A method and apparatus for probing the chemistry of a single droplet are provided. The technique uses a variation of the field-induced droplet ionization (FIDI) method, in which isolated droplets undergo heterogeneous reactions between solution phase analytes and gas-phase species. Following a specified reaction time, the application of a high electric field induces FIDI in the droplet, generating fine jets of highly charged progeny droplets that can then be characterized. Sampling over a range of delay times following exposure of the droplet to gas phase reactants, the spectra yield the temporal variation of reactant and product concentrations. Following the initial mass spectrometry studies, we developed an experiment to explore the parameter space associated with FIDI in an attempt to better understand and control the technique. In an alternative embodiment of the invention switched electric fields are integrated with the technique to allow for time-resolved studies of the droplet distortion, jetting, and charged progeny droplet formation associated with FIDI.

In the past twenty years, charged droplets and strong electric fields have quietly revolutionized chemistry. In combination with an atmospheric-sampling mass spectrometer, charged droplets containing biomolecules or polymers have become a source for desolvated, gas-phase ions of these analytes. The process by which charged droplets evaporate is remarkably "soft" in that the process imparts little to no energy to the resulting ions. One technique, electrospray ionization (ESI), is the current "state of the art" for biomolecule mass analysis.
A schematic of the electrospray process is shown in FIG. 1. Here an analyte-containing liquid is pumped through a capillary needle. A high voltage source establishes an electric field between the needle and a plate. Sufficiently high voltages produce strong fields within the liquid itself drawing the liquid to a tip as it exits the needle. From this tip, commonly referred to as a Taylor cone, the liquid sprays outward as charged droplets that are accelerated in the electric field toward the plate. When the plate contains an inlet to a mass spectrometer, analyte within the charged droplets may be mass analyzed. (See, e.g., Electrospray Ionization Mass Spectrometry; Cole, R. B., Ed.; John Wiley and Sons: New York, 1997, the disclosure of which is incorporated herein by reference.)
The phenomenon of electrospray was investigated long before it was applied to the study of gas phase ions transferred from solution. In 1750, French clergyman and physicist Jean-Antoine (Abbé) Nollet reported the earliest known reference to electrospray, over two hundred years before the term was coined. He demonstrated that water flowing from a vessel would aerosolize when the vessel was electrified and placed near electrical ground. He also observed that "a person, electrified by connection to a high-voltage generator, would not bleed normally if he were to cut himself; blood would spray from the wound." (For discussion, see ORNL Review, State of the Laboratory, vol. 29 no. 1-2 1995, the disclosure of which is incorporated herein by reference) Roughly one hundred years later, Lord Kelvin designed an apparatus consisting of two liquid nozzles connected to opposite collection reservoirs. Small statistical differences in charging between water dripping from the nozzles quickly led to kilovolt differences and electrosprays at the nozzles. (See, e.g., Smith, J. N. Fundamental Studies of Droplet Evaporation and Discharge Dynamics in Electrospray Ionization, California Institute of Technology, 2000.)
In the early twentieth century, refined experimental techniques allowed for a more rigorous understanding of the electrostatics and electrodynamics of these phenomena. John Zeleny classified the formation of ethanol electrosprays through photographs. (See, e.g., Zeleny, J. Phys. Rev. 1917, 10, 1.) The sprays characterized in Zeleny's work are structurally similar to those employed for mass spectrometry today in which liquid is drawn into a conical shape before breaking into a fine mist of charged droplets. This work was followed by rigorous studies of the field-dependent deformation of soap films over cylindrical tubes by Wilson and Taylor. The conical shape of these films resembled Zeleny's observations of ethanol, and indeed has come to be termed the "Taylor cone" based on later theoretical work by G. I. Taylor. (See, e.g., Taylor, G. Proc. R. Soc. London, Ser. A 1964, 280, 383; and Taylor, G. Proc. R. Soc. London, Ser. A 1966, 291, 159, the disclosures of which are incorporated herein by reference.)
By the middle of the twentieth century, electrospray had become a popular painting technique. Reports by Hines, Tilney and Peabody, and several patents demonstrate the ease with which paint is atomized and applied to vehicles, housewares, and various metal goods. (See, e.g., Hines, R. L. J. Appl. Phys. 1966, 37, 2730; and Tilney, R.; Peabody, H. W. Brit. J. Appl. Phys. 1953, 4, S51, the disclosures of which are incorporated herein by reference.) However, it was not until 1968 that electrospray was introduced as a scientific tool. Dole and coworkers employed electrospray ionization to transfer high molecular weight polystyrene ions into the gas phase from a benzene/acetone solution. (Dole, M.; Mack, L. L.; Hines, R. L.; Mobley, R. C.; Ferguson, L. D.; Alice, M. B. J. Chem. Phys. 1968, 49, 2240, the disclosure of which is incorporated herein by reference.) Their combination of electrospray and nozzle skimmer/pumping systems are similar to those employed today to transfer the charged species from atmospheric pressure into the vacuum system for analysis. Despite this novel approach, two decades would pass before the technique gained wide acceptance.
In the 1980s John Fenn and coworkers revolutionized the field of mass spectrometry by making electrospray easy and practical for the analysis of large biomolecules and polymers. Fenn's contributions to the body of knowledge surrounding electrospray culminated in his sharing of the 2002 Nobel prize in chemistry. Fenn and coworkers presented a series of papers that permanently established electrospray as a tool to introduce dissolved analytes including low molecular weight cationic clusters, negative ions, polyethylene glycol, and several biomolecules into the gas phase for mass analysis. (See, e.g., Yamashita, M.; Fenn, J. B. J. Phys. Chem. 1984, 88, 4451; Yamashita, M.; Fenn, J. B. J. Phys. Chem. 1984, 88, 4671; Wong, S. F.; Meng, C. K.; Fenn, J. B. J. Phys. Chem. 1988, 92, 546; and Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. Science 1989, 246, 64, the disclosure of which are incorporated herein by reference.) They noted that electrospray imparts multiple charges to large biomolecules and polymers thus lowering the m/z value allowing biomolecule analysis on mass spectrometers having only a modest m/z range. As a result of all this investigation and development, ESI-MS has become a popular tool for studying noncovalent interactions and characterizing biomolecules. Cole reviews the present state and the diverse applications of electrospray ionization. (Electrospray Ionization Mass Spectrometry; Cole, R. B., Ed.; John Wiley and Sons: New York, 1997, the disclosure of which is incorporated herein by reference.) More recent research has considered a broad range of applications from the technologically important processes of electrostatic spraying to the revolution in mass spectrometric studies of biological molecules made possible by electrospray ionization. (See, e.g., Bailey, A. G. Electrostatic spraying of liquids; Wiley: New York, 1988; Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. Science 1989, 246, 64; Yamashita, M.; Fenn, J. B. J. Phys. Chem. 1984, 88, 4451; Electrospray Ionization Mass Spectrometry; Cole, R. B., Ed.; John Wiley and Sons: New York, 1997; Kebarle, P. J. Mass Spectrom. 2000, 35, 804; Grimm, R. L.; Beauchamp, J. L. Anal. Chem. 2002, 74, 6291; and Smith, J. N.; Flagan, R. C.; Beauchamp, J. L. J. Phys. Chem. A 2002, 106, 9957, the disclosures of which are incorporated herein by reference.)
Although the electrospray process is relatively straightforward to implement as an analytical tool for biomolecule mass analysis, research continues to elucidate the mechanisms by which an analyte-containing electrospray generates charged droplets that ultimately result in desolvated, charged, gas-phase molecules. In 1882, Lord Rayleigh considered the electrical pressure resulting from excess charge q on a droplet of spherical radius r and surface tension σ. His theory predicts that the natural quadrupolar oscillation of a droplet in an electrical field-free environment becomes unstable when q exceeds the limit qR, now known as the "Rayleigh limit", defined in Equation 1.qR=8π(σε0r3)1/2  (1)The limit is reached either by solvent evaporation which decreases r or by application of charge in excess of qR. At q≧qR, Rayleigh postulated that the droplet would throw out liquid in "fine jets." (See, Rayleigh, L. Philos. Mag. 1882, 14, 184, the disclosure of which is incorporated herein by reference.) This event is referred to in the literature as Rayleigh discharge or Coulomb fission. (See, e.g., Smith, J. N.; Flagan, R. C.; Beauchamp, J. L. J. Phys. Chem. A 2002, 106, 9957; Grimm, R. L.; Beauchamp, J. L. Anal. Chem. 2002, 74, 6291; and Kebarle, P. J. Mass Spectrom. 2000, 35, 804, the disclosures of which are incorporated herein by reference.) Despite a rigorous prediction of when the event occurs, Rayleigh's analysis does little to describe the dynamics of the discharge event.
Recent articles by Cole and by Kebarle and Peschke summarize the research performed to further elucidate the dynamics of a Rayleigh discharge. (See, Cole, R. B. J. Mass Spectrom. 2000, 35, 763; and Kebarle, P.; Peschke, M. Analytica Chimica Acta 2000, 406, 11, the disclosures of which are incorporated herein by reference.) FIG. 2 presents a schematic summary of the current view of the "lifetime" of a charged droplet. In the consensus view, charged, micrometer-sized droplets eject numerous progeny droplets having a diameter roughly one-tenth that of the parent. Other experiments and models such as the ion desorption model and the charge residue model address phenomena involving smaller droplets in the nanometer regime. Ultimately the result of ion desorption or the charge residue mechanism is a desolvated ion, or in some cases an ion-bound solvent cluster such as water. (See, e.g., Lee, S. W.; Freivogel, P.; Schindler, T.; Beauchamp, J. L. J. Am. Chem. Soc. 1998, 120, 11758, the disclosure of which is incorporated herein by reference.)
Table 1, below, summarizes the conclusions of Rayleigh discharge experiments found in the literature. This list is not inclusive, but rather shows the breadth and scope of the studies and their conclusions. Charged droplets generally undergo Rayleigh discharge while they are at 70-120% of their Rayleigh limit of charge (i.e. q=0.7 qR to 1.2 qR). For instance, Taflin and co-workers found discharge occurring below 90% the Rayleigh limit with charge loss ranging from 10 to 18%, and 1-2% mass loss in dodecaonol, hexadecane, heptadecane, dibromooctane, and bromodecane. (See, e.g., Taflin, D. C.; Ward, T. L.; Davis, E. J. Langmuir 1989, 5, 376, the disclosure of which is incorporated herein by reference.)
TABLE 1DROPLET CHARACTERISTICSDroplet% q/qR atDiam.Rayleigh% Mass% ChargeAuthor(s)SolventLocation(μm)DischargeLostLostLi, Tu, and Ray,diethyl phthalatebalance 5-25962.3212005diethylene glycol100<0.338triethylene glycol100<0.341hexadecane971.515Duft et al., 2003ethylene glycolbalance481000.333Duft et al., 2002ethylene glycolbalance 3-25>95n/a~25 Smith, Flagan, andwaterIMS10-60100n/a20-40Beauchamp, 2002methanol12015-20acetonitrile10015-20Feng et al., 2001methanolbalance20-42~100n/a80Widmann et al.,50 BTD, 50 IDDbalance25-3032421199750 BTD, 50 IDD17-2837574hexanediol diacrylate2264n/an/aGomez, Tang, 1994heptaneESI plume32-8060-80n/an/aRichardson et al.,n-octanolbalance 1-101022.3151989sulfuric acid 1-1084<0.149Taflin, Ward, andbromododecanebalance4472n/a12Davis, 1989dibromooctane26-40861.816dibutyl phthalate2075n/an/adocecanol36-3885215hexadecane28-64731.617heptadecane28-36791.612Roulleau et al., 1972waterbalance 50-200~100n/an/aSchweizer et al., 1971n-octanolbalance15-40~100523Berg et al., 1970balancebalance 30-250 25-100n/an/aAtaman et al., 1969n-octanolbalance30-60~100n/an/aDoyle, et al., 1964n/abalance 60-200n/an/a30Abbreviations:BTD: 1-bromotetradecane,IDD: 1-iodododecane,IMS: ion mobility cell,balance: electrodynamic balance,ESI: electrospray ionization,n/a: not available.References: Taflin, D. C.; Ward, T. L.; Davis, E. J. Langmuir 1989, 5, 376; Gomez, A.; Tang, K. Phys. Fluids 1994, 6, 404; Duft, D.; Lebius, H.; Huber, B. A.; Guet, C.; Leisner, T. Phys. Rev. Lett. 2002, 89, art. no. 084503; Li, K.-Y.; Tu, H.; Ray, A. K. Langmuir 2005, 21, 3786; Duft, D.; Atchtzehn, T.; Muller, R.; Huber, B. A.; Leisner, T. Nature 2003, 421, 6919; Feng, X.; Bogan, M. J.; Agnes, G. R. Anal. Chem. 2001, 73, 4499; Widmann, J. F.;Aardahl, C. L.; Davis, E. J. Aerosol Science and Technology 1997, 27, 636; Richardson, C. B.; Pigg, A. L.; Hightower, R. L. Proc. Roy. Soc. A 1989, 422, 319; Roulleau, M.; Desbois, M. J. Atmos. Sci. 1972, 29, 565; Schweizer, J. D.; Hanson, D. N. J. Colloid and Interface Sci. 1971, 35, 417; Berg, T. G. O.; Trainor, R. J.; Vaughan, U. J. Atmos. Sci. 1970, 27, 1173; Ataman, S.; Hanson, D. N. Ind. Eng. Chem. Fundam. 1969, 8, 833; andDoyle, A.; Moffett, D. R.; Vonnegut, B. J. Colloid Sci. 1964, 19, 136.
High speed photography of charged droplets in an electrospray plume by Gomez and Tang support the prevailing theories of Rayleigh discharge. FIG. 3 shows a charged droplet undergoing jetting in an event attributed to Rayleigh discharge. In this event, it is clear that the parent is elongating and emitting a series of fine progeny droplets. Although they did not measure the charge lost during Rayleigh discharge, they noted the occurrence at ˜60 to 80% the Rayleigh limit, and the photograph supports other experimental findings of little mass loss. (See, e.g., Gomez, A.; Tang, K. Phys. Fluids 1994, 6, 404, the disclosure of which is incorporated herein by reference.)
More recently, Duft and co-workers explored Rayleigh discharge through accurate measurements of the quadrupolar oscillations in a droplet suspended in an alternating current electric field. Through a calculation of the Coloumb energy and surface energy of a droplet, they determined that ethylene glycol undergoes discharge at 100% qR without reliance on the bulk surface tension parameter σ to determine qR, allowing multiple characterizations and the development of a time profile of droplet size and charge. (See, e.g., Duft, D.; Lebius, H.; Huber, B. A.; Guet, C.; Leisner, T. Phys. Rev. Lett. 2002, 89, art. no. 084503, the disclosure of which is incorporated herein by reference.) That droplets are repeatedly characterized in a small measurement volume before and after Rayleigh discharge suggests a "soft" event in which little, if any, momentum is imparted to the parent droplet. This work also suggests a solvent dependence on the charge loss and the percent Rayleigh limit at discharge. (See, e.g., Smith, J. N.; Flagan, R. C.; Beauchamp, J. L. J. Phys. Chem. A 2002, 106, 9957, the disclosure of which is incorporated herein by reference.)
The Rayleigh discharge phenomenon is the result of excess electrical pressure within a droplet. In this case, the electrical pressure of high charge drives an instability leading to jetting of fine jets of charged progeny droplets. However, electrical pressure leading to droplet instability may also be due to an applied strong electric field. Concurrent with investigations into the electrospray phenomenon, investigators considered the behavior of electric fields on neutral water droplets. Early researchers saw meteorological implications and focused on how fields within clouds would affect rain and aerosol drops. (See, e.g., Wilson, C. T. R. Phil. Trans. A 1921, 221, 104; Wilson, C. T. R.; Taylor, G. I. Proc. Cambridge Philos. Soc. 1925, 22, 728; Nolan, J. J. Proc. R. Ir. Acad. Sect. A 1926, 37, 28; Macky, W. A. Proc. Roy. Soc. A 1931, 133, 565; O'Konski, C. T.; Thacher, H. C. J. Phys. Chem. 1953, 57, 955; and Taylor, G. Proc. R. Soc. London, Ser. A 1964, 280, 383, the disclosures of which are incorporated herein by reference.) In a classic 1931 experiment, Macky dropped ˜1 to 5 mm diameter water droplets through a strong electric field with the apparatus shown in FIG. 4a. (See, e.g., Macky, W. A. Proc. Roy. Soc. A 1931, 133, 565, the disclosure of which is incorporated herein by reference.) Here a voltage difference between plates (i) and (ii) defines a high electric field. Water droplets are produced from reservoir (iii) through a stopcock (v) and field-free region (iv). Macky observed that strong electric fields caused droplets to elongate into spheroids prolate to the electric field. At a critical field strength Ec0, droplets developed instabilities resulting in the formation of two symmetrical fine filaments from opposing sides of the droplet. FIG. 4b shows this elongation and instability in photographs of 5 mm diameter water droplets exposed to a 8250 V cm−1 electric field. We call this droplet instability and jetting phenomenon field-induced droplet ionization (FIDI). FIG. 5 shows a single 170 μm diameter methanol droplet undergoing FIDI elongation and jetting. (See, e.g., Grimm, R. L.; Beauchamp, J. L. J. Phys. Chem. B 2003, 107, 14161, the disclosure of which are incorporated herein by reference.)
In general terms, excess electrical pressure leading to FIDI develops in droplets of radius r and surface tension σ when the applied field exceeds a critical value, Ec0 known as the Taylor limit, shown in Equation (2), named for G. I. Taylor who pioneered the corresponding theory. (See, e.g., Taylor, G. Proc. R. Soc. London, Ser. A 1966, 291, 159; and Basaran, O. A.; Scriven, L. E. Phys. Fluids A 1989, 1, 799, the disclosures of which are incorporated herein by reference.)
                              E          c          0                =                              1.625                                          (                                  8                                                                                π                                )                                            1                /                2                                                                                (                                                2                                                                                σ                                                                      ɛ                    0                                                      r                                            )                                      1              /              2                                                          (        2        )            In Equation (2), the fitting constant c has been determined both empirically and theoretically, and the accepted value is 1.625 for liquid droplets in air. (See, e.g., Macky, W. A. Proc. Roy. Soc. A 1931, 133, 565; O'Konski, C. T.; Thacher, H. C. J. Phys. Chem. 1953, 57, 955; Taylor, G. Proc. R. Soc. London, Ser. A 1964, 280, 383; and Inculet, I. I.; Kromann, R. IEEE Trans. Ind. Appl. 1989, 25, 9454, S51, the disclosures of which are incorporated herein by reference.) Assuming droplets always distort into spheroidal shapes, Taylor additionally derived Equations (3) and (4), the general relationship between an applied electric field E<Ec0 and the resulting aspect ratio γ=a/b of the major to minor axis of the spheroid.
                    E        =                              I            2                                                                        γ                                                      -                    4                                    /                  3                                                                          (                                  2                  -                                      γ                                          -                      3                                                        -                                      γ                                          -                      1                                                                      )                                                    1              /              2                                                                    (                                                2                                                                                σ                                                                      ɛ                    0                                                      r                                            )                                      1              /              2                                                          (        3        )                                          I          2                =                                            1                              2                                                                      (                                          1                      -                                              γ                                                  -                          2                                                                                )                                                        3                    /                    2                                                                                ln                                      ⌊                                                1                  +                                                            (                                              1                        -                                                  γ                                                      -                            2                                                                                )                                                              1                      /                      2                                                                                1                  -                                                            (                                              1                        -                                                  γ                                                      -                            2                                                                                )                                                              1                      /                      2                                                                                ⌋                                -                      1                          1              -                              γ                                  -                  2                                                                                (        4        )
In Equation (3), the coefficient I2 is a higher-order function of γ represented by Equation (4). Although a simple relation does not exist for γ(E) in the spheroidal approximation, Equation (5) approximates the relationship between γ and E in Equation (3) to within 1% for fields less than 55% of the Taylor limit. (See, Saville, D. A. Annu. Rev. Fluid Mech. 1997, 29, 27, the disclosure of which is incorporated herein by reference.)
                              γ                                                                          (            E            )                          =                              (                          1              +                                                9                                    r                                                                                ɛ                    0                                                                          E                    2                                                                    16                                                                                σ                                                      )                                                        (                              1                -                                                      9                                        r                                                                                ɛ                      0                                                                                E                      2                                                                            16                                                                                σ                                                              )                                      -              1                                                          (        5        )            Equation (3) predicts γ increases with increasing E until γ=1.85 where the droplet becomes unstable corresponding to E=Ec0. This relationship is supported by experimental and theoretical evidence for neutral droplets and soap films in air. (See, e.g., Wilson, C. T. R.; Taylor, G. I. Proc. Cambridge Philos. Soc. 1925, 22, 728; and Basaran, O. A.; Scriven, L. E. Phys. Fluids A 1989, 1, 799, the disclosures of which are incorporated herein by reference.)
Using these theoretical predictions it is possible to determine the electrical field necessary to produce charged ions from droplets. For example, FIGS. 6 and 7 explore Taylor's spheroidal approximation as applied to droplets relevant to the current discussion. FIG. 6 shows Equation (3) plotted for 225 μm, 500 μm, and 2.25 mm diameter droplets. Each curve demonstrates that the equilibrium aspect ratio increases with applied field for 0<E<Ec0 and curves inward at higher aspect ratio values. This turning point agrees well with the Taylor limit presented by Equation (2). At the Taylor limit, the equilibrium aspect ratio is approximately 1.85. FIG. 6 demonstrates that for a given applied electric field, larger droplets will be more elliptical than smaller droplets and corroborates Equation (2), which suggests that larger droplets require lower field strengths to become unstable and exhibit jetting.
FIG. 7 plots the equilibrium aspect ratio for 225 μm diameter droplets of methanol and water. For a specific applied field and droplet size, droplets with a lower surface tension have a greater equilibrium aspect ratio. This plot also shows that 225 μm water droplets do not undergo jetting under standard atmospheric conditions because the necessary field is greater than the 3×106 V m−1 dielectric breakdown limit of air. For this droplet, air will break down and arc before the Taylor limit of field is reached. Indeed, inserting Ec0=3×106 V m−1 and σ=0.072 N m−1 into Equation (2), the smallest water droplet that demonstrates jetting and FIDI would be ˜380 μm in diameter. Practical considerations that lower the breakdown limit of air such as humidity and burrs on the electrodes could be used to raise the practical water droplet diameter minimum to about 500 μm.
Additionally, between the Rayleigh limit of charge and the Taylor limit of field exists the general case where excess electrical pressure within a droplet results from both net charge and the externally applied electric field. For a droplet of charge q, this shape becomes unstable at a critical electric field, Ecq. The critical field is a function of net charge as increasing charge reduces the field necessary to create an instability, or 0≦Ecq≦Ec0 for 0≦q≦qR.
Although chemistry on and within liquid droplets is ubiquitous in nature and anthropomorphic processes, investigators have only begun to understand and harness such reactions. Liu and Dasgupta review applications of liquid droplets to problems including window-less spectroscopy, solvent extraction, and trace gas detection. (See, Liu, H. H.; Dasgupta, P. K. Microchemical Journal 1997, 57, 127-136, the disclosure of which is incorporated herein by reference.) Because of the desire to understand the behavior of aerosols in the atmosphere, much of the recent work is devoted to understanding heterogeneous reactions between droplets and reactive gas-phase species. (See, Finlayson-Pitts, B. J.; Pitts Jr., J. N. Chemistry of the Upper and Lower Atmosphere: Theory, Experiments, and Applications; Academic Press: San Diego, 2000, the disclosure of which is incorporated herein by reference.) Popular techniques for studying atmospherically relevant heterogeneous chemistry include falling-drop and aerosol time-of-flight (ATOF) mass spectrometry (MS) experiments. For example, real-time Raman spectroscopy has enabled researchers to examine heterogeneous reactions on single droplets suspended in an electrodynamic balance. (See, e.g., Davis, E. J.; Aardahl, C. L.; Widmann, J. F. J. Dispersion Sci. Technol. 1998, 19, 293-309; Buehler, M. F.; Davis, E. J. Colloids Surf., A 1993, 79, 137-149; Musick, J.; Popp, J. Phys. Chem. Chem. Phys. 1999, 1, 5497-5502; and Musick, J.; Popp, J.; Trunk, M.; Kiefer, W. Appl. Spectrosc. 1998, 52, 692-701, the disclosures of which are incorporated herein by reference.) The Agnes group established the viability of offline mass spectrometric analysis of individual soft-landed droplets that had previously been suspended in an electrodynamic balance (EDB). They further demonstrated that the suspended droplet may undergo heterogeneous reactions that may be subsequently characterized through offline mass spectrometry. (See, Bogan, M. J.; Agnes, G. R. Anal. Chem. 2002, 74, 489-496; and Feng, X.; Bogan, M. J.; Chuah, E.; Agnes, G. R. J. Aerosol Sci. 2001, 32, 1147-1159, the disclosures of which are incorporated herein by reference.) More recently, using a constant stream of droplets generated by a vibrating orifice aerosol generator, it has been demonstrated that the charged progeny droplets emitted from parent droplets in a FIDI event are a viable source of gas-phase ions for mass analysis. (See, e.g., Grimm, R. L.; Beauchamp, J. L. J. Phys. Chem. B 2003, 107, 14161-14163, the disclosure of which is incorporated herein by reference.)
A great deal of work is still needed to develop a complete picture of both electrospray and field-induced droplet ionization mass spectrometry. For example, as a result of the complexity of examining a falling droplet or a spray of droplets few studies have probed the chemical aspects and implications of charged droplet phenomena. Specifically, because of their inherently transient nature, these droplet streams are difficult to manipulate and utilize as chemical probes. In addition, although Taylor's analysis predicts the field necessary for droplet instability and jetting through Equation (2), the analysis does not predict the timescales or the dynamics of the process. Accordingly more efficient ion sources and applications are needed for understanding and refining the use of droplets as a chemical probe, as well as new applications to mass spectrometry. These applications motivate the present disclosure.

Chemical probe using field-induced droplet ionization mass spectrometry


An electronic device including a main body, a cover and an assembling structure is provided. The main body has two first positioning structures. The assembling structure includes two sliding components, two second positioning components and two elastic components. Each sliding component is slidably disposed on the cover and has a pressing portion. The second positioning structures are connected to the sliding components respectively and aligned to the first positioning components respectively. The elastic components are connected to the cover and connected to the sliding components respectively. Each second positioning component is positioned at the corresponding first positioning component by elastic force of the corresponding elastic component, so as to stop the cover separating from the main body. When the pressing portions receive forces at the same time to drive the second positioning structures to move away from the first positioning structures respectively, the cover is separated from the main body.

1. Technical Field
The invention relates to an electronic device, an assembling structure and an assembling method. Particularly, the invention relates to an electronic device having a detachable cover and an assembling structure and an assembling method thereof.
2. Related Art
Along with quick development of electronic technology, various electronic products have been widely used in people's daily life. Besides focusing on performance of the electronic products, consumers also have requirements on appearance, safety and maintenance convenience, etc. of the electronic products.
Regarding networked attached storage (NAS) equipment, it generally has a cover for shielding internal structures thereof, so as to achieve a better appearance. In order to improve maintenance convenience of the NAS equipment, the cover of some of the NAS equipment are designed to be easily disassembled without using any tool, though such design results in a fact that the cover is easy to be unexpectedly dissembled to cause danger, for example, a child may disassemble the cover when casually operating the equipment to cause electric shock, scratch or scald, etc. If the NAS equipment is designed to be disassembled by using tools in order to avoid the above problem, the maintenance convenience thereof is decreased. Therefore, how to avoid the unexpected disassembling of the cover while maintaining the maintenance convenience of the equipment becomes an important issue in design of the equipment.

Electronic device, assembling structure and assembling method


A method implemented in a network apparatus used in a wavelength division multiplexing (WDM) optical network is disclosed. The method includes (a) selecting unconsidered virtual link (VL) (i,j) with a maximum cost, a cost being requested line rate rij on VL(i,j)×shortest distance between nodes i and j, (b) selecting unconsidered route k out of K-shortest routes between nodes i and j of VL(i,j), (c) determining a bit map of unconsidered route k, (d) finding a modulation format that supports requested line rate rij with minimum spectrum

The present invention relates to wavelength division multiplexing (WDM) optical networks and, more particularly, to virtual network embedding in the WDM optical networks.
Current network infrastructure consists of a large number of heterogeneous proprietary network elements. Any technological evolution within this infrastructure is compounded by the increasing cost of investment since the cycle of design-integrate-deploy needs to be repeated. Thus, such infrastructure ossifies deployment of new services and network innovations.
To enable rapid innovations, recently Software-Defined Optical (SDO) Network architecture is introduced [1], which offers network virtualization through a hypervisor plane to share the same physical substrate among multiple isolated virtual network instances. Network virtualization partitions the functional role of internet providers into Infrastructure Providers (InP) and Service Providers (SP) [2]. InPs manages and maintains hardware and software resources, while SPs offers network services and applications to end users. Network hypervisor acts as a broker between InPs and SPs by mapping the Virtual Network (VN) demands from SPs over physical substrates of InPs. The process of mapping virtual nodes over physical nodes and Virtual Links (VL) over physical routes is referred to as virtual network embedding. To maximize revenue for InPs and resource availability for SPs, One of the challenges in VN embedding is how to maximize the embedded VNs over physical substrates.
In wavelength division multiplexing (WDM) optical networks, upon an arrival of a demand requesting a line rate between end nodes, an optical channel is established by allocating finite amount of spectrum on all fibers along the route. If an intermediate node along the route does not support the wavelength conversion capability, then the channel routed through a node must follow the wavelength continuity constraint, which is defined as an allocation of the same center wavelength to the channel, and the spectral continuity constraint, which is defined as an allocation of the same amount of spectrum to the channel in ingress and egress fibers at the node. To support multiple such channels over a fiber, the spectral conflict constraint must be satisfied, which is defined as an allocation of non-overlapping spectrum to the channels routes over the same fiber. When an optical channel is routed through network equipments and fibers, it accumulates linear and non-linear impairments along the route, which deteriorate the optical signal quality. To ensure a successful transmission of data, at least minimum detectable signal quality must be maintained at a receiver.
Conventionally to address interoperability issues, the International Telecommunication Union Telecommunication Standardization Sector (ITU-T) has standardized fixed channel spacing [3]. The network that follows the ITU-T standard is referred to as fixed grid network as shown in FIG. 1(a). Fixed grid networks may not optimize spectral efficiency while supporting line rates with heterogeneous granularity for ever increasing bandwidth demands. Recently, flexible grid network architecture (as shown in FIG. 1(b)) is introduced in which flexible amount of spectrum is assigned to channels based on the requirements of requested bandwidth, transmission reach, and offered modulation formats. Flexible grid networks highly optimize network spectral efficiency; however, dynamic arrival and departure of channels with heterogeneous spectrum requirements causes fragmentations in spectrum (as shown in FIG. 2), and the network can no longer be in its optimal state. The state of fragmented spectrum in a network is referred to as network fragmentation. Network fragmentation is a serious issue in fixed and flexible grid networks. Spectral fragmentation can block a connection in spite of the availability of sufficient amount of spectrum for the connection, and thus, can deteriorate the network performance.
In a software-defined optical network, an open challenge is how to map virtual networks over a flexible grid transport network while assuring the transmission reach constraints. The problem is referred to as the impairment-aware virtual network embedding over software defined flexible grid networks. The detailed problem definition is as follows.
We are given a physical network Gp(Np, Lp), where Np represents a set of reconfigurable optical add-drop multiplexer (ROADM) nodes and Lp represents a set of fibers. A variable rate transponder at each node consists of an optical multicarrier modulator which can modulate subcarriers using a set Z of electrical modulation formats to vary the line rate, where Z={PM-BPSK, PM-QPSK, PM-16QAM}. Here, PM-BPSK stands for polarisation multiplexing binary phase shift-keying. PM-QPSK stands for polarisation multiplexing quadrature phase-shift keying. PM-16QAM stands for polarisation multiplexing 16 quadrature amplitude modulation.
Each modulation format z in Z can transmit a channel up to Dz km with spectral efficiency Sz b/s/Hz. VN demands (Gv(Nv, Lv), RLv) arrives in the network according to incremental traffic model [4] in which a permanent VN is provisioned on a one-by-one basis, where Nv denotes a set of virtual nodes, Lv denotes a set of virtual links, and RLv denotes a set of requested line rates. rij (εRLv) represents a requested line rate between a virtual link (i,j) in Lv. The network offers Y GHz of total spectrum to support the demands. We need to find mapping of VNs over the physical substrate such that the number of embedded VNs is maximized. Mapping of a VN over physical substrate requires to find routing of virtual links over physical routes, selection of modulation formats for virtual links, and wavelength and spectrum assignment to virtual links.
In [5], the authors formulated the VN embedding problem in fixed and flexible grid networks using Integer Linear Program for static traffic model in which a set of VN demands can be provisioned in any order. The solutions in [5] ignore the physical layer impairments while provisioning VN demands. Furthermore, the proposed formulations may not guarantee an optimal solution and are not scalable for a large problem instances.

Virtual networking embedding procedure in an optical wavelength division multiplexing (WDM) network

Abstract: ⌈                  r        ij                    s        z              ⌉    ,where Sz is spectral efficiency with which the modulation format transmits a channel, (e) finding

Abstract: ⌈            r      ij              s      z        ⌉consecutive spectrum slots at M lowest wavelengths in the bit map of selected route k, and (f) determining fragmentation factor Fkm after provisioning a channel at each wavelength m on selected route k, where 1≦m≦M. Other apparatuses, systems, and methods also are disclosed.


A wireless communication device (30) within a wireless communication system (10) includes a receiver (68) for receiving a message, a processor (78) coupled to the receiver (68) for processing the message, and a memory (80) coupled to the processor (78). The memory (80) includes a message memory (94) for storing the message and a location memory (96) for storing location information (100). The wireless communication device (30) further includes an operation mode management application (90) coupled to the processor (78). The operation mode management application (90) identifies at least one operation mode (112), and enables the operation mode (112) in response to a processor command (104) received from the processor (78).

1. Field of the Invention
This invention relates in general to wireless communication devices and in particular to wireless communication devices with speed sensitive operation.
2. Description of the Related Art
Wireless communication devices, such as two-way pagers and cellular telephones, have become more popular in recent years. This is due, in part, to the variety of conveniences they afford users. Much of the popularity of wireless communication devices comes from the added ability provided to the user to place and receive calls and messages wirelessly.
Recently, cellular telephones have been designed with the capability to be used in a xe2x80x9chands-freexe2x80x9d mode of operation using a full-duplex speakerphone. This xe2x80x9chands-freexe2x80x9d mode of operation is particularly beneficial when a user receives an incoming call. The user is able to answer the phone and have a conversation without having to manipulate buttons or hold the phone to the user""s ear.
One disadvantage with the current implementation of the xe2x80x9chands-freexe2x80x9d mode is the need to enter a specific sequence of button presses to place the handset in the xe2x80x9chands-freexe2x80x9d mode. This requires the user to remember the proper procedure for placing the phone in the xe2x80x9chands-freexe2x80x9d mode. Another disadvantage is that the xe2x80x9chands-freexe2x80x9d mode may not always be appropriate, such as when the user is attending a meeting. This requires the user to remember to disable the xe2x80x9chands-freexe2x80x9d mode before attending the meeting. The user is again required to remember the proper procedure for turning off the xe2x80x9chands-freexe2x80x9d mode.
Recently, some wireless communication devices have been designed to include the capability to determine the device""s current location. For example, a wireless communication system can use direction-finding equipment at each base station site in order to fix the location of the handset. The current location is computed by triangulation when two or more transmitter base stations receive the same signal. Once the wireless communication device""s location is determined, it may be used along with the current time to calculate the speed and direction of the wireless communication device.
Similarly, the portable wireless communication device can include a Global Positioning System (GPS) receiver for determining its location. The Global Positioning System (GPS) is a worldwide radio-navigation system formed from a constellation of 24 satellites and their ground stations. The GPS receiver uses signals received from the satellites to calculate the current position, heading, speed and even altitude of the wireless communication device equipped with the GPS receiver.
What is needed is an improved method of automatically placing a wireless communication device equipped with location finding capability in the proper operational mode based upon the surrounding conditions in which the wireless communication device is being used.

Apparatus and method for speed sensitive operation in a wireless communication device


A device for encapsulating a plurality of semiconductor die comprises a form having first and second halves such that as the first half contacts the second half the first and second halves have a plurality of cavities therein. The first and second halves each comprise a conduit therein for receiving a heated liquid. The device further comprises a runner block having a hole therein, a separate runner for each cavity, and a conduit therein for receiving a heated liquid. The runners have a rectangular cross section and a width to height ratio of at least 3:1. The device further comprises a mounting plate for mating with the runner block. The mounting plate comprises a concave recess and a hole in the mounting plate at the recess. The hole in the mounting plate passes through the mounting plate to align with the hole in the runner block such that an encapsulation material can be passed between the mounting plate and the runner block. The device further comprises a heated nozzle having a hole therethrough and a convex head wherein the concave recess is adapted to receive the convex head such that an encapsulation material can be passed between the nozzle and the mounting plate. The device further comprises a spring which urges the nozzle away from the mounting plate.

To form an encapsulated integrated circuit (IC), a plurality of semiconductor die are conventionally arranged on a lead frame. The lead frame functions as a carrier for the plurality of die and forms the leads for each IC device. Prior to encapsulation, bond wires are attached to bond pads on the die and to the lead fingers of the lead frame. The plurality of die and the bond wires are then encapsulated to form a housing from which only the ends of the leads extend. The encapsulation protects the die and makes it possible for the ICs to be used industrially.
The die is a very sensitive component and the encapsulation must fulfill various quality requirements. For example, the encapsulation must provide the following functions:
1. Protection against physical influences (bending, shock, vibration, etc.) and support for the die. PA1 2. Sufficient electrical insulation even after extended exposure to moisture and heat. PA1 3. Resistance to the corrosive action of chemicals to which the package may be exposed. PA1 4. Sufficiently high adhesion to other surfaces. High adhesion to surfaces reduces the possibility of the lead frame separating from the encapsulation which would allow moisture to enter the package along the leads. PA1 5. High thermal conductivity so heat generated by the die will conduct to the outside of the package and dissipate. PA1 6. Sufficient stability to avoid the production of byproducts which might damage the die encased within the encapsulation. PA1 7. Resistance to variations in temperature, for example between -65.degree. C. and +200.degree. C.
To help fulfill these requirements, the production of bubbles within the encapsulation is to be avoided. One method to avoid the production of bubbles is to encapsulate the die under an appropriately high pressure. However, overly high pressures are to be avoided as a die can be damaged by excessive pressures. In particular, the bond wires, often having a diameter of less than 2.5 micrometers (.mu.m), can drift or come loose from the bond pad or lead finger during encapsulation of the die in plastic. During drifting the conductor wires are deformed by the flowing plastic, and they can touch each other or come so close to each other that the insulation resistance between them is too small and short-circuiting can occur.
Transfer molding is often used to encapsulate semiconductor die. Using the transfer molding method, lead frames with die thereon are placed into a mold with correspondingly adapted hollow spaces. The encapsulation material, such as thermoset in the form of pellets filled with fillers such as glass fibers or mineral flakes, is placed into a piston-cylinder unit, heated, and then pressed by a piston via a system of casting conduits into the hollow spaces of the form.
Transfer molding includes manufacturing using large tools with only one transfer cylinder (multi-cavity system) and on small tools with several small transfer cylinders (multi-piston system). The manufacturing with large tools has the disadvantage that the larger they are the more difficult it becomes to achieve a uniform filling of the hollow spaces of the mold. The pressure produced by the equipment must be sufficient to fill the cavity which is the most difficult to fill. This results in a high pressure at the cavities closest to the transfer cylinder which can damage the die in those cavities. Moreover, the molds become increasingly imprecise as they become larger such that it becomes difficult to achieve the desired dimensional accuracy. Since the demand on the reliability and the dimensional accuracy becomes greater with increasing device density and increasing lead density, the trend to make the tools larger to increase efficiency stands in contrast to the increased demands for accuracy. In addition, the large tools have increased down-time because of increased loading and unloading, and the additional time required for cleaning the large-surface tools.
Encapsulating devices on small tools with several small transfer cylinders makes possible shorter cycle times, improved dimensional accuracy and, on account of the shorter injection paths, a generally improved encapsulation. However, the design of an injection unit operating with several transfer cylinders is expensive as a complete injection unit (which consists of the cylinder, the piston with hydraulic mechanism and control as well as the automatic charging of the cylinder with the molding material in pellet form) is required for each two to four cavities in the mold.
The construction of the tools, the arrangement of the numerous injection units, and the supply of material are determined by the component to be produced and by the type lead frame. The tools used are therefore determined by the length of the lead frame, number of die on each lead frame, the dimensions of the lead frame and of the final package, the weight and pellet size of the encapsulation material, as well as the injection rate and injection pressure. The complete block including the injection units must be replaced upon a change of product, which is expensive.
Even though the accuracy of small transfer molding tools produces quality components, the cost-performance ratio for small tools is unfavorable for the manufacturing production quantities of semiconductor devices.
There is a need for the ability to produce high density devices which require high accuracy due to increased lead density with less complexity and increased throughput.

Injection molding equipment for encapsulating semiconductor die and the like


A method for configuring an electronic device comprising: (A) substantially continuously detecting motion of the electronic device using an initiating device disposed within the electronic device, the electronic device further comprising a position determining component, and a wireless communications component; (B) substantially continuously receiving at least one external radio signal by using an initially selected antenna of the position determining component; (C) if reception of at least one external radio signal is not optimized, using the antenna/power supply switch to switch radio signal path between the initially selected antenna and a subsequently selected antenna to optimize the reception of at least one external radio signal; and (D) using the wireless communications component to transmit the current status of the external/internal antenna to the position tracking station.

1. Field of the Invention
The present invention relates to a position reporting device for determining and reporting the position of a person or an object, and more specifically, to a controllable external-to-internal antenna switch algorithm and circuit that enhances the functionality of the position reporting device.
2. Discussion of the Prior Art
The prior art position reporting devices are useful to locate and report the position of a person or object. A typical position reporting device comprises a navigation system such as the Global Positioning System (GPS) module and a mobile communications system such as a cellular modem.
The TrimTrac™ locator manufactured by Trimble Navigation Ltd, located at Sunnyvale, Calif., is a mobile tracking device that provides vehicle monitoring, security and recovery services to a broad number of subscribers. The TrimTrac locator device includes a GPS receiver and GSM modem that are integrated onto a single board and are controlled by a common microprocessor. A typical TrimTrac™ locator device includes two antennas: an internal GPA antenna and an external GPS antenna. However, only one antenna can be powered at the same time to avoid interference between the received GPS signals.
What is needed is to establish a procedure that would allow the TrimTrac™ locator the optimal usage of its two antennas.

Controllable external to internal antenna switching algorithm and circuit for position reporting device


A burner box assembly for a combustion air furnace includes a back wall, opposed side walls and top and bottom walls defining an interior space for one or more burner nozzles. A combustion air inlet opening is formed in the top wall and is covered by a generally rectangular inverted channel-shaped airflow guide and baffle member. A second generally rectangular box-shaped louvered airflow guide and baffle member is mounted on the interior side of the top wall over the combustion air inlet opening for distributing the flow of combustion air into the burner box assembly and to reduce acoustic emissions from the burner box assembly through the combustion air inlet opening. The combination of the louvered baffle member and the exterior mounted baffle member provides reduced acoustic emissions from the burner box assembly as well as more evenly distributed combustion airflow into and through the burner box assembly.

In the continued development of air-conditioning furnaces, one important consideration is to reduce acoustic emissions. For example, for forced air gas and oil fired residential air-conditioning furnaces, the furnace itself may be located in the building which is being heated in a location within the building where acoustic emissions are annoying to occupants of the building, or such emissions otherwise interfere with activities in the building. Accordingly, efforts have been made to reduce acoustic emissions caused by the combustion process as well as noise generated by airflow to and through the furnace.
However, prior art efforts to provide properly designed burner and burner box assemblies adapted to reduce acoustic emissions have not provided for as much reduction in such emissions from the burner box as desired without impeding airflow to and around the burners. Provisions for adequate airflow for proper combustion are, of course, important. Also of importance is to provide for the direction of the airflow to be such as to minimize any unwanted convection of heat in a direction which would reduce the thermal efficiency of the furnace. Accordingly, continued improvements in furnace burner box assemblies which provide for reduced acoustic emissions without restricting or misdirecting airflow have been sought. It is to these ends that the present invention has been developed.
The present invention provides a furnace burner box assembly having reduced acoustic emissions.
In accordance with one aspect of the present invention, a furnace burner box assembly is provided which includes one or more gas or oil-fired burners disposed therein and wherein a top wall of the burner box includes a large inlet opening for combustion air, and a multiple louvered baffle member supported on the underside of the burner box top wall. The burner box assembly also advantageously includes a second baffle member supported on the topside of the burner box top wall for reducing acoustic emissions from the burner box caused by the combustion process and by relatively high-velocity airflow into the burner box and then into the furnace heat exchanger in the combustion region.
The present invention also provides a burner box assembly with reduced acoustic emissions wherein a first baffle member is arranged depending from a top wall of the burner box and is provided with multiple air outlet openings for directing combustion air in a more even distribution through the burner box assembly. Multiple openings in the first baffle member are provided by louvers which form an angle with respect to the baffle bottom wall. The louvers are advantageously oriented to prevent direct or so-called line of sight noise transmission from the burner nozzle outlets to and through the primary combustion air inlet opening in the top wall of the burner box. Accordingly, the combustion air flowing into the burner box assembly is more evenly distributed, flow velocities are reduced and acoustic emissions are substantially prevented from exiting the burner box through the opening in the top wall. Still further, a second baffle member is mounted above the burner box top wall and further reduces acoustic emissions from the burner box assembly without impeding airflow thereto.
Those skilled in the art will further appreciate the above-mentioned advantages and superior features of the invention together with other important aspects thereof upon reading the detailed description which follows in conjunction with the drawings.

Furnace burner box assembly with reduced acoustic emissions


In some embodiments, a cathode assembly may include a cathode head that has a first electron emitter and a second electron emitter. The first electron emitter may have a first connection location and a second connection location. The second electron emitter may have a third connection location and a fourth connection location. The third connection location may be electrically coupled with the second connection location of the first electron emitter. The cathode assembly may include a receptacle having a first connector and a second connector. The first connector may be electrically coupled with the first connection location of the first electron emitter. The second connector may be electrically coupled with the second connection location of the first electron emitter and the third connection location of the second electron emitter. The third connector may be electrically coupled with the fourth connection location of the second electron emitter.

The present disclosure generally relates to cathode assemblies for X-ray tubes. In particular, the disclosure may relate to electrical connection configurations for cathode assemblies of X-ray tubes.
X-ray tubes are used in a variety of industrial and medical applications. For example, X-ray tubes are employed in medical diagnostic examination, therapeutic radiology, semiconductor fabrication, and material analysis. More specifically, X-ray tubes are often used in computed tomography (CT) or X-ray imaging systems to analyze patients in medical imaging procedures or objects during package scanning.
During operation of a typical X-ray tube, an electrical current may be supplied to an electron emitter, or filament, of a cathode. This causes electrons to be formed on the emitter via a process known as thermionic emission. The electrons accelerate from the emitter toward a target track formed on the anode in the presence of a high voltage differential applied between the anode and the cathode. Upon striking the anode, some of the resulting kinetic energy from the striking electrons is converted into X-rays. The region of the anode upon which the majority of the electrons collide is generally referred to as a "focal spot." The resulting X-rays may then pass through an X-ray transmissive window and are directed towards a patient or other object to be examined. In a typical environment, an image is generated based on the X-rays that pass through the patient/object. While a number of factors affect the quality of a resulting image, one factor is the size, quality and/or energy level of the electrons in the focal spot region.
The claimed subject matter is not limited to embodiments that solve any disadvantages or that operate only in environments such as those described above. This background is only provided to illustrate examples of where the present disclosure may be utilized.

Electrical connectors for multiple emitter cathodes


In a method of providing cellular telephone service to a mobile telephone located in an off-load cellular telephone system adjacent to a main cellular telephone system, the mobile telephone is registered with the off-load cellular telephone system upon the mobile telephone entering the off-load cellular telephone system, and then is registered with the main cellular telephone system as being located in the off-load cellular telephone system as a function of predetermined criteria. During the time in which the mobile telephone has entered the off-load cellular telephone system but has not yet registered with the main cellular telephone system as being located in the off-load cellular telephone system, rebroadcasting page signals from main cellular telephone system into the off-load cellular telephone system ensures delivery of incoming telephone calls to the mobile telephone.

1. Field Of The Invention
The present invention relates generally to a cellular communication system used to off-load telephone calls from a main cellular telephone system to an off-load cellular telephone system, and, more particularly, to a method of ensuring incoming call delivery to a mobile telephone located in the off-load cellular system.
2. Description Of The Related Art
Cellular mobile telephones (mobile telephones) are typically employed in automobiles, ships or the like, and thus are transportable with the user into various different geographic zones. In each of the different geographic zones, one or more mobile telephone switching offices (MTSO) are provided to complete call connections. Once connected to the MTSO, the mobile telephone may then be connected to another mobile telephone within a specific zone or, through land-based networks such as a public switching telephone network (PSTN) to a land-based telephone or to another cellular mobile telephone in a different zone.
Cellular mobile telephone systems (cellular systems) service specific geographic areas, or zones, each of which is typically divided into a plurality of cells. Each cell includes a stationary transmitter/receiver (transceiver) station coupled to transmit and receive antennas. The transceiver station broadcasts signals within its signal coverage area and provides radio communication connections with mobile telephones physically located within the associated cell. The stationary transceiver stations, in turn, are connected to a MTSO associated with the zone where the transceiver stations are located. The MTSO is generally a computer-based system and provides call processing and switching functions, between and among cells. Typical cellular systems use cells known as macrocells, which provide signal coverage over fairly large geographic areas, often from a radius of one mile to several miles.
Each cell within a specific zone of a cellular system has a number of frequencies assigned to it to establish radio communications with a mobile telephone. The frequencies are divided into control channels, paging channels and voice channels. The paging and control channels are used for the mutual identification between the mobile telephone and the cellular system providing the cellular mobile telephone service. The location or frequency of the control channels contained in the frequency range assigned to each cell identifies the type of cellular system which is being used. Typically, one set or range of frequencies is called an "A" cellular system and a second set of frequencies is called a "B" cellular system. Generally, a specific geographic area contains one of each type of cellular system (i.e., an A and a B cellular system), thereby providing alternative cellular service to that area.
A mobile telephone must identify itself to the cellular system provider before service for the mobile telephone can be established. The communications between a mobile telephone and its respective transceiver station must conform with the industry standard for such communications, set forth in the Mobile Station--Land Station Compatibility Specification EIA/TIA 553 (EIA/TIA 553). The identification process begins using the control channels. When a mobile telephone is first switched on, the mobile telephone scans through the forward control channels and measures the signal strength of each forward control channel. It will then tune to the strongest forward control channel and lock on to the forward control channel message stream. The forward control channel message stream is a continuous flow of data from the transceiver station to the mobile telephone and contains, for example, set-up parameters, global commands and registration identification information. The origination point of the forward control channel message stream is generally the MTSO. When the mobile telephone makes an access attempt, the mobile telephone must access a reverse control channel. A reverse control channel access message is generated by the mobile telephone and broadcasted over the reverse control channel. The reverse control channel access message contains various data which permits the cellular system to identify the mobile telephone and thereby determine whether the mobile telephone should be provided with cellular service.
In accordance with EIA/TIA 553, the mobile telephone will continuously scan for and lock onto the strongest available control channel. In addition, EIA/TIA 553 requires that a mobile telephone rescan the control channels at the end of a power-up process, tuning to the strongest control channel available. EIA/TIA 553 also requires rescanning for the strongest control channel after a mobile telephone accesses a reverse control channel and after an Autonomous Registration by a mobile telephone with its respective transceiver station. Autonomous Registration is a process used to track the location of a mobile telephone within a cellular system in which a mobile telephone periodically identifies itself to an associated transceiver station as being active in the system at the time the Autonomous Registration message is sent. EIA/TIA 553 does not require that a cellular system provide for Autonomous Registration of mobile telephones, but does specify the procedure for Autonomous Registration if it is used.
In a cellular system which implements Autonomous Registration in compliance with EIA/TIA 553, the Autonomous Registration generally works as follows. Included in the forward control channel message stream broadcasted by the transceiver station of each cell in a cellular system is a registration field. Periodically included in the message stream is a REGID value. Optionally included in the message stream as a Global Action Overhead Message is a REGINCR value. The REGID value is received by the mobile telephone and stored in a designated location where it can then be monitored by the mobile telephone. For example, when a mobile telephone is first powered on, the mobile telephone locks onto the forward control channel message stream of the selected control channel and then receives and stores a REGID value.
As the REGID value is periodically broadcasted, it is also incremented. The mobile telephone continues to receive the incremented REGID values and compares the current REGID value against the stored REGID value. When the differential between the current and stored REGID values, determined according to a predetermined algorithm, equals or exceeds the REGINCR value being broadcast to the mobile telephone, an Autonomous Registration is initiated by the mobile telephone. The REGID value at the time the Autonomous Registration is initiated is saved as the new stored REGID value. Before Autonomous Registration is completed, the mobile telephone performs a System Access Attempt in accordance with EIA/TIA 553. The first step in the System Access Attempt is a rescan for the strongest available forward control channel. Once the mobile telephone locks onto and seizes the strongest control channel, it completes Autonomous Registration.
In typical macrocellular systems, incoming calls are handled in the following manner. When a caller dials the number of a mobile telephone, the incoming call is routed to the MTSO of the macrocellular network which is the home network of the mobile telephone. The MTSO receives the incoming call and then attempts to locate the desired mobile telephone. The MTSO locates the mobile telephone via a Home Location Register (HLR). The HLR, which may be part of the MTSO or a separate device, maintains a list of the mobile telephones which are subscribers of the macrocellular system. The HLR also maintains a list of the current registration of the mobile telephone. The HLR may be, for example, a microprocessor based device. The registration of the mobile telephone generally will be one of two states: home registered; or IS-41 registered.
Home registered means that the mobile telephone is registered as being located within the macrocellular network. IS-41 registered means that the mobile telephone is registered with another cellular system in accordance with the industry standard EIA/TIA IS-41 Cellular Radiotelecommunications Intersystem Operations specification (EIA/TIA IS-41). EIA/TIA IS-41 provides an industry standard interface for communication between two separate macrocellular systems. For example, every cellular system is assigned a unique system identification number (SID) by the Federal Communications Commission (FCC). The SID is regularly broadcasted by the cells of a given cellular system. If a mobile telephone transitions between two cellular systems having different SIDs, the mobile telephone will detect the change of SID and initiate an Autonomous Registration in the new cellular system if the cellular system is configured for Autonomous Registration. The Autonomous Registration, in turn, will generally cause an IS-41 registration of the mobile telephone, thereby enabling the mobile telephone's home cellular system to continue delivering incoming calls via the IS-41 interface. If Autonomous Registration is not enabled in the cellular system, there will generally be no IS-41 registration even if the mobile telephone detects a change in SIDs. The transition of mobile telephone between two macrocells of the same cellular system will not create a change of SIDs and, thus, there would be no IS-41 registration in this circumstance. IS-41 registered is commonly referred to as "network registered."
If a mobile telephone is home registered, the MTSO will receive a message from the HLR indicating home registration. As a result, the MTSO will send a page signal to the macrocells associated with the MTSO and the macrocells will broadcast the page signal to notify the intended mobile telephone of the incoming call. If the intended mobile telephone receives the page signal, it will send a page response signal in response. The macrocellular system will then set up the incoming call.
If a mobile telephone is IS-41 registered, the MTSO will receive a routing number for the location of the mobile telephone as a result of EIA/TIA IS-41 procedures. This may be the case, for example, when a mobile telephone transitions between cellular systems having different SIDs. In this situation, the MTSO will not broadcast a page signal for the incoming call. The MTSO will, however, deliver the incoming call directly to the mobile telephone via a standard PSTN connection. The routing number is delivered to the HLR from a Visitor Location Register (VLR) associated with the cellular network where the mobile telephone is currently located. The VLR is similar to the HLR except that the VLR has no home customers and only registers mobile telephones that are currently within the cellular network associated with the VLR. The VLR may be, for example, a microprocessor based device and is generally connected to the HLR via an EIA/TIA IS-41 connection.
Outgoing calls from a mobile telephone, whether home registered or IS-41 registered, are handled in accordance with the specifications of EIA/TIA 553 by the cellular system where the mobile telephone is currently located.
In a typical cellular system, as a mobile telephone travels along a path that passes from one cell to another, a handoff occurs if the mobile telephone is active, i.e., the mobile telephone is attempting a telephone call or handling an existing call. The handoff action is controlled by the MTSO which monitors the signal strength received from the mobile telephone. The handoff command is typically generated when the signal received by the mobile telephone falls below a preselected signal strength, thus indicating that the mobile telephone is at the cell boundary of one cell and requires a transfer of the cellular service to an adjacent cell which is able to receive a signal from the mobile above the preselected signal strength.
As a mobile telephone passes from one cell to another cell, the handoff command instructs the new cell which the mobile telephone is entering to begin transmitting at a frequency which is different from the frequency which was transmitted by the cell from which the mobile telephone is exiting. This procedure is followed as the mobile telephone passes into each next successive, adjacent cell. The assigned frequencies of each adjacent cell are different, and such assigned frequencies are not repeated except for cells that are far enough away from each other so that no interference problems will occur.
The commercial success of cellular service has forced cellular carriers to substantially increase the capacity of cellular systems. Accordingly, cellular system providers desire to expand their systems to serve an increasing number of customers within a particular geographic location. Various solutions have been proposed to increase the capacity of cellular systems and thereby address the foregoing need. For example, a typical macrocell may be split into four smaller cells, each with a radius of half the radius of the original macrocell, thereby permitting cellular service to be increased four fold.
Another approach to increasing the capacity of cellular systems is to add additional cell sites to the cellular system to provide additional cellular service in small geographic areas having heavy cellular subscriber usage. These smaller cell sites are typically known as microcell sites. Microcells operate functionally similar to a traditional macrocellular or main cellular system, but only provide cellular service for a small geographic area. The microcell sites are typically directly connected to the macrocellular system using coaxial transmission lines, microwave links or an optical fiber cable network, via a nonstandard protocol which is proprietary to the manufacturer of the macrocellular equipment. Microcells, in general, improve frequency reuse by concentrating frequency channels in the area of greatest subscriber demand and allowing frequency reuse within a particular geographic area.
While cells may be subdivided into smaller cells to provide cellular service for an increasing number of customers, shrinking cell sites create additional considerations and problems. For example, the rate at which mobile telephones move through the cell and the non-uniformity of the electromagnetic field generated in the cell affect the performance of a microcell system. Both factors relate to the time required to determine the relative location of the mobile telephone and to process a handoff of the mobile telephone from the transceiver station of one microcell where the mobile telephone is currently located but is preparing to exit, to the transceiver station of another microcell where the mobile telephone is entering. Naturally, the smaller the cell, the greater the number of handoffs that are required as a mobile telephone moves through the cellular system. If a handoff is required, one or more candidate microcells must be queried for their idle channel status and for a verification of the mobile telephone's signal strength in that candidate microcell. The processing of the decision, status, and verification usually requires the intervention of higher level system control functions in addition to the control function in the serving and candidate microcells. In addition, the mobile telephone must be instructed to tune to a frequency available in the candidate microcell and verification of its presence after the handoff must be made by the candidate cell. Thus, the increased number of handoffs within a microcell system requires a significant amount of time for handoff processing.
In addition, since microcellular systems are usually directly connected to the macrocellular system via a nonstandard proprietary protocol, it is impossible to integrate or include a generic microcell system to off-load cellular service from the macrocellular systems. Generally, the microcellular equipment must be from the manufacturer of the macrocellular equipment for a particular cellular system. The difficulty of competing products to provide cellular service results in microcellular systems being expensive, difficult to integrate with other cellular systems and presents problems with incoming call delivery to a mobile telephone located in the microcellular system.
In a typical macrocellular system which employs a microcellular system to off-load cellular subscribers in an area of heavy subscriber usage, missed incoming calls are a problem. In particular, if a cellular system provider integrates a current microcellular system into an existing macrocellular system and uses microcellular equipment that was not manufactured by the macrocellular equipment manufacturer, then incoming calls may be missed. The missed calls result when a mobile telephone transitions from the macrocellular system to the microcellular system. When the mobile telephone enters the microcellular system, it automatically locks onto a frequency of the microcell in accordance with EIA/TIA 553 because the microcellular control channel is the strongest signal available to the mobile telephone at that time. As a microcellular system is designed to off-load traffic from the macrocellular system, the microcellular system must broadcast the same SID as the macrocellular system. Thus, because the mobile telephone detects no change in SIDs, there is no registration of the mobile telephone with the macrocellular system as being in the microcellular system upon the transition into the microcellular system. Accordingly, the location of the mobile telephone will be unknown to the macrocellular system while the mobile telephone remains in the microcellular system.
As a result, on an incoming telephone call, the macrocellular system HLR will still have the mobile telephone listed as being home registered and a page signal will be broadcast on macrocellular frequencies while the mobile telephone is locked onto a microcellular frequency. Consequently, the mobile telephone located in the microcellular network and locked onto a microcellular frequency will miss the page signal and the incoming telephone call.
In current microcellular systems having equipment manufactured by the manufacturer of the macrocellular equipment and being directly connected to the macrocellular system, such as by coaxial transmission lines, microwave links or an optical fiber cable network, via a matched nonstandard proprietary interface, incoming calls may not be missed. In this circumstance, the new microcells are essentially additional macrocells. A mobile telephone located within this type of microcellular network will be tracked by the HLR as being home registered and the MTSO will broadcast a page signal for incoming calls. The page signal will be sent to both the macrocells and the microcells because the microcells are directly connected to the macrocellular system. If the intended mobile telephone provides a page response signal, the incoming call will be set up. In this situation, however, the cellular system provider is constrained to purchase microcellular equipment from the manufacturer of the macrocellular equipment due to the nonstandard proprietary interface between the equipments, thus making the microcellular equipment expensive.
Thus, current microcellular systems which are integrated into existing macrocellular systems must have the same manufacturer as the existing macrocellular equipment to implement the nonstandard proprietary interface between the macrocellular and microcellular equipment and ensure incoming call delivery. Such microcellular systems, however, are unduly expensive. If microcellular equipment not manufactured by the maker of the macrocellular equipment is used, then incoming calls may be missed if a mobile telephone is located in the microcellular system.
Thus, it is desirable to provide for easy and inexpensive off-load cellular service for a macrocellular system by establishing an off-load microcellular system in a small area which requires a high concentration of cellular service. For example, a large office building or shopping mall may require a significant amount of cellular service which could be easily provided using a microcellular system since mobile telephone users typically establish cellular service while walking from office to office in a building or from store to store in a shopping mall. Thus, mobile telephones in these small areas are less likely to rapidly move across large geographic areas, making use of a microcellular system ideal.
In addition, there is currently no method of off-loading cellular service from a macrocellular system to another macrocellular system or to an off-load microcellular system without reconfiguring the macrocellular system to ignore the cellular service in the microcellular system which is providing cellular service in the same area where the macrocellular system had previously provided the cellular service. It is, therefore, desirable to provide this additional or off-load microcellular service for customers in a high concentration area of a macrocellular system without reconfiguring the main cellular system, thereby providing off-load microcellular service which is transparent to the main cellular system.
It is also desirable to provide off-load cellular service for customers in a high concentration area served by a main cellular system by replacing the macrocellular system in the high concentration area with off-load microcellular service without reconfiguring the macrocellular system, thereby providing off-load microcellular service which is transparent to the macrocellular system.
Further, it is desirable to off-load cellular service from a main cellular system using, for example, an off-load microcellular system to provide cellular service in an area of high concentration, without requiring all traffic in the microcellular system to interface with the MTSO. The reason that it is undesirable for the off-load microcellular system to always be required to interface with the MTSO is to reduce the processing burden of the MTSO and because no standard interface has been developed which allows the off-load microcellular system to be easily integrated with the MTSO without the off-load microcellular system being required to implement the specific interface requirements of the MTSO.
It is also desirable to support industry standard methods for mobile telephone registration and incoming call processing between the macrocellular system and the off-load microcellular system. Since various vendors provide MTSOs for cellular service using different interface protocols, an off-load microcellular system that did not support industry standards would be required to know the interface protocol used by each cellular system. Such an off-load microcellular system would be complex and not easily integratable into an already existing cellular system.
Finally, it is desirable that a mobile telephone which is being serviced by the off-load microcellular system be able to establish telephone service with telephone equipment which is located outside the microcellular system. Thus, even though the off-load microcellular system is transparent to the main cellular system, the off-load microcellular system must still be able to provide telephone service with telephone equipment located outside the serving area of the off-load cellular system, such as a PSTN.

Mobility management method for delivering calls in a microcellular network


The present disclosure relates to methods and compositions that allow one to identify in vivo edited cells when employing nucleic-acid guided editing. Additionally provided are automated multi-module instruments for performing editing and selection methods and using the compositions.

In the following discussion certain articles and methods will be described for background and introductory purposes. Nothing contained herein is to be construed as an "admission" of prior art. Applicant expressly reserves the right to demonstrate, where appropriate, that the articles and methods referenced herein do not constitute prior art under the applicable statutory provisions.
The ability to make precise, targeted changes to the genome of living cells has been a long-standing goal in biomedical research and development Recently, various nucleases have been identified that allow for manipulation of gene sequences, and hence gene function. The nucleases include nucleic acid-guided nucleases, which enable researchers to generate permanent edits in live cells. Of course, it is desirable to be able to identify cells that have been properly edited in a resulting cell population; however, in many instances the percentage of edited cells resulting from nucleic acid-guided nuclease editing can be in the single digits.
There is thus a need in the art of nucleic acid-guided nuclease editing for improved methods, compositions, modules and instruments for rapid and accurate identification in vivo of cells that have been properly edited. The present disclosure addresses this need.

Cascade/dCas3 complementation assays for in vivo detection of nucleic acid-guided nuclease edited cells


It is the object of the present invention to provide a sealed container which comprises a container comprising a thermoplastic resin and a stopper which is hardly slackening even when used in combination with the container, and a vacuum specimen-sampling container comprising the sealed container.

Various vacuum specimen-sampling containers, wherein sealed containers, the inside being under a reduced atmospheric pressure state, is known. Among such vacuum specimen-sampling containers, for example, vacuum blood-sampling tubes are most generally used. An example of such vacuum blood-sampling tubes is disclosed in Patent Document 1, for instance.
One example of the vacuum blood-sampling system disclosed in Patent Document 1 is shown in FIGS. 21(a) to 21(c). This vacuum blood-sampling system comprises a vacuum blood-sampling container 80 shown in FIG. 21(a), a vacuum blood-sampling holder 83 shown in FIG. 21(b) and a vacuum blood-sampling needle 85 shown in FIG. 21(c). The vacuum blood-sampling container 80 comprises a blood-sampling tube 82 with an opening at an end and a stopper 81 which seals the opening of the blood-sampling tube 82. The stopper 81 is made of an elastic material having a needle-hole sealing property and a gas barrier property. Here, the vacuum blood-sampling holder 83 is designed so that the vacuum blood-sampling container 80 is inserted therein from the opening at an end. A blood-sampling needle holding hole 84 is formed at the other end of the vacuum blood-sampling holder 83, an internal thread is formed in the blood-sampling needle holding hole 84. On the other hand, the vacuum blood-sampling needle 85 has needle tips 87 and 88 at the both ends. A hub 86 on which an external thread portion is formed is formed on the needle tip 87 side. The hub 86 is designed to be screwed into the blood-sampling needle holding hole 84 of the vacuum blood-sampling holder 83 to be secured therein.
FIG. 23 is a schematic perspective view to explain a method of sampling blood by using the vacuum blood-sampling system disclosed in Patent Document 1. Referring to FIGS. 21(a) to (c)and FIG. 23, the blood-sampling step is explained.
In sampling blood, the vacuum blood-sampling needle 85 is threadedly engaged with the blood-sampling needle holding hole 84 of the vacuum blood-sampling holder 83. Next, the vacuum blood-sampling container 80 is inserted into the holder 83, and pushed in such a degree that the needle tip 87 of the vacuum blood-sampling needle 85 does not penetrate the stopper 81, and the needle tip 87 is once sealed. This makes it possible to prevent blood leaking from the needle tip 87, in insertion of the needle tip 88 into a blood vessel. As shown in FIG. 23, while holding the entire structure of the blood-sampling needle 85, the holder 83 and the blood-sampling container 80 coupled to one after another with the hands in a manner so as to align it along the direction of a blood vessel axis, the blood-sampling operator inserts the tip of the needle 88 on the blood-vessel piercing side into a blood vessel. Next, when the blood-sampling container 80 is further pushed into the holder 83, the needle tip 87 penetrates the stopper 81, and blood flows into the blood-sampling container 80 in accordance with a pressure difference between the blood-sampling container side and the blood vessel side. When the pressure difference between the both sides is reduced to zero, the flow of the blood is stopped, and in this state, the entire blood-sampling system is shifted so that the needle tip 88 is drawn from the blood vessel.
The blood-sampling needle 85 is called as a so-called single blood-sampling needle, which is used when the blood sampling is carried out into a single vacuum blood-sampling container. In carrying out the blood sampling into a plurality of blood-sampling containers, this single blood-sampling needle cannot be used. In other words, since, in exchanging blood-sampling containers, the needle tip 88 needs to be kept inserted into the blood vessel, blood is leaked from the needle tip 87 in the case of using the single blood-sampling needle. In contrast, in the case when a multiple blood-sampling needle 89 having a structure shown in FIG. 22 is used, since an elastic sheath 90 is externally inserted to the needle tip 87 on the stopper piercing side, with the needle tip 87 being coated in an air-tight manner, the leak of blood can be prevented.
In the case when such a multiple blood-sampling needle 89 is used, after an assembled body comprising the multiple blood-sampling needle 89 and the holder 83 is prepared, the needle tip 88 of the multiple blood-sampling needle 89 is inserted into a blood vessel. Then, the blood-sampling container 80 is inserted into the holder 83 so that the blood-sampling container 80 is allowed to communicate with the blood vessel.
With respect to a material used for the blood-sampling tube 82 shown in FIG. 21(a), conventionally, glass has been used, however, in recent years, in place of the blood-sampling tube made of glass, a plastic blood-sampling tube made of a thermoplastic resin having a superior gas-barrier property, such as polyethylene terephthalate, has been used in many cases.
With respect to the elastic material used for the stopper 81 shown in FIG. 21(a), since a superior gas-barrier property is required so as to maintain a proper reduced atmospheric pressure degree inside the blood-sampling container, and since a proper needle-hole sealing property after the withdrawal of the needle tip is required, cross-linking isobutylene-isoprene rubber (cross-linking IIR, cross-linking butyl rubber) has been conventionally used. However, the cross-linking rubber requires a long period of time for a curing reaction step and post-steps, such as water-washing and removing steps of a curing reaction agent and elusive substances derived from side products, etc. of the curing reaction, resulting in degradation in the productivity. For this reason, in recent years, stoppers, prepared by using a thermoplastic resin and a thermoplastic elastomer which can be injection-molded, is proposed, for example, in Patent Documents 2 to 7.
After the blood-sampling by using the vacuum blood-sampling system shown in FIGS. 21(a) to (c), in the case when, for example, a biochemical inspection is carried out thereon, carrying out a centrifugal separation after the completion of coagulation of the blood, serum is obtained as a supernatant fluid so that after the stopper 81 is removed, one portion of the serum is taken by using a pipette and the like and various components, such as electrolytes, enzymes and lipids, are subjected to concentration analyses by using an analyzing device. With respect to the residual specimen, the blood-sampling container is again sealed with the stopper 81 for re-inspection, and stored in a cold state or in a frozen state. In this case, however, when, after a blood-sampling container is once opened and a specimen is partially taken for inspections, the container is re-sealed, the inner air of the container is compressed due to the superior sealing property of the stopper to cause an increase in the inner pressure, and the stopper is gradually raised to eventually come off to often cause a problem, that is, a so-called pop-up phenomenon.
Patent Document 8, on the other hand, discloses a stopper for a bottle having a fit-in structure in which a ring-shaped rib, which protrudes on an internal wall surface or on an external wall surface in the vicinity of an open end of a blood-sampling tube made of glass or plastics, is formed and a ring-shaped groove which is engaged with the ring-shaped rib is formed in a rubber stopper. Moreover, Patent Document 10 discloses an opening and closing device for a cylinder-shaped case in which a screw cap and a rubber stopper are combined with each other.
These fit-in structure or screw cap structure provide effective means for preventing the pop-up phenomenon. However, although the blood-sampling tube made of glass may adopt these structures, the blood-sampling tube made of plastics has a difficulty in adopting these structures because the dimension of the protrusion of the ring-shaped rib to be prepared is limited to only a small one which does not impair the releasing property from the metal mold, unless a complex sliding mechanism is incorporated into a molding metal mold, and it becomes difficult to obtain a clear fitting-in effect. Moreover, the screw cap structure requires frequent attaching and detaching operations to consume much labor in repeating the opening and closing operations of a number of blood-sampling tubes. Since polyethylene terephthalate, which has been adopted as a material for blood-sampling tubes made of plastics in recent years, has a comparatively low thermally deforming temperature of about 65° C., the internal diameter of the blood-sampling tube open portion tends to become larger due to a fitting force exerted by the stopper with a lapse of time, easily resulting in the pop-up phenomenon.
In the case when a thermoplastic resin or a thermoplastic elastomer is used as the stopper, the thermoplastic resin and the thermoplastic elastomer are extremely greater in compression permanent strain in comparison with thermosetting elastomers. For this reason, as time elapses after such a stopper was attached to a blood-sampling tube, in particular, when left for a long time under high temperatures in summer, the fitting force between the stopper and the blood-sampling tube is almost lost in a very short time of days. Therefore, in the case when a stopper made of a thermoplastic resin or a thermoplastic elastomer is used in combination with a blood-sampling tube made of polyethylene terephthalate, a problem arises in which the deformation of the blood-sampling tube and the slackening of the stopper due to the compression permanent strain jointly cause further slackening.    Patent Document 1: Japanese Kokai Publication Sho-62-227316    Patent Document 2: Japanese Kokai Publication Sho-57-59536    Patent Document 3: Japanese Kokai Publication Hei-3-97450    Patent Document 4: Japanese Kokai Publication Hei-4-279152    Patent Document 5: Japanese Kokai Publication Hei-7-51253    Patent Document 6: Japanese Kokai Publication Hei-10-201742    Patent Document 7: Japanese Kokai Publication Hei-11-318868    Patent Document 8: Japanese Kokai Publication Sho-58-142256    Patent Document 9: Japanese Kokai Publication Sho-52-112481    Patent Document 10: Japanese Kohyo Publication Hei-3-505320

Hermetically sealed container and vacuum test substance-collecting container

Abstract: The present invention is a sealed container, which comprises a container with an end being closed and the other end being open, comprising a thermoplastic resin, and a stopper being detachable and capable of sealing the open end of the container, the stopper having a head portion capable of being grasped, a leg portion A being extended downward from the head portion, being along an internal wall surface of the open end of the container, and being capable of exerting a fitting force to the internal wall surface, and a leg portion B being extended downward from the head portion, being along an external wall surface of the open end of the container, and being capable of exerting a fitting force to the external wall surface, and at least a portion of the leg portion B of the stopper contacting with the container and at least a portion of the container contacting with the leg portion A of the stopper having a deflection temperature under load of 60° C. or more under a load of 0.45 MPa or 0.46 MPa.