BACKGROUND

1. Field

The present disclosure pertains to a system and method for performing a disease diagnostic using an integrated lab on a chip device.

2. Description of the Related Art

Infectious diseases have been sources of large-scale epidemics and pandemics resulting in millions of casualties worldwide. Detection of these biological agents normally involves several lab processes including sample preparation, nucleic acid separation and amplification, and diagnostic analysis. These steps, either performed manually or automated by high-throughput machinery, are tedious, expensive, and highly susceptible to cross-contamination.

SUMMARY

The following is a non-exhaustive listing of some aspects of the present techniques. These and other aspects are described in the following disclosure.

Accordingly, one or more aspects of the present disclosure relate to a disease diagnostic system. The system comprises a chip body, a mixing chamber, first, second, and third pumps, a main channel, a separation area, a waste chamber, an amplification chamber, first and second valves, and/or other components. The mixing chamber may be formed in the chip body. The mixing chamber may be configured to receive a biological sample for disease diagnosis. The mixing chamber may comprise magnetic beads, a cell lysis buffer, oligonucleotide binding receptors, and/or other components. The mixing chamber may be configured to receive energy to facilitate mixing in the mixing chamber to form a solution. The first pump may be formed in the chip body and coupled to the mixing chamber. The first pump may be configured to pump the solution out of the mixing chamber. The main channel may be formed in the chip body and coupled to the mixing chamber. The main channel may be configured to receive the solution pumped from the mixing chamber. The separation area may be formed in the main channel. The separation area may be configured to receive a magnet that traps bound ribonucleic acid (RNA) and/or deoxyribonucleic acid (DNA) molecules in the solution on a surface of the separation area. The waste chamber may be formed in the chip body and coupled to the main channel downstream from the separation area. The waste chamber may be configured to receive solution comprising unbound RNA and/or DNA molecules. The first valve may be positioned between the main channel and the waste chamber and configured to control flow of the solution without the bound RNA and/or DNA molecules through the main channel to the waste chamber. The amplification chamber may be formed in the chip body and coupled to the main channel downstream from the separation area. The amplification chamber may be configured to receive the bound RNA and/or DNA molecules for analysis. The second valve may be positioned between the main channel and the amplification chamber and configured to control flow of the bound RNA and/or DNA molecules through the main channel to the amplification chamber. The second pump may be formed in the chip body and coupled to the main channel. The second pump may be coupled to a cavity holding a wash buffer solution. The third pump may be formed in the chip body and coupled to the main channel. The third pump may be coupled to a cavity holding amplification solution.

With the first and second valves in a first configuration that allows flow through the main channel to the waste chamber and blocks flow to the amplification chamber, and with the bound RNA and/or DNA molecules trapped in the separation area, activation of the second pump pumps the wash buffer solution and the solution comprising the unbound RNA and/or DNA molecules through the main channel into the waste chamber. With the first and second valves in a second configuration that allows flow through the main channel to the amplification chamber and blocks flow to the waste chamber, and with the bound RNA and/or DNA molecules released from the separation area, actuation of the third pump pumps the amplification solution and the bound RNA and/or DNA molecules through the main channel into the amplification chamber.

In some embodiments, the mixing chamber comprises one or more cavities configured to trap air bubbles when fluid is loaded into the mixing chamber. The air bubbles may be configured to function as mechanical actuators during mixing in the mixing chamber. In some embodiments, the mixing chamber may be configured to receive external energy from a piezoelectric transducer (PZT) such that vibrations are transferred from the PZT to the mixing chamber and cause the air bubbles to oscillate and produce acoustic incident waves in the mixing chamber to cause the RNA and/or DNA molecules to couple with the magnetic beads. In some embodiments, the first pump comprises an electrochemical decomposition reaction (electrolysis) of water in a sodium chloride solution. In some embodiments, the second pump comprises a first blister formed in the chip body. The first blister may be configured to be actuated by a first mechanical external force. In some embodiments, the third pump comprises a second blister formed in the chip body. The second blister may be configured to be actuated by a second mechanical external force. In some embodiments, the first valve and the second valve may be wax valves. In some embodiments, the first valve and the second valve may be actuated by one or more heat sources coupled to a surface of the chip body at or near the first valve and the second valve. In some embodiments, the amplification chamber is configured to facilitate, for RNA molecules: amplification using transcription-mediated amplification; and analysis for fluorescent signals with a real-time polymerase chain reaction. In some embodiments, the system further comprises an external fixture configured to: receive the chip body and removably couple with the chip body to retain the chip body in a predetermined orientation with respect to the external fixture; actuate the PZT; activate the first pump; trap and untrap the bound RNA and/or DNA molecules; actuate the first and second valves to cause the system to change from the first configuration to the second configuration, and actuate the second and third pumps.

Further, one or more aspects of the present disclosure relate to a disease diagnosis method performed with a diagnostic system. The system comprises a chip body, a mixing chamber, first, second, and third pumps, a main channel, a separation area, a waste chamber, an amplification chamber, first and second valves, and/or other components. The method comprises forming the mixing chamber in the chip body. The mixing chamber may be configured to receive a biological sample for disease diagnosis. The mixing chamber may comprise magnetic beads, a cell lysis buffer, oligonucleotide binding receptors, and/or other components. The mixing chamber may receive energy to facilitate mixing in the mixing chamber to form a solution. The method comprises forming the first pump in the chip body, coupling the first pump to the mixing chamber, and pumping the solution out of the mixing chamber with the first pump. The method comprises forming the main channel in the chip body, coupling the main channel to the mixing chamber, and receiving the solution pumped from the mixing chamber with the main channel. The method comprises forming the separation area in the main channel and receiving a magnet that traps bound RNA and/or DNA molecules in the solution on a surface of the separation area. The method comprises forming the waste chamber in the chip body, coupling the waste chamber to the main channel downstream from the separation area, and receiving solution comprising unbound RNA molecules with the waste chamber. The method comprises positioning the first valve between the main channel and the waste chamber to control flow of the solution comprising the unbound RNA and/or DNA molecules through the main channel to the waste chamber. The method comprises forming the amplification chamber in the chip body, coupling the amplification chamber to the main channel downstream from the separation area, and receiving the bound RNA and/or DNA molecules for analysis with the amplification chamber. The method comprises positioning the second valve between the main channel and the amplification chamber to control flow of the bound RNA and/or RNA molecules through the main channel to the amplification chamber. The method comprises forming the second pump in the chip body and coupling the second pump to the main channel and a cavity holding a wash buffer solution. The method comprises forming the third pump in the chip body and coupling the third pump to the main channel and a cavity holding amplification solution. The method comprises, with the first and second valves in a first configuration that allows flow through the main channel to the waste chamber and blocks flow to the amplification chamber, and with the bound RNA and/or DNA molecules trapped in the separation area, actuating the second pump to pump the wash buffer solution and the solution comprising the unbound RNA and/or DNA molecules through the main channel into the waste chamber. The method comprises, with the first and second valves in a second configuration that allows flow through the main channel to the amplification chamber and blocks flow to the waste chamber, and with the bound RNA and/or DNA molecules released from the separation area, actuating the third pump to pump the amplification solution and the bound RNA and/or DNA molecules through the main channel into the amplification chamber.

In some embodiments, the mixing chamber further comprises one or more cavities configured to trap air bubbles when fluid is loaded into the mixing chamber. The air bubbles may be configured to function as mechanical actuators during mixing in the mixing chamber. In some embodiments, the method further comprises receiving, with the mixing chamber, external energy from a PZT such that vibrations are transferred from the PZT to the mixing chamber and cause the air bubbles to oscillate and produce acoustic incident waves in the mixing chamber to cause the RNA and/or DNA molecules to couple with the magnetic beads. In some embodiments, the first pump comprises an electrochemical decomposition reaction (electrolysis) of water in a sodium chloride solution. In some embodiments, the second pump comprises a first blister formed in the chip body, the method further comprising actuating the first blister with a first mechanical external force. In some embodiments, the third pump comprises a second blister formed in the chip body. The method further comprises actuating the second blister with a second mechanical external force. In some embodiments, the first valve and the second valve are wax valves. In some embodiments, the method further comprises actuating the first valve and the second valve with one or more heat sources coupled to a surface of the chip body at or near the first valve and the second valve. In some embodiments, the method further comprises facilitating, with the amplification chamber, for RNA molecules: amplification using transcription-mediated amplification; and analysis for fluorescent signals with a real-time polymerase chain reaction. In some embodiments, the system further comprises an external fixture. The method further comprises: receiving, with the external fixture, the chip body and removably coupling with the chip body to retain the chip body in a predetermined orientation with respect to the external fixture; actuating, with the external fixture, the PZT; activating, with the external fixture, the first pump; trapping and untrapping, with the external fixture, the bound RNA and/or DNA molecules; actuating, with the external fixture, the first and second valves to cause the system to change from the first configuration to the second configuration, and actuating, with the external fixture, the second and third pumps.

These and other objects, features, and characteristics of the system or method disclosed herein, as well as the methods of operation and functions of the related elements of structure and the combination of parts and economies of manufacture, will become more apparent upon consideration of the following description and the appended claims with reference to the accompanying drawings, all of which form a part of this specification, wherein like reference numerals designate corresponding parts in the various figures. It is to be expressly understood, however, that the drawings are for the purpose of illustration and description only and are not intended as a definition of the limits of the invention. As used in the specification and in the claims, the singular form of “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise.

