device (including a flash IC and its controller); a printed circuit board (PCB) substrate; and an exterior cover that is typically manufactured from plastic. There are commonly two conventional methods of making these thin form factor digital memory cards.
The first method requires that semiconductor packages are surface mounted on the PCB substrate by way of a SMT production line. In this case, the active components (i.e., the flash memory and controller ICs) are located inside the semiconductor packages. These IC packages along with the necessary passive components (including surface mounted resistors and capacitors) form a complete subassembly that is known as a printed circuit board assembly (PCA). The finished card assembly is then completed by mating a plastic cover on top or two separate plastic covers on the top and bottom thereof in accordance with the standard design specifications. The thin cover top is typically molded plastic, but other materials (e.g., including a combination of metal and plastic) can also be employed.
The second conventional method for making a thin form factor digital flash card having a PCA subassembly is by means of a chip-on-board (COB). In the usual COB process, the active flash IC chips and their respective controller chips are mounted to the PCB substrate in a "chip and wire" process. That is, bare chips are assembled on the PCB substrate using wirebonds. However, the ICs are not assembled in a package as would otherwise occur in the aforementioned SMT production line assembly process. Nevertheless, when using the COB process, the supporting passive components may still need to be surface mounted to the substrate by means of an SMT assembly line. For a COB, the flash IC and its controller may be placed face up and a conventional wirebond (i.e., chip and wire) method is used to interconnect the I/O of the IC to the PCB substrate to thereby form the PCA subassembly. After the die attach and wirebond, it is usually necessary to apply an encapsulant over the bare flash and controller chips and their respective wires to provide suitable protection. This encapsulation step can be achieved by using either liquid encapsulants (globtop) or electronic molding compound (EMC) that are applied to the COB by means of a transfer mold. After encapsulation by either globtop or transfer mold, the finished PCA subassembly is then completed with an appropriate cover to achieve the final form factor for the intended memory card assembly.
It can be appreciated that for either of the two memory card assembly methods described above, the final step of making the finished card is attaching a (e.g., plastic) preformed cover. This cover can be a separate molded part and attached to the PCA by means of a thin layer of adhesive film. In the alternative, the cover can be bonded to the substrate of the PCA by ultrasonic fusion of the plastic material.
Alternatively, there is a more desirable method for forming and attaching the cover atop the PCA subassembly. This method includes injection molding directly over the PCA subassembly where the cover is formed in situ above the PCA packages. Therefore, there is no need to assemble a separate, preformed cover. This approach lowers the cost relative to requiring an adhesive or ultrasonic bonding of a separately preformed cover to the PCA subassembly.
What is more, injection molded parts have many advantages over a memory card assembly that requires a two part assembly process. In injection molding, the molded resin material will fill up all of the internal spaces inside the PCA subassembly. Thus, the finished memory card is mechanically more rigid and robust. Similarly, the card assembly will be more moisture resistant because there are no voids inside the card and no recessed grooves or large seams formed in the bond lines that are otherwise formed in the conventional two part (PCA and preformed cover) assembly. Injection molded parts also permit better dimensional stability and compliance to the design specifications of the memory card.
Even though such an injection molded method is more desirable and cost efficient, this method is presently applicable only to those PCAs that are manufactured by the COB process. The desirable injection molded method has not typically been applicable to PCAs that are made from the IC package/SMT process. The reason for this limitation is that IC packages having a commonly used TSOP (thin small outline package) format are thicker than the COB bare dice. Hence, any PCA using conventional TSOP packages would have a higher profile or body height than those made with the COB chip and wire process. A lower PCA assembly profile is necessary to permit injection molding such that sufficient resin material will flow into the narrow gap above the TSOP package while complying with the final finished memory card thickness requirement. When a conventional TSOP package is used to carry the flash IC in the PCA, the height of the TSOP package plus its substrate in the PCA is already approaching the maximum allowed overall thickness of the final memory card assembly. This leaves very little room for injection molding in areas directly above the TSOP package. Therefore, a PCA containing relatively tall packages, like the standard TSOP package, is unsuitable for injection molding. In other words, only COB PCAs having lower heights can be successfully used with an injection mold process.
Although the injection mold process to form an integral cover for the final memory card assembly is more direct and less costly, the conventional assembly steps of making a PCA by means of COB has other drawbacks which could reduce the advantage of the final injection mold step. One reason for some COB process drawbacks includes the requirement that the PCB substrates must have a soft gold surface finish on the wirebond pad area for gold wirebonding. This requirement increases the cost, because gold is plated onto the substrate and additional provisions must be provided to have plating bus lines running to the pads during such electric plating.
Another drawback is the result of the wirebond IC requiring protection by means of a liquid encapsulant in either globtop dispensing or transfer mold. This protection step requires additional time and cost. In addition, the cover is injection molded over the encapsulated PCA.
Yet another process drawback of COB is that the bare die that is mounted on the PCA typically cannot be fully tested and replaced, if necessary. After the assembly, if the flash IC or controller is found to be defective, the entire PCA subassembly will have to be discarded in its entirety.
Hence, there is a need for a manufacturing process by which to make a memory card assembly that can be used in high volume production with high yield and low assembly cost that is applicable to both a COB assembled PCA and to a TSOP assembled PCA. The injection mold material should be capable of fitting in the narrow space limitations above the TSOP package area while not causing damage to the connection of the TSOP package and the IC that is carried therewithin.

Method for molding a small form factor digital memory card


A photo film cassette has a spool about which photo film is wound in a roll form. A cassette shell contains the spool in a rotatable manner, and has first and second plastic shell halves joined together via a joining line. A first extended portion is disposed on the first shell half, to project from the joining line toward the second shell half. A first claw is disposed on an end of the first extended portion, to project inwards, and has a first engaging face confronted with the joining line. A securing cutout is formed in the second shell half and disposed close to the joining line, for receiving the first extended portion. A second extended portion is disposed on the second shell half, to project from an edge of the securing cutout, and is extended inwards, and covered by the first extended portion partially. A second claw is disposed on an end of the second extended portion, to project outwards, and retains the first claw to secure the first shell half to the second shell half. The second claw has a second engaging face, which is confronted with the edge of the securing cutout, is fitted on the first engaging face, and keeps the second claw engaged with the first claw. Two ridges project from the second engaging face, are extended in a direction of access of the first claw, and are pushed by the first engaging face. The ridges are deformed partially by the first engaging face, to tighten a contact between the first and second claws.

1. Field of the Invention
The present invention relates to a photo film cassette and a cassette containing case for the same. More particularly, the present invention relates to a photo film cassette of which a cassette shell consists of a pair of shell halves secured to one another via engagement of claws, a cassette containing case for the same.
2. Description Related to the Prior Art
There is an IX240 type of photo film cassette, in which a photo film including its leader is pre-contained in a cassette shell, and the leader of the photo film is advanced to the outside when a spool is rotated. U.S. Pat. No. 5,476,232 (corresponding to JP-A 6-266053) discloses a construction of the cassette shell in combination of a pair of shell halves of resin. There is a first arm formed on one of the shell halves and protruded inwards for retention. A second arm is formed on the other of the shell halves and protruded outwards for receiving the retention. The first arm is engaged with the second arm in a snap connection to join the shell halves fixedly. There are two retainer mechanisms each of which includes the first and second arms, and which are located in respective lateral positions beside a photo film passageway through which the photo film is passed. The first and second arms have such a sufficient width in a direction of an exit slot of the passageway that lateral ends of the passageway is enclosed in a reliably light-tight manner.
There is a problem in the simple snap connection as described in the prior art portion of U.S. Pat. No. 5,647,552 (corresponding to JP-A 8-146561). The photo film cassette was subjected to a test of dropping down to an iron plate from a height of 2 (two) meters. A considerable number of sample cassettes resulted in disengagement of the snap connection. U.S. Pat. No. 5,647,552 suggests an idea of reinforcing the snap connection. The second arm is constituted by a second claw protruded outwards and an engaging face or recessed face. The second claw prevents the first arm from being disengaged. The engaging face receives a first claw protruded inwards from the first arm. The first arm is formed in such a size that, when the first arm is fitted at the engaging face, the first claw and the engaging face are pressed against each other. To form the first arm, the same document discloses relevant values, including: a height of the first claw of the first arm, a shifting amount at which the first arm is shifted for passing by the second claw, and a sectional area of an erected support supporting the first claw of the first arm for the purpose of maintaining the shifted amount thus determined.
However there occurs a problem of play between the first and second arms or failure in the retention between them, because a height of the second arm is not determined suitably. If heights of the first and second arms are determined, dimensional tolerances are provided for the heights. The shell halves are molded by respective separate molds. When shell halves are combined randomly, deviations in the ranges of the dimensional tolerances becomes dimensional errors. Of course it is conceivable to reduce such dimensional errors. Then another problem arises in narrowing ranges of the dimensional tolerances, and increasing costs of production by use of molds.

Photo film cassette and cassette containing case for the same


The present invention provides several classes of compounds which can be used to inactivate retroviruses, such as HIV-1, by attacking the CCHC zinc fingers of the viral nucleocapsid protein and ejecting the zinc therefrom. In addition, kits for identifying compounds that can react with CCHC zinc fingers of the nucleocapsid proteins of a large number of different retroviruses have also been developed. The kits of the present invention describe a set of specific tests and reagents that can be used to screen and identify compounds based on their ability to react with and disrupt retroviral zinc fingers in the viral NC proteins and, in turn, inactivate the retrovirus of interest.

Most antiviral drugs used to control the spread of HIV-1 have proven to be of limited use because under the selection pressure of the drug, the virus soon mutates to a drug-resistant strain. This tendency to develop drug resistance is a survival strategy used by many classes of viruses and is particularly pronounced among the members of the retrovirus family. One way to defeat this survival strategy is to focus on drugs attacking specific elements of the virus that are intolerant to mutations. Such elements can be identified by searching the proteins present in all viruses within the virus class to identify common or highly conserved structures.
A search of all known retroviruses reveals a highly conserved structure in their nucleocapsid (NC) proteins. All NC proteins of the Oncovirinae and Lentivirinae subfamilies of Retroviridae contain sequences of 14 amino acids with 4 invariant residues, Cys(X).sub.2 Cys(X).sub.4 His(X).sub.4 Cys (L. E. Henderson et al. J. Biol. Chem. 256, 8400 (1981)), which chelate zinc through histidine imidazole and cysteine thiolates with a K.sub.d less than 10.sup.-13 (J. M. Berg, Science 232, 485 (1986); J. W. Bess, Jr., et al., J. Virol. 66, 840 (1992); M. R. Chance et al., Proc. Natl. Acad. Sci. U.S.A. 89, 10041 (1992); T. L. South and M. F. Summers, Adv. Inorg. Biochem. 8, 199 (1990); T. L. South, et al., Biochem. Pharmacol. 40, 123 (1990)) (see, FIG. 1). These structures are referred to as retroviral CCHC zinc fingers, and are one of the most highly conserved features of retroviruses. Examples of retroviruses which possess at least one CCHC type zinc finger per nucleocapsid protein include, but are not limited to, HIV-1, HIV-2, SIV, BIV, EIAV, Visna, CaEV, HTLV-1, BLV, MPMV, MMTV, RSV, MuLV, FeLV, BaEV, and SSV. The distribution of CCHC zinc fingers among known subgroups of retroviruses is indicated by the diagram set forth in FIG. 1. Due to their highly conserved nature, it is thought that CCHC zinc fingers perform an essential function in viral infectivity. In fact, it has been discovered that mutations of the chelating residues (CCHC) in the zinc fingers yield a non-infectious virus.
HIV-1 NC contains two zinc fingers separated by only 7 amino acids (L. E. Henderson et al., J. Virol. 66, 1856 (1992)). The location of the CCHC zinc fingers in the HIV-1 NC protein is indicated in the diagram shown in FIG. 2 (see also, Henderson et al., J. Virology, supra, 1992). The zinc fingers are not only required for packaging genomic RNA, but are also essential for early events in virus infection. Both fingers are essential for infectivity (A. Aldovini and R. A. Young, J. Virol. 64, 1920 (1990); R. J. Gorelick et al., J. Virol. 64, 3207 (1990).
Incubation of HIV-1 with 3-nitrosobenzamide (NOBA), a C-nitroso compound, results in the loss of zinc from the HIV-1 CCHC zinc finger array and viral inactivation (W. G. Rice et al., Nature 361, 473 (1993); W. G. Rice et al. PNAS 90, 9721 (1993)). Moreover, removal of zinc from the eukaryotic CCHC zinc finger of poly(ADP-ribose) polymerase by C-nitroso compounds has been reported (K. G. Buki, et al., FEBS Letters 290, 181 (1991)). Unfortunately, to date, the mechanism by which such CCHC zinc fingers are disrupted has not been discovered. Without an understanding of the reaction mechanism, investigators have had no way to predict which compounds would be effective in selectively disrupting CCHC zinc fingers.
In view of the foregoing, there exists a need in the art for a mechanism and method which can be used to predict compounds that can effectively disrupt CCHC zinc fingers and, in turn, inactivate the retrovirus of choice.

Method for identifying and using compounds that inactivate HIV-1 and other retroviruses by attacking highly conserved zinc fingers in the viral nucleocapsid protein

The United States of America as represented by the Department of Health and Human Services


A tapered airline directional coupler includes a housing having a length with an input end and an output end, the housing having a slot formed therein extending between the input end and the output end. The coupler also includes a main conductor in electrical communication with an input port connector mounted on the housing at the input end thereof and with an output port connector mounted on the housing at the output end thereof, and a coupled conductor in electrical communication with and extending between a forward coupling port connector mounted on the housing adjacent to the input end thereof and a reverse coupling port connector mounted on the housing adjacent to the output end thereof. Each of the slot, the main conductor and the coupled conductor has a cross-sectional area that varies depending upon where the cross-section is taken along the length of the housing.

The term "directional coupler" refers in general to a four-port, or a three-port when internally terminated, passive microwave device, where a main line conductor (also called the "through" line) carries radio frequency (RF) power. The main line conductor is in close proximity and is coupled to a secondary conductor by the electromagnetic field generated by the RF signal. The RF current flowing forward through the main line will induce RF current flow in the coupled conductor flowing in the opposite direction, and will only appear at one of the coupled ports (i.e., a signal current flowing from left to right on the main line will induce a signal current flowing from right to left in the coupled conductor and appear only from the left coupled output). As a result, the coupled output of forward and reverse flow of RF current, on the main line, will appear at different coupled outputs.
Many different designs for directional couplers, including both single and dual directional couplers, have been historically known, for example, from U.S. Pat. Nos. 6,066,994, 6,573,807 and 6,600,307. However, the directional couplers disclosed in these references suffer from a number of disadvantages, particularly in their design and their manufacturability.
U.S. Pat. No. 7,429,903 represented a significant advancement over the theretofore known designs, in providing an airline directional coupler that exhibited relatively high power, relatively low passive intermodulation (PIM), relatively low loss, and relatively wide bandwidth, all in a package that was relatively simple in design and relatively inexpensive and easy to manufacture. Though U.S. Pat. No. 7,429,903 was specifically directed to a dual directional coupler, the teachings thereof would be applicable to a single directional coupler.
However, while U.S. Pat. No. 7,429,903 was indeed an advancement over the prior art thereto, the teachings thereof still suffer from significant disadvantages. For example, although the frequency bandwidth of the design disclosed in U.S. Pat. No. 7,429,903 was relatively wide, as compared to historical designs, it still resulted in limitations. More specifically, the stepped configuration taught be U.S. Pat. No. 7,429,903 is frequency limited by the number of ¼ wave sections or 'n-sections', and is not practical to implement for a large number of sections.
What is desired, therefore, is a high power, low passive intermodulation (PIM), low loss, wide bandwidth airline directional coupler that is relatively simple in design and relatively inexpensive and easy to manufacture as compared to known designs, while at the same time also providing for wider bandwidth than has heretofore known designs.


Poly(vinylamine) homopolymers and copolymers are hydrophobically modified by reaction of amine units present in the polymer with a saturated aliphatic or aromatic glycidyl ether compound. The resulting polymers are useful as flocculants in separating water from suspended solids and are especially effective in improving fines retention in papermaking. Poly(vinylamine hydrochloride) modified in this manner with butyl glycidyl ether is shown to be very efficient in retaining the paper product fines present in recycle paper pulps.

Amine functional polymers are of growing commercial interest because of their versatility in being tailored for specific uses. The amine functionality of these polymers enables them to interact chemically so as to enhance their performance in certain applications. For example, amine functional polymers have been found useful as crosslinking agents for epoxy resins and polyurethanes, in enhanced oil recovery, as flocculants in processes such as wastewater treatment, and in papermaking as wet-end additives to improve paper wet strength.
It is known that the amine functionality in polymers can react with epoxy compositions in a curing process. U.S. Pat. Nos. 4,238,579, Leonard, Jr. et al. (1980) and 4,260,714, Wingard, Jr. et al. (1981) disclose that certain vinylamine copolymers can be used to cure epoxy resins in the manufacture of adhesives, potting resins, self-supporting reinforced composites and the like. Also, U.S. Pat. No. 4,778,725, Serizawa et al. (1988) describes making polymers having side chains containing terminal allyl groups by reacting a poly(vinylamine) with an allyl compound containing an epoxy group. The purpose of adding these side chains is to use the crosslinking properties of these unsaturated groups in the formation of self-supporting films and coated substrates. Ikemura, Kobunshi Kagaku, 26(288), pp 306-10 (1969) describes synthesizing polymers by graft copolymerization of ethylene oxide or propylene oxide onto poly(vinylamine). The result is said to be increased water solubility of the poly(vinylamine).
One of the more promising markets for vinylamine polymers takes advantage of the flocculating properties of these materials in operatons which require separation of water from suspended solids. Use of high molecular weight poly(vinylamine hydrochloride) as a flocculating agent is disclosed by U.S. Pat. No. 4,217,214, Dubin (1980). U.S. Pat. No. 4,421,602, Brunnmueller, et al. (1983) describes partially hydrolyzed homopolymers of N-vinylformamide as being useful as retention agents, drainage aids and flocculants in papermaking. European Patent Application 0,331,047 (1989) notes the utility of high molecular weight poly(vinylamine) as a wet-end additive in papermaking for improving dry strength of the product and as a filler retention aid.
U.S. Pat. No. 4,952,656, Lai et al. (1990) describes high molecular weight vinylamine homopolymers which can be made by inverse emulsion polymerization of N-vinylamides such as N-vinylformamide. Use as wet-end papermaking additives is among several utilities mentioned. Also, U.S. Pat. No. 4,978,427, Pfohl et al. (1990) discloses hydrolyzed copolymers of N-vinylformamide and ethylenically unsaturated monomers, such as vinyl acetate, which can be used in papermaking to increase product wet strength by addition of the copolymer to the pulp stock suspension in amounts of 0.1 to 5 weight percent based upon the dry fiber.
Market demand for tailored additives has stimulated further interest im modification of vinylamine polymers to increase their usefulness in specific applications. This has been done to increase their hydrophobic character, for example, by reaction with monoaldehydes. U.S. Pat. No. 5,086,111, Pinschmidt, Jr., et al. (1992) describes polyvinyl acetals containing amine functionality made by reacting a monoaldehyde and a poly(vinylamine) which includes both vinylamine homopolymers and copolymers containing ester and/or hydroxy groups. Such poly(vinylamines) have weight average molecular weights from 10,000 to 7 million. These polyvinyl acetals are shown to be useful as floculating agents.
It remains highly desirable to find ways to modify vinylamine polymers in order to change their hydrophobic character or alter other properties to increase their effectiveness in specific applications. One such application is in the retention of fines in papermaking processes. This is particularly a problem when dealing with recycled pulps because of the higher fines levels. Loss of fines during dewatering typically results in poorer physical properties of the finished product as well as reducing yield. This also causes higher fines levels in the processing water leading to costlier and more frequent clean-up.
At present, several types of polymers are being used in various ways to improve fines retention in papermaking. Polymer types used include cationic polymers such as copolymers of acrylamides and quaternary amines, anionic polymers such as copolymers of acrylamide and acrylic acid, and amphoteric polymers such as a polymer of a quaternary amine and acrylic acid. A common method for retaining these fine particles is first to add alum which negates the repulsive forces between the negatively charged cellulosic surface of the fiber and the negatively charged filler particles. Then a cationic polymer is added which bridges the two types of anionic surfaces and binds them together. Several newer systems now being used in this service include blends of cationic polyacrylamides with anionic fillers such as kaolin clays. Another type of blend is a cationic starch with anionic colloidal silica. Despite the wide variety of retention aids available, there continues to be a need for even better fines retention agents as the use of recycled papers continues to grow.


There is disclosed an improved insect bait station and a method of treating insects with a toxicant. The improved insect bait station comprises a body member, the body member defining a bait area within the body member and an opening in the body member so that insects can enter the body member and feed on an attractant bait in the bait area. The insect bait station further comprises a toxicant applicator disposed in the body member, the toxicant applicator and the body member defining a passage of predetermined dimensions such that an insect which enters the body member or feeds on the bait therein contacts the toxicant applicator so that a toxicant substance is applied to the insect.

Various types of devices have been known in the prior art for destroying insects. In some devices, the insects are trapped in the device after entering, either by mechanical construction or by sticking to a gummy substance. In either instance, the device is soon full and useless. In devices which contain a poison, it is relatively easy to shake out loose poison, or to probe through openings to reach the poison, thus making them dangerous to children and domestic animals.
In order to attract insects into an insect destroying device, it is necessary to include an insect attractant or bait, such as a food or a pheromone used in conjunction with a food. The insect attractant of prior art devices is typically blended with an insect toxicant so that the insect will be encouraged to ingest the toxicant when it feeds on the attractant. However, many toxicants have a flavor which is distasteful or repellent to the insect thereby discouraging the insect from ingesting the toxicant. The flavor of the toxicant can, in some instances, mask the attractant aspect of the bait. Therefore, a toxicant and a bait sometimes have opposite effects on insects. Therefore, it is sometimes necessary to use special baits, increased amounts of baits or feeding stimulants to overcome the undesirable effect of the toxicant with which the bait is mixed.
Examples of prior art insect destroying devices can be found in U.S. Pat. Nos. 552,644; 1,573,278; 1,887,771; 2,837,861; 4,823,506; 4,841,669; 4,761,912; 4,793,093; 4,837,969; 4,563,836; 4,485,582; 4,563,836; 5,033,229; 5,057,315; and 5,057,316.
Thus, there is a need in the art for an insect destroying device in which the toxicant is securely contained within the device. There is also a need in the art for an insect destroying device in which the insect attractant and the toxicant do not have opposite or competing effects upon the target insect. Furthermore, there is a need in the art for an insect destroying device in which the toxicant is more efficiently applied to an insect and/or subsequently spread to other members of an insect colony.

Insect bait station and method of treating insects with toxicant


A method and apparatus for reacting a plurality of different mixtures in parallel in a semi-batch or continuous mode is provided. Each reaction is contained within a reactor vessel, the reactor vessels combined into a reactor block. Reactant(s) to be added during the reaction are kept in a header barrel, which has a plunger to feed reactant(s) from the header barrel through a transfer line into the reactor vessel. The plunger is moved using a drive system. The header barrels are optionally combined in a header block. The header block is sealed to a plate containing the transfer lines, which in turn is sealed to the reactor block. A latch mechanism is provided for easy sealing of the reactor and header blocks to the plate. The entire apparatus may be placed on a rocker or rotating plate for mixture as the reaction is proceeding.

1. Technical Field
The present invention relates to a method and apparatus for rapidly making, screening, and characterizing an array of materials in which process conditions are controlled and monitored, and in particular where the feed to each reactor vessel is continuously fed.
2. Discussion
Combinatorial materials science generally refers to methods for creating a collection of diverse compounds or materials using a relatively small set of precursors and/or methods for rapidly testing or screening the collection of compounds or materials for desirable performance characteristics and properties. As currently practiced, combinatorial materials science permits scientists to systematically explore the influence of structural variations in candidates by dramatically accelerating the rates at which they are created and evaluated. Compared to traditional discovery methods, combinatorial methods sharply reduce the costs associated with preparing and screening each candidate.
Combinatorial chemistry has revolutionized the process of drug discovery. See, for example, 29 Acc. Chem. Res. 1–170 (1996); 97 Chem. Rev. 349–509 (1997); S. Borman, Chem. Eng. News 43–62 (Feb. 24, 1997); A. M. Thayer, Chem. Eng. News 57–64 (Feb. 12, 1996); N. Terret, 1 Drug Discovery Today 402 (1996)). One can view drug discovery as a two-step process: acquiring candidate compounds through laboratory synthesis or through natural product collection, followed by evaluation or screening for efficacy. Pharmaceutical researchers have long used high-throughput screening (HTS) protocols to rapidly evaluate the therapeutic value of natural products and libraries of compounds synthesized and cataloged over many years. However, compared to HTS protocols, chemical synthesis has historically been a slow, arduous process. With the advent of combinatorial methods, scientists can now create large libraries of organic molecules at a pace on par with HTS protocols.
Recently, combinatorial approaches have been used for discovery programs unrelated to drugs. For example, some researchers have recognized that combinatorial strategies also offer promise for the discovery of inorganic compounds such as high-temperature superconductors, magnetoresistive materials, luminescent materials, and catalytic materials. See, for example, U.S. Pat. No. 5,776,359, as well as U.S. patent application Ser. No. 08/327,513 "The Combinatorial Synthesis of Novel Materials" (published as WO 96/11878) and co-pending U.S. patent application Ser. No. 08/898,715 "Combinatorial Synthesis and Analysis of Organometallic Compounds and Catalysts" (published as WO 98/03251), which are each herein incorporated by reference.
Because of its success in eliminating the synthesis bottleneck in drug discovery, many researchers have come to narrowly view combinatorial methods as tools for creating structural diversity. Few researchers have emphasized that, during synthesis, variations in temperature, pressure and other process conditions can strongly influence the properties of library members. For instance, reaction conditions are particularly important in formulation chemistry, where one combines a set of components under different reaction conditions or concentrations to determine their influence on product properties. Moreover, it is often beneficial to mimic industrial processes that are different than in pharmaceutical research so that many workers have failed to realize that processes often can be used to distinguish among library members. Some parallel reactors are known; see for example WO 98/36826 and U.S. Pat. Nos. 4,099,923 and 4,944,923, that are each incorporated herein by reference. However, what is needed is an apparatus for preparing and screening combinatorial libraries in which an industrial process can be followed.

This patent is subject to a terminal disclaimer.

Parallel semi-continuous or continuous reactor system


A device and system for thin wafer cleaning is disclosed. A preferred embodiment comprises a spin chuck having at least three holding clamps. A thin wafer with a wafer frame is mounted on the spin chuck through a tape layer. When the holding clamps are unlocked, there is no interference with the removal and placement of the wafer frame. On the other hand, when the holding clamps are locked, the holding clamps are brought into contact with the outer edge of the wafer frame so as to prevent the wafer frame from moving laterally. Furthermore, the shape of the holding clamps in a locked position is capable of preventing the wafer frame from moving vertically.

Emerging applications, such as radio frequency identification (RFID) integrated circuits, high density memory devices have an increasing demand for thin semiconductor devices. Thin semiconductor devices, and the like, enable more sophisticated manufacturing technologies, including micro-electro-mechanical systems (MEMS), through-silicon via (TSV) and novel 3D packaging technologies.
In the manufacturing process of thin semiconductor devices, an important step is thin wafer cleaning after the semiconductor manufacturing process. For example, after a chemical-mechanical polishing process, some residues such as carbon or adhesive films and particles may stay on the surface of the thin wafer. These films and particles may cause surface roughness leading to defects in subsequent fabrication processes, such as a defect in the photolithography process due to the uneven surface of the wafer.
In the conventional art, wet wafer cleaning is commonly employed to remove unwanted residues by spraying various cleaning chemical solvents on a wafer. When a wafer is in this wafer cleaning process, it may be directly placed on a vacuum chuck and then a variety of spray nozzles spray chemical solvents first onto the wafer while the vacuum chuck is spinning. After carbon and adhesive films and particles are dissolved or decomposed, the chemical solvents wash dislodged films and particles away from the wafer. In the last step of the cleaning process, de-ionized water is sprayed while the wafer is spinning to allow complete cleaning.
However, thin wafers are fragile and must be supported over their full dimensions to prevent unnecessary damage. A common method of protecting a thin wafer involves using an adhesive layer to temporarily bond the thin wafer on a plate and employing a wafer frame to prevent the thin wafer from moving laterally. As such, it is desirable to clean a thin wafer while the thin wafer is bonded on a tape layer and protected by a wafer frame.
Corresponding numerals and symbols in the different figures generally refer to corresponding parts unless otherwise indicated. The figures are drawn to clearly illustrate the relevant aspects of the various embodiments and are not necessarily drawn to scale.

Taiwan Semiconductor Manufacturing Company, Ltd.