A method and system for testing the wireless signal propagation model of the cellular network is provided in the invention. The method comprising: selecting a testing site to install a receiving testing apparatus; moving a transmission apparatus along a testing route transmitting a testing signal upon moving; the receiving testing apparatus receiving the testing signal, and detecting the strength of the received testing signal; and obtaining field strength testing data along the testing route based on a synchronization established between the transmission apparatus and the receiving testing apparatus. By this invention, the testing efficiency of the wireless signal propagation model correction in the area covered by the cellular network can be improved.

Nowadays, the cellular networking is the commonest networking mode in the wireless communication. FIG. 1 is a topology structure of a cellular network constructed by three-sector base stations. Since the network topology structure looks like a honeycomb, it is called as cellular network. As shown in FIG. 1, the circles 1 represent the locations of the three-sector base stations, the arrowheads 2 show the orientation of each of the sectors, and each hexagonal cellular unit 3 in the cellular network denotes the coverage range, known as cell, of the transceiver of one base station. In the coverage area of the cell, a terminal can establish a wireless communication link with the base station. Multiple transceivers form a network to continually cover an area so as to provide user terminals with a seamless wireless communication service.
FIG. 2 is the flow of the traditional network planning. As shown in FIG. 2, the wireless network planning is begun with the user requirements 202, including the designed capacity, coverage range and coverage rate, network performance KPI index. When the designed requirement is clear, it comes to the requirement analysis 204 of the wireless network design, including the prediction of the coverage radius of the coverage area and the analysis of the distribution of the user capacity. The capacity distribution of the coverage area means to determine the equipment configuration and the size of the coverage radius of the cell according to the potential of the user development in the network coverage area. The original design 206 of the network topology structure is completed on the map by combining the two factors, i.e., the network coverage and the user distribution.
Based on the original design of the network topology structure, the process of selecting the appropriate base station sites in the actual coverage environment is called site survey 208. During the site survey, the engineering survey may be performed at the same time to discuss with the owners about the matters concerned such as site rental. Due to various factors, the practically available sites are not necessarily identical with the designed sites. But after the site survey, it is basically ascertained which sites possess the essential conditions for establishing the base stations. Therefore, after the sites are selected, it is necessary to use the network simulation 210 to verify whether the network design requirement is satisfied 212. If the design requirement is satisfied, the network design is output and it comes to the network engineering construction stage 214; otherwise, adjust the site parameters on the simulation platform to find the appropriate site places, antenna heights, and etc., and return to the sites to survey more appropriate sites. The wireless signal propagation model used by the network simulation can be the standard statistic model in the industry, and the corrected model can also be used.
Based on the wireless signal propagation model, the typical propagation model for the traditional cell coverage prediction includes Hata, Cost231 and etc. In order to improve the accuracy of the cell coverage prediction, the propagation model is usually needed to be corrected for typical topographic and geomorphologic environment.
The model correction can be performed at any place before step 210 as shown in the flow of FIG. 2, and its working procedure is as shown in FIG. 3:
Step 302, selecting 3-5 typical areas in a certain urban environment, and choosing typical sites. One or more typical sites can be selected.
Step 304, erecting the continuous wave transmitter at a typical site height for transmission at a fixed power. The vehicular continuous wave receiver moves in the typical area to measure the receiving field strength.
Step 306, collecting sufficient testing data (the data of multiple testing sites with similar topography and geomorphology may be merged, the quantity of one-time testing data may also be increased for the area, and etc.).
Step 308, performing a preprocess for the testing data, including averaging the testing data on the repeated route, eliminating the data too near to or too far from the testing site, merging the testing data of multiple testing sites in the typical areas of a single type, and etc.
Step 310, modifying the parameters of the propagation model using the model correction tool, so as to make its predicted coverage even closer to the actual wireless propagation model of the typical coverage area of this type.
Step 312, forming a model database for the wireless propagation models of several typical areas for the usage of the wireless network simulation.
The traditional method of the propagation model correction corrects the wireless propagation model by collecting sufficient field strength testing data through selecting the typical sites with respect to the typical topography and geomorphology (multiple testing sites are usually needed to be selected such that the testing data covers various topography, geomorphology and site heights).
For the sake of improving the model accuracy, the more the testing sites are selected, the more sufficient the testing data is collected, the better the model correction effect is (multiple parameters in the model are corrected and the parameters corresponding to various geomorphology are corrected).
When testing the wireless signal field strength, transmission apparatus need to be installed in sequence at each testing site in the testing area, and the receiving field strength of the wireless signal is tested for the coverage area of each site in sequence. If n sites are to be tested, the apparatus installation and the testing need to be performed n times, which results in quite large workload.

Method and system for testing the wireless signal propagation model of the cellular network


The tire includes a tread portion to come into contact with a road surface. A lateral groove portion extending in a direction intersecting with a tire circumferential direction, and a land portion partitioned by the lateral groove portion are formed in the tread portion. The land portion includes: a ground-contact face to come into contact with the road surface; a side face formed on an outer side in a tread width direction of the land portion; a lateral groove face constituting a groove wall of the lateral groove portion formed on one end in the tire circumferential direction of the land portion; and a tapered face which meets the ground-contact face, the side face, and the lateral groove face in a corner portion formed by the ground-contact face, the side face, and the lateral groove face.

A rubber material having viscoelasticity exhibits a hysteresis behavior. Accordingly, a tread portion of a tire generates heat as a consequence of repeating deformations and contractions associated with rolling motions. An increase in an amount of the rubber material constituting the tread portion leads to an increase in a hysteresis loss attributed to bending deformations and shearing deformations during rolling motions of the tire. For this reason, the tire having the tread portion with a larger thickness tends to become higher in temperature. In particular, a large tire employed for a large vehicle used in a mine, a construction site or the like has a characteristic that the tire is prone to generate heat because such large tire not only requires a large amount of the rubber material used therein but also is used in a heavily loaded state, on bad road surfaces, and under severe traction conditions, thereby repeating deformations and contractions. If the tire reaches a high temperature while the vehicle is traveling, such a rise in temperature causes problems such as detachment (separation) of the rubber material constituting the tread portion from belt layers, and leads to shortening a replacement cycle of the tire.
Accordingly, there has heretofore been known a method in which sub-grooves are formed in a tread portion in a tread width direction, whereby an amount of a rubber material as a heat generation source is reduced and a surface area of the tread portion is increased so as to promote heat radiation from the tread portion (PTL 1, for example).


An aqueous ink printer is operated to insert media sheets from a first supply tray into a plurality of media sheets from a second tray on which ink images are being formed by the printer to absorb condensed vapors on media guides. The media sheets from the first tray are uncoated media and the media sheets from the second tray are coated media. In some embodiments, the inserted media sheets are printed with an ink image that has areas that contact the media guides with a greater ink density than other areas of the ink image that do not contact the media guides. Additionally or alternatively, the inserted media sheets are printed with an ink image that has areas that contact the media guides with an ink color that is different than an ink color used in other areas of the ink image that do not contact the media guides.

Known aqueous ink printing systems print images on uncoated and coated substrates. Whether an image is printed directly onto a substrate or transferred from a blanket configured about an intermediate transfer member, once the image is on the substrate, the water and other solvents in the ink must be substantially removed to fix the image to the substrate. A dryer is typically positioned after the transfer of the image from the blanket or after the image has been printed on the substrate for removal of the water and solvents from the ejected ink. To enable relatively high speed operation of the printer, the dryer heats the substrate and ink to temperatures that typically reach 100° C. Uncoated substrates generally require exposure to the high temperatures generated by the dryer for a relatively brief period of time, such as about 500 to 750 msec, for effective removal of the liquids from the surfaces of the substrates.
Coated substrates are typically used for high quality image brochures and magazine covers. Printing images with high area ink coverage on coated media releases significant amounts of water and cosolvent vapors inside the dryer module. Air flow through the dryer module carries this vapor downstream through the simplex and duplex media paths. Water and cosolvents not evaporated within the dryer module continue to vaporize from the hot media exiting the dryer so they continue to release vapors inside the downstream media path. This vapor on the printed media guides gradually accumulates to a level that condenses into droplets on the guides. These droplets grow in size until a sheet of media contacts the droplets or the droplets drip from the guide onto the sheet passing under the guide. These condensed vapor drops can produce IQ defects in the image on the printed substrate. Developing systems and methods that more effectively remove ink solvent and water vapors from an aqueous ink printer, particularly when coated media are being printed, would be beneficial.

System and method for removing ink solvent and water vapors in aqueous ink printers


A sprinkler assembly comprising in combination a sprinkler mounting stake and a sprinkler comprising. The sprinkler comprises a sprinkler body formed with a support member receptacle and locking portion. The sprinkler mounting stake comprises a ground insertion portion and a sprinkler support portion. The sprinkler support portion comprises a lateral support member extending parallel to a longitudinal axis of the stake and retention member. The support member is insertable within the support member receptacle and a retention member prevents unintentional disengagement of the sprinkler body from the mounting stake.

Sprinklers of many types, in particular but not restricted thereto, mini sprinklers and sprayers, are often supported by using a ground stake to which it is known to fix also a supply conduit providing irrigation water to the sprinkler. Typically, such conduits are flexible rubber tubes.
Stakes of the concerned type should be on the one hand cheap and easy to manufacture and assemble and, on the other hand, be sufficiently strong for inserting them into the ground and for supporting a sprinkler thereto with a supply conduit extending to the sprinkler which is often dislocated owing to rough handling or extreme temperature changes between day time and night.
U.S. Pat. No. 4,944,476 discloses a ground stake designed for insertion into the ground and adapted for retaining a flexible irrigation conduit coupled to the sprinkler.
Israel Patent No. 123907 discloses a sprinkler assembly comprising a sprinkler mounting stake formed at an upper portion thereof with a sprinkler body gripping portion fitted with a pair of sprinkler body gripping flanges defining between them a sprinkler body receiving recess and a pair of aligned edges of said flanges equally inclined with respect to a median plane of the gripping portion which gripping portion is adapted for snapping engagement over a body portion of a sprinkler formed with a pair of aligning ribs formed on the body which ribs are symmetrically disposed and equi-angularly inclined with respect to a median plane of the body.
This arrangement requires some significant force for engagement of the mini sprinkler with the sprinkler gripping portion and the same applies for a disengagement process.
It is an object of the present invention to provide a sprinkler assembly comprising in combination a sprinkler and a sprinkler mounting stake whilst ensuring that the sprinkler is effectively attached to the stake whilst retaining a predetermined orientation, i.e. always mounted in the same position over the stake. Further objects of the present invention are to provide a sprinkler mounting stake and a sprinkler for use in conjunction with one another.

Irrigation unit support stake and system


The present invention is directed towards an electrical switch. The switch has a first board to which input and output leads are attached proximate one end of a plurality of buses on the first board. Proximate the other ends of the plurality of buses are electrical contacts. The switch also has a second board which is interchangeably attachable to the first board. The second board includes a plurality of electrical buses that are selectively arranged to electronically connect the contacts on the first board. The connections electrically connect the input and output leads on the first board to provide a predetermined arrangement of electrical connections.

The present invention relates to a switch, and more particularly to a switch for changing the electrical output of a generator.
It is often necessary to change the electrical output of an electrical generator to meet the electrical requirements of the circuitry being powered by the generator. One way of accomplishing this with existing generators is to utilize what are referred to as shorting bars which are attached to the generator electrical contacts in an appropriate fashion to derive the desired electrical output. However, this typically requires that many fasteners holding down individual shorting bars be removed so as to allow reconfiguring of the shorting bars. The shorting bars are then reconfigured and reattached to the generator by the fasteners. Additionally, the electrical input and output leads of the generator must also be removed and reattached onto the proper terminals formed by the new configuration of shorting bars. This is a rather time consuming, complicated process. Moreover, one has to be very careful to make sure that the generator leads are properly connected to the shorting bars.
The present invention solves many of the problems associated with existing apparatus and methods for changing the electrical output of a generator.


A wave gear drive in which wide-area meshing of the rigid internal gear and flexible external gear is achieved, reducing stresses on the bottom rim of the gear teeth and in the vicinity of the major axis of the inner ring surfaces of the wave generator, thereby improving the load capabilities of the wave gear drive.

Since the wave gear drive was invented by C. W. Musser (see U.S. Pat. No. 2,906,143), various types of wave gear drive have been invented by many researchers, including Musser and the present inventor. There have also been various inventions relating to the tooth profile of the gears used in wave gear drives. The present inventor has proposed making the basic tooth profile an involute tooth profile (see JP-B 45-41171), and a method of designing a tooth profile in which the addendum profiles for wide contact between the rigid internal gear and flexible external gear are derived using a rack approximation of the meshing between the two gears (see JP-A 63-115943 and JP-A 64-79448). There has also been proposed an invention for avoiding interference between rack-approximated tooth profiles (see JP-A 7-167228).
There is a strong market demand for wave gear drives with improved performance, especially improved load capability. The main elements that govern the load capability of a wave gear drive are the fatigue strength of the tooth bottom rim of the flexible external gear and the fatigue strength of the inner rolling contact surface of the wave generator, particularly at locations in the vicinity of the major axis of the elliptically deformed flexible external gear.
An object of the present invention is to provide a wave gear drive having a tooth profile that is able to reduce the stresses generated at the above two locations.

This patent is subject to a terminal disclaimer.

Wave gear drive with wide mesh three-dimensional tooth profile


A piston-cylinder unit includes a piston which divides the cylinder into two working chambers, a sealing valve seals a flow path between the two working chambers in the stationary operating condition of the unit. The sealing valve has a valve element consisting of an axially movable radially sealing sealing ring in conjunction with a valve ring, which at its back is supported by a spring-biased member. The slide member and the valve ring form therebetween a flow-off chamber having a flow-off opening that is sized so that unrestricted fluid flow is permitted so as to prevent the formation of a ram pressure in the flow-off chamber. The sealing ring is movable between three axial positions relative to the valve ring. At a center position, the sealing ring seals the flow path against fluid flow. At the two other positions, the sealing ring permits fluid flow in opposite directions.

1. Field of the Invention
The present invention relates to a fluid piston-cylinder unit in which a piston, movably carried by a piston rod, divides a cylinder into two working chambers, and a sealing valve closes a fluid flow path across the piston when the piston rod is stationary.
2. The Prior Art
DE 3,301,544 A1 discloses a piston-cylinder unit comprising a piston, which is carried for axial movement by a piston rod, and a cylinder divided into two working chambers by the piston. A sealing valve seals off a fluid flow connection between the two working chambers when the piston rod is in a stationary operating condition. The sealing valve includes a valve element consisting of an axially movable sealing ring in the form of a packing washer in conjunction with a valve seat. The problem in this piston-cylinder unit is that very precise finishing is required to achieve tightness of the sealing valve. A spring, which prestresses the packing washer on the valve seat, is arranged at the back of the washer. The spring is designed with a ground end coil. As a result, under some circumstances the force of the spring on the valve washer is not uniform, so that the washer may become slightly distorted. The resulting fluid leakage is to be avoided. Structural difficulties ensue from the fact that, on the one hand, a considerable annular clearance (see reference numeral 13) and, in addition, a valve opening (reference numeral 18) must be provided for satisfactory operation. The small radial space available limits the possible cross sectional area of the fluid connection between the working chambers.
DE 4,431,626 A1 discloses a piston-cylinder unit having a sealing valve wherein unlike large pressure-impacted surfaces, in conjunction with a ram pressure, hold the sealing valve in an open position. The logic of this valve design lies in that the sealing valve remains in the open position with the application of as small a force as possible. Once the sealing valve is opened, a pressurized piston-cylinder unit with gas prestress will continue to travel out until the unit is brought to a standstill by hand and a pressure equalization that releases the ram pressure is produced. The basic idea of this sealing valve is quite different from that of DE 3,301,544.
DE 3,301,266 A1 describes a gas spring with hydraulic or pneumatic attenuation as a slide-in safety device in the event of loss of pressure. The gas spring has a piston arranged on a piston rod, the piston on the side opposite the piston rod being provided with a piston bore. The piston bore contains a spring chamber, in which a helical spring or a pressurizing gas is arranged. The spring or gas biases a valve pin towards sealing engagement with a valve seat. In normal operation, the operating pressure of the gas spring is higher than the spring force of the helical spring so that the sealing valve is normally open. If the operating pressure in the gas spring drops, the helical spring seals the valve opening and thus prevents sudden retraction of the piston rod.
DE 2,653,552 C2 concerns a gas spring which is designed as a lifting aid for opening and holding tailgates and trunk lids of motor vehicles. The gas spring includes a cylinder filled with pressurized gas, a piston rod arranged displaceable coaxially in the cylinder and extending in a sealed manner out of one end of the cylinder. The piston rod carries a guide piston which sealingly engages the inner wall of the cylinder and which includes a pressure-dependent valve for holding the piston stationary against a specified push-in force exceeding the weight of the tailgate or of the trunk lid. The guide piston has at least one fluid flow channel for connecting the two working chambers. When the specified push-in force is exceeded, the valve opens to permit fluid flow through the channel, thereby permitting inward travel of the piston rod.

Piston-cylinder unit having a sealing valve


Various apparatuses and methods are disclosed. The system describes a pulse generator comprising a first stage configured to be powered by a first voltage; and a second stage configured to be powered by a second voltage different from the first voltage, wherein the second stage is further configured to generate a pulse in response to an input to the first stage comprising a trigger and feedback from the second stage.

1. Field
The present disclosure relates generally to electronic circuits, and more particularly, to pulse generation in dual supply systems.
2. Background
With the ever increasing demand for more processing capability in mobile devices, low power consumption has become a key design requirement. Various techniques are currently employed to reduce power consumption in such devices. One such technique involves reducing the operating voltage of certain circuits operating on a chip. As a result, different circuits on the chip operate at different voltages. Level shifters are used to convert one voltage level to another voltage level. Level shifters allow a signal to pass from one voltage domain to another voltage domain.
A common circuit used today in dual voltage systems is a one-shot pulse generator. A pulse is generated in a first voltage domain by the one-shot and then level shifted to a second voltage domain. The pulse is generated by gating a trigger with a delayed version of the trigger. The pulse-width is defined by the time between the trigger and the delayed trigger. However, the delay circuit may not track well with process, voltage and temperature (PVT) variations. The pulse width can be very narrow under extreme PVT conditions. This can cause a functional failure if the level-shifted pulse fails to switch from rail-to-rail. The only way to recover is by tuning the delay circuit. The can cost real estate and add timing complexities


A semiconductor structure and method for forming the same. The semiconductor structure includes (a) a substrate and (b) a chip which includes N chip solder balls, N is a positive integer, and the N chip solder balls are in electrical contact with the substrate. The semiconductor structure further includes (c) first, second, third, and fourth corner underfill regions which are respectively at first, second, third, and fourth corners of the chip, and sandwiched between the chip and the substrate. The semiconductor structure further includes (d) a main underfill region sandwiched between the chip and the substrate. The first, second, third, and fourth corner underfill regions, and the main underfill region occupy essentially an entire space between the chip and the substrate. A corner underfill material of the first, second, third, and fourth corner underfill regions is different from a main underfill material of the main underfill region.

1. Technical Field
The present invention relates to flip-chip technologies, and more specifically, to flip chip underfill in flip-chip technologies.
2. Related Art
In flip-chip technologies, chip solder balls are typically formed on top of a semiconductor chip and then the chip is flipped upside down and bonded to a substrate.
The difference in thermal expansion coefficients of the chip and the substrate may cause solder ball fatigue or cracking in the chip resulting in chip failure. Therefore, there is a need for a structure (and a method for forming the same) in which the difference between thermal expansion coefficients of the chip and the substrate does not cause solder ball fatigue or chip cracking as in the prior art.

Chip underfill in flip-chip technologies

International Business Machines Corporation


A multi-layered composite comprising a protective layer, a retaining layer, a conductive layer and a filler layer intermediate the retainer and conductive layers. The filler layer is impregnated with liquid absorbent particles. A protective layer having specific characteristic for protection against extreme temperatures, physical impacts and the like is specifically disclosed for use in combination with the retainer, filler and conductive layers. The protective layer provides additional protection of the person from catastrophic events such as exposure of a person to fire and/or severe impact such as may be caused by gunfire.

Many inventions appear in prior art which relate to providing composites and/or garments for the comfort and/or protection of a persons body. These inventions relate to: heating or cooling of a person's body; keeping the body wet or dry; the protection of the body from outside conditions of extreme heat or cold, as well as to the protection of the body from impact. The use of liquid absorbent composites has been utilized in many ways to aid in the effectiveness of such composites and garments. Examples of U.S. patents relating in one way or another to this art are as follows: U.S. Pat. Nos. 2,855,758; 3,429,138; 3,670,731; 3,971,373; 4,105,033; 4,133,055; 4,235,237; 4,429,001; 4,556,055; 5,113,666; 5,289,695; 5,328,759; 5,419,955; and 5,486,410.

Protective multi-layered liquid retaining composite


A device-forming region where a semiconductor device is formed is arranged on a substrate in the matrix of 2.times.2. A linear laser beam has a cross-section having a length longer than the width of the device-forming region. When the irradiation of the laser beam is performed, the region irradiated with the end portions of the linear laser beams overlapped with each other or brought into contact with each other, is made positioned outside the device-forming region.

The present invention relates to a laser processing method and a laser processing apparatus, and particularly, to an improvement of a throughput in an optical annealing step with respect to the manufacture of an insulated gate type semiconductor device such as a thin-film transistor (TFT) which is formed on a substrate having a crystalline silicon film of non-single crystal and other semiconductor devices.
Particularly, the present invention relates to the manufacture of a semiconductor device which is formed on an insulating substrate made of glass or the like and having a large area.
Recently, studies have been made of an insulated gate type semiconductor device including a thin-film like active layer (also referred to as active region) on an insulating substrate. Particularly, studies have been made earnestly of thin-film like gate transistors, so-called thin-film transistors (TFT). These transistors are classified by the material and crystalline state of a used semiconductor into an amorphous silicon TFT, a crystalline silicon TFT, and the like. The crystalline silicon is not a single crystal but a non-single crystal. Accordingly, the general term for these transistors is a non-single crystal TFT.
In general, the mobility of an amorphous semiconductor is small, so that it can not be used as a TFT which is required high sped operation. Further, since the mobility of a P-type amorphous silicon is extremely small, thereby being unable to manufacture a P-channel TFT (TFT of PMOS) so that it is impossible to form a complementary MOS circuit (CMOS) by combining the P-channel TFT with an N-channel TFT (TFT of NMOS).
On the other hand, the crystalline semiconductor has a mobility larger than that of the amorphous semiconductor, so that high speed operation can be achieved. By the crystalline silicon, not only TFT of NMOS but also TFT of PMOS can be obtained, so that it is possible to form a CMOS circuit.
The crystalline silicon film of non-single crystal has been obtained by thermally annealing an amorphous silicon film obtained by a vapor phase deposition method for a long time at an appropriate temperature (normally more than 600.degree. C.) or by irradiating it with the intense light such as a laser beam (optical annealing).
However, in the case where a glass substrate which is cheap and rich in workability, is used as an insulating substrate, it has been extremely difficult to obtain the crystalline silicon having a sufficiently high mobility (so high that a CMOS circuit can be formed) by only the thermal annealing. This is because the above-mentioned glass substrate has generally a low distortion point temperature (about 600.degree. C.), so that it is impossible to increase the substrate temperature up to a temperature required to form the crystalline silicon film having the sufficiently high mobility.
On the other hand, in the case where the optical annealing is used to crystallize a silicon film based on a glass substrate, it is possible to give a high energy to only the silicon film without increasing the substrate temperature to a very high temperature. Thus, the optical annealing technique is regarded as very effective for crystallizing the silicon film based on the glass substrate.
At present, a high power pulse laser such as an excimer laser is most preferable as an optical source for the optical annealing. The maximum energy of this laser is very large as compared with a continuous-wave laser such as an argon ion laser, so that it has been possible to improve the throughput by using a large spot of more than several cm.sup.2. However, when a normally used square or rectangular beam is used, it must be moved up and down and right and left to process one substrate having a large area. Thus, there is a room for improvement from the viewpoint of the throughput.
Concerning this, much improvement has been obtained by transforming a beam into a liner beam to extend the length of the beam (largeness of the cross section of the linear beam in the longitudinal direction) over a substrate to be processed, and by moving this beam relatively to the substrate to scan.
Here, the scanning means that irradiation of the laser beam is performed while the linear laser beam is moved in the line width direction (direction orthogonal to the longitudinal direction of the cross section of the linear beam), and the irradiated regions are overlapped with each other not to separate the irradiated regions. Also, in general, when the irradiation of the linear laser beam is performed for a large area, the scanning paths are made parallel to each other.
Further, before the optical annealing, when the thermal annealing is carried out, it is possible to form a silicon film having more superior crystallinity. With respect to the method of the thermal annealing, as disclosed in Japanese Patent Unexamined Publication No. Hei. 6-244104, by using the effect that an element such as nickel, iron, cobalt, platinum, or palladium (hereinafter referred to as crystallization catalytic element or simply referred to as catalytic element) accelerates the crystallization of amorphous silicon, the crystalline silicon film can be obtained by the thermal annealing at a lower temperature for a shorter time than a normal case.
However, in the above irradiation of the linear laser, in relation to the maximum energy thereof, the length of the linear laser beam (largeness of the cross section of the laser beam in the longitudinal direction) has been limited to about 20 cm at best.
If the processing is performed by the linear laser beam having a length longer than the limit, the energy density of the laser beam becomes insufficient to, for example, crystallize the amorphous silicon film. Thus, when a substrate having a large area is used and laser processing is performed for a region longer than the length of a linear laser beam, it has been necessary to perform scanning of the laser beam up and down and left and right, that is, both in the line width direction and in the longitudinal direction. FIG. 13(B) schematically shows scanning paths of a conventional laser beam.
FIG. 13(A) is a sectional view of a linear laser beam, and FIG. 13(B) is a view showing a surface to be irradiated viewed from the above. As shown in FIG. 13(A), an end portion la of a linear laser beam 1 is not completely rectangular, and the energy density in this portion is dispersed.
As shown in FIG. 13(B), the scanning of the linear laser beam 1 is performed along two scanning paths 2 and 3. For example, after the downward scanning of the linear laser beam 1 is performed along the left scanning path 2, the downward scanning is performed along the right scanning path 3. At this time, it is necessary to perform scanning so that the end portions 1a of the linear laser beams 1 are overlapped with each other. Then, it becomes a problem how to overlap the end portions la of the linear laser beams 1. In FIG. 13(B), a region 4 shown in a rectangle is a region where scanning is performed by the overlapped end portions la of the linear laser beams 1 in the surface to be irradiated.
However, in general, since it is difficult to control the energy density at the end portion 1a of the linear laser beam 1, semiconductor devices formed in the region 4 and in the neighborhood thereof are of extremely uneven characteristics as compared with devices formed in other region. Thus, the semiconductor material in the region 4 is not suitable for processing of semiconductor devices.
As a countermeasure to the above problem, by irradiation of a laser beam through a slit, the end portion in the longitudinal direction in which the control of energy density is difficult, is shielded to shape the end portion of the laser beam. FIG. 14(A) is a sectional view showing a linear laser beam shaped by the slit, and FIG. 14(B) is a schematic view showing scanning paths of the laser beam and is a view showing a surface to be irradiated viewed from the above.
As shown in FIG. 14(A), through the slit, an end portion 5a of a laser beam 5 is shaped into a rectangle, so that the distribution of the energy density in the end portion 5a becomes uniform than the linear laser beam 1 shown in FIG. 13(A). As shown in FIG. 14(B), when the irradiation of the linear laser beam 5 is performed, for example, the following scanning steps may be made: after the downward scanning of the linear laser beam 5 is performed along a left scanning path 6, the downward scanning is performed along a right scanning path 7. At this time, the scanning is performed so that the end portions 5a of the linear laser beams 5 are overlapped with each other. However, since the end portion 5a of the laser beam 5 is shaped into a rectangle, and the energy density distribution is uniform, it is sufficient to overlap the end portions 5a of the linear laser beam 5 with each other to the extent that the end portions 5a are brought into contact with each other, as shown by reference numeral 8. Thus, it is possible to reduce the region 8 where the ends 5a are overlapped with each other.
However, even if the energy density in the end portion 5a of the laser beam 5 is controlled by using the slit, the semiconductor devices formed in the region 8 to be scanned with the overlapped end portions 5a of the laser beam 5, are of remarkably uneven characteristics as compared with devices formed in other region.

Semiconductor Energy Laboratory Co. Ltd.


An occupant detection system includes occupant sensors on each of plural seats, first resistors in connection to each of the occupant sensors with different resistance values, a power supply line that supplies electric power to the sensors and resistors from a power source by connecting those parts and the power source, and a control unit that detects occupancy of each of the plural seats based on an electric current value of the power supply line. The occupant detection system having the above configuration detects the occupancy of each of the plural seats without increasing the number of input terminals on the control unit.

In recent years, various techniques for detecting an occupant in a seat of a vehicle has been proposed. That is, an occupant detection system is used mainly to detect respective occupants in driver's and passenger's seat in a front row of the vehicle for use with devices such as an air-bag system, a seat belt warning system or the like. However, a requirement for providing the occupant protection system for the occupants in rear seats is on a rise, and that leads to a demand for detecting more occupants in the vehicle. Therefore, a conventional occupant detection system disclosed in, for example, Japanese patent documents JP-A-H10-39045 and JP-A-2005-153556 (latter one is published as US publication document No. 20050140210) and other reference for use in the passenger's seat is also disposed on the rear seat for achieving the goal of rear seat occupant detection.
In this case, a control unit in the occupant protection system detects the occupancy of each of the seats based on occupant sensors disposed on each of the seats. However, according to the configuration of the occupant protection system disclosed in the above documents, input terminals on the control unit for connection to the occupant sensors increases in number.

Occupant detection system and occupant protection system


Methods and apparatus for tracking and evaluating the relative value, such as the net present value, of medical services provided to patients associated with third party payors (“TPPs”). Under various embodiments of the present invention, the relative value of medical services is considered in evaluating whether to enter into an agreement with a TPP, whether to accept a new patient, when and for how long to schedule a patient appointment, and how long a physician should meet with the patient. Methods and apparatus for improving the efficiency of a medical office are also disclosed whereby a physician may more effectively supply a patient with relevant information and provide prescriptions, record billing information, order supplies, and collect payment for services provided. Methods and apparatus for improving security within a medical office and reducing employee fraud are also disclosed.

1. Field of the Invention
The present invention relates generally to determining and tracking a relative value, such as the net present value, of services provided by medical practitioners and staff. More particularly, the present invention relates to coordinating and tracking medical services and related information, and evaluating managed care organization payment patterns for medical services to reduce medical practitioner losses from unpaid, partial-paid and late-paid services. The invention is an integral part of an overall process of providing medical services designed to minimize costs, and restructure medical offices to take advantage of information technologies, wireless systems, local area networks, wide area networks, and the Internet to reduce operating costs and maximize efficiency. The invention also relates to methods and apparatus for streamlining medical practices to more efficiently serve patients and improve physician profitability.
2. State of the Art
The conventional practice of medicine is the result of centuries of improvements in medical technology. Yet, even as medical technologies have improved, the foundation of the medical practice has remained the same. Patients schedule an appointment, are greeted when they arrive for their appointment, and then meet with one or more physicians or other medical services providers. Medical services providers evaluate each patient, diagnose any problems, and recommend tests, prescriptions and other medical procedures as necessary. The patient is then charged for the medical services provided.
Another recent aspect of medical practice relates to medical services providers' relationships with insurance companies, medical managed care organizations or other third party payors ("TPPs"). As used herein, the term "TPP" is intended to include any organization through which one or more patients receive medical services to be billed through a common payment manager which may pay all or a portion of the charges to a medical practice or facility. Examples of TPPs include, but are not limited to, insurance companies, health maintenance organizations ("HMOs"), physician-hospital organizations ("PHOs"), managed services organizations ("MSOs"), preferred provider organization ("PPOs"), various physician alliances, physician-hospital and physician-medical facility agreements, and Medicare, Medicaid or other indigent, uninsured or under-insured payor supplement organizations.
A TPP may enter into separate or joint agreements with physicians and other medical services providers. Then, through agreements with patients in exchange for risk-adjusted paid premiums to the TPP, the TPP pays all or part of a patient's medical expenses. The level of care (i.e. type of service, access to service, duration of service, type and amount of medication, etc.) is adjusted by the TPP to set premiums and determine profitability. Medical services providers, based on their agreements with a particular TPP, agree to charge no more than a specified rate for each type of medical service provided according to a predetermined fee schedule. In exchange for agreeing to the predetermined fee schedule, medical services providers are placed on the TPP's list of preferred providers, or some other list which may determine what portion of the allowable fees the TPP will pay and what, if any, portion of the allowable fees the patient will pay. Other TPPs may agree to pay for all or a portion of medical services regardless of which medical services provider the patient visits. As used herein, the term "medical services provider" is intended to include one or more medical practitioners of any medical field or specialty which may have an opportunity to bill for medical services provided through a TPP. The term "medical services provider" specifically includes, but is not limited to, physicians in any medical field or specialty, nurses, medical assistants and other medical staff such as medical administration and counseling, and any offices, groups or groups of associated offices employing one or more physicians, independent medical contractors, nursing facilities, long and short-term care facilities, off-site providers (home care providers), occupational and physical therapists, behavioral health providers and ambulatory care facilities.
TPPs are formed as for profit businesses and generate profits from coordinating the delivery of medical care and there are benefits to medical service providers who sign agreements with TPPs. Particularly in more recent years, however, medical services providers who charge for services through TPPs have experienced problems.
One of the problems experienced by medical services providers is that TPPs have intentionally rationed parts of the health care delivery system to minimize costs and maximize profit. Examples of TPP rationing include: limiting allowable services, limiting access to medical care, increasing patient premiums, increasing the patient responsibility portion of medical costs, reducing allowable fees for providing medical services, increasing physician liability, decreasing, delaying or refusing payment to medical services providers, and driving up the costs of medical services providers who attempt to claim outstanding unpaid or partially paid claims. These "adjustments" to the process of compensating medical services has the net effect of reducing physician income. The United States Consumer Price Index (CPI) has steadily increased at the rate of 2% to 3% per year since 1994. Nevertheless, physician net income has steadily decreased from a 2.4% increase in 1994 to a 5.8% decrease in 1997. Studies show that physicians are working longer hours, face increasing liability, and have experienced a significant drop in job satisfaction.
Attempts have been made to increase provider income by streamlining medical practices through medical management systems. FIG. 1 illustrates a flow diagram of a conventional medical services process such as that employed by a medical services provider dealing with a TPP. For many TPP plans, prior to visiting a specialist, a referral from a primary care practitioner is required. The primary care physician must request permission for a referral from the TPP. The TPP must then issue a formal approval for a referral to the requesting physician/service provider. The authorization must also be in the specialists' office prior to a patient's visit to the specialist. Many authorizations state that the TPP's approval does not guarantee payment. Without the formal approval, however, no payment will be made to the specialist for medical services provided. More than 98% of referral requests are eventually approved, but the wait to obtain an approval may extend several weeks. The result of such approval requirements may significantly delay the delivery of health care, potentially harm the patient, and delay compensation for the medical services provided.
With a proper referral 2, if required, authorization 4 from the TPP for the medical services requested must be obtained. Conventionally, authorization 4 is accomplished by a medical services provider staff member contacting the TPP by phone or facsimile to exchange information regarding a patient requesting medical services. The exchanged information typically includes such information as the TPP plan with which the patient is associated, the type of services requested, and the name of the medical services provider who will provide the services. The TPP may refuse authorization or automatically authorize specified services, such as routine physician visits, based on the contract terms.
Once authorization 4 is granted, or in conjunction therewith, a patient's demographics 6 are recorded in the patient's records. To record a patient's demographics, conventionally, a patient completes a form including such information as the patient's name, addresses, relevant numbers, guarantor, employer or TPP information, summary of medical history, allergies, and the like. Once all or part of a patient's demographics are recorded 6, or in conjunction therewith, the patient is scheduled 8 for an appointment. The decision of when to schedule a patient for an appointment conventionally involves such factors as: the type of services requested, medical services provider availability, medical office resources availability and patient condition urgency. After an appointment is scheduled 8, the patient's relevant medical records are retrieved 10 prior to the patient's appointment.
At the time of the patient's appointment, the patient is welcomed by medical office staff and signs-in 12. Sign-in 12 signals to the medical staff that the patient has arrived, and typically also involves collecting a co-pay amount from the patient. The exact amount of the co-pay, whatever it may be, must be determined and collected prior to providing medical services. Co-pay amounts vary considerably and can fluctuate without warning. Sign-in 12, however, may also involve a more detailed record by the patient of the patient's medical history, a description of symptoms, or other patient demographics as needed. Various medical services providers request and retrieve different information from patients at different times throughout the process of providing medical services. When a patient's turn to be seen has arrived, the patient is conventionally greeted by a nurse or medical assistant who confirms basic patient information such as name, address, insurer and purpose of visit, and prepares the patient to be seen by the primary medical services provider, such as a physician or a nurse practitioner, for example by checking the patient's weight, blood pressure, pulse, medications, etc.
The patient is then seen by a primary medical services provider 16, such as a physician, who evaluates the present complaints of the patient or otherwise responds to the purpose for the patient visit, such as by performing a routine physical, the primary medical services provider diagnoses any problems found during the examination, recommends any treatment for problems found, prescribes any medications, procedures, tests, surgery, or the like, and explains the patient's condition to the patient. Either simultaneously with or subsequent to meeting with the patient, the primary medical services provider either dictates for later transcription, or otherwise records a report to the file describing the examination, diagnosis, recommendations for treatment, prescriptions and the like. A copy of the report is generated, signed and sent to the referring entity as well as being filed in the patient's records.
Following the patient's visit, the medical services provider bills 18 the patient, either directly or through the patient's TPP. Completed medical services are typically "checked-off" on a printed form and sent to a data entry clerk to enter diagnoses, codes and "list" prices into the existing office accounting system. Charges are forwarded to the TPP at the billing clerk's convenience. Once the TPP receives the charges, they are reviewed and eventually paid according to the rules and policies of the TPP who may pay according to their fee schedules on a time frame based on their cash flow requirements. Each office independently verifies payment accuracy and follows-up on late payments or non-payments. Gross charges are posted to a traditional accounts receivable system. Payments, discounts and write-offs are entered as received in the "explanation of benefits." The operation of medical services providers, including the details of the process as illustrated in FIG. 1, is well known to those of ordinary skill in the art.
One example of a company which provides computer systems to assist in managing medical services is Datamedic Corporation of Massachusetts. Datamedic offers software/hardware packages for patient scheduling, billing, claims processing and collections. In particular, Datamedic's PMstation system operates from the medical services provider's in-house computer server and may be used in any Windows®-based system. The PMstation system assists in coordinating multiple resources for a single patient visit such as a physician, nurse, examination room, examining instruments, etc. Datamedic also sells CHARTnote and CHARTstation systems which integrate with the PMstation system to store codified data directly into a local patient database to eliminate the need to separately transcribe and record the information into the patient's file, to reduce paper records, and to more easily access patient records. The CHARTstation system also includes features such as: an autofax to immediately send a letter or report to a referring clinician, a full history of a patient's prior visits, allergies and laboratory results, patient record database search and electronic prescription writing capabilities, risk management alerts such as drug-to-drug and drug allergy warnings and automatic TPP codings for payment. The Datamedic systems may be accessed from any Windows NT/95 computer, including handheld, pen-based computers such as those from Fujitsu and Mitsubishi.
Another medical management computer system sold to medical services providers is that distributed by QuadraMED of San Rafael, Calif. The QuadraMED Affinity system focuses on centralizing clinical and financial data by providing a database of patient management information such as insurer, age, gender, contact information, visit schedules and chart location. The database of patient management information is centralized by providing access to it through the Internet via a secured Web browser, allowing medical services providers to retrieve real-time patient management information from any location with a connection to the Internet. The QuadraMED system also manages financial and clinical information and attempts to increase practice profitability by checking for and reducing redundant data entry and generating summary and detailed management reports on practice efficiency.
Yet another medical management computer system sold to medical services providers is that distributed by Healtheon/WebMD of Atlanta, Ga. The Healtheon/WebMD system integrates numerous sub-systems which include sub-systems to confirm and process referrals and authorization, submit and track insurance claims for collecting, order and check laboratory tests, distribute text-based and administration information across email, fax, mail, and retrieve patient information from a common patient database. One sub-system of the Healtheon/WebMD system permits medical services providers to access medical dictionaries, encyclopedias, databases and other literature electronically for research purposes. Another sub-system permits medical services providers to select a lab test, confirm patient eligibility based on insurance coverage and then submit the test request electronically. Medical services providers may also access individual completed test results through the Internet. Yet another sub-system of the Healtheon/WebMD system permits a medical services provider to generate medication prescriptions and refill medication prescriptions electronically. The prescription sub-system also provides a patient's medication history, drug reference information, clinical alerts and drug-drug interactions to both authorized medical services providers and to patients.
The Healtheon/WebMD system is a transaction-based system that improves the transfer and storage of data through the Internet. It does not specifically address physician cost/profitability, although it does speed-up many labor intensive transactions to make the physician and other health care entities more efficient.
Conventional medical management systems presently sold focus on accepting patient demographics, scheduling patient visits, and creating charges and submitting them to a TPP or other payor. While a number of systems are available, most concentrate on a traditional accounts receivable system. These systems do not attempt to track TPP payments, nor do they assist in more efficient time management based on a value of the medical services provided against the resources required to deliver those services.
Fee schedules may be provided by an insurer. Such fee schedules are independently produced by TPPs and may or may not be linked to "official" Medicare or other fee schedules. More importantly, however, the allowable fee schedule amounts have very little, if anything, to do with the actual value of the promise of future payment by a particular TPP to a medical services provider. Because each TPP has a different method, timing, and strategy for payment, has a different financial strength behind the promise of payment, and has a different risk of becoming insolvent before providing payment, each TPP's promise for payment does not actually have the same practical value.
A.M. Best Company of Oldwick, N.J., generates an annual listing of its ratings of insurance companies, each insurance company in the list having assigned thereto a rating based upon A.M. Best Company's opinion of the financial strength of each company and its ability to meet its financial obligations as of the date of the listing. Not all companies are listed, however, and the listings do not provide an indication of the payment methods and strategies employed by the insurance companies or rankings for those insurance companies who have requested their rankings not be listed. Furthermore, the A.M. Best Company's listing does not provide an indication of the future likelihood of payment, or whether the insurance company has a worsening cash flow at any point after the annual data is collected.
For many patients associated with TPPs, there is a patient co-pay required at the time of a visit with a medical services provider. The co-pay amount may be only $10 or $20, but for a medical services provider with several physicians, there may be a large amount of co-pay money at the end of a day. One problem sometimes experienced by medical services providers is employees stealing the co-pay money rather than placing it in the account where it belongs. To avoid being caught, the employees may adjust the data entry records to indicate that they money was paid and accounted for at a different time so that a daily accounting will not reveal the missing money. Eventually, the fact that money is missing may become apparent, but by that time it may be difficult to determine who made the changes, a significant amount of money may have been stolen, and the money may already be spent and practically uncollectable. Another problem sometimes experienced by medical services providers is employees mis-stating their hours worked. When medical employees work at less than ideal efficiency and/or mis-state hours worked, physician profits are affected and unnecessary staffing adjustments may be made to accommodate the sharply increased work-load created by managed care. Appropriate staffing levels for the workload, accurate time keeping and employee accountability must be maintained to control medical costs. Medical facility loss due to employee theft of time, supplies, and the like is commonly called "shrinkage."
Additionally, conventional medical management systems still include many redundant activities which may be improved upon to enable medical practitioners to more efficiently and effectively treat patients. Therefore, it is desirable to have a medical management system which intelligently schedules patient visits and evaluates the efficiency of a medical practice based on a more reliable measurement of the value of the patient's method of payment. It is further desirable to simplify medical practice activities to increase efficiency and decrease fraud losses and, therefore, increase profits for medical practitioners.

Method and apparatus for tracking the relative value of medical services


A web can comprise a substantially continuous fiber mass and a separation means dispersed into the fiber. The web having a preferred thickness resulting from forming a polymer material and a particulate into a fine fiber layer can have a variety of end uses. A filtration media can include a structure comprising such a web of fine fiber and a substantial volume of particulate embodiment of the separation means. The resulting fine fiber structure provides an improved filtration medium having substantial depth, thickness, and a layered structure. The improved properties of the web results from inclusion of the separation or spacer particulate.

Filters can be made of fine fiber webs of polymer materials. Polymer webs can be made by electrospinning, extrusion, melt spinning, air laid and wet laid processing, etc. The manufacturing technology of filter structures is vast for obtaining structures that can separate the particulate load from a mobile fluid stream. Such filtration media include surface loading media and depth media in which these media can be produced in a variety of geometric structures. Principles relating to the use of such media are described in Kahlbaugh et al., U.S. Pat. Nos. 5,082,476; 5,238,474; 5,364,456 and 5,672,399. In any filter structure containing any arbitrary selected filtration medium, the filter must remove a defined particle size, and at the same time, have sufficient lifetime to be economically justifiable in its particulate removing properties. Lifetime is generally considered to be the time between insulation and the time a filter obtains sufficient particulate load such that the pressure drop across the filter is greater than a predetermined level. An increased pressure drop can cause filter bypass, mechanical filter failure, fluid starvation, or other operating problems.
Nanofiber filter media have fueled new levels of performance in air filtration in commercial, industrial and defense applications where efficiency requirements have been low in comparison to HEPA (High Efficiency Particle Air) or ULPA (Ultra Low Penetration Air) levels.
Recent advancements in the nanofiber enhanced filtration field have extended the usability of nanofibers into applications with higher filtration efficiencies. In particular, these nanofiber matrices provide comparable performance to other commercially available HEPA media composed of sub-micron glass or expanded-PTFE membranes. Such performance is shown along with benefits of the technology. Nanofiber filter media is a viable solution in high efficiency applications with strict performance requirements.
A web can comprise a substantially continuous fiber mass and dispersed in the fiber a fiber spacer, spacer particulate or web separation means. The spacer or separation means causes the fiber web to attain a structure, in which the fiber mass or web portion, even though filled with particulate, has reduced solidity, separated fibers or separated web portions within the structure, increased the depth of the fiber web without increasing the amount of polymer or the number of fibers within the web. The resulting structure obtains improved filtration properties such as resistance to increased pressure drop, improved Figure of Merit, permeability and efficiency. Filtration efficiency is the characteristic of the filtration media that is related to the fraction of the particulate removed from the mobile stream. Efficiency is typically measured by a set test protocol defined below.
Surface loading filter media often comprise dense mats of fiber having a non-woven structure that are placed across the path of a mobile fluid stream. While the mobile fluid stream passes through the structure of the formed non-woven fibers, the particulate is typically removed from the streams at the filter surface with a certain efficiency and remains on the surface. In contrast to surface loading structures, depth media typically include a relatively (compared to surface loading media) thick structure of fiber having a defined solidity, porosity, layer thickness and efficiency. Depth media and in particular, gradient density depth media are shown in Kahlbaugh et al., U.S. Pat. Nos. 5,082,476; 5,238,474 and 5,364,456. In general, depth media act in filtration operations by impeding the particulate loading in a mobile fluid stream within the filter layer. As the particulates impinge the depth media fibrous structure, the particulate remains within the depth media and typically distributed onto and held with internal fibers and throughout the filter volume. In contrast, surface loading media typically accumulate particulate in a surface layer.
Groeger et al., U.S. Pat. No. 5,486,410, teach a fibrous structure typically made from a bicomponent, core/shell fiber, containing a particulate material. The particulate comprising an immobilized functional material held in the fiber structure. The functional material is designed to interact with and modify the fluid stream. Typical materials include silicas, zeolite, alumina, molecular sieves, etc. that can either react with or absorb materials in the fluid stream. Markell et al, U.S. Pat. No. 5,328,758, uses a melt blown thermoplastic web and a sorbtive material in the web for separation processing. Errede et al., U.S. Pat. No. 4,460,642, teach a composite sheet of PTFE that is water swellable and contains hydrophilic absorptive particles. This sheet is useful as a wound dressing, as a material for absorbing and removing non-aqueous solvents or as a separation chromatographic material. Kolpin et al., U.S. Pat. No. 4,429,001, teach a sorbent sheet comprising a melt blown fiber containing super absorbent polymer particles. Deodorizing or air purifying filters are shown in, for example, Mitsutoshi et al., JP 7265640 and Eiichiro et al., JP 10165731.
While both surface loading and depth media have been used in the past and have obtained certain levels of performance, a substantial need remains in the industry for filtration media that can provide new and different performance characteristics than formerly obtained.

Reduced solidity web comprising fiber and fiber spacer or separation means


Provided are methods for detecting or isolating circulating tumor cells (CTCs) in a subject. The methods may include detecting the expression of at least one epithelial mesenchymal transition (EMT) biomarker. Further provided are kits for detecting or isolating CTCs. The kits may include antibodies to at least one EMT biomarker. Further provided are methods of predicting the responsiveness of a subject to a cancer drug, methods of targeting delivery of a cancer drug in a subject, methods of providing a cancer prognosis to a subject, and methods for following the progress of cancer in a subject.

Most metazoan cells can be classified as either epithelial or mesenchymal based on morphology, behavior and molecular signatures. Epithelial tumor cells can become mesenchymal cells and vice versa via phenotypic transitions, a process known as epithelial plasticity. Epithelial cells are generally polar in the apico-basal direction, adherent to adjacent cells in the plane perpendicular to the polarity, and non-motile in the polar direction. Mesenchymal cells, in contrast, lack polarity, do not form tight interactions with neighboring cells, and are motile. In adult animals, epithelial and mesenchymal cells remain stably in one state or the other; that is, an epithelial cell does not change its properties and become mesenchymal. During development, however, epithelial cells of the early embryo give rise to all three embryonal layers (endoderm, mesoderm and ectoderm), which include mesenchymal cells (Hay, E.D., et al. Am. J. Kidney Dis. 1995, 26, 678-690). Therefore, these early embryonal cells have the ability to transition between epithelial and mesenchymal states. Embryos have been shown to undergo epithelial-mesenchymal transitions (EMTs) as well as mesenchymal-epithelial transitions (METs) (Acloque, H., et al. J. Clin. Invest. 2009, 119, 1438-1449).
Epithelial plasticity (EP) refers to the reversible loss of the epithelial cellular phenotype, a process known to occur during cancer metastasis. This EP biology has been linked in multiple studies to the risk of cancer metastasis and the acquisition of mesenchymal and/or stemness properties through the EMT process. EMT has been linked to chemoresistance, invasion, intravasation, and dissemination in multiple preclinical models of cancer. The MET process, which results in the re-expression of the epithelial phenotype, is also likely of great importance in development and metastasis and has been linked to metastatic colonization and survival of tumor cells in the metastatic niche. For example, in prostate cancer, mesenchymal biomarkers may be upregulated during androgen deprivation in prostate cancer cell lines, animal models, and in patient tumor specimens. Moreover, these biomarkers are plastic, revert upon replacement of testosterone, and are linked to an increased metastatic propensity and chemoresistance. Mesenchymal-like tumor cells may better promote local tumor invasion and intravasation/extravasation, but epithelial tumor cells may be necessary for eventual survival and proliferation in the metastatic niche, illustrating the potential relevance of the dual nature of EP in mediating the full process of metastasis.
Circulating tumor cells (CTCs), which are cells that have detached from a primary tumor and circulate in the bloodstream, have potential prognostic, predictive and surrogate implications in oncology. CTCs may constitute seeds for subsequent growth of additional tumors (metastasis) in different tissues. Thus, detection of CTCs can provide a diagnosis and/or prognosis for overall survival and therapeutic implications in subjects with cancers such as metastatic prostate and breast cancer. The number of CTCs in any patient sample (e.g., a blood sample) can be very small, which can make detection difficult. Current methods for detecting CTCs are based on the detection of epithelial cell adhesion molecule (EpCAM) expression, which is a biomarker associated with epithelial cells. However, during the process of metastasis, circulating tumor cells (CTCs) may lose their epithelial phenotype and acquire a mesenchymal phenotype that is not sufficiently captured by existing epithelial-based CTC technologies. During metastasis, tumor cells may exist as a spectrum of epithelial to mesenchymal phenotypes. CTCs may lose their epithelial phenotype and acquire a mesenchymal phenotype, which may not be captured with existing epithelial-based CTC technology and thus lead to the under-detection of CTCs under circumstances where cells undergo a decrease or loss of EpCAM expression, such as during biologic processes including EMT. Because of the role CTCs can play in the diagnosis, monitoring, and prognosis of disease in patients having cancer, any shortcoming in the detection technology needs to be addressed by the art.
There is recent evidence to suggest that CTCs with a mesenchymal phenotype are missed by CELLSEARCH® and other epithelial-based technologies. Accordingly, there is a need for methods and systems for capturing CTCs that do not rely on existing capture technologies, and methods for correlating CTC detection to diagnosis, monitoring, and prognosis of disease in cancer patients.

Method of isolating circulating tumor cells