WO2009048827A1

WO2009048827A1 - Enclosed micro-dispenser and reader

Info

Publication number: WO2009048827A1
Application number: PCT/US2008/078888
Authority: WO
Inventors: Michael J. Pugia; James A. Profitt; Chris T. Zimmerle
Original assignee: Siemens Healthcare Diagnostics Inc
Priority date: 2007-10-08
Filing date: 2008-10-06
Publication date: 2009-04-16

Abstract

An enclosed reagent micro-dispenser and optical reader that takes the position of the micro-dispenser and the reader relative to the dry reagent format and makes it convenient so that it is easy to access the reagents (i.e., put them in and take them out) while at the same time making the timing cycle of the instrument efficient. In addition, the enclosed the reagent micro- dispenser and reader may utilize micro-dispensing and micro-fluidics technologies so that the micro-dispenser and reader may be conveniently located, while at the same time the two do not interfere with one another.

Description

ENCLOSED MICRO-DISPENSER AND READER

TECHNOLOGY FIELD

[0001] The present disclosure relates to reagents and instruments used to measure the quantity of analytes in biological samples. More particularly, the present disclosure relates to an enclosed reagent micro-dispenser and reader used to dispense and read reactions involving analytes in biological samples and reagents to produce an optical response.

BACKGROUND

[0002] Many instruments have been developed to measure the quantity of analytes in various biological samples such as, for example, urine, blood, salvia, extracts of mucus or tissue, etc. Typically, a sample liquid is applied to a surface containing reagents that react with the analyte. The reagents produce a detectable response that may be measured and related to the amount of the analyte.

[0003] Optically, as well as electrochemically, read dry reagents are commonly used for diagnostics and may be read with an instrument, such as an optical reader and/or electrochemical reader. There are several formats of interest, including strip format, card format, and micro-fluidic chip format. For example, dry reagents may be placed on strips as pads or in lateral flow and vertical flow formats; multiple areas of different and discreet dry reagents may be placed on cards; and micro-fluidic chips may include capillary devices that may be used to direct and control flow into the dry reagent stored on the micro-fluidic chip.

[0004] In the typical test, a strip or card containing reagents may be manually dipped in a liquid sample or liquid reagents may be applied to the strip/card, and the reaction between the analyte in the sample and the reagents may be measured. Microchip device formats may include substrates connected by capillaries for delivery of the liquid reagents or biological samples to the format reagents. The reagents themselves can be water soluble or insoluble and dried onto the supporting surface, as in test strips or cards. Alternatively, the reagents may be added as a liquid to, for example, a microchip format. Typically, this application occurs after a sample has been applied. The sample volume should be as small as possible for obvious reasons relating to cost and convenience. What is less obvious is that it is often difficult to obtain uniform and accurate responses when applying small amounts of liquid reagents or biological samples to surfaces containing reagents.

[0005] Deposition of liquid reagents is a familiar operation. Examples include the ink jet-printer, either piezoelectric or bubble actuated, which forms print from the controlled deposition of multiple small droplets. Other methods of depositing small droplets have been proposed, which generally employ piezoelectric principles to create droplets, although they differ from typical ink-jet printers. Examples are found in U.S. Pat. Nos. 5,063,396; 5,518,179; 6,394,363; and 6,656,432. Deposition of droplets of larger droplets through syringe type pipette is also known to be reproducible in diagnostic systems. A commercial example of such pipette systems is the CLINITEK ALTAS ® urinalysis analyzer.

[0006] Micro-dispensing a diagnostic liquid onto a diagnostic reagent is known, see for example, US 2006/0263902 Al, published November 23, 2006. Micro-dispensing systems allow dry reagents to be used without separation of reacted reagent areas from non-reacted areas. A card concept with random access/dispense on demand usage is disclosed in US 2006/0263902. An additional example disclosed in US 2006/0263902 shows the placement of dry reagents in a micro fluidic chip. In this case, the dry reagent is sealed with a cover and the liquid, whether sample or liquid reagent, enters the dry reagent through a capillary.

[0007] After contact between dispensed liquids and reagents is complete, the results may be read using one of several methods. Optical methods are commonly used, which rely on spectroscopic signals to produce responses. Reproducible results may be useful. Optical measurements are affected by the reagent area viewed and by the time allowed for the dispensed liquids and reagents to react. Also, interference between the micro-dispenser and the reader may introduce errors and adversely affect results.

[0008] The instrument to read dry reagents, such as strips, cards and micro-fluidic devices, may be integrated into a small space as the size of medical testing equipment is typically limited. For practical use, the instrument may have a user interface such as a touch screen or buttons, a microprocessor, power supply, and an output method such as, for example, a printer, a display, a communication port, and the like. In addition, when used in the laboratory setting, a sample rack and bi-directional communication are often useful. All of these features may use space and may cause the reagent reader to be larger than desired.

[0009] The position of the dry reagent in relationship to the optical and fluidic components may be used for obtaining the correct optical signal and fluidic flow. This alignment may be achieved using position markers on the dry reagent or reagent holder. These position markers may be detected and adjustments may be made to correct the position, fluidics, and/or signal.

[0010] In addition, in order to ensure accuracy of readings, the sample and reagents may be protected from the environment as reagents may be typically light, heat and moisture sensitive. The impact of environmental factors may be exacerbated for dispensed samples of small volumes, such as those from micro-dispensing systems.

[0011] Thus, in view of the foregoing, there is a need for systems and methods that overcome the limitations and drawbacks of the prior art. In particular, there is a need for a smaller reagent micro-dispenser and reader that protects the sample and reagents from the environment and provides accurate and reproducible results.

SUMMARY

[0012] The following is a simplified summary of the invention in order to provide a basic understanding of some of the aspects of the invention. This summary is not intended to identify key or critical elements of the invention or to define the scope of the invention.

[0013] The present invention is directed to embodiments of an enclosed micro- dispenser and reader that reduces the space required for the device, increases the convenience to the customer, and protects the reagents from the environment.

[0014] An exemplary system for dispensing a liquid onto a dry reagent and for reading a reaction between the liquid and the dry reagent includes a housing, a micro-dispenser, a reader, and a table. The liquid may be any diagnostic liquid. For example, the liquid may be liquid reagent, liquid biological sample, such as blood, urine, and the like, a liquid buffer solution, and the like. The housing defines a cavity, within which the micro-dispenser, reader, and table are secured. The micro-dispenser has a chamber that holds the liquid and a dispensing portion that dispenses the liquid onto the dry reagent. The reader is used to read a response, for example a color response, of the reaction between the liquid and the dry reagent. The reader may be an optical reader or an electrochemical reader. The table is adapted to secure a format on which the dry reagent is disposed. The housing may secure a precision locating and/or positioning system. A motor may be connected to at least the table, optical reader, and/or micro- dispenser to facilitate positioning and aligning the components of the system, as described in greater detail below.

[0015] At least one of the micro-dispenser, reader, and table may move to orient the format in a first position and a second position. In the first position, the micro-dispenser dispenses liquid at a first point on the dry reagent. In the second position, the first point is aligned with the reader.

[0016] The use of micro-dispensing technology allows liquid reagent and/or liquid biological sample to be held in a chamber of a micro-dispenser separate and/or distanced from the dry reagent format. A dispensing portion of the micro-dispenser separates the liquid and the dry reagent format. The dispensing portion includes one or more open nozzles. The nozzles are sized such that little liquid leaks into the enclosed environment.

[0017] The dispensing portion controls the volume and/or area of the dispensed liquid. The dispensing portion may dispense the liquid droplets having diameters in the range of about 0.05 mm to about 1 mm (and/or the area/volume equivalent) onto designated areas of the dry reagent. The dispensing may occur in an area of the dry reagent with a diameter of about 0.05 mm to about 5 mm (and/or the area equivalent). The dispensing area may be any shape. For example, the dispensing area may be made square, linear, circular, and/or the like. These areas can be the same or separate areas and/or connected by a fluidic path. Since the reacted reagent areas are small, they do not threaten unreacted reagent. Consequently, reacted reagent areas may be situated in close proximity on the same dry reagent format, thereby using less reagent per sample. The table which secures and positions the dry reagent format, the optical reader, and the micro-dispenser may be disposed in a single housing. The housing's cavity may have a minimum cross section diameter of about 5 cm to 10 cm and/or a cubic volume of about 125 cm² to about 1000 cm².

[0018] Additional features and advantages of the invention will be made apparent from the following detailed description of illustrative embodiments that proceeds with reference to the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The foregoing summary, as well as the following detailed description of preferred embodiments, is better understood when read in conjunction with the appended drawings. For the purpose of illustrating the invention, there is shown in the drawings exemplary constructions of the invention; however, the invention is not limited to the specific methods and instrumentalities disclosed. Included in the drawing are the following Figures:

[0020] FIG. 1 is a block diagram of an exemplary enclosure system for dispensing a liquid onto a dry reagent and reading a resultant reaction between the liquid and the dry reagent;

[0021] FIGs. 2A-C depict exemplary dry reagents in strip, card, and micro-fluidic chip formats, respectively;

[0022] FIG. 3 is a three-dimensional rendered view of an exemplary micro-fluidic chip format;

[0023] FIGs. 4A and 4B are three-dimensional rendered views of various aspects of an exemplary micro-fluidic chip format; [0024] FIGs. 5A-D depict stages of operation of an exemplary enclosure system for dispensing a liquid onto a dry reagent and reading a resultant reaction between the liquid and the dry reagent;

[0025] FIG. 6 depicts an exemplary footprint for a moving micro-dispenser and optical reader with a stationary reagent format;

[0026] FIG. 7 depicts an exemplary footprint for a vertically moving micro-dispenser and optical reader with a laterally moving reagent format;

[0027] FIG. 8 depicts an exemplary footprint for a laterally moving micro-dispenser and optical reader with a vertical moving reagent format;

[0028] FIG. 9 depicts an exemplary footprint for a moving reagent format and a stationary micro-dispenser and optical reader;

[0029] FIG. 10 shows a sectional view of a first exemplary micro-dispensing system with a multiple hole nozzle depositing liquid droplets;

[0030] FIG. 11 shows a sectional view of a second exemplary micro-dispensing system with a moving nozzle depositing liquid droplets;

[0031] FIG. 12 shows a sectional view of a third exemplary embodiment of the micro-dispensing system; and

[0032] FIG. 13 is a process flow for dispensing a liquid and for reading a reaction between the liquid and a dry reagent.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0033] The following is a description of several exemplary embodiments of systems and methods for dispensing and reading reagents involving analytes in biological samples and reagents to produce an optical response. An enclosed reagent micro-dispenser and reader may be used to more efficiently measure the quantity of analytes in biological samples. The enclosed micro-dispenser and reader conveniently positions the reagent micro-dispenser and the reader relative to the dry reagent format, or vice-versa, so that it is easy to access the reagents (e.g., put them in and take them out), reduces interference between the micro-dispenser and reader, and at the same time improves or maintains the timing cycle of the instrument. The enclosed reagent micro-dispenser and reader may utilize micro-dispensing and/or micro-fluidic technologies so that the micro-dispenser and reader may be more conveniently located, while at the same time reducing / eliminating interference between one another.

[0034] The enclosure reduces the space required for dispensing liquid and reading reactions involving analytes in biological samples and reagents. Further, the enclosure helps protect the sample and reagents from the environment, including light, heat, moisture, etc. [0035] FIG. 1 is a block diagram of an exemplary system for dispensing a liquid 112 onto a dry reagent (not shown) and reading a resultant reaction between the liquid 112 and the dry reagent. The system includes a micro-dispenser 100, an optical reader 102, and a table 104 each enclosed in a housing 106. The housing 106 defines a cavity 108 within which the micro- dispenser 100, optical reader 102, and table 104 are secured. The table 104 secures and/or positions a dry reagent format 110, such as a strip, card, and/or micro-fluidic chip. The format 110 is aligned with micro-dispenser 100, and the micro-dispenser 100 dispenses a liquid 112 onto the format 110. In one embodiment, the liquid 112 may be a liquid reagent and/or a biological sample. In a second embodiment, the micro-dispenser 100 may deposit biological fluid samples to produce, for example, a uniform layer of the sample over a reagent-containing surface. The liquid 112 and the dry reagent may react to produce a color spot (See FIG. 5B). The format 110 may then be aligned with the optical reader 102, and light 114 reflected from color spot (See FIG. 5C) may reach the optical reader 102. The optical reader 102 measures the color response of the reaction between the dispensed liquid and the dry reagent on the format 110.

[0036] The micro-dispensing system 100 may be used to cover a reagent-containing surface of the format 110 with a uniform layer of a liquid 112 to obtain improved accuracy of results. Each portion of dispensed liquid 112 preferably contacts the reagent-containing surface and makes direct contact to a corresponding portion of the reagents, so that the reaction of the analyte in each portion of the sample occurs where the liquid 112 was deposited.

[0037] The micro-dispenser 100 provides dispensing that is more accurate and precise than that which is obtained with standard pipette systems. The improved accuracy and precision result from the more controlled dispensing, as well as the ability to read the results of the response of the reagents to the sample by viewing a focused spectroscopic image across the entire reagent area as a function of time and position. The micro-dispenser 100 may be located and designed to reduce carry-over between adjacent reagent areas and contamination of or interference with the optical reader 102.

[0038] The micro-dispensing of liquid volumes of about 1 uL can be done with the stop/start accuracy as low as about 50 uL for one drop. This may be a minimum error of about 50 x 10^"6uL (and/or 0.005% at 1 uL). The range of total volume dispensed as can as high a several hundred uL comprised of multiple small droplets.

[0039] In one embodiment, the micro-dispenser 100 may be any system, subsystem, and/or component suitable for dispensing a discrete volume of liquid 112 onto a format 110. For example, the micro-dispenser 100 may dispense droplets of liquid 112 with volumes between microliters and nano liters. The micro-dispenser 100 may include a dispensing portion 116, a chamber 118, and a receiving portion 120. In another embodiment, the dispensing portion 116 may include a piezoelectric device and one or more nozzles. The nozzles may include a small aperture through which the liquid 112 may be dispensed. For example, the aperture may be between about 0.1 mm to about 1.0 mm in diameter. The liquid 112 may be driven through the nozzles via the piezoelectric device. The nozzles are sized to reduce and or prevent leakage of the liquid 112 when the piezoelectric device is not engaged. The dispensing portion 116 may have an array of nozzles to dispense the liquid 112 within an area of dry reagent. For example, the area may have a diameter of about 0.05 mm to about 5 mm (and/or the area equivalent). Such micro-dispensing may allow more results per reagent area thereby reducing the overall space needed to enclose the format 110.

[0040] The chamber 118 is suitable for storing liquid sample and/or liquid reagent. The chamber 118 is connected to the dispensing portion 116 and/or the receiving portion 120, such that liquid 112 from the chamber 118 may be dispensed via the dispensing portion 116. The micro-dispenser 100 may include one or more chambers 118. For example, a first chamber (not shown) may hold a liquid reagent, while a second chamber (not shown) may hold a liquid biological sample. A third chamber (not shown) may, for example, hold a buffer solution. The chambers 118 may be connected to discrete nozzles of the dispensing portion 116 or the nozzles may be shared.

[0041] In another embodiment, the chamber 118 may receive one or more removable cartridges (not shown). The removable cartridges may hold the liquid 112. The removable cartridges may be inserted and/or removed from the chamber 118 via the receiving portion 120 of the micro-dispenser 100. When the removable cartridge is inserted in the chamber 118, the liquid 112 within the removable cartridge may be available to the dispensing portion 116 of the micro-dispenser 100.

[0042] The receiving portion 120 may be connected to the dispensing portion 116 and/or the chamber 118, such that liquid 112 received at the receiving portion 120 may flow to the chamber 118. The receiving portion 120 may be situated such that the liquid 112 may be received outside of the housing 106. For example, the receiving portion 120 may be disposed through the top of the housing 106 and accessible from outside of the housing 106. The receiving portion 120 may include an access/closure 122. The access/closure 122 may be a door, hatch, and the like that protects the liquid 112 in the chamber 118 from environmental factors outside of the housing 106. A seal (not shown) may be provided between the access/closure 122 and the opening in the housing 106. [0043] The reaction between the biological sample and the reagents may be read by the optical reader 102. In another embodiment, electrochemical sensors may be placed in the dry reagent area. For example, electrochemical sensors may be positioned to an electrical input/ output connector to allow the signals to be transferred to the instrument circuit. As in the case of the optical reader, the electrochemical sensors may be positioned for signal and fluidic accuracy. In another embodiment, a spectrographic image of the reagent-containing surface may be obtained by optical methods. For example, the optical reader 102 may include a photo-diode, a Charge Coupled Device (CCD) imager, and the like. The optical reader 102 may include one or more optical devices such as a lens, optical fiber, light guide, and the like. The optical reader 102 may include an illumination unit, such as a Light Emitting Diode (LED), incandescent light, florescent light, and the like. The optical devices may direct the light from the illumination unit to the surface of the format 110. The light 114 reflected from the surface of the format 110 may reach the optical reader 102 and be measured.

[0044] The housing 106 may be any enclosure suitable for securing the micro- dispenser 100, optical reader 102, and/or table 104. The housing 106 is selected to be suitable for protecting the liquid 112 sample and/or reagent from the environment, including light, air, moisture, and the like. The housing 106 may, optionally, be hermetically sealed and/or made of an opaque material. The housing 106 may be a plastic or metal enclosure. The housing 106 has a top, a bottom, and one or more side walls. The housing 106 may have an access/closure 122 for the receiving portion 120 of the micro-dispenser 100 and/or an access/closure 124 for receiving the table 104 and/or the format 110. In an embodiment, the access/closure 122 for the receiving portion 120 may be disposed through the top of the housing 106. In an embodiment, the access/closure 124 for the table and/or the format 110 may be disposed through the sidewall of the housing 106. Seals may be provided at the access/closure 122 and/or access/closure 124.

[0045] The housing 106 defines the cavity 108. The construction of the micro- dispenser 100 and optical reader 102 of the present invention provide for a reduced space requirement. For example, the cavity 108 may have an effective minimum cross section diameter of about 5 to about 10 cm and/or a cubic volume of about 125 to about 1000 cm².

[0046] The table 104 may be secured to the base of the housing 106. The table 104 secures the format 110 for dispensing and reading by the micro-dispenser 100 and optical reader 102, respectively. For example, the table 104 may secure the format 110 physically by rails along the sides of the format 110. The table 104 may include a depression that corresponds to the size of the format 110, such that the format 110 is secured within the depression. The table 104 may include a vacuum that generates an area of low air pressure between the table 104 and the format 110; thus securing the format 110 to the table 104. The table 104 may include mechanical tabs and/or arms that provide pressure to the surface of the format 110 at the handling region (see FIGs. 2A and 2B).

[0047] The table 104 may be disposed beneath the micro-dispenser 100 and/or the optical reader 102 within the housing 106. For example, as shown in FIG. 1, the table 104 may be disposed horizontally along a base portion of the housing 106 with the micro-dispenser 100 and/or optical reader 102 oriented vertically above the table 104. For example, the dispensing portion 116 may be between about 1 mm to about 5 mm above the surface of the format 110 when the format 110 is secured by the table 104. In an alternative embodiment (not shown), the table 104 may be positioned vertically, with the micro-dispenser 100 and optical reader 102 oriented horizontally. The dispensing portion 116 may use a micro-dispensing jet that projects the droplets from the dispensing portion 116 to the dry reagent. The table 104, the micro- dispenser 100, and optical reader 102 may be positioned at any angle relative to the housing 106.

[0048] The table 104 may include a magnet (not shown) disposed under the format 110 when the format 110 is secured by the table 104. The magnet may be used for the separation of magnetic particles within the liquid 112 sample and/or liquid 112 reagent dispensed on the dry reagent. In an embodiment, the magnet may be a controllable electromagnet.

[0049] The format 110 may include a dry reagents disposed on a body suitable for receiving a dispensed liquid 112 and presenting a color spot for reading. For example, the format 110 may be a strip, card, and micro-fluidic chip, and the like. (See FIGs. 2A-C)

[0050] The table 104, micro-dispenser 100, and/or optical reader 102 may be secured within the cavity 108 of the housing 106. The table 104, micro-dispenser 100, and/or optical reader 102 may be movably secured within the cavity 108 such that the format 110, secured by the table 104, may be positioned relative to micro-dispenser 100 and/or the optical reader 102. For example, at least one of the micro-dispenser 100, the optical reader 102, and/or the table 104 may move to orient the format 110 in one or more positions including, for example, a first position and a second position. The micro-dispenser 100, the optical reader 102, and/or the table 104 may move together and/or individually vertically, horizontally, rotationally, and the like.

[0051] In the first position, a first point of the format 110 may be aligned with the micro-dispenser 100. The micro-dispenser 100 may dispense one or more liquids 112. For example, the micro-dispenser 100 may dispense a liquid sample, a liquid reagent, and/or the like. The dispensed liquid 112 may cause a reaction on the format 110. The site of this reaction may create a color spot. The format 110 may then be oriented in the second position. [0052] In the second position, the first point, at which the liquid 112 was dispensed, may be optically aligned with the optical reader 102. Thus, the optical reader 102 may measure the color response of the color response and may determine a reading from the reaction.

[0053] The position of the dry reagent format 110 in relationship to the optical reader 102 and micro-dispenser 100 may be established by movement of the table 104, optical reader 102, and/or micro-dispenser 100 by motors, rails, slides, conveyors, rotation and/or other movement means.

[0054] To guide and/or provide feedback for the movement, position markers on the dry reagent and/or table 104 may be used. These position markers may be detected and adjustments may be made to correct the position. It may be expected that the optical reader 102 optically align with the center of the area in which the liquid 112 was dispensed.

[0055] The position tolerance for the center of the micro-dispenser 100 may be dependent on the area on dry reagent format 110 expected to receive the fluid and the size of the droplets. Liquid receiving areas having diameters of about the same as the droplet diameters may be at about 1% position accuracy. As the ratio of receiving diameter to droplet diameters decreases, the position tolerance may widen, to be at least less than about 10% of the droplet diameters. Similarly, reacted areas with diameters of about 0.05 mm to about 5 mm may have an optical reader 102 on center by about 0.0005 mm to about 0.05mm (for 1% position accuracy). This position tolerance may be dependent on the optical design. The position tolerance may be less than about 10% of the reacted areas diameters.

[0056] The system may include a processor (not shown) that may control the various aspects of the operation of the dispensing, reading, and moving. For example, the processor may be operable communication with the micro-dispenser 100, optical reader 102, and/or a motor. The motor may move the micro-dispenser 100, the optical reader 102, and/or the table. The processor may be in operable communication with a user interface and/or display for receiving input from the user and for displaying results and/or messages to the user.

[0057] FIGs. 2A-C depict exemplary dry reagents. The dry reagent on which the liquid is dispensed may be in a variety of formats. Exemplary formats include strip format 202 as shown in FIG. 2A, card format 204 as shown in FIG. 2B, and micro-fluidic chip format 206 as shown in FIG. 2C.

[0058] As shown in FIGs. 2A and 2B, the strip format 202 and/or the card format 204 may include one or more reagent regions 208 and a handling region 210. Cards are typically similar to strips but may include a wider reagent region 208. In the reagent region 208, one or more dry reagents may be placed on strips and/or in lateral flow and vertical flow formats. As shown, reagents may be deposited as ribbons (as in the card format 204) and/or squares (as in the strip format 202). Each dry reagent may represent a different test and/or analyte. For example, the reagents may include tests for PH and/or urinalysis. The card format 204 may allow for multiple tests to be processed on a single dry reagent ribbon. The handling region 210 may include a piece of plastic, paper, glass, etc. having a handle. The handling region 210 may be suitable for text and barcode printing.

[0059] Generally, the strips and/or cards may be shipped in re-sealable foil bags, plastic enclosures, and the like. The container for the strips and/or cards may also contain calibration labels. The calibration labels may include information encoded on the label. For example, the information may be encoded via a printed serial numbers, bar code, Radio Frequency Identification (RFID), and the like. The information may be indicative of variable characteristics of the dry reagent that is consistent among the dry reagent stored in the container. For example, the dry reagent in the container may have been produced from the same manufacturing batch. The encoded information may be indicative of that batch. The use of calibration labels may reduce variance and may increase stability. The system may include a sub-system that reads the encoded information and/or adjusts the micro-dispenser 100 and/or optical reader 102 on the basis of the encoded information.

[0060] The optical reader 102 may be calibrated. In an embodiment, the optical reader 102 may take a signal from a standard area, such as a white calibration chip, for example. The optical reader 102 may redefine the detected signal to the predefined expected value. In an embodiment with a electrochemical reader, electronic signals and data may be used to redefine the signal detected. In an embodiment, the response profile for the reagent may be read. This may be pre-measured values or newly measured values using a calibration solution of a defined composition. The response profile for the reagent may be adjusted accordingly. In an embodiment, the micro-dispenser 100 may use the signal from a standard area measured at a time, to adjust dispensing and achieve a target rate.

[0061] Like the strip format 202 and the card format 204, the micro-fluidic chip format 206, as shown in FIG. 2C, may have one or more dry reagents. The dry reagents may be contained in reagent chambers 210. The reagent chambers 210 may be connected by capillaries 212 that are connected to an inlet port 214. Liquid dispensed at the inlet port may be directed via the capillaries 212 to the dry reagent chambers 210 at which a reaction may occur. The reagent chambers 210, capillaries 212, and inlet port may be embedded in a chip housing 216.

[0062] Generally, the use of micro-fluidic formats, including micro-chip technology and micro-fluidics, in an enclosure provides a system that is convenient and improves the efficiencies of the system. For example, the micro-fluidic chip may improve efficiencies by reducing the range of movement required between the dispensing position 100 and reading position 102 of the enclosure. Because, the micro-fluidic chip may use capillaries 212 to transport the liquid from the inlet port 214 to the reagent chamber 210, the table 104, micro- dispenser 100, and/or optical reader 102 may have less distance to move to optically align the optical reader 102 with the color spot formed at the dry reagent chamber 210. This smaller distance may translate into shorter read times and an improved user experience. In an embodiment, the capillary distance may be matched to the distance between the micro-dispenser 100 and the optical reader 102, such that a stationary micro-dispenser 100 and optical reader 102 may operate in connection with the micro-fluidic chip format 206.

[0063] FIG. 3 is a three-dimensional rendered view of an exemplary micro-fluidic chip format 302. The use of micro-fluidic chip technology that is compatible with conventional dry-reagent technology may provide a highly compact system that may be incorporated into the enclosed micro-dispenser and/or optical reader to support complex assay sequences with minimal or no manual manipulations and simple operation.

[0064] Micro-fluidics may include micron-sized (or nano-sized) structures and/or capillaries embedded in disposable plastics (e.g. , micro-fluidic formats) with mechanisms for fluidic control, metering, specimen application, separation, and mixing of nano liter to microliter volumes. Designs may allow dry reagents to be on separate substrates and liquid reagents to be added. Flow propulsion may occur, for example, by absorbent, flow-through, chromatographic, or capillary actions. Fluid stops may be overcome by movement of the format (i.e., spinning) or dispensing additional liquid. Control of surface energy and mechanical tolerances may be used to control flow propulsion into adsorptive, chromatographic, and capillary zones.

[0065] The design and construction of the reagent format and micro-fluidics may allow for the starting and stopping of liquid reagents and samples, such as blood, urine, or buffer. In this regard, a variety of microstructures may be employed for fluidic control, metering, liquid application, mixing, separation, and the like. For example, vents or vented chambers may be provided for metering and splitting; specimen inlets may be provided for specimen entry and containment; wells or capillary manifolds may be provided to mixing; microstructure interfaces may be provided for homogeneous transfer into separation membranes; miniaturized containers or wells may be provided for liquid storage and release; moisture vapor barrier seals may be provided for ease of use; chambers for reagents; etc.

[0066] As shown in FIG. 3, the micro-fluidic chip 302 may include an inlet port 304, at which the sample may be dispensed. The micro-fluidic chip 302 may include a well 306 for liquid reagent. The liquid reagent and the sample may be mixed and/or transported by one or more capillaries 308. The capillaries may direct the resultant liquid into one or more reagent chambers 310. The reaction that occurs in the one or more reagent chambers 310 may produce readable color spots.

[0067] FIGs. 4A and 4B are three-dimensional rendered views of various aspects and/or microstructures of exemplary micro-fluidic chip formats. As shown in FIG. 4A, an exemplary glucose micro-chip is shown having an inlet 402 connected to a lead channel 404. The lead channel 404 may be connected to a post area inlet 406 leading to a substrate placement area 408 having a plurality of assay areas 410 (48 individual areas shown). Vents 412 may connect the substrate placement area 408 to an overflow well 414. The overflow well 414 may be connected to a well vent 416.

[0068] As shown in FIG. 4B, the micro-fluidic chip may have an inlet 418 connected via a capillary 420 to a containment area 422. The inlet 418 may be a conical inlet used to aid sample transfer from, for example, a fmgerstick drop or a transfer capillary. Conical inlets may reduce dependence on alignment and back pressure. Channels 424 may connect the inlet to a containment area and to reaction chambers 426. Metering 428, vents 430, and liquid wells 432 are also provided to facilitate and/or control fluid flow.

[0069] Grooves and/or vents 430 may be placed across the exit path to achieve a uniform amount of specimen leaving the chamber 426. An overflow chamber may be useful for lowering operator dependence and allowed overfilling. Samples and reagent fluids (i.e., dilution or wash buffers) may be loaded on the chip either at the time of assay or before, within liquid- holding wells. Liquid wells 432 with micrometer-sized exit capillaries and stops at the exits may be used to prevent leakage. Pressure may prompt release of liquids as long as the chamber is properly vented. Seals (not shown) may be used to prevent vapor diffusion through, for example, exit capillaries into other assay areas. Sealed designs may include foils and breakaway designs. Additional microstructures may include: chambers for the separation of particles from fluids; membranes for affinity separation; fluid passageways and capillaries for mixing of reagents and/or samples.

[0070] FIGs. 5A-D depict stages of operation of an exemplary system for dispensing a liquid 112 onto a dry reagent (not shown) and reading a resultant reaction between the liquid 112 and the dry reagent. As shown in FIG. 5 A, the access/closure 122 to the receiving portion 120 of the micro-dispenser 100 may be opened such that liquid 112 sample and/or liquid 112 reagent may be received into the chamber 118 of the micro-dispenser 100. The liquid 112 sample and/or liquid 112 reagent may be received by the receiving portion 120 of the micro- dispenser 100 from outside of the housing 106. Once the liquid 112 sample and/or liquid 112 reagent has been received by the micro-dispenser 100, the access/closure 122 to the receiving portion 120 of the micro-dispenser 100 may be closed.

[0071] The access/closure 124 for receiving the table 104 and format 110 containing the dry reagent may be opened. The table 104 may be accessible from outside of the housing 106. The format 110 may be secured by the table 104 outside of the housing 106. Once the format 110 has been secured by the table 104, the format 110 and the table 104 may be received by the housing 106, and the access/closure 124 may be closed.

[0072] As shown in FIG. 5B, the table 104 may move into a first position. In this first position, the micro-dispenser 100 may align with a first point on the format 110. The micro- dispenser 100 may dispense the liquid 112 sample and/or liquid 112 reagent onto the format 110 at the first point. The table 104 may move into the first position manually and/or automatically. For example the table 104 may be moved into the first position by hand, motor, and the like.

[0073] In an embodiment, the format 110 and/or the table 104 may have a registration mark (not shown). The mark may be in a pre-defined position on the format 110 and/or table 104. The mark may be used for initial positioning of the table 104, micro-dispenser 100, and/or optical reader 102.

[0074] In an embodiment, the table 104 and/or micro-dispenser 100 may move, and the micro-dispenser 100 may at dispense at multiple points on the format 110. For example, the micro-dispenser 100 may contain multiple chambers, each holding a different sample, and the micro-dispenser 100 may dispense each sample at a different point on the format 110.

[0075] The liquid sample, liquid reagent, and/or dry reagent may react according to the analyte being tested. The reaction may cause a color change of the dry reagent on the format 110. Thus, a color spot 502 may develop at the first point.

[0076] As shown in FIG. 5C, the table 104 may move to a second position. In the second position, the color spot 502 developed at the first point may optically align with the optical reader 102. light 114 reflected from the color spot 502 may be received by the optical reader 102. The optical reader 102 may measure the color response of the color spot 502. This measurement may be indicative of the presence or absence and/or concentration of the analyte being tested.

[0077] In an embodiment, the format 110 may be a micro-fluidic chip 302 (See e.g., FIG. 3). The table 104 may move to a first position where the inlet of the micro-fluidic chip 302 aligns with the dispensing portion 116 of the micro-dispenser 100. The micro-fluidic chip 302 and the table 104 may oriented such that when the inlet of the micro-fluidic chip 302 aligns with the dispensing portion 116 of the micro-dispenser 100, the dry reagent chamber 310 of the micro-fluidic chip 302 aligns with the optical reader 102. Thus, the table 104 and format 110 may remain stationary after the liquid reagent and/or liquid sample has been dispensed. The liquid reagent and/or liquid sample may travel via the capillaries 308 of the micro-fluidic chip 302 to the dry reagent chamber 310 which is aligned with the optical reader 102.

[0078] As shown in FIG. 5D, the access/closure 124 for receiving the table 104 and format 110 may be opened. The table 104 and format 110 may be removed from within the housing 106, and the format 110 may be removed from the table 104. The result of the test may be displayed to the user via a user interface and/or display (not shown). In an embodiment, the dry reagent format, the liquid reagent, and/or the liquid sample may be automatically discarded into a waste receptacle (not shown).

[0079] As shown in FIGs. 6-9, movement of the micro-dispenser 100, the optical reader 102, and the format 110 (as moved by the table 104), may define different footprints 602, 702, 802, 902. The footprint 602, 702, 802, 902 may influence the overall size of the cavity and/or housing. The micro-dispenser 100 and optical reader 102 may be coupled into a unit 604. For purposes of describing the geometry, an imaginary line 606 may connect the micro-dispenser 100 and the optical reader 102. As shown in FIGs. 6-9, a lateral direction 608 may be substantially parallel to the imaginary line 606, and a vertical direction 610 may be substantially perpendicular to the imaginary line 606.

[0080] The motion of the components described in FIGs. 6-8 may be actuated by a motor (not shown). The motor may be a geared controllable motor, a stepper motor, a piezoelectric motor, and the like. The motor may provide precise control of the position of the components described in FIGs. 6-8. The position tolerance for the center of the micro-dispenser 100 may be dependent on the area of dry reagent expected to receive the fluid. For example, the position tolerance may be less than about 10% of the droplet diameters. For example, the position tolerance for the center of the receiver for optical reader may be less than 10% of the reacted areas diameters.

[0081] FIG. 6 depicts an exemplary footprint 602 for a moving micro-dispenser 100 and optical reader 102 with a stationary reagent format 110. The unit 604 may move in the lateral direction 608 and in the vertical direction 610 relative to the stationary reagent format 110.

[0082] The size of the unit 604 may define the overall footprint 602. The footprint 602 may include the area swept by the unit 604 as it moves in the lateral direction 608 and in the vertical direction 610 to cover the entire reagent format 110. FIG. 6 shows the unit 604 in four extreme positions relative to the reagent format 110. For example, the unit 604 may move to a first position 612 at the first corner of the reagent format 110. For example, the unit 604 may move to a second position 614 at the second corner of the reagent format 110. For example, the unit 604 may move to a third position 616 at the third corner of the reagent format 110. For example, the unit 604 may move to a fourth position 618 at the fourth corner of the reagent format 110. For example, the unit 604 may move in the lateral direction 608 and in the vertical direction 610 to dispense and/or read at any point on the reagent format 110.

[0083] FIG. 7 depicts an exemplary footprint 702 for a moving micro-dispenser 100 and optical reader 102 with a moving reagent format 110. The unit 604 may move in the vertical direction 610, and the reagent 110 may move in the lateral direction 608. The size of the unit 604 and the reagent format 110 may define the footprint 702. The unit 604 may be in a first position 704, and the unit 604 may move in the vertical direction 610 to a second position 706. The reagent format 110 may be a first position 708 and the reagent format 110 may move in the lateral direction 608 to a second position 710.

[0084] FIG. 8 depicts an exemplary footprint 802 for a moving micro-dispenser 100 and optical reader 102 with a moving reagent format 110. Here, the unit 604 may move in the lateral direction 608, and the reagent 110 may move in the vertical direction 610. Again, the footprint 802 may be defined by the size of the unit 604 and/or reagent format 110. The unit 604 may be in a first position 804, and the unit 604 may move in the lateral direction 608 to a second position 806. The reagent format 110 may be in a first position 808, and the reagent format 110 may move in the vertical direction 610 to a second position 810.

[0085] FIG. 9 depicts a exemplary footprint 902 for a moving reagent format 110 with a stationary micro-dispenser 100 and optical reader 102. Here, the unit 604 may be stationary, and the reagent format 110 may move in both the vertical direction 610 and the lateral direction 608. For example, the reagent format 110 may move to a first position 904, the reagent format 110 may move to a second position 906, the reagent format 110 may move to a third position 908, and the reagent format 110 may move to a fourth position 910. The reagent format 110 may be in any position between and/or among these four extreme positions. The size of the reagent format 110 may define the overall footprint 902.

[0086] FIGs. 10-12 show exemplary dispensing portions lOOOa-c for depositing a diagnostic fluid 1006a-c onto reagent formats 1008a-c. The micro-dispensing system may include a nozzle 1002a-c having one or more openings arranged in an array. Multiple openings may be used to deposit sample over the reagent-containing surface simultaneously. Alternatively, single droplets of the sample may be deposited in a pattern on the reagent- containing surface.

[0087] In FIGs. 10-12, the nozzles 1002a-c have openings such that the droplets fall vertically onto the test area. A plate may have holes that define the openings. The plate may be curved with the droplets falling at an angle. To minimize cross contamination and to reduce the size of the overall device, the distance between the nozzle 1002a-c and the format 1008a-c may be preferably as small as possible; typically greater than about 1 mm and less than about 5 mm for accurate droplet 1006a-c placement, as determined by the size of the droplets 1006a-c and their trajectory.

[0088] Precisely depositing liquid 1006a-c makes it possible to space test areas closely on a format 1008a-c containing reagents, while avoiding cross-contamination. The number and size of the nozzle openings will vary depending on the application. Since the nozzles 1002a-c may be sized to dispense droplets 1006a-c over a given size test area, it will normally be the case that the nozzles 1002a-c may be roughly the size of the test area as a minimum, or much smaller when using multiple holes or multiple passes over the test area. The test area of course may be small, for example about 1 to 25 mm square, and may have any desired shape such as, for example, squares and circles. Use of a micro-dispenser lOOOa-c having nozzles 1002a-c that provide accurate placement of the liquid 1006a-c allow the test areas to be closely spaced. This feature improves efficiency and accuracy of the analysis and reduces the size of the device.

[0089] Depending on the reagents, the test areas may be spaced as close as about 1 mm to about 10 mm (from center to center) with only about 0.3 mm to about 8 mm between adjacent edges of the test areas. Spacing may be set to prevent cross contamination of chemicals in adjacent reagent areas, especially when the reagent areas are sharing the small spaces and air.

[0090] When this method of dispensing a small droplets 1006a-c onto a reagent area is adopted, it is possible to improve the method of reading the optical response of the reagents to the sample. In the conventional technology, the response of the reagents (i.e., color development), is determined for the entire reagent area by supplying light having the desired wavelengths to the area and measuring the returned or transmitted light to a reader (i.e., a photo detector). The amount of light measured is correlated with the amount of the analyte in the sample that has reacted. In effect, an average of the color developed over the reagent area is read. A more accurate measurement would ruminate the reagent area in a pattern and manner corresponding to the deposition of the sample liquid 1006a-c. That is, a light beam could traverse (scan) the reaction area and the returned or transmitted light could be received and measured, one spot (pixel) at a time. As a result, a scanned spectroscopic image can be obtained at predetermined times to provide spectral information at various pixel positions across the reagent surface.

[0091] The nozzles 1002a-c may be supplied with sample fluid or reagent under pressure from a source, which may be for instance, a syringe pump, diaphragm pump, pressurized container, piezo actuator, diaphragm, peristaltic, vortex, suction, centrifugal and the like with or without check-valves, splitters, air supply and venting.

[0092] Many arrangements of the micro-dispenser lOOOa-c are contemplated within the scope of the invention. It is expected that the nozzles 1002a-c will be used in automated analyzers where advantage can be taken of their superior coverage of the test area. For example, more than one nozzle 1002a-c could be used, arranged in groups of 1 to n, supplied by 1 to n liquid sources, either individually or in groups. The nozzles 1002a-c could be supplied and replaced individually or in groups. Since the nozzles 1002a-c may require replacement after depositing 100 to 1000 samples, either for cleaning or for disposal, they would be likely made in groups that are easily removed and replaced.

[0093] In another embodiment, the entire reagent area is not covered simultaneously with sample liquid 1006a-c by deposition from a nozzle containing many openings. Instead, the reagent area is covered with small droplets 1006a-c, one at a time, tracing out patterns in the reagent area. This process is analogous to the ink jet printer in that droplets 1006a-c are deposited in lines, but rather than forming characters separated by spaces free of ink, the present process covers substantially all of the reagent area and assures that all of the reagents react with the sample and as uniformly as possible. Depositing droplets 1006a-c in this matter requires movement of the depositing nozzle 1002a-c or the reagent area, or both.

[0094] In addition to using single nozzles 1002a-c, other possible arrangements include multiple nozzles 1006a-c, each one supplied from one or more containers for the liquids to be dispensed. The nozzles 1002a-c could be moved from one test area to another, or the test areas could be moved under stationary nozzles 1002a-c. In one arrangement, multiple nozzles 1006a-c are used to dispense different liquids 1006a-c onto reagents. The chamber 1004a-c supplying the nozzles 1002a-c also may be washable between samples. Alternatively, an array of nozzles 1002a-c with separate containers 1004a-c could be used, with each dispensing a separate sample or with each dispensing the same sample onto separate test areas.

[0095] Precise deposition of the biological sample and the spectroscopic imaging of the reagent area makes it possible to deposit additional reagents as desired at the time the biological sample is being tested. In one embodiment of the invention, after the biological sample has been deposited on the reagent area, an additional reagent (or reagents) is deposited on all or selected portions of the reagent area.

[0096] Alternatively, additional reagent (or reagents) could be deposited before the biological sample is placed on the reagent area. This could serve to activate other reagents already in place, for example, or to add a reagent having a short shelf life that could otherwise not be used.

[0097] In still another embodiment, the additional reagent (or reagents) could be added simultaneously with the biological sample. This method could provide mixing needed for lysis of cells, affinity reactions, chemical reaction, dilutions, etc. Further, a liquid 1006a-c may be dispensed onto a reagent area after the sample has been added.

[0098] FIG. 10 shows a sectional view of a first exemplary micro-dispenser 1000a with a multiple hole nozzle 1002a dispensing system depositing liquid droplets 1006a. The micro-dispenser 1000a is an exemplarily embodiment that may be used in the micro-dispenser 1000a and reader, in which a nozzle 1002a may be supplied from liquid chamber 1004a and multiple nozzle openings dispense droplets 1006a onto a dry reagent format 1008a. The dry reagent format may be secured by a table 1010a.

[0099] FIG. 11 shows a sectional view of a second exemplary moving nozzle dispensing system depositing liquid droplets 1006b. A second exemplary embodiment of the micro-dispenser 1000b is shown in FIG. 11, in which a nozzle 1002b may be supplied from liquid chamber 1004b and a single nozzle opening dispenses droplets 1006b onto a dry reagent area 1008b. The dry reagent format may be secured by the table 1010b.

[0100] FIG. 12 shows a sectional view of a third exemplary nozzle dispensing system depositing liquid droplets 1006c. The liquid chamber 1004c supplies the nozzle 1002c that dispenses droplets 1006c to a hydrophobic surface 1010 of the format 1008c adjacent to a dry reagent area 1012. The dispensed droplets 1006c may migrate to the dry reagent area 1012 via capillary action. For example, the hydrophobic surface 1010 and the dry reagent area 1012 may be disposed on a micro-fluidic chip and/or may be separated by one or more capillaries. The droplets 1006c may be smaller than the capillaries to facilitate transfer and reduce the formation of a bubble.

[0101] FIG. 13 is a process flow for dispensing a liquid and for reading a reaction between the liquid and a dry reagent. At 1302, a liquid may be received by the receiving portion of the micro-dispenser. The liquid may be liquid reagent and/or liquid sample. The liquid sample may be blood, urine, saliva, extracts of mucus and/or tissue, and the like. [0102] At 1304, the format may be received by the table. The table may secure the format. The table may be movably secured to the base of the housing. The format may include one or more areas of dry reagent.

[0103] At 1306, the format may be oriented relative to the micro-dispenser. In an embodiment, the table may move the format relative to the micro-dispenser such that an area of dry reagent is aligned with the micro-dispenser. In an embodiment, the micro-dispenser may move relative to the format such that the area of dry reagent is aligned with the micro-dispenser. In an embodiment, a combination of the table and the micro-dispenser may move such that the area of dry reagent is aligned with the micro-dispenser.

[0104] At 1308, the micro-dispenser may dispense the liquid onto the area of dry reagent. The total volume of the liquid dispensed from multiple drops maybe between about 300 nL and about 500 μL. The dispensed liquid may react with the dry reagent. Reaction may develop a color spot indicative of analyte being tested.

[0105] At 1310, the format may be positioned such that the color spot aligns with an optical reader. In an embodiment, the table may move the format relative to the optical reader. In an embodiment, the optical reader may move relative to the format. In an embodiment, a combination of the table and the optical reader may move such that the color spot aligns with the optical reader. Aligning the color spot with the optical reader enables light reflected from the color spot to reach the optical reader.

[0106] At 1312, the optical reader may measure the intensity of the color spot. The optical reader may measure the intensity of the color spot by measuring the intensity and/or wavelength of light reflected from the color spot. The measurement may be provided to a user via a user interface and/or display. The measurement may be indicative of the presence or absence and/or concentration of the analyte being tested.

[0107] Embodiments of the present invention may be useful in applications such as immunoassay, chemistry, blood gas, electrolyte, nucleic acid, hematology, coagulation testing, and the like. The embodiments preferably support complex processing for the quantitative analysis of blood and urine specimens (e.g., urinalysis, blood glucose, hemoglobin (Hb) AIc testing).

[0108] While the present invention has been described in connection with the exemplary embodiments of the various figures, it is not limited thereto and it is to be understood that other similar embodiments may be used or modifications and additions may be made to the described embodiments for performing the same function of the present invention without deviating therefrom. Furthermore, it should be emphasized that a variety of dry reagent format shapes and sizes are contemplated. Still further, the present invention may be implemented in or across a plurality of chemical processes involving multiple samples, liquid reagents, buffers, and/or dry reagents. Therefore, the present invention should not be limited to any single embodiment, but rather should be construed in breadth and scope in accordance with the appended claims. Also, the appended claims should be construed to include other variants and embodiments of the invention, which may be made by those skilled in the art without departing from the true spirit and scope of the present invention.

Claims

What is Claimed:

1. A system for dispensing a liquid onto a dry reagent and for reading a reaction between said liquid and said dry reagent, wherein said dry reagent is disposed on a format and said reaction causing a color response, the system comprising: an enclosed housing that defines a cavity; a micro-dispenser held by said housing, said micro-dispenser having a dispensing portion disposed within said cavity that dispenses the liquid onto the dry reagent; a reader held by said housing and disposed within said cavity, said reader adapted to measure said color response; and a table in connection with the housing and adapted to removeably hold the format thereon, wherein at least one of said micro-dispenser, said reader, and said table moves to orient the format between a first position and a second position, wherein the first position aligns a first point of the format with the dispensing portion and the second position aligns the first point with the reader.

2. The system of claim 1 , wherein the reader is an optical reader.

3. The system of claim 1, wherein the reader is an electrochemical sensor.

4. The system of claim 1, wherein the format is strip format.

5. The system of claim 1, wherein the format is card format.

6. The system of claim 1, wherein the housing defines a base, a top, and at least one side wall, wherein the base, top, and sidewall are opaque.

7. The system of claim 6, wherein the table is movably secured to the base.

8. The system of claim 6, wherein the micro-dispenser defines receiving portion connected to the dispensing portion, and wherein the receiving portion is disposed through the top of the housing, such that the liquid is received by the receiving portion from outside the housing.

9. The system of claim 6, wherein the housing defines an access aperture therethrough.

10. The system of claim 9, wherein access aperture is adapted to received the format, such that the format is placed on the table while the table is inside the housing.

11. The system of claim 9, wherein the access aperture is adapted to receive the table and wherein the table moves through the aperture outside of the housing, such that the format is placed on the table while the table is outside the housing.

12. The system of claim 9, further comprising a closure coupled to the aperture, wherein the closure is adapted to cover the aperture.

13. The system of claim 1 , wherein the table moves to orient the format in the first position and the second position.

14. The system of claim 1 , wherein the said micro-dispenser and the reader move to orient the format in the first position and the second position.

15. The system of claim 1, wherein the table, micro-dispenser, and the reader move to orient the format in the first position and the second position.

16. The system of claim 15, wherein the table moves in a first direction, and the micro- dispenser and the reader move in a second direction, perpendicular to the first direction.

17. The system of claim 15, wherein a first imaginary line is defined between the reader and the micro-dispenser, and wherein the first direction is parallel to the first imaginary line.

18. The system of claim 15, wherein a first imaginary line is defined between the reader and the micro-dispenser, and wherein the first direction is perpendicular to the first imaginary line.

19. The system of claim 1, wherein at least one of said micro-dispenser, said reader, and said table moves to orient the format in a third position and a forth position, wherein the third position aligns a second point of the format with the dispensing portion and the forth position aligns the second point with the reader.

20. The system of claim 1, wherein the dispensing portion comprises a piezoelectric device.

21. The system of claim 1 , wherein the dispensing portion comprises a nozzle with an aperture therethrough, wherein the aperture is between 0.1 mm and 1.0 mm in diameter.

22. A system for dispensing a liquid and for reading a reaction between said liquid and a dry reagent, said reaction creating a color response, the system comprising: an enclosed housing that defines a cavity; a micro-dispenser held by said housing, said micro-dispenser having a dispensing portion disposed within said cavity that dispenses the liquid; a reader held by said housing and disposed within said cavity, said reader adapted to measure said color response; a micro-fluidic chip comprising an inlet port, a reagent chamber, and a capillary connecting the inlet port and the reagent chamber; and a table disposed within said cavity and adapted to removably hold the micro-fluidic chip, wherein the micro-fluidic chip is first oriented such that the inlet port aligns with the dispensing portion and is second oriented such that the reagent chamber aligns with the reader.

23. The system of claim 22, wherein the reader is an optical reader.

24. The system of claim 22, wherein the reader is an electrochemical sensor.

25. The system of claim 22, wherein the micro-dispenser and reader are spaced such that the micro-fluidic chip is first oriented and second oriented concurrently.

26. The system of claim 22, wherein the micro-fluidic chip is first oriented and second oriented by the moving at least one of the micro-dispenser, reader, and table.

27. A method for dispensing a liquid and for reading a reaction between said liquid and a dry reagent, said dry reagent said dry reagent being disposed on a format, and said reaction creating a color spot, the method comprising: receiving the liquid in a micro-dispenser positioned within an enclosure; receiving the format at a table; positioning the format relative to the micro-dispenser; dispensing, within the enclosure, the liquid from the micro-dispenser onto the dry reagent at a first point; positioning, within the enclosure, the format such that the first point aligns with a reader, the reader positioned within the enclosure; and measuring, within an enclosure, an intensity of the color response with the reader.

28. The method of claim 27, wherein the micro-dispenser defines a receiving portion disposed through the enclosure and wherein said receiving the liquid comprises receiving the liquid via the receiving portion from outside the enclosure.

29. The method of claim 27, further comprising second dispensing, within the enclosure, the liquid from the micro-dispenser onto the dry reagent at a second point.

30. The method of claim 29, further comprising second positioning, within the enclosure, the format such that the second point aligns with the reader.

31. The method of claim 27, wherein said receiving the format comprises receiving the format on the table within the enclosure.

32. The method of claim 31 , wherein said positioning comprises moving the table.

33. The method of claim 32, wherein said positioning comprises moving the reader.

34. The method of claim 27, wherein said positioning comprises moving the reader.