It concerns a monomer, a polymer obtained from the monomer and a process for obtaining the said polymer. The monomer consists of a polyether containing at least 3 ether units and pyrrole or thiophene units bonded to the ends of the chains of this polyether via, for each of these heterocycic compounds, either their carbon atoms in the 3,3'-positions of their heterocycles or, as regards more particularly the pyrrole groups, via their respective nitrogen atoms, the 2- and 2'-positions of these heterocycles being, however, free of all substitutions or, at the very most, substituted by easily removable groups (protective groups, for example).. Application to the purification and recovery of metal ions such as radioactive silver.

Salts of polymers of compounds of aromatic nature possessing complexing cavities have already been produced by molecular electrochemistry techniques (1), these techniques involving an electrodeposition of certain polytriphenylenes on essentially non-corrodible supports, such as precious metals (platinum, gold) or vitreous carbons. The most common example relates to the polymerization of the compound known under the name DB-18-C-6 (I) to polytriphenylene: ##STR1##
The direct formation of a doped form of the polymer (doubtless of redox nature) has been demonstrated. These polymer salts can be easily reduced or "dedoped" by chemical agents such as tertiary amines or tetraalkylammonium hydroxides. It is possible, in this way, to obtain neutral, non-conductive resins which are resistant to chemical agents and to solvents, which have an electronic conductivity and which have both polyaromatic linkages and polyether units, obtained from certain biaromatic polyethers (II), ##STR2## in which the anodic activation is increased by the presence of donor groups on the aromatic systems (example: ether groups). When the polymerization is carried out at a sufficiently oxidizing potential, conductive polyparaphenylenes can be obtained by virtue of the high concentration of redox sites produced in the matrix (oxidation at 4 electrons per monomer unit). These redox sites make the material sufficiently permeable to the flows of electrons necessary for the growth in thickness of the films formed, by virtue of the electron jumps induced between these sites, during the development of the deposits. It has already been proposed to use such polymers for extracting certain metal ions present in aqueous or organic solutions brought into contact with them (2). However, they are not always effective, as regards, for example, removing (or recovering) traces of silver contained in certain effluents. The production costs are high. Difficulties also accompany the synthesis of the monomers, especially from hydroquinones, and then the oxidation of these monomers, which must be carried out at a fairly strongly oxidizing potential even if the aryl groups have been activated beforehand.

Derivatives of polyethers and of pentacyclic heterocycles, their polymers and their applications, particularly to the complexing of metal ions


A plastic drum assembly includes a preformed insert fused to at least a portion of the corner of the drum. In order to facilitate lifting and handling the drum, the insert is formed with a pair of indentations on opposite sides of a ridge. The method involves placing the preformed plastic insert across at least a portion of a corner of a mold cavity and blow molding the drum in the cavity to form the drum and fuse the drum corner to the insert. The disclosure also is concerned with methods for forming indentations in a blow molded plastic drum and with a method of reinforcing the corner of a blow molded drum.

This invention relates to plastic drums and drum assemblies, preformed plastic inserts for use in plastic drum assemblies, and methods of forming plastic drums and plastic drum assemblies.
Steel and fiber drums have long been utilized for the shipment and storage of liquid, paste, powder, and solid products. A fundamental requirement of all such drums is the need for safe and convenient handling. For this purpose, a number of specialized devices have been developed including fork-lift trucks which can grasp the drum around its center girth or by other means. One such means which is widely used is the "parrot's beak" mechanism; this device includes a pair of jaws which engage a structure on the steel lid and locking band of such drums. More recently, plastic drums blow molded from high density polyethylene have become popular. These drums have rounded corners at the ends, and such corners and the slick surface of the polyethylene plastic make the handling of these drums very difficult. It is not feasible to apply the "parrot's beak" jaws to the top rim of such a plastic drum due to the absence of a suitable structure to be engaged by the jaws of the "parrot's beak." This has led to a number of attempts to modify the plastic drum construction to accommodate the " parrot's beak" jaws. A number of these prior art expedients will be discussed more fully hereinafter with reference to the drawings. It will be noted here, however, that the most promising of the prior art expedients involves the provision of a preformed plastic insert fused to the corner of the drum with the insert surmounted on the normal drum structure. This is accomplished by altering the conventional mold cavity used for blow molding the plastic drum; a groove is cut through the corner of the mold cavity wall for holding the preformed plastic insert. However, this procedure unduly complicates the design, construction and operation of the metal mold.

Plastic drums and drum assemblies with preformed inserts


Systems and methods for amplifying signals. In some embodiments, the signals may be amplified using a diode steering network with an amplifier operated in class AB mode. In some embodiments, distortion in the amplified signal may be corrected using a feed forward cancellation circuit operated in class A mode.

The subject matter of this application relates to amplifiers capable of being used in CATV transmission networks.
Linear RF amplifiers are often designed as class A amplifiers, which are one of the most commonly used amplifiers because of their excellent linearity. In a class A amplifier, the transistor is always biased "ON" so that it conducts during one complete cycle of the input signal waveform, producing minimum distortion and maximum amplitude to the output since there is no crossover distortion to the output waveform, even during the negative half of the cycle. However, because the transistor is always biased "ON," one of the main disadvantages of class A amplifiers is that their efficiency is very low as the constant and usually large currents cause a considerable amount of power to be lost.
This is particularly true in CATV transmission networks. When operated with a broadband signal containing many RF channels, the voltage bias point of the amplifier must typically be around 5 times the rms output voltage of the output stage when the probability of clipping must be in the ppm range. This is necessary in order to ensure that the amplifier can support peak output voltages. Such low clip probabilities are typical in CATV systems that support QAM channels with high complexity such as QAM256. The bias current of the amplifier similarly must be around 5 times the rms signal current in the amplifier output stage. As a result the power efficiency that can be attained is very low, on the order of 4% and often less.
A class B amplifier, conversely, has a pair of transistors that each conduct alternatingly only for one half cycle of the input signal. Since the active devices are switched off for half the input cycle, the active device dissipates less power and hence the efficiency is improved. However, since each active device truncates half the input signal and the output signal is the sum of the outputs of the active devices cross-over distortion that occurs when one device switches off and the other switches on is high in Class B amplifiers.
Class AB amplifiers, which are widely used in audio systems, use a bias current set at a non-zero value with a magnitude much lower than the peak output current, resulting in improved power efficiency relative to class A amplifiers. The output is configured with a transistor pair such that one transistor pulls positive voltages high and a second transistor can push negative voltages low. For small voltage magnitudes, both transistors are active but for large voltage magnitudes (either positive or negative) only one transistor is active whereas the current on the other output transistor can reach zero or is often held at a low minimum value. While some signal distortion is induced due to the transition in operation where either or both transistors are active, such distortions can be minimized by designing strong negative feedback into the amplifier; a fraction of the output signal is compared to the input signal and a correction signal is provided with high gain to the output signal if the output signal fraction deviates from the input signal. As a result, the output signal is held close to a multiple of the input signal and distortions are low.
In RF amplifiers in a push-pull configuration, typically an output transformer is used where both transistors can for instance be N-type FETs, and both can be driven with a signal set relative to ground, as opposed to some floating node. The output transformer has a differential input such that the difference of the transistor output is presented at the transformer output. Feedback in an RF amplifier is generally limited, due to the high signal bandwidth that needs to be amplified. Too much delay in the feedback path combined with a high gain for the correction signal will lead to amplifier oscillation due to the inevitable signal delay or phase shift in the feedback path. This complicates the implementation of a class AB amplifier, which produces distortions due to the transitions in the operating mode of the output transistors. Second, turning an RF transistor off can produce very high distortions when the transistor needs to be turned on again, it is preferable to prevent a complete turn-off under all conditions and instead ensure a minimum controlled current. Whereas ensuring a minimum current is not difficult when using a floating (output) node where the two transistors are connected it is less trivial in the RF amplifier where transistors are referenced to ground; use of the floating output node would be very difficult due to parasitic capacitance of that node to ground. This is very significant at the high output frequencies produced by an RF amplifier.
In RF amplifiers an alternate method to reduce distortion using feedback is feed-forward distortion compensation. When using feed-forward distortion compensation, the output of a first RF amplifier is provided to an RF coupler. A fraction of the output signal is coupled out and that fraction is compared to the input signal. The difference, due to distortion, is provided to a second, smaller amplifier with the same gain as the first amplifier and added to the output of the first amplifier such that the distortion in the combined signal is cancelled. Because the distortion power is typically much lower than signal power, the power handling capability of the second amplifier that only handles distortion may be much lower than that of the first RF amplifier. However, such a design suffers from complexity; it requires two extra couplers, an extra amplifiers and fine tuning of the gain and phase delay of the signal paths to ensure consistent distortion cancellation. Nevertheless results can be good such as 20 dB of distortion cancellation. A second disadvantage of the use of couplers is the inevitable loss of RF couplers; a fraction of the output power of the amplifier is dissipated in the output couplers.
What is desired, therefore, is an improved amplifier suitable for use in CATV networks such that high power efficiency can be achieved with linearity.

RF class AB cascode amplifier with linearization and steering diodes


According to an infrared sensor calibration apparatus, one end of a cylindrical cover member is connected to the radiation surface of a blackbody such that they are thermally independent of each other, the other end thereof is provided opposite to an incidence entry of the infrared sensor, the blackbody and cylindrical cover member are controlled so as to have their respective predetermined temperatures, the intensity of the infrared rays incident upon the infrared-rays entrance based on the temperatures and the emissivity of the blackbody and cylindrical cover member, and the intensity is compared with an output of the infrared sensor, thereby calibrating the infrared sensor.

1. Field of the Invention
The present invention relates to an infrared sensor calibration apparatus used for calibrating an infrared sensor loaded into a space navigating object such as an artificial satellite.
2. Description of the Related Art
It is well-known that a blackbody is employed in an apparatus for calibrating an infrared sensor.
The strength of infrared rays radiating from the surface of the blackbody univocally depends upon the temperature and the emissivity of the surface by the Planck radiation law. Using this law, the infrared sensor measures the strength of the infrared rays radiating from the blackbody having a known temperature thereby to perform calibration, i.e., so-called graduation on the basis of the relationship between the voltage output from the infrared sensor and the temperature of the blackbody.
FIG. 3 shows a prior art apparatus for calibrating an infrared sensor 1 as described above. In this apparatus, a blackbody 2 is provided opposite to an incidence entry 1a of the sensor 1. A heating/cooling system 5 is buried into the blackbody 2. The system 5 is driven by a temperature controller 3 in response to a command signal and set to have a predetermined temperature. The infrared rays whose intensity are determined by the temperature of the system radiates from the blackbody 2 toward the incidence entry 1a.
The output of the infrared sensor 1 is connected to a data processing unit 4. The processing unit 4 processes data of voltage generated from a detector of the sensor 1. The output of a temperature detector 6 for detecting the temperature of the blackbody 2 is also connected to the data processing unit 4. The processing unit 4 is supplied with data of the temperature of the surface of the blackbody 2. Thus, the data processing unit 4 is so constructed that it compares the voltage data obtained from the infrared sensor 1 and the temperature data of the blackbody 2 to calibrate the infrared sensor.
Generally, the relationship between emissivity .epsilon. and reflectance r of the surface of an object is expressed by the following equation, assuming that the surface of the object does not absorb any infrared rays (absorptance .alpha.=0). EQU .epsilon.+r=1 (1)
Using the Planck's radiation law, the radiant intensity L of infrared rays radiating from the surface of an object having a temperature of T1, can be given by the following. EQU L=.epsilon.L (T1) (2)
In actuality, however, since the emissivity .epsilon. cannot be "1", the object has some reflectance r. Let us consider a model in which an object 7 is covered with an atmosphere 8 of temperature T2, as shown in FIG. 4. The effective radiant intensity L of this model is expressed as follows. EQU L=.epsilon.L(T1)+rL(T2) (3)
In the foregoing prior art infrared sensor calibration apparatus, it is desirable that the emissivity .epsilon. of the radiating surface of the blackbody 2 should be "1" in order to calibrate the infrared sensor with high precision. If .epsilon.=1, r becomes zero from the equation (1) and thus the second term of the equation (3) need not be taken into consideration, with the result that the radiant intensity of the blackbody 2 has only to be evaluated by the equation (2).
In the prior art apparatus described above, however, the emissivity .epsilon. of the radiation surface of the blackbody 2 is 0.8 to 0.9 and thus the reflectance r is 0.1 to 0.2. Since, as shown in FIG. 5, infrared rays B radiated from the environment and then reflected by the blackbody 2 and infrared rays C radiated directly from the environment as well as infrared rays A radiated from the blackbody 2, are incident upon the entry 1a of the sensor 1, these infrared rays B and C will become errors, in other words, an error will occur in the second term of the equation (3).
The intensity of infrared rays A can be easily obtained from the temperature of the blackbody 2, but that of infrared rays B or C cannot be correctly done in actuality. Therefore, the prior art infrared sensor calibration apparatus has the drawbacks wherein it is difficult to eliminate the errors of the infrared rays B and C and also difficult to compare the output voltage of the infrared sensor 1 and the temperature of the blackbody 2 with high precision.

Infrared sensor calibration apparatus using a blackbody


A waterproof connector with sealing capability includes a connector housing with a plurality of conductive terminals mounted therein. The terminals are arranged around the perimeter of a circle with contact portions exposed at the radial outermost extents along the circle. The housing has a central opening around which the terminals are arranged and the terminals are each bent into a circular arc in their mounting on the housing. The housing is over molded around the terminal at intermediate portions thereof to provide a liquid proof barrier.

The present invention relates generally to a watertight connector and a method of manufacturing the same.
In a conventional connector, terminals made of metal rod-like members are press-fit in through holes formed in a bottom plate of a housing made of an insulating material such as a synthetic resin. In this case, a gap inevitably occurs between the inner wall surface of the through hole and the outer circumference of the terminal, and therefore, it is difficult to maintain a sealing performance between one surface side of the bottom plate from which tip portions of the terminals project to make contact with counterpart connector terminals and the other surface side of the bottom plate from which root portions of the terminals project to make contact with electrical wires or the like of a cable.
For this reason, in the case of a connector requiring cleaning such as a connector used for medical devices, for instance, cleaning liquid, used for cleaning the side of the bottom plate from which the tip portions of the terminals project to contact the counterpart connector terminals, may enter the side of the bottom plate at which the terminals are to be connected to the electrical wires or the like of the cable, and it may have adverse effects such as corrosion of the connecting portions of the root portions of the terminals and the electrical wires or the like, and cracking caused by deterioration.
Also, in a cable including a further linear member such as an optical fiber or the like and electrical wires integrally arranged with the further linear member, the electrical wires, in some cases, are annularly arranged around the centrally arranged further linear member so as to surround the latter. Such a cylindrical connector for connecting the annularly arranged electrical wires is proposed (refer to Japanese Patent Application Laid-Open Publication (Kokai) No. S61-237383, for instance).
FIG. 19 is a cross-sectional view of such a conventional cylindrical connector.
In FIG. 19, reference numeral 801 designates a connector terminal, and a plurality of terminals are annularly arranged so as to surround the center axis of the connector. Also, reference numeral 802 designates an elementary portion in which the terminal 801 is fitted, and the elementary portions are integrally connected to a belt-like strip 803. The elementary portions 802 and the strip 803 are made of an elastic plastic and are integrally molded by a molding method such as injection molding or the like. In this case, the elementary portions 802 having a trapezoidal cross-section are arranged in a line and mutually coupled by the linear strip 803. It is to be noted that each terminal 801 is embedded in each elementary portion 802. In addition, a core portion 804 having a cylindrical or polygonal outer surface is integrally connected to one end of the strip 803.
Then, a cylinder as illustrated in the figure is formed by winding the strip 803 around the core portion 804, with the core portion 804 being in the center. In this case, the strip 803 is arranged on the outside of the cylinder, the elementary portions 802 face the inside of the cylinder, and slanted side surfaces of the adjacent elementary portions 802 are brought into contact with each other. The thus formed cylinder is attached inside a metal or plastic bush 805 to obtain a cylindrical connector.

Watertight connector and method of manufacturing the same


A retrievable cane disclosed includes a cane body to which there is attached a retrieval line that is anchored at a lower end and extends from the inside of the cane body at the lower end up through the cane body out through the rear of the cane body below the grip. The retrieval line has an elastic section that allows an attachment end outside the cane body to be releasably attached to the body of the user preferably having the grip portion at the waist allowing normal walking by the user. The elastic section allows the user to pull the cane body away from the waist for use during walking and the elastic section automatically returns the cane to the user's waist when released.

Canes frequently become misplaced by the user. This may result from memory disorders or in some cases people lack strength, physical flexibility, dexterity, vision and the like. If these people drop the cane many time there is great difficulty in retrieving the cane. Also, it is an advantage to have the cane ready for use while at the same time allowing mobility and the use of both hands by the cane user.
Wading fishermen encounter irregular surfaces, slippery rocks or fast water so a cane would stabilize the fisherman. A cane according to the present invention can be used for moving through the stream and then return to the waist of the user while fishing allowing the use of both hands for fishing.


In certain aspects, the disclosure provides methods for producing polymers from alkenone-producing algae, such as algae species of the Isochrysis family.

The broad class of polymeric materials includes polymers with excellent processability, chemical resistance, and mechanical properties. These properties allow polymers to be used to produce extrusion molded articles, injection molded articles, hollow molded articles, films, sheets and the like, in a wide variety of industries. Numerous polymers are derived from petroleum and natural gas. Market prices for these fossil fuels are increasing, due to a number of factors including a depletion of easily accessible deposits, growth of emerging economies, political instabilities, and environmental concerns. There is an unmet need in the art for polymer production methods that do not rely on fossil fuels.

Use of marine algae for producing polymers


Provided is a retracting device which can decrease a difference of restoring force of a tension coil spring between a retracted position and a stop position. The retracting device of the present invention includes a base 12, a slider 14 which can catch a trigger 8 and move from the stop position to the retracted position with respect to the base 12 and a tension coil spring (B) for relatively moving the slider 14 which has caught the trigger 8 from the stop position to the retracted position with respect to the base 12 to apply force for assisting the closing operation to a sliding door 1. The tension coil spring (B) is an initially-tensioned spring in which a coil closely contacts and which has initial tension in a direction in which the coil closely contacts when it is in a natural length.

A retracting device for assisting a closing operation of a door or a furniture component for facilitating closing of the door or the furniture component has been known. The retracting device for assisting the closing operation is also called as a closer. When a user moves the door or the furniture component to a predetermined position in a closing direction, the retracting device applies force in the closing direction to the door or the furniture component so that the door or the furniture component automatically moves to a closing position.
As shown in FIGS. 14A and 14B, in a patent document 1: JP H5-23763A, there is disclosed a retracting device including a base 51 to be attached to a furniture main body, a slider 52 which can move from a stop position (see FIG. 14A) to a retracted position (see FIG. 14B) with respect to the base 51 and a tension coil spring 53 for moving the slider 52 from the stop position to the retracted position. A trigger 54 is attached to a drawer. When the user moves the drawer at an opened position toward the closing direction to locate the drawer at the stop position shown in FIG. 14A, the slider 52 catches the trigger 54 and rotates. Then, the tension coil spring 53 moves the slider 52 from the stop position to the retracted position to apply the force for assisting the closing operation to the drawer.
In this regard, as described in a patent document 2: JP 2008-190275A, a retracting device for assisting the closing operation and the opening operation of the door or the furniture component is existed. This is a retracting device in which a slider for assisting the closing operation and a slider for assisting the opening operation are movably provided on a base, and an operating principle thereof is the same as that of the retracting device described in the patent document 1.


An uninterrupted AC supply includes an AC to DC converter having several DC storage devices which maintain a constant DC voltage in the event of a failure of several cycles of the AC source. Each of the storage devices is connected to a separate branch circuit. Each branch circuit includes a transistor that is driven in a linear manner during a portion of a quarter cycle of an AC reference source, so that only one branch conducts current at a time. The DC voltage supplied to each branch and the conducting interval of each branch are such that equal energy dissipation occurs in each branch during each quarter cycle. To enable only one set of branches to be used for opposite polarity variations of the AC reference source, the current from all of the branches flows to a single node, then to opposite terminals of a center tapped transformer primary winding via a pair of switches. During first and second opposite polarity half cycles of the AC reference source, the first and second switches are respectively open and closed so that current flows in the transformer winding in opposite directions during the opposite polarity half cycles of the AC reference source.. For a sinusoidal source energy dissipation is equalized in each branch by selecting the phase angle, .theta..sub.k, when branch circuit k changes from a conducting to a non-conducting state and the phase angle .theta..sub.k-1 when branch circuit k begins to conduct such that sin.theta..sub.k cos.theta..sub.k-1 -.theta..sub.k -.theta..sub.k-1 /2-1/4(sin2.theta..sub.k +sin2.theta..sub.k-1) is the same for each branch circuit.

Many different types of DC to AC inverters have been designed and are utilized in practice. One such inverter, disclosed in U.S. Pat. No. 3,832,643, to Van Heyningen et al, employs a tapped DC power supply, with each tap being connected via a separate branch circuit to a load. Each branch circuit includes a transistor switch activated so that at any particular time only one switch couples current from one of the taps to the load. By sequentially energising the different switches the voltage impressed on the load is varied. The several branches are driven by a common signal source, having a wave shape that is reflected in the wave shape of voltage and/or current applied to a load.
In one embodiment, different switches are activated at different times in response to the signal source voltage by connecting Zener diodes having different thresholds to base control electrodes of the transistors. Each Zener diode is connected in series with a transformer winding coupled to the signal source, with the series combination being connected between the base and emitter of a separate switching transistor. In response to the signal source being in a predetermined range, only one of the transistors is activated into a conducting state. The transistor of each branch conducts between cut off and saturation.
The power dissipated by each amplifying transistor in each branch is minimized by selecting the voltage, E, applied to each branch such that at one point during one half of the quarter cycles of the control source the dissipated power in the transistor is zero. In particular, the power dissipated in the transistor of each branch is minimized by varying the applied voltage in steps during each cycle of the input signal to minimize the expression E-IR, where E is the voltage applied across the branch, I is the current flowing in the branch and R is the resistance of each branch, while conducting.
In a first embodiment, a different voltage E is applied to each of the different branches and the resistance R of the different branches is the same. Because of the different values of E, different currents flow through the different branches. Thus, if a control input signal has a small amplitude, a first branch conducts and applies a low voltage to the load. When the control signal has a higher value a second branch conducts and applies a second, higher voltage to the load. The first and second branches insert the same resistance between the voltage they apply to the load. The values of E and R are selected so that E-IR is minimized in each branch at one instant while it is conducting.
In a second embodiment, the same voltage is applied to each branch, but the resistance and current of each branch differ while the branch is conducting. When the signal source has a small amplitude, a relatively small current flows through a first conducting branch to the load, because the branch has a relatively high impedance. In contrast, when the control input signal has a high amplitude, a large current is supplied by a second conducting branch to the load, due to the second conducting branch having a relatively low resistance. The values of I and R are chosen such that the product IR is substantially equal to the common voltage E applied to all of the branches, so that the expression E-IR is substantially zero for each branch.
A possible problem with the prior art device disclosed in the Van Heyningen et al patent is that it is dependent upon the emitter collector impedance of a number of power transistors being precisely equal to each other or precisely different from each other by predetermined amounts. If the conducting emitter collector impedance of the transistor switches in the different branch circuits in the prior art circuit are not precisely determined, it is not possible to minimize E-IR. Another possible problem with the Van Heyningen et al circuit is obtaining Zener diodes having sufficiently precise voltage characteristics to enable the different branches to be activated into the conducting and cut off states in response to different voltages of the control signal source.
It is, accordingly, an object of the present invention to provide a new and improved high efficiency DC to AC inverter employing plural switched branches, and method of operating same.
Another object of the present invention is to provide a new and improved high efficiency DC to AC inverter having switched branches employing virtually identical transistor switching circuits.
Still another object of the present invention is to provide a new and improved high efficiency DC to AC inverter having switched branch circuits connected in a relatively simple circuit configuration, wherein the switching for each branch is determined by the amplitude of a conventional gradually varying signal source.

Power converter apparatus and method employing plural branches


Post-column reaction-ion chromatography (PCR-IC) analysis of drinking water samples for quantity measurements and species identification of haloacetic acid contaminants therein is provided. With the necessity to chlorinate drinking water to remove harmful bacteria and other potential toxins, haloacetic acid byproducts are generated that may harm humans after consumption as well. A reliable manner of measuring such drinking water supplies for haloacetic acids at locations far from the source and closer to dispensers is highly desirable. The PCR-IC analysis method of the invention has been found to be nearly as reliable as source measuring methods for the same purpose, but with the versatility to measure for such haloacetic acid contaminants anywhere along the drinking water supply line.

Drinking water has been, and continues to be, heavily treated for bacteria and other microscopic organisms that may cause infection in humans and other animals subsequent to consumption. In order to disinfect water supplies, halogenated materials have been introduced therein that have proven more than adequate for such a purpose. Unfortunately, although such halogenated compounds (chlorinated and chloraminated types, primarily) exhibit excellent disinfection capabilities, when present within aqueous environments at certain pH levels these halogenated compounds may generate byproducts that may themselves create health concerns. The United States Environmental Protection Agency (USEPA) in fact regulates five specific types of haloacetic acids within drinking water: monochloroacetic acid, dichloroacetic acid, trichloroacetic acid, monobromoacetic acid, and dibromoacetic acid. Removal of such compounds from drinking water is not possible as for typical chlorinated and brominated disinfecting compounds, at least not at the same reliability level as for the disinfecting agents. Thus, residual amounts may remain within treated water supplies that may require further removal processes to be undertaken. Of course, if the level of contamination is sufficiently low, initiation of such potentially expensive removal steps would be unwise from an economic perspective.
The USEPA currently has set a maximum contaminant level for these five haloacetic acids (collectively referred to as HAA5; four other haloacetic acids are currently not regulated by the USEPA, bromochloroacetic acid, bromodichloroacetic acid, dibromochloroacetic acid, and tribromoacetic acid; including these, the total haloacetic acid group is known as HAA9) at a total amount of 0.060 mg/L. It is thus important to reliably analyze and measure the total amount of such contaminants in order to determine if removal if necessary.
The USEPA has instituted its own testing methods for such a purpose. One, known as EPA 552.2, involves the liquid-liquid extraction of haloacetic acids from water sources into methyl-t-butyl ether, followed by derivatization with acidic methanol to form the corresponding haloacetic acid methyl esters. Analysis by gas chromatography-electron capture detection provides reliable measurements of the haloacetic acid amounts present within the subject water supply. The other, USEPA 552.3, is a derivative of the first with optimizations of acidic methanol neutralization procedures for improvement in brominated trishalogenated haloacetic acid species. These general processes have been found to have numerous drawbacks, however. For instance, injection port temperature can affect debromination of certain haloacetic acid species (particularly tribrominated types) that may lead to under-representation of the amount of such contaminants present within the tested water source. Likewise the water content of the methyl-t-butyl ether extract may decarboxylate the haloacetic acids, again leading to an under-reporting of the actual amounts present within the test sample. Furthermore, the involved processing needed to actually undergo such analysis makes an on-line protocol rather difficult to implement, particularly when hourly sampling is necessary. Other derivatization methods have been either followed or suggested for gas chromatography analyses of drinking water sources as well, including utilizing diazomethane, acidic ethanol, and aniline. Such reactant-based measurements, however, all suffer the same time and labor-intensive problems as with the two EPA test procedures noted above. As such, on-line analysis through these protocols are difficult, expensive, and labor intensive to implement.
Measurement at the source (i.e., within a water purification plant location) may be effective for system-wide average readings; however, in the large supplies of water at such locations, the chances of proper sampling to that effect may be suspect since the contaminants may be present in varied locations, rather than definitely mixed throughout the tested water supply itself. Additionally, testing may not uncover the actual level of residual haloacetic acid disinfection byproducts prior to the water supply being disbursed to distant dispense sites (transfer pipes, homes, schools, businesses, etc.). In any event, there is a relatively new rule in place that requires utilities to provide evidence of compliance with haloacetic acid levels at multiple locations, rather than a straightforward system-wide average. Thus, since the above-described derivatization procedures with gas chromatography-electron capture detection analytical methods are not suitable for a uniform haloacetic acid measurement scheme. There is thus a drive to implement remote testing via real-time, on-line methods for water supply HAA5, and, more importantly, for HAA9 contaminant level measurements.
Such a desirable on-line procedure has been difficult to achieve, however, particularly as it pertains to the determination of not only the amount of HAA9 within water supplies, but also the amount of each species of the HAA9 group present within the tested water source. High performance liquid chromatography, utilizing electrospray ionization-mass spectrometry or ultraviolet absorbance as the detector, has been attempted, as well as ion chromatography, with membrane-suppressed conductivity detection or, as well, ultraviolet absorbance detection. Other attempts with inductively coupled plasma-mass spectrometry and electrospray ionization-mass spectrometry coupled with ion chromatography have been followed as well for this same purpose. The detection level can be as low as 0.5 to less than 10 μg/L for HAA9 species, but only subsequent to sample preparations. The sensitivity and selectivity of ion chromatography and high performance liquid chromatography methods are easily sacrificed without the cumbersome preparations in place, therefore requiring operator intervention during analysis. Again, this issue leads to serious drawbacks when on-line implementation is attempted as well.
Another methodology that has proven effective to a degree is post-column reaction-ion chromatography. This has shown promise, but only in terms of quantifying bromate ion concentrations in drinking water samples at a single microgram per liter level. This dual selectivity form (separation by ion chromatography column as well as the selective reaction with the post-column reagent with the analyte) offers an advantageous test method over the others noted above, except for the presence of more common anions, specifically chloride, at much higher concentrations within the sampled drinking water supply (mg/L instead of μg/L). It was then undertaken to combine the separation capabilities of ion chromatography with the reaction of the haloacetic acid species with nicotinamide, followed by fluorescene detection to measure the individual and total HAA5 concentrations in drinking water at the single μg/L level. The problem with such a protocol, unfortunately, was that bromochloroacetic acid interfered with dichloro- and dibromo-acetic acid quantifications. Despite this problematic limitation, it was determined that fluorescence detection provided a much improved detection protocol in comparison with ultraviolet absorbance and mass spectrometry possibilities. Thus, although such a fluorescence method of detection, coupled with the post-column reaction (again with nicotinamide reagent) and ion chromatography, exhibited the best results in terms of an on-line test method for HAA5 drinking water contaminant measurement levels, there remained a definite need for improvements in total haloacetic acid measurements and identifications within such test samples. To date, however, there has not been an analytical test protocol that has permitted implementation of such a system within an on-line real-time monitoring procedure with an acceptable degree of reliability.

Real-time, on-line analysis of haloacetic acid species and amounts thereof in drinking water supplies

The University of Memphis Research Foundation


In a general aspect, a computer-implemented method for executing a query on a table of a database, where the table has multiple partitions, can include receiving a query requesting a view on the table. The view on the table can be based on data included in a partition of the multiple partitions of the table. The method can also include determining a cached result to the query is not available in the database and generating a result to the query from, at least, the data of the partition of the multiple partitions. After the generating, the method can include building a cache including the result to the query, associating a transaction identifier for the query with the result to the query result in the cache; and returning the result to the query.

In certain database applications, aggregates of historical data can be required (e.g., in response to queries on a table (or tables) of a database). For example, a sum of financial data for previous years may be requested on a database table that is partitioned by calendar year. Persistently storing such aggregates of historical data may be an inefficient use of memory in a databases (e.g., in an in-memory database), and can require complex logic to implement. A significant effort may be needed for application developers to modify such logic, thus reducing their flexibility to add new features to a given product. However, if aggregates of historical data are not persistently stored, they would then have to be computed "on the fly" (e.g., when they are requested). Such computing of historical data aggregates on the fly can require loading respective data (e.g., historical partition data) from disk each time a given aggregate (or view including that aggregate) is requested. Such an approach can also be an inefficient use of database resources (e.g., repeated loading of historical partitions from disk).


A formulation suitable for inducing bone formation contains about 0.5 .mu.g to about 5 mg of transforming growth factor-.beta. and about 140 mg to about 50 g of tricalcium phosphate and excludes a bone morphogenetic cofactor. In another embodiment, the formulation contains about 0.5 .mu.g to 5 mg transforming growth factor-.beta., about 140 mg to 50 g of tricalcium phosphate particles, and an amount of amylopectin ranging from about 01:1 to 1:1 amylopectin:tricalcium phosphate.

1. Field of the Invention
This invention relates to the use of transforming growth factor-beta (TGF-.beta.) to induce bone growth in vivo and to formulations of TGF-.beta. and tricalcium phosphate useful for this purpose.
2. Description of Related Art
The disorders associated with bone loss present major public health problems for Western societies. Osteoporosis alone may affect 20 million Americans in the early years of the next century. Hence, there is wide interest in identifying factors or potential therapeutic agents that inhibit bone loss and stimulate the formation of healthy new bone.
Bone is an extremely complex, but highly organized, connective tissue that is continuously remodeled during the life of an adult by cellular events that initially break it down (osteoclastic resorption) and then rebuild it (osteoblastic formation). This remodeling process occurs in discrete packets throughout the skeleton, i.e., in both cortical bone and trabecular bone. It has recently been reported that mouse bone marrow cells can be stimulated to generate osteoclasts in the presence of parathyroid hormone-related protein or vitamin D. See Akatsu et al., Endocrinology, 125: 20-27 (1989); Takahashi et al., Endocrinology, 123: 2600-2602 (1988) and Takahashi et al., Endocrinology, 123: 1504-1510 (1988).
The currently available therapeutic agents known to stimulate bone formation are fluoride, estrogen, and vitamin D. Fluoride clearly increases trabecular bone mass, but questions remain about the quality of the new bone formed, the side effects observed in some patients, whether there are beneficial effects on vertebral fracture rates, and whether increased fragility of cortical bone with subsequent propensity to hip fracture follows.
Another approach is using agents that promote resorption (parathyroid hormone) and then interrupt resorption (calcitonin). One proposed, but not validated, such sequential therapeutic regimen is coherence therapy, where bone metabolic units are activated by oral phosphate administration and then resorption is inhibited by either diphosphonates or calcitonin.
Within the past few years several factors that stimulate osteoblasts were identified in bone, including TGF-.beta., fibroblast growth factor, platelet-derived growth factor, insulin-like growth factor I, and .beta.2 macroglobulin. Of these, TGF-.beta. and IGF-I were deemed attractive candidates for factors linking previous bone resorption with subsequent bone formation. Mundy, The Journal of NIH Research, 1: 65-68 (1989).
Other proteins stored in the bone matrix may also be important for bone formation. When demineralized bone was injected into the muscle or subcutaneous tissue of rats, a cascade of events, including chondrogenesis, ensued. Urist, Science, 150: 893 (1965). This observed activity was due to bone morphogenetic protein (BMP). Since the 1960s several investigators have attempted to identify and characterize this activity. Thus, a protein of 22 Kd, called osteogenin, was identified that possessed the activity. Sampath et al., Proc. Natl. Acad. Sci. USA, 84: 7109 (1987). Three proteins from demineralized ovine bone matrix were identified as having this activity. Wang et al., Proc. Natl. Acad. Sci., 85: 9484 (1988) and Wozney et al., Science, 242: 1528 (1988). These proteins were named BMP-1, BMP-2A, and BMP-3, the latter two of which belong to the extended TGF-.beta. family by limited sequence homology. These workers modified the assay for bone induction to show cartilage formation but did not show that the proteins ultimately stimulate formation of bone.
The TGF-.beta. group of molecules are each dimers containing two identical polypeptide chains linked by disulfide bonds. The molecular mass of these dimers is about 25 Kd. Biologically active TGF-.beta. has been defined as a molecule capable of inducing anchorage independent growth of target cell lines or rat fibroblasts in in vitro cell culture, when added together with EGF or TGF-.alpha. as a co-factor. TGF-.beta. is secreted by virtually all cell types in an inactive form. This latent form can be activated by proteolytic cleavage of mature TGF-.beta. from its precursor (at the Arg-Ala bond in position 278). A non-covalent complex is formed from the association of the mature TGF-.beta. with the precursor remainder or with a protein binding to TGF-.beta. or with alpha.sub.2 -macroglobulin. This complex is disrupted so as to activate the TGF-.beta. either by exposure to transient acidification or by the action of exogenous proteases such as plasmin or plasminogen activator.
There are at least five forms of TGF-.beta. currently identified, TGF-.beta.1, TGF-.beta.2, TGF-.beta.3, TGF-.beta.4, and TGF-.beta.5. Suitable methods are known for purifying this family of TGF-.beta.s from various species such as human, mouse, monkey, pig, bovine, chick, and frog, and from various body sources such as bone, platelets, or placenta, for producing it in recombinant cell culture, and for determining its activity. See, for example, Derynck et al., Nature, 316: 701-705 (1985); European Pat. Pub. Nos. 200,341 published Dec. 10, 1986, 169,016 published Jan. 22, 1986, 268,561 published May 25, 1988, and 267,463 published May 18, 1988; U.S. Pat. No. 4,774,322; Seyedin et al, J. Biol. Chem., 262: 1946-1949 (1987); Cheifetz et al, Cell, 48: 409-415 (1987); Jakowlew et al., Molecular Endocrin., 2: 747-755 (1988); Dijke et al., Proc. Natl. Acad. Sci. (U.S.A. ), 85: 4715-4719 (1988); Derynck et al., J. Biol. Chem., 261: 4377-4379 (1986); Sharples et al., DNA, 6: 239-244 (1987); Derynck et al., Nucl. Acids. Res., 15: 3188-3189 (1987); Derynck et al., Nucl. Acids, Res., 15: 3187 (1987); Derynck et al., EMBO J., 7: 3737-3743 (1988)); Seyedin et al., J. Biol. Chem., 261: 5693-5695 (1986); Madisen et al., DNA, 7: 1-8 (1988); and Hanks et al., Proc. Natl. Acad. Sci. (U.S.A. ), 85: 79- 82 (1988), the entire contents of these publications being expressly incorporated by reference.
TGF-.beta.3, TGF-.beta.4, and TGF-.beta.5, which are the most recently discovered forms of TGF-.beta., were identified by screening cDNA libraries. None of these three putative proteins has been isolated from natural sources, although Northern blots demonstrate expression of the corresponding mRNAs. TGF-.beta.4 and TGF-.beta.5 were cloned from a chicken chondrocyte cDNA library (Jakowlew et al., Molec. Endocrinol., 2: 1186-1195 [1988]) and from a frog oocyte cDNA library, respectively. The frog oocyte cDNA library can be screened using a probe derived from one or more sequences of another type of TGF-.beta.. TGF-.beta.4 mRNA is detectable in chick embryo chondrocytes, but is far less abundant than TGF-.beta.3 mRNA in developing embryos or in chick embryo fibroblasts. TGF-.beta.5 mRNA is expressed in frog embryos beyond the neurula state and in Xenopus tadpole (XTC) cells.
TGF-.beta. has been shown to have numerous regulatory actions on a wide variety of both normal and neoplastic cells. TGF-.beta. is multifunctional, as it can either stimulate or inhibit cell proliferation, differentiation, and other critical processes in cell function (M. Sporn, Science, 233: 532 [1986]). For a general review of TGF-.beta. and its actions, see Sporn et al., J. Cell Biol., 105: 1039-1045 (1987>, Sporn and Roberts, Nature., 332: 217-219 (1988), and Sporn and Roberts, in Sporn and Roberts, ed., Handbook of Experimental Pharmacology: Peptide Growth Factors and Their Receptors I, Springer-Verlag, New York, pp. 3-15 (1990).
The multifunctional activity of TGF-.beta. is modulated by the influence of other growth factors present together with the TGF-.beta.. TGF-.beta. can function as either an inhibitor or an enhancer of anchorage-independent growth, depending on the particular set of growth factors, e.g., EGF or TGF-.alpha., operant in the cell together with TGF-.beta. (Roberts et al., Proc. Natl. Acad. Sci. U.S.A., 82: 119 [1985]). TGF-.beta. also can act in concert with EGF to cause proliferation and piling up of normal (but not rheumatoid) synovial cells (Brinkerhoff et al., Arthritis and Rheumatism, 26: 1370 [1983]).
Although TGF-.beta. has been purified from several tissues and cell types, as indicated above, it is especially abundant in bones (Hauschka et al., J. Biol. Chem., 261: 12665 [1986]) and platelets (Assoian et al., J. Biol. Chem., 258: 7155 [1983]). TGF-.beta. is postulated to be one of the local mediators of bone generation and resorption, because of its presence in large amounts in bone and cartilage, because cells with osteoblast and chondrocyte lineage increase replication after exposure to TGF-.beta., and because TGF-.beta. regulates differentiation of skeletal precursor cells. See Centrella et al., Fed. Proc. J., 2: 3066-3073 (1988).
Immunohistochemical studies have shown that TGF-.beta. is involved in the formation of the axial skeleton of the mouse embryo. TGF-.beta. is also present in other embryos in the cytoplasm of osteoblasts in centers of endochondral ossification and in areas of intramembranous ossification of flat bones, such as the calvarium. Heine et al., J. Cell. Biol., 105: 2861-2876 (1987). Following in situ hybridization of TGF-.beta.1 probes, localization of TGF-.beta. in both osteoclasts and osteoblasts has been described in development of human long bones and calvarial bones. Sandberg et al., Development, 102: 461-470 (1988); Sandberg et al., Devel. Biol., 130: 324-334 (1988). TGF-.beta. is found in adult bone matrix (Seyedin et al., Proc. Natl. Acad. Sci. USA, 82: 2267-2271 [1985], Seyedin et al., J. BIOL, Chem., 261: 5693-5695 [1986]) and appears at the time of endochondral ossification in an in vivo model of bone formation (Carrington et al., J. Cell. Biol., 107: 1969-1975 [1988]). Cultured fetal bovine bone osteoblasts as well as rat osteosarcoma cells have high mRNA levels for TGF-.beta. and secrete relatively high concentrations of TGF-.beta. (Robey et al., J. Cell. Biol., 105: 457-463 [1987]).
In certain in vitro models, TGF-.beta. was found to stimulate the synthesis of collagen, osteopontin, osteonectin, and alkaline phosphatase, and to stimulate replication in osteoblast-like cells. See Centrella et al., J. Biol. Chem., 262: 2869-2874 (1987); Noda et al., J. Biol. Chem., 263: 13916 (1988); Wrana et al., J. Cell. Biol., 106: 915 (1988); Noda et al., J. Cell. Physiol., 133: 426 (1987); Pfeilshifter et al., Endocrinology, 121: 212 (1987); Centrella et al., Endocrinology, 119: 2306 (1986); Roby et al., J. Cell. Biol., 105: 457 (1987). In other in vitro models, TGF-.beta. was found to inhibit proliferation and expression of alkaline phosphatase and osteocalcin. See, for example, Noda and Rodan, Biochem. Biophys. Res. Commun., 140: 56 (1986); Noda, Endocrinology, 124: 612 (1989).
Further, while Centrella et al., supra, showed increased collagen synthesis after treatment of osteoblasts from rat calvaria with TGF-.beta., Robey et al., supra, could not show increased synthesis of collagen in fetal bovine bone osteoblasts, postulating that the increased collagen production is secondary to the effects of TGF-.beta. on the proliferation of osteoblasts. In organ culture, TGF-.beta. was reported to stimulate bone resorption in neonatal mouse calvarias, but inhibit resorption in the fetal rat long bone system. See Tashjian et al., Proc. Natl. Acad. Sci. USA, 82: 4535 (1981); Pfeilshifter et al., J. Clin. Invest., 82: 680 (1988). TGF-.beta. activity was reported to be increased in cultures of fetal rat calvaria and in calvarial cells incubated with stimulators of bone resorption, such as parathyroid hormone, 1,25-dihydroxyvitamin D.sub.3, and IL-1 (Petkovich et al., J. Biol. Chem., 262: 13424-13428 [1987], Pfeilschifter and Mundy, Proc. Natl. Acad. Sci. USA, 84: 2024-2028 [1987]). Furthermore, it was reported that TGF-.beta. inhibits the formation of osteoclasts in bone marrow cultures. Chenu et al., Proc. Natl. Acad. Sci. USA, 85: 5683-5687 (1988). The showing that TGF-.beta. has effects on both osteoclasts and osteoblasts led Pfeilschifter and Mundy, supra, to propose that it is involved in the strict coupling of the processes of bone resorption and bone formation characteristic of the remodeling process in adult bone. It has also been postulated that the local acidic, proteolytic environment provided by the osteoclasts results in activation of matrix-associated latent TGF-.beta.. Oreffo et al., Calcified Tiss. Internatl., 42: Suppl:A15 (1988).
In view of the conflicting results reported for in vitro activities, it is not clear whether in vitro models can be used to predict the effects of TGF-.beta. on bone formation and resorption in vivo. See Roberts et al., Proc. Natl. Acad. Sci. USA, 82: 119 (1985).
Additional references reporting that TGF-.beta. promotes the proliferation of connective and soft tissue for wound healing applications include U.S. Pat. No. 4,810,691 issued Mar. 7, 1989, U.S. Pat. No. 4,774,228 issued Sep. 27, 1988, Ignotz et al., J. Biol. Chem., 261: 4337 (1986); Varga et al., Biochem. Biophys. Res. Comm., 138: 974 (1986); Roberts et al., Proc. Natl. Acad. Sci. USA, 78: 5339 (1981); Roberts et al., Fed. Proc., 42: 2621 (1983); U.S. Pat. No. 4,774,228 to Seyedin et al. TGF-.beta. stimulates the proliferation of epithelia (Matsui et al., Proc. Natl. Acad. Sci. USA, 83: 2438 [1986]; Shipley et al. Cancer Res., 46: 2068 [1986]); induces collagen secretion in human fibroblast cultures (Chua et al., J. Biol. Chem., 260: 5213-5216 [1983]); stimulates the release of prostaglandins and mobilization of calcium (Tashjian et al., Proc. Natl. Acad. Sci. USA, 82: 4535 [1985]); and inhibits endothelial regeneration (Heimark et al., Science, 233: 1078 [1986]).
In wound chambers implanted subcutaneously, TGF-.beta. increased DNA and collagen production. Sporn et al., Science, 219: 1329 (1983); Sprugel et al., Am. J. Pathol., 129: 601 (1987). Moreover, TGF-.beta. produced collagen fibrosis when injected subcutaneously (Roberts et al., Proc. Natl Acad. Sci. USA, 83: 4167-4171 [1986]) and promoted healing of skin incisions in rats (Mustoe et al., Science, 237: 1333 [1987]). Nevertheless, although TGF-.beta. induced chondrogenesis in muscle-derived cells in vitro (Seyedin et al., Proc. Natl. Acad. Sci. USA, 82: 2267 [1985]; Seyedin et al., J. Biol. Chem., 261: 5693 [1986]), it did not produce cartilage in vivo even when implanted with collagenous substrates, a system used for a long time as a bone induction model in animals (Sampath et al., Proc. Natl. Acad. Sci. USA, 84: 7109 [1987]; Howes et al., Calcif. Tissue Int., 42: 34 [1988]).
New studies have shown a time-dependent appearance of mRNA for TGF-.beta.1 at a fracture site in a rat and have localized the peptide immunohistochemically in the periosteum of the healing fracture; the same researchers reported that injections of TGF-.beta.1 into the periosteal area of the femur of young rats have caused significant formation of new cartilage. Bolander et al., New York Academy of Sciences, "Transforming Growth Factor-.beta.s: Chemistry, Biology and Therapeutics, May 18-20, 1989. It has been found that injections of TGF-.beta.1 into the parietal bone of young rats stimulated periosteal bone formation, resulting in a thickening of the calvarium. Noda et al., J. Cell. Biol., 107: 48 (1988).
TGF-.beta. was reported to stimulate local periosteal woven bone formation when injected daily onto the periostea of parietal bones of neonatal rats. Noda and Camilliere, Endocrinology, 124: 2991-2994 (1989). The fact that TGF-.beta. increases bone thickness when applied adjacent to periosteum in vivo is also reported in Joyce et al., J. Cell Biol., 110: 2195-2207 (1990); Marcelli et al., J. Bone Min. Rest., 5: 1087-1096 (1990); Mackie et al., Bone, 11: 295-300 (1990).
Certain researchers reported that TGF-.beta. does not induce bone formation unless it is administered concurrently with a cofactor, e.g., an osteoinductive factor purified from bovine demineralized bone. Bentz et al., supra, U.S. Pat. No. 4,843,063 issued Jun. 27, 1989 to Seyedin et al., and U.S. Pat. No. 4,774,322 issued Sep. 27, 1988.
The remodeling of bone with TGF-.beta. is also described by Centrella et al., J., Bone and Jt, Surg., 73A: 1418-1428 (1991). Multiple applications of TGF-.beta.1 to rat femur induced a profound stimulatory effect with increased deposition of bone at the site of injection. Joyce et al., J. Bone Min. Res., 4: 255-259 (1989). Additionally, a single local application of TGF-.beta.1 in a methylcellulose gel formulation to sites of cartilage damage accelerated the onset and increased the incidence of bone formation adjacent to the cartilage. Beck et al., J. Bone and Mineral Research, 6: 961-968 (1991). A single local application of this same formulation in the rabbit skull defect model increased the amount of bone formation in a dose-dependent manner when measured 28 days after injury. Beck et al., J. Bone Min. Res., 6: 1257-1265 (1991).
Phosphate biomaterials have been prepared and investigated in a number of forms. The most widely studied are biodegradable beta tricalcium phosphate (TCP) and hydroxyapatite. A detailed description of the variety of calcium phosphate compositions studied can be found in deGroot, Bioceramics of Calcium Phosphate, Boca Raton, Fla., CRC Press, 1983. TCP is used as an in vivo scaffold for bone repair. Perhaps the most consistent and desirable property of TCP as well as other calcium phosphate ceramics is biocompatibility. Also, calcium phosphate ceramics are able to bond directly to bone. Driskell, Proc. Ann. Conf. Biomed. Eng., 15: 199 (1973).
While TCP has low impact resistance, it has application as a bone graft substitute or extender to the extent that proper fixation can be included during the TCP resorption and bone repair processes. It has been demonstrated that TCP in granular form can be used as an autogenous bone extender in the repair of long-bone discontinuities in rabbits. Lemons et al., First World Biomat. Cong. (Baden, Austria), 1980, 4. 10.3 (Abstract). The surgically created defects filled with 50:50 TCP:autogenous bone healed in six weeks as compared with four to six weeks when autogenous bone alone was used. These results indicate that some applications of the granular TCP may be possible in humans where a degree of stress-bearing is a factor. Porous TCP has been applied in block form with some success in mandibular discontinuities in dogs. Tortorelli and Posey, J. Dent. Res., 60: Special Issue A: 601 (1981) (abstract).
The principal clinical application of TCP has been in dentistry. Powdered TCP has been used for initiating apical closure in teeth and for treating periapical defects. Biodegradables may play a role as carriers for bone-inductive agents or bone-cell chemotactic factors. Dipolar microspheres or packets of osteoprogenitor cells donated by an individual may be incorporated within a polymer or ceramic, and in conjunction with characterized bone inductive proteins can be expected to enhance bone repair and augmentation at any chosen skeletal site. Hollinger et al., Biodegradable Bone Repair Materials, 207: 290-305 (1986).
TGF-.beta. is typically formulated at an acidic pH at which it is active. Various methods for its formulation include adding 2-5% methylcellulose to form a gel (Beck et al., Growth Factors, 3: 267-275 [1990] reporting the effects on wound healing of TGF-.beta. in 3% methylcellulose), adding collagen to form an ointment or suspension (EP 105,014 published 4 Apr. 1984; EP 243,179 published 28 Oct. 1987; EP 213,776 published 11 Mar. 1987), or adding a cosmetically acceptable vehicle to the TGF-.beta. for a topical formulation (U.S. Pat. No. 5,037,643 issued 6 Aug. 1991).
Additionally, human topical applications containing growth factors such as TGF-.beta. are described in EP 261,599 published 30 Mar. 1988. A slow-release composition of a carbohydrate polymer such as a cellulose and a protein such as a growth factor is disclosed in EP 193,917 published 10 Sep. 1986. A formulation of a bioactive protein and a polysaccharide is described in GB Pat. No. 2,160,528 granted 9 Mar. 1988. An intranasally applicable powdery pharmaceutical composition containing an active polypeptide, a quaternary ammonium compound, and a lower alkyl ether of cellulose is described in EP 193,372 published 3 Sep. 1986. See also U.S. Pat. No. 4,609,640 issued 2 Sep. 1986 disclosing a therapeutic agent and a water-soluble chelating agent selected from polysaccharides, celluloses, starches, dextroses, polypeptides, and synthetic polymers able to chelate Ca and Mg; and JP 57/026625 published 12 Feb. 1982 disclosing a preparation of a protein and water-soluble polymer such as soluble cellulose. In addition, a method for entrapping enzymes in gel beads for use as a biocatalyst is described in U.S. Pat. No. 3,859,169. Also, a method for preparing polyvinyl alcohol gel intended as a transdermal vehicle for water-soluble synthetic drugs is disclosed in JP 62/205035 published 9 Sep. 1987.
A purified particulate bone mineral product for use in medicine impregnated with a gel-forming protein or polysaccharide such as gelatin is disclosed that may also carry one or more absorbed drugs such as transforming bone growth factor. WO 90/01955 published 8 Mar. 1990. Use of TGF-.beta. and a biocompatible controlled release polymer is described by Langer and Moses, J. Cell. Biochem., 45: 340-345 (1991). An osteoinductive pharmaceutical formulation comprising an anti-fibrinolytic agent such as epsilon amino acid caproic acid or other lysine analogue or serine protease inhibitor and a cartilage and/or bone inductive protein such as bone morphogenetic protein is disclosed in WO 91/19510 published 26 Dec. 1991. The formulation may additionally contain a growth factor such as TGF-.beta. and may be encased in a TCP matrix. Biologically active polypeptides based on TGF-.beta. sequences disclosed as useful Ln the treatment of wounds and bone fractures are described in WO 90/14359 published 29 Nov. 1990. In addition, TGF-.beta. has been disclosed as a treatment for gingivitis and periodontal disease in the form of implants, microspheres, an absorbable putty-like matrix, or a polymeric material having the drug impregnated thereon. WO 90/04974 published 17 May 1990. Compositions with activin, also optionally containing a TGF-.beta., a bone morphogenetic protein, or bone marrow, have been formulated with hydroxyapatite and TCP as a dental and orthopedic implant and for bone growth induction. WO 92/14481 published 3 Sep. 1992. Also, TGF-.beta. formulated for treatment of inflammatory disorders is described in EP 269,408 published 1 Jun. 1988. Additionally disclosed are cytokines such as TGF-.beta. bound to a solid support, which may include ceramics and polymeric materials as well as insoluble protein materials such as gelatin, collagen, or albumin. WO 90/09798 published 7 Sep. 1990.
Stable lyophilized formulations of polypeptide growth factors such as TGF-.beta. containing polymers to impart viscosity to a reconstituted solution or polysaccharides to stabilize against loss of biological activity are described in EP 308,238 published 22 Mar. 1989 and EP 267,015 published 11 May 1988, respectively. See also EP 335,554 published 4 Oct. 1989 on a cosmetic composition suitable for topical application to mammalian skin or hair that can contain collagen, a gelatin, and powders such as starch and aluminum silicates. Gels with polymeric material for providing viscosity that may contain a polypeptide growth factor such as TGF-.beta. are described in EP 312,208 published 19 Apr. 1989. Collagen-polymer conjugates in admixture with particulate matter such as TCP are described by WO 90/05755 published 31 May 1990. A controlled drug delivery system for placement in a periodontal pocket containing discrete microparticles comprising the drug (e.g., TGF-.beta.) and a polymer is described in EP 451,390 published 16 Oct. 1991. A bioactive compound associated with liposomes that may include TGF-.beta. is described in EP 393,707 published 24 Oct. 1990 and in Strassman et al., Clin. Exp. Immunol., 86: 532-536 (1991).
A sustained-release formulation containing an active ingredient such as TGF and collagen and a least one organic acidic compound is described in EP 326,151 published 2 Aug. 1989. TGF-.beta. in combination with a proteinaceous matrix that may comprise collagen and/or fibrinogen is described by WO 91/03491 published 21 Mar. 1991. A collagen sponge useful as an implant for a wound-healing matrix for TGF-.beta. and FGF is described in U.S. Pat. No. 4,950,483 issued 21 Aug. 1990. A therapeutic drug that contains a growth factor may be formulated in the form of powder, granules, etc., for example, with gelatin. JP 1-153647 published 15 Jun. 1989. Cicatrising compositions containing activated TGF-.beta. may be formulated with polysaccharides and humectants such as glycerol. FR 2,667,789 published 17 Apr. 1992.
It has also been known to mix an active medicament unstable to heat with a biodegradable protein carrier such as collagen, atelocollagen, or gelatin to form a carrier matrix having sustained-release properties. The resultant mixture is then dried, and the dried material is formed into an appropriate shape, as described in U.S. Pat. No. 4,774,091.
It would be desirable to provide a formulation for TGF-.beta. with the proper consistency suitable for molding to fill in bone gaps where needed.
Accordingly, it is an object of the present invention to provide a suitable formulation of exogenous TGF-.beta. to a local site on an animal where skeletal (bony) tissue is deficient so as to produce in every case mature, morphologically normal bone at the site of administration where it is needed.
It is another object to provide a bone-inducing composition that is clinically relevant for filling in smaller bone defects than is required for prosthetic devices.
It is further object to provide a TGF-.beta. formulation with enhanced consistency for improved application to the desired bone defect site.
These and other objects will become apparent to those skilled in the art.

TGF-.beta.formulation for inducing bone growth


In broadband signal switching equipment having a cross point matrix in FET technology whose switch elements respectively controlled by a holding memory cell are respectively formed by a series circuit of a switching transistor and of an input transistor, an n-channel series pass transistor that has its control electrode connected to a reference potential source is respectively inserted between the matrix output line and the following output amplifier circuit. This n-channel series pass transistor, together with a matrix output line pre-charging transistor connected to the input of the output amplifier circuit, forms a charge transfer circuit that effects a voltage amplification. A pre-charging transistor that also has its control electrode connected to the pre-charging phase/evaluation phase clock signal line is also connected to the input of an input driver circuit that precedes a matrix input line, a transfer gate that precedes the input driver circuit also being simultaneously controlled proceeding from this pre-charging phase/evaluation phase clock signal line.

If ECL technology can be characterized by properties such as high operating speed, (medium) high degree of integration and (medium) high dissipated power, then FET technology, having only medium operating speeds in comparison thereto, can be characterized by extremely high degree of integration and extremely low dissipated powers. These latter properties have led to efforts to provide integrated circuits in FET technology that operate in speed ranges that were previously found only in bipolar technology.
Thus, (for example, disclosed in European reference EP-A-0 262 79 corresponding to U.S. Pat. No. 4,801,936) prior art broadband signal switching equipment has a cross point matrix in FET technology whose switch elements are each respectively formed with a switching transistor that has its control electrode charged with a through-connect, or, respectively, inhibit signal and has its main electrode connected to the appertaining matrix output line. The switch elements each respectively have an auxiliary transistor that forms a series circuit with the switching transistor, this auxiliary transistor having its control electrode connected to the appertaining matrix input line and having its main electrode facing away from the series circuit connected via a sampling transistor to one terminal of the operating voltage source to whose other terminal the respective matrix output line is connected via a pre-charging transistor. The pre-charging transistor and sampling transistor (oppositely relative to one another) respectively have their control electrode charged with a switching matrix network drive clock that subdivides a bit through-connection time span into a pre-charging phase and into the actual through-connection phase. As a result, given an inhibited sampling transistor, the matrix output line in every pre-phase is at least approximately charged via the pre-charging transistor to the potential prevailing at the other terminal of the operating voltage source. This known broadband signal switching equipment that can have sampling transistors individually associated to switch elements or sampling transistors individually associated to a matrix input line or a matrix output line requires its own clock lines for driving these sampling transistors, these clock lines passing through the cross point matrix. This requires a corresponding surface area and involves a corresponding, capacitative loading of the matrix output lines. In order to guarantee an adequate resistance to noise, clock distribution and couplings between matrix input lines and matrix output lines require adequately high signal amplitudes on the matrix output lines, resulting in a relatively high power consumption.
Another known (for example, European reference EP-A-0 354 252 corresponding to U.S. Pat. No. 4,998,404) broadband signal switching equipment has a cross point matrix in FET technology whose inputs can each be respectively provided with an input driver circuit, whose outputs are respectively provided with an output amplifier circuit and whose switch elements respectively controlled by a holding memory cell are each respectively formed with a series circuit of a switching transistor that has its control electrode charged with a through-connect, respectively, inhibit signal and of an input transistor that has its control electrode connected to the appertaining matrix input line. This series circuit has the main electrode of the one transistor that faces away from the series circuit connected to the appertaining matrix output line, whereby the matrix output line is connected via a transistor to the one terminal of the operating voltage source. The main electrode of the other transistor facing away from the series circuit is continuously connected to the other terminal of the operating voltage source and the transistor series circuit of every switch element forms the cross point - associated, one branch of a differential amplifier whose other branch respectively shared by the cross points leading to one and the same output line is formed by the output amplifier circuit individually associated to matrix output line. The output amplifier circuit comprises a series circuit of a first transistor that has its control electrode line at the other terminal of the operating source and of a second transistor that has its control electrode charged with a reference voltage. This series circuit has the main electrode of the one transistor facing away from the series circuit connected to the appertaining matrix output line and has the main electrode of the other transistor that faces away from the series circuit and leads to the amplifier output connected via a load transistor to the other terminal of the operating voltage source.
This concept of a "distributed" differential amplifier requires, first, a relatively high precision of the said reference voltage and, thus, a correspondingly involved reference voltage generator; second, what is referred to as the transistor matching is also problematical for the distributed differential amplifier, i.e., offering transistors whose characteristics correspond to one another.


The present invention provides a unique, high density, electronic package having a conductive composition for filling vias or through holes to make reliable vertical or Z-connects from a dielectric layer to adjacent electrical circuits. The through holes may be plated or non-plated prior to filling. A description for making high density electronic packaging using this feature is also disclosed.

The present invention relates to printed circuit board and card manufacture and, more particularly, to a unique conductive composition for filling vias or through holes to make reliable vertical or Z-connects.
With the continued trend toward reduced size of electronic components and the resulting high density requirements for electronic packaging, there has been an increased demand to design a process that will efficiently generate high quality, high density electronic packaging such as printed wiring board structures.
In the past decade the density per unit area of electronic devices, such as very large scale integrated circuits (VLSIs), has greatly increased. By some estimates this increase in density has been on the order of 10,000 times what it was in the earliest days of the technology. The space or area available outside of a VLSI in which to make the large number of necessary connections to and from it and to provide the necessary circuitry is becoming almost vanishingly small, measured by previous standards. Contrary to the density increase of VLSIs, the density of the passive circuits on printed wiring boards has increased (i.e., the parts have decreased in size) by only a relatively small factor: less than about 4 to 1. This presents the difficult problem of providing circuitry on the printed wiring board to the VLSIs which is small enough to fit the spaces available, while being sufficiently reliable and manufacturable to be economically useful.
Perhaps one of the most significant limitations for creating high density fine line circuitry on printed wiring boards is the generally known problem of anisotropic etching. It is known that etching metals, especially copper metal, is not an anisotropic process. That is, vertical etching is not feasible without some amount of unwanted horizontal etching. This creates a situation in which the features and circuitry so formed can be severely undercut, leading to different types of failures and reject material. The problem is exacerbated by having thick metal layers and thick photoresist layers. However, this is precisely the situation that occurs when plated through holes are part of conventional manufacturing process.
It is also well known that due to the nature of the plating process, the metal plating within a through hole or via is thinner than the plating on the external surfaces of the dielectric substrate; yet a minimum thickness in the through hole is required in order to provide an adequate and reliable electrical connection between circuitry on opposing surfaces or at various vertical levels within the printed wiring board structure. Therefore, the general practice is to plate excess material on the lateral faces in order to ensure sufficient plating of the through holes. The excessive thickness of the lateral surface plating causes greater amounts of undercutting during the later circuitization/etching process. To compensate for this effect, the circuitry lines are designed wider and farther apart than otherwise would be required or desired. In an attempt to resolve this problem, thinning down the lateral surface by uniform etching prior to circuitization has been attempted. If chemically performed, this process can also undesirably etch within the plated through hole. Mechanical etching of the lateral surface plating is possible, but requires an unacceptably long period of time.
Another difficulty in obtaining sufficient plating thickness within the through hole, as compared to plating the lateral surfaces, is the significant increase in expense associated with plating high aspect vias.
A land or pad around the through hole is required to provide a reliable electrical connection in the eventuality that there is a break in the plating on the rim of the through hole. The trade-off for applying a reliable land or pad is a thicker than necessary metallized region. Consequently, a thicker than usual photoresist layer must be applied to obtain a level surface for placement of the mask and to ensure the photoresist spanning over the hole (tenting) does not rupture and result in etchant entering the plated through hole. Thus, through holes cause an undesirable increase in thickness both of the surface plating and of the photoresist layer.
In addition to the problem of layer thickness discussed supra, the prior art process of plating through holes requires the land or pad on the lateral surface of the commoning layer to connect in a dog-bone configuration to the plated through holes. The land utilizes valuable space on the lateral surface that could otherwise be used for circuitry. Consequently, there has been a long standing desire to eliminate the need for such lands or pads.
The plated through hole itself also consumes valuable space for several reasons. Firstly, the diameter of the hole is typically dictated by the cost of plating high aspect vias and the cost of small diameter drilling bits. To avoid the expense of high aspect plated through holes, larger plated through holes are typically utilized, but they must be placed at a distance from the areas containing fine line circuitry. This design, known as xe2x80x9cfan-outxe2x80x9d, however, contributes to loss of circuitry space due to the need for greater routing space.
Another known problem associated with conventional plated through holes is the different expansion rate between copper plating and the dielectric or pre-preg layer. When subjected to heating and cooling cycles, the plating on the through hole is susceptible to cracking.
Prior art literature addresses the problems associated with plated through holes and describes processes and materials of making alternative designs. Relevant prior art patents are summarized hereinbelow.
Hayakawa et al. in U.S. Pat. No. 4,383,363, teach the benefit of using conductive materials for filling through holes. The patent is directed toward the process of filling through holes and describes only a limited selection of conductive fillers.
Lambert et al. in U.S. Pat. No. 4,820,340, disclose a method of fabricating a conductive polymer interconnect (CPI) which employs chains of electrically conductive particles within an elastomeric matrix. The process requires removing a thin layer of elastomeric material from the outer surfaces by use of plasma etching in order to provide a conductive surface. Gold- or silver-plated nickel particles are used, but no mention is made of using copper as the conductive material. Particles are approximately 100 micron and are imbedded in an elastomer of polysiloxane room temperature vulcanizing (RTV) rubber. Magnetic fields are used to align the particles and then a heat cure step is performed. Subsequently, the surface layer of the cured rubber is removed by plasma etching. As reported in Lambert, et al., U.S. Pat. No. 4,820,376, plasma etching removes the gold shell leaving the nickel core exposed to air. To prevent aerial oxidation of the nickel, the material is plated with electroless gold.
Kawakami et al. disclose, in U.S. Pat. No. 5,220,135, a conductive filling within the through hole of an insulative substrate. Conductive resins are described which include silver, copper, and carbon conductive materials. No mention is made of a core-shell particle having a fusible shell.
Higgins, III et al. in U.S. Pat. Nos. 4,967,314 and 5,117,069, describe a method and material for eliminating plating in through holes by filling the through holes with a silver epoxy conductive paste. Higgins, III et al. employ a process wherein the vias are slightly overfilled with the conductive epoxy in order to create bumps at each end of the via. Then several printed wiring boards and prepreg layers are stacked up and subsequently laminated. During the lamination process, the excess epoxy is squeezed from the ends and spreads out over the printed wiring board layer to create intimate contact between the circuitry and the conductive polymer within the through hole. Higgins, III et al. teach away from the use of a copper epoxy by indicating that the copper epoxy would have a higher resistance than the silver epoxy. Furthermore, Higgins, III et al. prefer the use of thermoplastic paste compositions. Lastly, the epoxy composition is limited to high viscosity materials of approximately 100 centipoise in order to provide adequate adhesion of the epoxy within the via.
Bhatt et al. in U.S. Pat. Nos. 5,557,844 and 5,487,218, disclose a process and a material for forming filled through holes and blind holes. The filler material is an organic polymeric material, optionally with a particulate filler. The filler composition is compounded to have a coefficient of thermal expansion matching the coefficient of thermal expansion of the dielectric substrate. The fill material may be either conductive or non-conductive. These patents teach laminating a copper foil to a dielectric substrate, followed by thinning the foil to an acceptable thickness, then drilling through holes and subsequently electrolessly plating into the through holes to create a conductive layer therein. The filling in the ""844 patent occurs after the etching process of the lateral metallized layers. Conductive filling compositions include resins made from epoxy- or cyanate-containing materials and have conductive material derived from carbon, copper, silver, nickel, molybdenum, gold, platinum, and aluminum. Particle size for the conductive materials ranges from 0.1 to 75 micron, the most preferred size being between 0.5 and 10 micron.
Chong et al., in U.S. Pat. Nos. 5,699,613 and 5,758,413, describe a method of manufacturing a multiple layer circuit board with stacked vias. These patents disclose a filled through hole having a conductive plug comprising a 70-80% copper fill.
Boyko et al., in U.S. Pat. No. 5,450,290, describe an integrated chip carrier and a technique for manufacturing same. The through hole is formed after copper sheets have been applied to the dielectric substrate and are initially plated by conventional electroless or electroplating techniques. Then a conductive paste is applied to the through holes. The paste is a epoxy novalak containing copper powder.
Gaynes et al., in U.S. Pat. No. 5,542,602, describe a conductive adhesive comprising a core-shell material having an inner core of copper, silver or gold and an outer shell of indium, tin or lead. Particles are approximately 10-15 micron in size and have a shell thickness of 1.0-1.5 micron. The patent is directed toward a solder replacement that can be used to affix two layers at temperatures below 220xc2x0 C. and exploits a transient liquid phase (TLP) reaction for alloying on metals. A second application of the ""602 patent replaces conventional conductive adhesives which require high concentrations of conductive particles in intimate contact to achieve a connector structure that is itself conductive. A polymeric material is used as a matrix or binder for the conductive particles. Upon curing, the binder creates compressive forces that ensure intimate contact of the conductive particles. The underlying concept of both applications in the ""602 patent is that the shell metal, having a lower melting point than the core, will melt and alloy with the core upon reaching a critical temperature, creating a second phase that is between, but still electrically connected to, the core particles. In this manner, a low melting eutectic is formed which will create an isotropic stable conductive connection that can survive repeated thermal cycles. The patent is directed toward forming a metallurgical bond between two metal surfaces. No mention is made of using this material or similar materials as a filler within a through hole, nor is any mention made of the benefit that would be derived from such a process (i.e., the elimination of various processing steps such as electroless copper plating). Further, for the process to perform optimally, the curing temperature must be below the TLP temperature.
Other references to transient liquid phase bonding include: Wilcox et al., in U.S. Pat. No. 5,038,996; Davis et al., in U.S. Pat. No. 5,280,414; Galasco et al., in U.S. Pat. No. 5,432,998; Davis et al., in U.S. Pat. No. 5,620,782; and Gaynes et al., in U.S. Pat. No. 5,713,508.
Having discussed the general problem associated with the current practice of plating through holes to create Z-connects and the current attempts at solving the problem, it is understood that additional improvements would still be beneficial.
In summary, having the flexibility to eliminate or replace the thick lands surrounding the plated vias and to eliminate the plating of the vias would constitute a significant advancement in electronic package manufacturing and would alleviate the constraints imposed by the through hole plating process.
Therefore it is an object of the current invention to provide a high density (low pitch) fine line circuitry printed wiring board structure without the need for plating through holes.
It is another object of the invention to provide a high density (low pitch) fine line circuitry printed wiring board having multiple layers of circuitry interconnected with filled conductive through holes or blind holes.
It is another object of the invention to provide filled through holes to eliminate or reduce the need for thick lands, thereby providing higher density circuitry.
It is another object of the invention to utilize a thin, non-tenting resist in order to obtain high density circuitry.
It is yet another object of the invention to provide a process of filling the vias by vacuum fixturing without the need to plug via holes separately.
It is still another object of the invention to design a conductive fill material that can wet copper as well as dielectric material and also that can be directly solderable.
It is yet another object of the invention to reduce the registration budget by providing landless vias, having eliminated the concern for hole breakout.
Yet another object of this invention is to provide a method of making a circuitized substrate capable of being used as a chip carrier assembly, the method being performed in a facile and relatively inexpensive manner in comparison to existing carrier manufacturing processes.
It is a more particular object of the invention to provide such a process which is readily adaptable to existing manufacturing equipment without extensive modification thereof.
The present invention is designed to address the deficiencies in the art as well as the specific objects disclosed hereinabove.
In order to meet the objectives listed supra, a process has been designed to provide vias filled with a unique and novel conductive material.
The primary feature of the invention is to provide a conductive material that can be used to fill through holes or vias to Z-connect two or more layers of circuitry or conductor runs. The vias may optionally be plated with a conductive material; however, in one preferred aspect of the invention this is not required.
In accordance with another aspect of this invention, there is defined a method of making a circuitized substrate, the method comprising the steps of providing an electrically insulative base member having first and second surfaces, formation of at least one via hole, filling said via with a conductive material, optional planarization of the filled via on at least one of the first and second surfaces, and applying a first electrically conductive layer onto the first and second surfaces of the base member. The method still further includes applying a photoimaging material onto the thinned first conductive layer, then exposing and developing selected portions of the photoimaging material to define a pattern within the photoimaging material on the thinned first conductive layer. The method even further includes circuitizing the first conductive layer and then removing the photoimaging material from the first conductive layer. The fill material contained in the plated vias is not removed and can optionally be used to act as a solder point for surface mounting various components.
If multilayer structures are desired, the material described supra can be laminated to dielectric substrates containing a pre-preg and/or copper foil surfaces. In this manner, electrically conductive filled vias can connect external circuitry to internal circuitry or conductor runs.
The inventive fill material comprises a core-shell particle in a polymeric media that, under a defined pressure and temperature regime, cures to generate a solid plug having minimal shrinkage, thereby essentially filling the via volume. For purposes of definition, the curing temperature is considered the temperature at which a glass, viscous liquid, or rubber state resinous composition is converted into a solid three dimensional structure. The temperature at which this occurs is not necessarily a precise point and is affected by such factors as catalyst amount, pressure, and radiation. Therefore, the curing process occurs over a range of temperatures, but is easily observable as a physical change in state. The shells of the core-shell particles are designed to fuse with each other to generate an electrically connected network within the cured medium. The fusing temperature is defined as the melting temperature of the pure metal in the shell or the eutectic melting point of an alloy with core metal, should that occur. Therefore, in a single process, the invention provides a means for generating a solid conductive plug which can be electrically connected to later formed circuitry on the surfaces of the base member and to optional internal circuitry.
The benefit of the present invention is the ability to produce higher density circuitry than is currently available from existing designs. This invention can produce circuitry having a cross-section width of 0.7-2.0 mil and spacing between the circuitry of 1-2 mil. No other photolithographic processes are known to the inventors that can generate these same dimensions.
Other benefits and further scope of applicability of the present invention will become apparent from the detailed description given hereinbelow. It should be understood, however, that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only and are not to be construed as limitations of the current invention, since various changes and modifications within the scope and spirit of the invention will become apparent to those skilled in the art from this detailed description.
Furthermore, as is known in the art, changes in the amount of most critical parameters affect the benefit of an invention by a matter of degree and not normally with a precise point of success or failure. This is especially true when multiple variables might be involved. In this case, the situation is further complicated by interactions between such variables. Therefore, where parameters are given a value or range of values, it should be understood that these well defined areas clearly are within the scope of the invention. Yet other values might still be within the scope of the invention if the desired beneficial effects of the invention are demonstrated. For this reason, words such as xe2x80x9capproximatelyxe2x80x9d or xe2x80x9caboutxe2x80x9d are used to indicate that the values presented are not necessarily true limits to the invention. The true inventive scope can be readily determined by experimentation.

Electronic package having substrate with electrically conductive through holes filled with polymer and conductive composition

International Business Machines Corporation