BIO DISC, BIO-DRIVER APPARATUS, AND ASSAY METHOD USING THE SAME

• US 20100234237A1
• Filed: 05/02/2006
• Published: 09/16/2010
• Est. Priority Date: 04/30/2005
• Status: Active Grant

• Current Assignee: Precision Biosensor Inc.
• Original Assignee: Samsung Electronics Co. Ltd.
• Inventors: Yoo, Jae Chern
• Granted Patent: US 8,993,487 B2
• Time in Patent Office: Days
• US Class Current: 506/9
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/143 Quality control, feedback systems
• CPC Class Codes: B01L 2300/0806 Standardised forms, e.g. compact disc [CD] format
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0633 with moving parts
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: F16K 99/0001 Microvalves microdevices B81B1/00; manufacture or treatment of devices or systems in or on a substrate B81C1/00; microfluidic structures B01L3/5027; micropumps F04B19/006

Abstract

A bio-disc device including new valve control means and fluid movement system, a bio-driver apparatus in which a controller disc including a controller for the bio-disc is installed, and an assay method using the same, which are suitable for labs-on-a-chips for various diagnostic assays, nucleic acid hybridization assays, and immunoassays, are provided. The bio-driver apparatus is compatible with general optical discs, including audio CDs, CD-Rs, game CDs, DVDs, etc., and the assay method is compatible with general optical disc drivers, including CD-ROMs, DVD players, etc. Thus, the bio-driver apparatus and the assay method offer and economical and convenient alternative to existing products. In addition, the bio-driver apparatus can be readily and easily applied in connection with a computer for remote diagnosis via the Internet.

Claims

1. A bio-disc comprising:

a sample inlet;

a chamber which reserves a buffer solution or a reaction solution;

an assay site where bio materials are arrayed on a substrate;

channels through which fluid flows between the sample inlet, the chamber, and the assay site;

a hole which connects the channels; and

a valve which is used to open and close the hole, wherein the valve is constructed with a micro bead, a permanent magnet disposed above the micro bead, and an electromagnetic or movable permanent magnet disposed under the micro bead.

2. The bio-disc according to claim 1, wherein the permanent magnet is mounted as a substitute of an optical pickup module of a general addressable optical pick up apparatus or together with the optical module.

3. The bio-disc according to claim 1, wherein the micro bead is a film-like cylindrical magnet or a film-like cylindrical magnet coated with a cushion material.

9. The bio-disc according to claim 1, wherein the fluid movement is controlled by a centrifugal force due to rotation of the bio-disc and opening and closing of the valve.

11. The bio-disc according to claim 1, the bio material is at least one selected from DNA, oligo-nucleotide, RNA, PNA, ligand, receptor, antigen, antibody, and protein.

12. The bio-disc according to claim 1, wherein the chamber comprises at least one selected from the group consisting of:

a preparation chamber for preparing a DNA sample from blood, cells, or RNA;

a PCR chamber for amplifying the DNA sample through a polymerase chain reaction (PCR);

a label chamber for reserving a label indicator;

a hybridization chamber in which assay and diagnostic probes are arrayed on the substrate for hybridization with the amplified DNA from the PCR; and

a trash chamber for collecting wastes generated from washing.

13. The bio-disc according to claim 12, wherein the preparation chamber reserves a lysis buffer solution used to destruct a cell and extract a DNA through lysis and particles or ferromagnetic beads having affinity to the extracted DNA.

14. The bio-disc according to claim 12, wherein the bio-disc comprises a plurality of the PCR chambers and each PCR chamber reserves one type or several types of primer or all the PCR chambers reserves the same type of primer.

15. The bio-disc according to claim 1, wherein the chamber comprises at least one chamber selected from the group consisting of:

a preparation chamber for preparing a serum sample, an antigen, or an antibody from blood or cells;

an antigen-antibody reaction chamber in which immuno probes are arrayed on the substrate for an antigen-antibody reaction with the prepared antigen or antibody; and

a trash chamber for collecting waste generated from washing.

16. The bio-disc according to claim 15, in the preparation chamber, the serum sample is prepared by using a centrifugal force generated by rotation of the disc.

17. The bio-disc according to claim 16, wherein the preparation chamber has a shape of a conical beaker or a flask in order to facilitate separating serum in centrifugal separation and a channel at a neck portion in order to be connected to a next chamber.

18. The bio-disc according to claim 15, wherein the chamber further comprises a label chamber for reserving a labeled antibody.

19. The bio-disc according to claim 18, wherein the label of the labeled antibody has gold, latex, a fluorescent material, an enzyme, or a radioactive isotope as a coloring particle.

20. The bio-disc according to claim 15, wherein the immuno probe array is constructed by arraying tumor markers on a substrate.

21. The bio-disc according to claim 15, wherein the tumor marker is at least one selected from AFP, PSA, CEA, CA19-9, CA125, and CA15-3.

22. The bio-disc according to claim 15, wherein the immuno probe is at least one selected from myoglobin, CK-MB, and Troponin I (TnI) as a cardiac infraction marker and GS (Glutamine Synthetase) as an Alzheimer'"'"'s disease marker.

23. The bio-disc according to claim 1, wherein the assay site is detected by a detection device coupled with a transforming device and the detection device includes a light transmission type measuring device, an electro-chemical detection device, a capacitance and impedance measuring device, or an image sensor.

24. The bio-disc according to claim 23, wherein the light transmission type detection device comprises:

a laser device (light transmitting unit) which emits a laser beam onto a confined signal element and a released signal element; and

an optical detector (light receiving unit) which detects a differential light transmission signal between the signal elements.

25. The bio-disc according to claim 24, wherein at least one optical detector (light receiving unit) is arrayed and integrated along a circumference of the bio-disc to correspond to each assay site.

26. The bio-disc according to claim 24, wherein at least one laser device (light transmitting unit) and at least one optical detector (light receiving unit) is arrayed and integrated along a circumference of the bio-disc to correspond to each assay site.

27. The bio-disc according to claim 23, wherein the electro-chemical detection device or the capacitance and impedance measuring device comprises:

interdigitated array electrodes disposed on the substrate of the assay site; and

an HRP (Horse Radish Peroxidase) and/or enzyme and/or a metal micro-sphere attached to the end of confined signal elements.

28. The bio-disc according to claim 27, wherein the interdigitated array electrodes is constructed by coating a surface of a porous membrane with a conductive material.

29. The bio-disc according to claim 23, wherein the image sensor is constructed with a CCD (charge coupled Device) sensor or a CMOS (Complementary Metal-Oxide Semiconductor) sensor with or without a fluorescent filter to pick up an image of the label (coloring particle) linked with the probe in the assay site.

30. The bio-disc according to claim 1, wherein the assay site comprises an immuno assay sector and a nucleic acid probe assay sector arranged in an angular or radial direction to enable an immuno assay and a nucleic acid probe assay to be performed concurrently.

31. The bio-disc according to claim 12, which further comprises an impedance measuring device or an image sensor in the preparation chamber in order to detect a sample injection.

32. The bio-disc according to claim 31, wherein the impedance measuring device is an interdigitated array.

33. The bio-disc according to claim 1, wherein the body of the bio-disc is constructed with an upper substrate, an intermediate substrate, and a lower substrate, and these substrates are adhered and assembled by using ultrasonic fusing, UV adhesive, or double-sided tape to form a single body.

34. The bio-disc according to claim 1, which further comprises a memory or other storage means or RF IC for storing a protocol of the bio-disc, assay interpretive algorithms, standard control values for analysis, positional information on analysis sites, bioinformatics information, self-diagnostics information, bio-disc driver software, educational information for patients on clinical assays, a variety of web sites and links enabling a patient to communicate with a doctor or hospital at a remote location based on his/her diagnosis result, or encrypted personal information.

35. The bio-disc according to claim 1, which further comprises statistic software and storage means for managing a history of the detection results of the assay site and provides periodical diagnosis information to a user.

36. A bio-disc device comprising;

the bio-disc according to claim 1;

a controller disc including a controller which supplies power or a control signal to the bio-disc; and

an interfacing zone for connecting the bio-disc and the controller disc.

37. The bio-disc device according to claim 36, wherein the interfacing zone comprises:

a plurality of control signal nodes through which the control signal is supplied; and

/or a power node through which power is supplied.

38. The bio-disc device according to claim 37, the interfacing zone comprises:

grooves formed in the bio-disc and coated with a conductive material; and

conductive arms protruding from the controller disc and engaging the grooves.

39. The bio-disc device according to claim 36, wherein the controller disc is fixed to a turntable on which the bio-disc is mounted and further include an electromagnetic magnet or a movable permanent magnet for controlling a valve embedded in the bio-disc.

40. The bio-disc device according to claim 36, wherein the gap between the bio-disc and the controller disc is in a range of from 0.1 mm to 2 mm.

41. The bio-disc device according to claim 36, wherein the power is supplied to the controller disc through a brush or an electrical contact connected to an external power supply.

42. The bio-disc device according to claim 36, wherein the controller disc comprises an integrated circuit in a printed circuit board (PCB) or in a silicon wafer.

43. The bio-disc device according to claim 36, wherein the controller disc further comprises a non-contact interface selected from among an infrared interface, an optical interface, and a wireless interface to transmit the result of a detection from the assay site by the detector to an external central control system, a storage unit, or an input output unit via the non-contact interface.

44. The bio-disc device according to claim 36, wherein the bio-disc and the controller disc is integrated as a single body to form a controller disc-combined bio-disc.

45. The bio-disc device according to claim 44, wherein the controller disc-combined bio-disc has a monolithic circuit structure integrated into a silicon wafer via photolithography and etching processes, the monolithic circuit structure including the controller, the RF IC, a non-contact interface, an electrode plate or electromagnet for valve control, various circuit patterns, chambers, and channels.

65. A nucleic acid assay method using the bio-disc according to claim 12, the method comprising:

preparing a DNA sample from blood, cells, or RNA;

amplifying the prepared DNA through polymerase chain reaction (PCR);

hybridizing amplified DNA products from the PCR to the assay and diagnostic probe arrayed on the assay site; and

detecting a result of hybridization reaction in the assay site by using a detection device coupled with a transforming device, wherein the detection device includes a light transmission type measuring device, an electro-chemical detection device, a capacitance or impedance measuring device, or an image sensor.

66. The nucleic acid assay method according to claim 65, wherein the preparing of the DNA sample comprises:

injecting blood via a sample inlet into the preparation chamber;

performing incubation in the preparation chamber to allow particles or ferromagnetic bead in the preparation chamber to attract DNA extracted through cell lysis;

fixing the particles or ferromagnetic bead and slowly rotating the bio-disc to wash out and flow the cell debris into the trash chamber; and

separating the DNA from the particles or ferromagnetic beads or resuspending the DNA in a resuspension buffer.

67. The nucleic acid assay method according to claim 65, wherein the amplifying of the prepared DNA sample through PCR comprises:

slowly rotating the bio-disc to allow the prepared DNA sample to flow into the PCR chamber; and

repeating a PCR cycle several times using a heater and a thermo-sensor installed in the PCR chamber to amplify the DNA sample.

68. The nucleic acid assay method according to claim 67, which further comprise, after the PCR process:

slowly rotating the bio-disc to allow a DNAse to flow into the PCR chamber; and

heating the PCR chamber at a high temperature to deactivate the DNAse and form single-stranded DNA fragments (denaturing process).

69. The nucleic acid assay method according to claim 68, wherein each PCR chamber may comprise a heater which is controlled independently from the heaters of the other PCR chambers (in independent incubation time) to form the DNA fragments having different lengths.

70. An immuno assay method using the bio-disc according to claim 18, the method comprising:

high speed rotating the bio-disc to extract serum or an antigen from blood;

introducing the extracted antigen into a label chamber and performing incubation in the chamber for 1-2 minutes to bind the antigen to labeled antibodies and form a label-antigen complex;

moving the label-antigen complex into the assay site; and

performing cultivation in the bio-disc in a stationary state to induce an antigen-antibody reaction between the label-antigen complex and the capture antibodies; and

adding a washing buffer and washing the assay site.

71. The immuno assay method according to claim 70, wherein, in the moving of the label-antigen complex or the DNA into the assay site, the label-antigen complex or the DNA is allow to flow in to a porous membrane of the assay site by opening a just-before valve of the assay site and using a hydrophilic affinity of a hydrophilic channel without a centrifugal force.

72. The immuno assay method according to claim 71, which further comprises, after the performing cultivation to induce an antigen-antibody reaction or hybridization reaction between the label-antigen complex or the DNA and the capture antibodies on the porous membrane, drying the porous membrane by a high speed rotation of the disc.

73. The immuno assay method according to claim 72, which further comprises, after the drying, moving a washing buffer by opening a just-before valve of the assay site and using a hydrophilic affinity of a hydrophilic channel and cleaning the assay site by using the washing buffer.

74. The immuno assay method according to claim 73, which further comprises, after the cleaning, drying the porous membrane by a high speed rotation of the disc.

75. The immuno assay method according to claim 70, which further comprises picking up an image with the image sensor in order to detect a result of an antigen-antibody reaction in the assay site.

76. The immuno assay method according to claim 70, which further comprises performing remote transmission of the result of the antigen-antibody together with a questionnaire sheet to a specialist at a remote location.

4. A bio-disc comprising:

a sample inlet;

a chamber which reserves a buffer solution or a reaction solution;

an assay site where bio materials are arrayed on a substrate;

channels through which fluid flows between the sample inlet, the chamber, and the assay site;

a hole which connects the channels; and

a valve which is used to open and close the hole, wherein the substrate in the assay site is a porous membrane, and wherein a before channel of a just-before valve of the assay site is a hydrophobic channel, and an after channel is a hydrophilic channel.

5. The bio-disc according to claim 4, wherein the porous membrane is one selected from a group consisting a NC (nitrocellose) membrane, a nylon membrane, and aligned nanotubes.

6. The bio-disc according to claim 4, wherein the hydrophilic channel is constructed by coating a surface of a hydrophobic channel with a hydrophilic acrylate, an ultra-hydrophilic poly (N-isopropylacrylamide) (PIPAAm) or an optical catalyst selected from a group consisting ZrO₂, ZnO, Fe₂O₃, and TiO₂ or by performing a surface modification on the hydrophobic channel with plasma.

7. The bio-disc according to claim 4, wherein the hydrophilic channel is divided into at least one branch channel, and the hydrophilic channel is connected to the porous membrane through a hole provided to a distal end of the branch channel.

8. The bio-disc according to claim 4, wherein the assay site has air holes disposed at the both sides of the assay site to dry the porous membrane.

10. The bio-disc according to claim 4, wherein the fluid movement into the assay site is performed by the opening of the just before valve and hydrophilic affinity of the hydrophilic channel and the reaction solution without using a centrifugal force.

64. The bio-disc driver apparatus according to claim 4, wherein the bio-disc driver apparatus has a plurality of turn tables so as to load a plurality of the bio-discs in one time.

46. A bio-disc driver apparatus comprising:

a controller disc including a controller which supplies a power signal or a control signal to a bio-disc;

a motor which rotates the controller disc and the bio-disc;

a power supply unit which supplies power to the controller of the controller disc;

an interface through which the control signal and/or the power signal are transmitted from the controller to the bio-disc; and

a body which supports the bio-disc driver apparatus.

47. The bio-disc driver apparatus according to claim 46, which further comprises a turntable on which the bio-disc is mounted, wherein the controller disc is fixed to the turntable and includes an electromagnetic magnet or a movable permanent magnet for controlling a valve embedded in the bio-disc.

48. The bio-disc driver apparatus according to claim 46, wherein the power supply unit supplies a positive power (+) to the controller disc by contact between an annular electrode and a brush and a negative power (−

) to the controller disc through an electrical connection to a grounded motor body or a grounded motor shaft.

49. The bio-disc driver apparatus according to claim 46, which further comprises a detection device coupled with a transforming device including an image sensor for detecting the assay site.

50. The bio-disc driver apparatus according to claim 46, wherein the controller disc further comprises non-contact means for transmitting a detection result of the assay site to an external central control system, a storage device, or an input output device or receiving a command from the central control system.

51. The bio-disc driver apparatus according to claim 46, wherein a circuit board on which the central control system, the storage device, or the input output device is disposed is connected and engaged with the bio-disc driver body, and the central control system rotates or stops a motor for rotating and stopping the bio-disc and the controller disc.

52. The bio-disc driver apparatus according to claim 51, wherein the input output device is a USB (Universal Serial Bus) device or a device according to IEEE-1394, ATAPI or Internet communication standard.

53. The bio-disc driver apparatus according to claim 46, which further comprises an optical pickup device for reading a general optical disc selected from a group consisting an audio CD, a CD-R, a game CD, and a DVD.

54. The bio-disc driver apparatus according to claim 53, which further comprises a bio-disc detection unit for determining whether a disc currently loaded on the bio-disc driver apparatus is a bio-disc or a general optical disc selected from among an audio CD, a CD-R, a game CD, and a DVD.

55. The bio-disc driver apparatus according to claim 54, wherein an optical pickup device reads a groove pattern or a data pattern at a particular area on a surface of the bio-disc to allow the central control system to recognize that a disc currently loaded on the bio-disc driver is a bio-disc.

56. The bio-disc driver apparatus according to claim 54, wherein the central control system determines whether a currently loaded disc is a bio-disc or a general optical disc selected from among an audio CD, a CD-R, a game CD, and a DVD;

transmits information read from the general optical disc using the optical pickup to a storage or output unit, transmit to the optical pickup information to be written, or output various read/write control signals if the currently loaded disc is determined to be a general optical disc; and

transmits various control signals for the bio-disc via a non-contact interface to the controller if the currently loaded disc is determined to be a bio-disc.

57. The bio-disc driver apparatus according to claim 54, wherein, at the time of loading the bio-disc, a new loading of the bio-disc is transmitted to the central control system in a wireless manner through a non-contact interface or an RF IC on the bio-disc, so that the central control system recognizes that the disc loaded on the bio-disc driver is the bio-disc.

58. The bio-disc driver apparatus according to claim 46, wherein the bio-disc driver apparatus sends an eject message or a warning message to a user if a bio-disc into which a sample has not be injected is loaded.

59. The bio-disc driver apparatus according to claim 46, wherein, when an eject (unloading) or a stop command is input to the bio-disc driver apparatus during assay or diagnosis, the bio-disc driver apparatus sends a warning message or requests a user'"'"'s password while continuing assay and diagnosis.

60. The bio-disc driver apparatus according to claim 46, which further comprises a memory for storing information on how many times the bio-disc device has been used, its validation period, and kinds of diseases which can be diagnosed, so as to provide a user with the stored information on the bio-disc or the availability of the bio-disc every time when the bio-disc is loaded.

61. The bio-disc driver apparatus according to claim 46, wherein the bio-disc driver apparatus comprises:

a play and search button and a stop button for general optical discs; and

a light emitting diode (LED) indicating that a bio-disc has been loaded.

62. The bio-disc driver apparatus according to claim 46, wherein the bio-disc driver apparatus comprises a liquid crystal display or a monitor to display the status of progress in main processes performed in the bio-disc in percentages or as a bar graph or a pie graph.

63. The bio-disc driver apparatus according to claim 46, wherein the body which supports the bio-disc driver allows bio-disc top loading or bio-disc front loading.