Patent Document

FIELD OF THE INVENTION 
       [0001]    This invention relates to the field of optical measurements and particularly to spectrophotometry and more particularly to such measurements made upon liquid drops on the order of 2 microliters or less. 
       BACKGROUND OF THE INVENTION 
       [0002]    Robertson, in U.S. Pat. Nos. 6,628,382 and 6,809,826, teaches containment of small droplets by surface tension. These patents are incorporated in their entirety by reference. In addition the method and apparatus disclosed may be applied to fluorometry with apparatus and method as taught in Robertson et al.&#39;s application PCT/US 2006/04406 with inclusion of the special optical requirements in fluorometry to keep the signal from being overwhelmed by incident light. The disclosure of that application is incorporated herein in its entirety by reference. 
         [0003]    In making these measurements, the need for high productivity in the work of the laboratory involved is plain. Instrumentation and method that permit simultaneous, or near simultaneous, operation on multiple samples is most desirable. It is to this end that this invention is directed. 
       SUMMARY OF THE INVENTION 
       [0004]    In brief, the invention is directed to processing in an optical measuring device a plurality of small droplets of liquid (“nanodrops” of micro-liter volume) simultaneously or nearly so. The preferred embodiment of the invention has eight fibers, which preferably are 100 micron, individually picking up light from a flash lamp and feeding the upper fiber bushings of an array of eight paired measurement fiber optic (FO) bushings. Light from the eight receiving fibers, which preferably are 400 micron, is fed to a fiber optic switch or multiplexer where a precision linear actuator scans a single 400-micron fiber across the spaced ends of the eight sample-signal-receiving fibers. The fibers are spaced in the multiplexer by interleaving dead fibers (in the expanded view seen in  FIG. 2   b  these dead fibers are shown as black circles which is a long used industry practice) or can be spaced with the use of a micro machined V-groove block or by packing custom coated the fibers into a cavity machined to be an exact fit. 
         [0005]    Unlike the prior art apparatus disclosed in U.S. Pat. Nos. 6,628,382 and 6,809,826, the upper arm is moved by a stepper motor or servo motor linear actuator to accommodate the weight of the arm. Like the prior art apparatus, the moveable, upper arm after sample loading is moved to a substantially closed position to spread the samples and wet the opposing anvil surfaces and then to a selected more open position to pull the samples into columns to establish optical paths for optical measurements. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0006]      FIG. 1   a  is a view in perspective of the apparatus in the open position. 
           [0007]      FIG. 1   b  is a view in perspective of the apparatus in a closed position. 
           [0008]      FIG. 2   a  is a somewhat schematic partial view in perspective of the scanning apparatus enlarged from  FIGS. 1   a  and  b.    
           [0009]      FIG. 2   b  is a somewhat schematic view in perspective of the fiber array with the scanning means removed and shows a further enlargement to show the spacing of the fibers. 
           [0010]      FIG. 3  shows the perspective view of the apparatus where more than one fiber is scanned across the sample measurement fiber each feeding a separate spectral analysis system. 
           [0011]      FIGS. 4   a  and  b  show an alternate arrangement for holding the source fibers to the moving arm of the apparatus with  4   a  showing the apparatus open without the source fibers and  4   b  showing the apparatus closed with the source fibers. 
           [0012]      FIGS. 5   a, b , and  c  show alternate fiber spacing arrangements with  5   a  also schematically indicating rotary scanning means. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0013]    Consider  FIG. 1   a  showing the apparatus of the invention  10  in the open position which is used for loading and  FIG. 1   b  showing it closed either in the first instance where the surfaces are proximate to spread the samples and wet the surfaces or in the measuring position where the surfaces are moved sufficiently apart to pull the samples into liquid columns for measuring. Light is generated in flash-lamp  12 . We use a lamp from Hamamatsu of Hamamatsu City, Japan. The light is carried by eight supply fibers  14 , preferably 100 micron, to upper arm  16  of the 8-channel measuring instrument  10 . The fibers pass through upper arm  16  and are finished proud of the surface  20  of upper arm  16 . These form the eight upper anvils  22  of the apparatus. Upper arm  16  is pivotally mounted at  18  to fixed arm  24  which serves as a base for the instrument or can be mounted to a base. Eight receiving/detection fibers  26  pass through fixed arm  24  and are finished so as to stand slightly proud of the surface  28  thereof to form eight lower anvils  30 . Preferably the receiving/detecting fibers are 400 micron. These lead to optical switch  32  in which a single fiber  34  is scanned across the eight fibers  26  with apparatus which will be described in detail below—The single scanning fiber  34  leads the signals in turn to measuring means  36 , preferably a spectrometer or fluorometer (see  FIG. 3 ). 
         [0014]    Consider  FIGS. 2   a  and  2   b . Here the scanning mechanism of optical switch  32  is shown in greater detail. In  FIG. 2   a  it is seen that optical switch  32  comprises feed block  38 , scanning block  40 , base/guide slide assembly  42 , and linear actuating mechanism  44 . 
         [0015]    Feed block  38  holds the ends of fibers  26  in spaced linear array. The fiber ends  48  are finished flush with face  46  of feed block  38 . This is seen in more detail in  FIG. 2   b  with both a view in the same scale as  FIG. 2   a  where scanning block  40  is removed and, in greater detail, in the enlarged view. Spacing is provided by inter-leaving active fiber ends  48  with dead fiber ends  50  as seen in the enlargement. “Dead fibers” are simply suitable lengths of fiber not connected to a source. Spacing is important in limiting any cross-talk in reading the signals output by the individual fibers  26 . For convenience, the known convention is used showing the ends of the dead fibers as black circles. Feed block  38  in the physical embodiment is an assembly custom made by Romack of Williamsburg, Va. 
         [0016]    Scanning block  40  mounted on base/guide slide assembly  42 , is constrained by means not shown in detail in base/guide slide assembly  42  to move linearly along the face of feed block  38  so that one end of fiber  34  moves across the eight ends  48  of spaced fibers  26 . It is moved by linear actuating mechanism  44 . In the physical embodiment of the invention, single opposing fiber  34  is a custom SMA terminated fiber optic patch cord also from Romack. 
         [0017]    Base guide slide assembly  42  functions to linearly guide scanning block  40  in orthogonal relationship with fiber ends  48 . In the physical embodiment it is a ball bearing slide from Deltron of Bethel, Conn. p/n E-1. An end stop detector  54  is provided to establish a reference point for the motion of the scanning block. Linear actuating mechanism  44  is a stepper motor linear actuator. We use one fabricated by Haydon Switch of Waterbury Conn. p/n 28H43-05-036. It is plain to one skilled in the art that the linear array of the embodiment and the linear scanning means  32  described and shown, for example, in  FIG. 2   b  could be replaced by a toroidal array scanned by rotary means  32  carrying scanning fiber  34  as schematically indicated in  FIG. 5   a . Alternatively the fibers can be spaced by location in V-shaped grooves in the assembly (see  FIG. 5   c ). Still another embodiment would be to use fibers custom coated to yield suitable spacing in a suitable cavity or to enclose each fiber end in a sleeve  27  as indicated schematically in  FIG. 5   b.    
         [0018]    In a physical embodiment we use a spectrometer fabricated by Ocean Optics of Dunedin, Fla. p/n USB2000 UV/Vis. 
         [0019]    Not shown is the control means of a suitably programmed computer that controls illumination and scanning. Such means and the programming thereof are within the skill of the skilled instrument designer and require no further explication here. 
         [0020]    In use, with the instrument open as shown in  FIG. 1   a , the eight lower anvils  30  are loaded each with a sample of fluid preferably using a pipette permitting simultaneous loading of all 8 samples. Then the instrument  10  is closed as shown in  FIG. 1   b , first to a close sample compression position (as taught in the prior Robertson patents). This spreads the samples and wets both the lower set of anvils  30  and the upper set of anvils  22 . Then, as described in the prior Robertson patents, the two arms  16  and  24  are spaced apart a controlled distance in a substantially parallel relationship to draw each sample into a measuring column between the opposing ends of fibers  14  and  26 . This establishes a substantially parallel relationship between the fiber ends forming the opposing anvils establishing an optical path between the wetted areas on each of the fiber ends The flash-lamp  12  is actuated as the light source, a measurement signal is formed in each measuring column, and fiber  34  is scanned across the eight ends  48  of fibers  26 . Fiber  34  transmits each signal in turn to spectrometer  36  which in practice is connected to means such as a computer for information processing and output display as well as instrument sequencing. 
         [0021]    Because upper arm  16  is much heavier than those in prior instruments described in the prior Robertson patents and application, improved means for actuating the relative motion between pivotally-mounted upper arm  16  and fixed arm  24  have been developed. One such implementation uses a DC servo motor  60  to activate a screw  61  that when turned controls the level of the upper arm when closed. The end of screw  61  bears on a suitable bushing  64  in surface  20  of upper arm  16 . 
         [0022]    In applications needing more complex spectral analysis, a second collecting fiber can be used to collect data simultaneously with the primary fiber as is shown in  FIG. 3 . Here the second fiber  74  is spaced one or more intervals away from the primary scanning fiber  34  and may be associated with a second spectrometer  37 , or other optical measuring instrument as will be seen, as shown in the figure. If the spacing is one interval, then only a single spectrometer will be employed for measurement on either end of the scan. Such measurements could be used to extend the measurement wavelength range beyond that covered by a single spectrometer or the second instrument could be used for entirely different sorts of measurements like fluorescence, the latter requiring additional light sources if the measurement is to be made in the orthogonal illumination fashion of the fluorescence instrument of application PCT/US2006?00406. Multiple fiber measurements can also be used to decrease the time needed to make measurements on the multiple samples. More than 2 spectrometers can be similarly employed by using additional scanning fibers spaced at the same interval as the fiber end group  48 . 
         [0023]    Additionally the supply fibers  14  connecting the moving upper arm  16  to the lamp  12  can be mounted entirely on the arm as is shown in  FIG. 4   a  with the lamp  12  mounted directly to the lower arm  24 . The fibers are coupled by passing through ports  13  in both the lower  24  and upper arm  16 .

Technology Category: g