FILM-FLIPPING MECHANISM FOR MOLECULAR TESTING, NUCLEIC ACID EXTRACTION DEVICE WITH THE SAME, AND NUCLEIC ACID EXTRACTION METHOD FOR MOLECULAR TESTING

A nucleic acid extraction device for molecular testing comprises a film-flipping mechanism, a cap mechanism, a dispensing mechanism, an extraction plate transfer mechanism, and a nucleic acid extraction module. A sealing film is adhered onto top of an extraction plate and folded along an outer edge of the extraction plate. A film-flipping head of the film-flipping mechanism abuts against a bottom surface of the extraction plate and pushes an edge of the sealing film to unfold the sealing film. A film gripper clamps and removes the unfolded sealing film. The cap mechanism opens the specimen containers. The dispensing mechanism transfers the specimens from the specimen containers to the extraction plate. The extraction plate transfer mechanism moves the extraction plate with the specimens to the nucleic acid extraction module. As a result, molecular testing is automated to reduce labor and improve quality.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to an automation equipment for biology and chemistry laboratories, especially to a nucleic acid extraction device for molecular testing.

2. Description of the Prior Art

In a molecular testing such as a RNA detection for COVID-19 (coronavirus disease 2019), a first step is to perform nucleic acid extraction process to collected specimens that are each stored in a specimen container. In the nucleic acid extraction process, first peel off a sealing film on top of a 96-well plate for nucleic acid extraction, and then transfer 96 of the collected specimens to the 96-well plate. To be specific, the 96 specimen containers need to be opened one by one in order to transfer each of the 96 collected specimens to a respective one of the wells on the 96-well plate.

After transferring the collected specimens, the 96 specimen containers need to be sealed carefully and be disposed of as medical waste, and the 96-well plate for nucleic acid extraction is placed into a nucleic acid extraction machine to prepare the collected specimens for a Q-PCR (Real-time Quantitative Polymerase Chain Reaction) test later on.

However, peeling off the sealing films and transferring the collected specimens are operated manually in the conventional nucleic acid extraction process, making the process time-consuming and laborious. Moreover, the risk of human error and contamination due to manual operation is also considerable, affecting test precision and personnel safety.

To overcome the shortcomings, the present invention provides a film-flipping mechanism for molecular testing, a nucleic acid extraction device with the same, and a nucleic acid extraction method for molecular testing to mitigate or obviate the aforementioned problems.

SUMMARY OF THE INVENTION

The main objective of the present invention is to provide a film-flipping mechanism for molecular testing, a nucleic acid extraction device with the same, and a nucleic acid extraction method for molecular testing to automate nucleic acid extraction process to reduce labor and improve quality.

The film-flipping mechanism for molecular testing is configured to remove a sealing film from an extraction plate. A flange protrudes from an outer annular surface on a top of the extraction plate. The sealing film is adhered onto a top surface of the extraction plate. The sealing film is folded along an outer edge of the flange such that a folded peripheral portion of the sealing film is disposed under the flange of the extraction plate. The film-flipping mechanism comprises a film-flipping seat, a film-flipping assembly, and a film gripper. The film-flipping seat is configured to fix the extraction plate. The film-flipping assembly is mounted on the film-flipping seat and is movable toward the folded peripheral portion of the sealing film. The film-flipping assembly has a film-flipping head protruding from a top surface of the film-flipping assembly and configured to abut against a bottom surface of the flange of the extraction plate. When the film-flipping assembly is moved toward the folded peripheral portion, a side surface of the film-flipping head pushes the folded peripheral portion to unfold the folded peripheral portion such that the folded peripheral portion is flipped from an underside of the flange to a lateral side of the flange. The film gripper is movably and rotatably disposed on the film-flipping seat. The film gripper is configured to clamp the folded peripheral portion that is flipped to the lateral side of the flange and peel the sealing film away from the extraction plate.

The nucleic acid extraction device for molecular testing is configured to process multiple specimen containers and an extraction plate. Each of the specimen containers has a containing body and a cap. Each of the specimen containers has a specimen placed therein and sealed by the cap. The extraction plate has multiple extraction recesses and a sealing film. The sealing film is adhered onto a top of the extraction plate and seals the extraction recesses. The nucleic acid extraction has a main base, a film-flipping mechanism, a cap mechanism, a dispensing mechanism, an extraction plate transfer mechanism, and a nucleic acid extraction module. The film-flipping mechanism, the cap mechanism, the dispensing mechanism, the extraction plate transfer mechanism, and the nucleic acid extraction module are mounted on the main base. The film-flipping mechanism is configured to remove the sealing film from the extraction plate. A flange protrudes from an outer annular surface on a top of the extraction plate. The sealing film is folded along an outer edge of the flange such that a folded peripheral portion of the sealing film is disposed under the flange of the extraction plate. The film-flipping mechanism comprises a film-flipping seat, a film-flipping assembly, and a film gripper. The film-flipping seat is mounted on the main base and is configured to fix the extraction plate. The film-flipping assembly is mounted on the film-flipping seat and is movable toward the folded peripheral portion of the sealing film. The film-flipping assembly has a film-flipping head protruding from a top surface of the film-flipping assembly and configured to abut against a bottom surface of the flange of the extraction plate. When the film-flipping assembly is moved toward the folded peripheral portion, a side surface of the film-flipping head pushes the folded peripheral portion to unfold the folded peripheral portion such that the folded peripheral portion is flipped from an underside of the flange to a lateral side of the flange. The film gripper is movably and rotatably disposed on the film-flipping seat. The film gripper is configured to clamp the folded peripheral portion flipped to the lateral side of the flange and peel the sealing film away from the extraction plate. The cap mechanism is configured to separate the cap of each of the specimen containers from the corresponding containing body. The dispensing mechanism has at least one pipette. Each of the at least one pipette is configured to aspirate the specimen in one of the specimen containers and inject the aspirated specimen into one of the extraction recesses of the extraction plate. The extraction plate transfer mechanism is configured to move the extraction plate having the specimens injected in the extraction recess to the nucleic acid extraction module.

A nucleic acid extraction method for molecular testing comprises steps as follows:(a) Preparation of extraction plate and specimens, wherein an extraction plate is prepared; a flange protrudes from an outer annular surface on a top of the extraction plate; a sealing film is adhered onto a top surface of the extraction plate; the sealing film is folded along an outer edge of the flange such that a folded peripheral portion of the sealing film is disposed under the flange of the extraction plate; a film-flipping head of a film-flipping mechanism abuts against a bottom surface of the flange of the extraction plate, and meanwhile moves the film-flipping head toward the folded peripheral portion of the sealing film to push the folded peripheral portion such that the folded peripheral portion is flipped from an underside of the flange to a lateral side of the flange; a film gripper clamps the folded peripheral portion that is flipped to the lateral side of the flange, and then the film gripper moves and rotates to peel the sealing film away from the extraction plate; a cap mechanism separates a cap from a containing body of one of multiple specimen containers.(b) Dispensing and extraction, wherein each of at least one pipette of a dispensing mechanism aspirates a specimen inside one of the specimen containers and injects the aspirated specimen into one of multiple extraction recesses of the extraction plate, and then the cap mechanism and the dispensing mechanism continue to process rest of the specimen containers such that rest of the specimens in said specimen containers are injected into rest of the extraction recesses on the extraction plate; an extraction plate transfer mechanism moves the extraction plate with the specimens inside the extraction recesses to a nucleic acid extraction module.

The advantage of the present invention is that the film-flipping mechanism automatically separates the sealing film from the extraction plate; the cap mechanism automatically opens up the specimen container; the dispensing mechanism automatically transfers the specimens from the specimen containers to the extraction plate; the extraction plate transfer mechanism automatically moves the extraction plate to the nucleic acid extraction module to perform nucleic acid extraction process. As a result, nucleic acid extraction is highly automated to greatly reduce labor and improve processing quality.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

With reference toFIGS.1,3,18,19, and23, a nucleic acid extraction device for molecular testing in accordance with the present invention is configured to process multiple specimen containers91and an extraction plate92. Each of the specimen containers91has a containing body911and a cap912, and a liquid specimen is sealed in the containing body911by the cap912. The extraction plate92has multiple extraction recesses921and a sealing film922; the sealing film922is adhered onto a top surface of the extraction plate92and seals all the extraction recesses921.

A flange923protrudes from an outer annular surface on a top of the extraction plate92. The flange923is preferably annular and surrounds the extraction plate92. The sealing film922is folded along an outer edge of the flange923such that a folded peripheral portion9221of the sealing film922is disposed under the flange923of the extraction plate92.

To be precise, a number of the extraction recesses921on the extraction plate92is 96, and the extraction recesses921are formed on the top surface of the extraction plate92. The containing body911of each of the specimen containers91is a tube. The specimen containers91are delivered into the nucleic acid extraction device by multiple specimen-organizing plates93, and each of the specimen-organizing plates93has 96 specimen containers91mounted thereon.

Main function of the nucleic acid extraction device is to transfer the specimen inside each of the 96 specimen containers91into a respective one of the 96 extraction recesses921on the extraction plate92, and then carry out other processes to the extraction plate92.

The nucleic acid extraction device has: a main base10, a film-flipping mechanism20, a cap mechanism30, a dispensing mechanism40, an extraction plate transfer mechanism50, and a nucleic acid extraction module60, wherein the film-flipping mechanism20, the cap mechanism30, the dispensing mechanism40, the extraction plate transfer mechanism50, and the nucleic acid extraction module60are mounted on the main base10. In the preferred embodiment the nucleic acid extraction device has a specimen-supplying mechanism70and a specimen transfer module80.

With reference toFIGS.1,2, and4, a plate rack11is mounted on the main base10. The plate rack11forms multiple stacking spaces that are independent from each other. Multiple unused extraction plates92are stacked in one of the stacking spaces, and plates with different extraction medicines are stacked in the rest of the stacking spaces.

With reference toFIGS.1and14-18, the film-flipping mechanism20is configured to remove the sealing film922from the extraction plate92. The film-flipping mechanism20comprises a film-flipping seat21, a film-flipping assembly25, and a film gripper27. In the preferred embodiment, the film-flipping mechanism20has a first linear module22, a second linear module23, a third linear module24, and a gripper-rotating seat26.

The film-flipping seat21is mounted on the main base10and is configured to fix the extraction plate92in place. To be specific, a positioning recess is formed on the film-flipping seat21, and multiple clamping cylinders211are mounted on the film-flipping seat21. A bottom of the extraction plate92can be placed in the positioning recess, and then the clamping cylinders211are used to fix the extraction plate92in the positioning recess.

The first linear module22is mounted on the film-flipping seat21and has a first slider221(as shown inFIG.16). The first slider221is movable along a first direction D1and movement of the first slider221is controllable.

The second linear module23is mounted on the first slider221of the first linear module22and has a second slider231. The second slider231is movable along a second direction D2and movement of the second slider231is controllable, wherein the second direction D2is non-parallel to the first direction D1. To be precise, the first direction D1, the second direction D2, and a direction along which the third slider241moves are perpendicular to each other.

With reference toFIGS.18to20, the film-flipping assembly25is mounted on the third slider241such that the film-flipping assembly25is movable toward the folded peripheral portion9221of the sealing film922, but the film-flipping assembly25is not limited thereto as long as the film-flipping assembly25is mounted on the film-flipping seat21and is movable toward the folded peripheral portion9221of the sealing film922.

The film-flipping assembly25has a film-flipping head251, a film-flipping body252, and a raising resilient element253. An accommodating recess is formed on a top surface of the film-flipping body252. The film-flipping head251is slidably mounted in the accommodating recess of the film-flipping body252and is slidable upwards and downwards.

An upper end of the film-flipping head251protrudes from the top surface of the film-flipping body252and forms a right angle. The upper end of the film-flipping head251is configured to abut against a bottom surface of the flange923of the extraction plate92; as a result, when the film-flipping assembly25is moved toward the folded peripheral portion9221of the sealing film922, a side surface of the film-flipping head251pushes the folded peripheral portion9221to unfold the folded peripheral portion9221such that the folded peripheral portion9221is flipped from an underside of the flange to a lateral side of the flange923.

The raising resilient element253is mounted in the accommodating recess of the film-flipping body252and drives the film-flipping head251to move upwards such that the tip of the film-flipping head251tends to protrude from the top surface of the film-flipping body252and keeps abutting the bottom surface of the flange923.

With reference toFIGS.17,21, and22, the gripper-rotating seat26is rotatably mounted on the third slider241of the third linear module24. The film gripper27is mounted on the gripper-rotating seat26such that the film gripper27is movably and rotatably disposed on the film-flipping seat21. The film gripper27is configured to clamp the folded peripheral portion9221that is flipped to the lateral side of the flange923and peel the sealing film922away from the extraction plate92via the movement from the linear module22,23,24and the rotation from the gripper-rotating seat26.

With reference toFIGS.1and3, the specimen-supplying mechanism70is configured to transfer the unprocessed specimen containers91to an organizing area12on the main base10. The specimen-supplying mechanism70includes an input rack71, an output rack72, and a specimen plate transfer mechanism73. The specimen-organizing plates93are vertically stacked in the input rack71. The unprocessed specimen containers91are disposed on the specimen-organizing plates93. The specimen plate transfer mechanism73is configured to move the bottommost specimen-organizing plate93in the input rack71to the organizing area12on the main base10for subsequent processes.

After all the specimen containers91on one of the specimen-organizing plates93are processed, the specimen plate transfer mechanism73moves said specimen-organizing plate93from the organizing area12into the output rack72for storage. The specimen-supplying mechanism70is a conventional mechanism; therefore detailed description of the specimen-supplying mechanism70is omitted.

With reference toFIGS.1,7and10, the specimen transfer module80is mounted on the main base10and has a container gripper81. The container gripper81is movable between the organizing area12and the cap mechanism30. The container gripper81is configured to clamp one of the specimen containers91on the organizing area12and transfer said specimen container91to the cap mechanism30.

With reference toFIGS.1and8-10, the cap mechanism30is configured to separate the cap912of each of the specimen containers91from the corresponding containing body911. In the preferred embodiment, the cap mechanism30includes a fixing seat31, a rotating table32, multiple containing body fixtures33, a cap-loosening assembly34, a cap-moving assembly35, and a cap-tightening assembly36.

The fixing seat31is mounted on the main base10. The rotating table32is mounted on the fixing seat31and is rotatable around a rotation axis L1. The containing body fixtures33are mounted on the rotating table32and are preferably annularly disposed apart from each other around the rotation axis L1along a periphery of the rotating table32.

To be precise, a number of the containing body fixtures33is eight. The containing body fixtures33are divided into four sets that are annularly disposed apart from each at same interval. Each of the containing body fixtures33is capable of clamping one of the specimen containers91.

With reference toFIGS.9and11, the cap-loosening assembly34includes two cap-loosening linear modules341, two cap-loosening motors342, and two cap-loosening grippers343. The cap-loosening linear modules341are mounted on the fixing seat31and each have a lid-opening slider3411. The lid-opening slider3411is movable upwards and downwards. The cap-loosening motors342and the cap-loosening grippers343are mounted on the lid-opening slider3411. The two cap-loosening grippers343are connected to shafts of the two cap-loosening motors342respectively such that each of the cap-loosening motors342is capable of rotating the respective cap-loosening gripper343to loosen the caps912of the two specimen containers91that are clamped by the two containing body fixtures33of the same set (as shown inFIG.11).

With reference toFIGS.9and12, the cap-moving assembly35includes two cap-moving grippers351that are configured to clamp the two caps912of the two specimen containers91gripped by the two containing body fixtures33of the same set, and the two cap-moving grippers351are configured to move the caps912that are loosened by the two cap-loosening gripper351to a lateral side of the corresponding containing bodies911such that upper openings of said containing bodies911are uncovered (as shown inFIG.12).

To be specific, the cap-moving assembly35has a first cap-moving actuator352and a second cap-moving actuator353. The first cap-moving actuator352is preferably a gas cylinder mounted on the fixing seat31and has a first cap-moving block3521. The first cap-moving block3521can be driven by compressed air to move relative to the fixing seat31.

The second cap-moving actuator353is mounted on the first cap-moving block3521of the first cap-moving actuator352and has a second cap-moving block3531. The second cap-moving block3531is movable upwards and downwards. A moving direction of the first cap-moving block3521is non-parallel to a moving direction of the second cap-moving block3531, and said two moving directions are preferably perpendicular.

To be more specific, the first cap-moving block3521is controllable such that it is linearly movable along a rotation axis of the rotating table32to change a distance between the second cap-moving actuator353and the rotation axis L1.

The two cap-moving grippers351are mounted on the second cap-moving block3531of the second cap-moving actuator353such that the cap-moving gripper351can first be moved horizontally over one of the specimen containers91, and then the second cap-moving actuator353moves downward to clamp the cap912, and then separates the cap912from the corresponding containing body911via the cap-moving actuators352,353.

With reference toFIGS.9and13, the cap-tightening assembly36has two cap-tightening grippers361configured to clamp two of the caps912of the two specimen containers91that are clamped by two of containing body fixtures33of the same set, and the two cap-tightening grippers361are configured to tighten said two cap912(as shown inFIG.13). The cap-tightening assembly36is structurally same as the cap-loosening assembly34, and therefore detailed structure is omitted.

With reference toFIGS.10to13, the cap-loosening assembly34, the cap-moving assembly35, and the cap-tightening assembly36are mounted on the fixing seat31and annularly disposed apart from each other around the rotation axis Li. Rotation of the rotating table32makes the two specimen containers91clamped by the two containing body fixtures33correspond in position to the two cap-loosening grippers343, the two cap-moving grippers351, and the two cap-tightening grippers361in a sequential manner such that the grippers343,351,361loosen, move, and tighten the caps912in a sequential manner.

With reference toFIGS.1,5, and23, the dispensing mechanism40has two pipettes41. Each of the two pipettes41is configured to aspirate the specimen in a respective one of the two specimen containers91that are clamped by the two cap-moving grippers351, and then inject the aspired specimen into one of the extraction recesses921of the extraction plate92. To be precise, the dispensing mechanism40has multiple dispensing linear modules42that are serially connected such that the dispensing linear modules42allow the pipettes41to be positioned above the main base with multiple degrees of freedom. The dispensing mechanism40is a conventional mechanism, and therefore detailed description is omitted.

With reference toFIGS.1and6, the extraction plate transfer mechanism50is configured to move the extraction plate92having the specimens injected in the extraction recesses921to the nucleic acid extraction module60(as shown inFIG.1). To be specific, the extraction plate transfer mechanism50is mounted under transverse beams (not shown in figures) that are disposed over the main base10.

The extraction plate transfer mechanism50has a plate gripper51and multiple plate transfer linear modules52that are serially connected. The plate gripper51is configured to clamp the extraction plates92; the plate transfer linear modules52allow the plate gripper51to be positioned above the main base10with multiple degrees of freedom. The extraction plate transfer mechanism50is a conventional mechanism, and therefore detailed description is omitted.

The nucleic acid extraction module60is a conventional standard molecular testing instrument, and therefore detailed description is omitted.

With reference toFIG.24, a nucleic acid extraction method for molecular testing in accordance with the present invention comprises the following steps: the first step (S1) is preparation of extraction plate and specimens; the second step (S2) is dispensing and extraction. The nucleic acid extraction method is preferably performed by the aforementioned nucleic acid extraction device, but not limited thereto.

Preparation of extraction plate (S1): with reference toFIGS.1and15, prepare the extraction plates92and put the extraction plates92in the plate rack11on the main base10. Then, the extraction plate transfer mechanism50moves one of the extraction plates92from the plate rack11to the film-flipping seat21of the film-flipping mechanism20and fix said extraction plate92onto the film-flipping seat21.

With reference toFIGS.18to20, the film-flipping head251of the film-flipping mechanism20is moved to a position under the flange923of the extraction plate92, and the top of the film-flipping head251abuts upwards against the bottom surface of the flange923, and meanwhile moves the film-flipping head251toward the folded peripheral portion9221of the sealing film922to push the folded peripheral portion9221such that the folded peripheral portion9221is flipped from the underside of the flange923to the lateral side of the flange923.

With reference toFIGS.21and22, then the film gripper27clamps the folded peripheral portion9221that is flipped to the lateral side of the flange923, and then the film gripper27moves and rotates to peel the sealing film922away from the extraction plate92such that the openings of the extraction recesses921are exposed. After removing the sealing film922, the extraction plate transfer mechanism50moves the extraction plate92to the receiving area13that is adjacent to the dispensing mechanism40.

With reference toFIGS.1,7, and10, while the extraction plate transfer mechanism50and the film-flipping mechanism20are in operation, the specimen transfer module80moves the specimen containers91on the organizing area12to the cap mechanism30simultaneously and clamps two of the specimen containers91with one set of the containing body fixtures33.

Then, the rotating table32rotates 90 degrees to make said specimen containers91correspond in position to the cap-loosening assembly34(as shown inFIG.11). The cap-loosening grippers343loosen the caps912of the specimen containers91.

After loosening the caps912, the rotating table32rotates 90 degrees again to make the specimen containers91correspond in position to the cap-moving assembly35(as shown inFIG.12). Then, the cap-moving grippers351separate the cap912from the containing bodies911and move the caps912to the lateral side of the containing bodies911such that upper openings of the containing bodies911are exposed.

Dispensing and extraction (S2): with reference toFIG.23, the two pipettes41of the dispensing mechanism40aspirate the specimens inside two of the specimen containers91corresponding in position to the cap-moving assembly35, and then inject the aspirated specimens into two of the extraction recesses921of the extraction plate92.

After injecting the specimens, the cap-moving grippers351of the cap mechanism30moves the caps912back to the containing bodies911(status not shown in figures), the rotating table32rotates 90 degrees again to make the specimen containers91correspond in position to the cap-tightening assembly36(as shown inFIG.13). The cap-tightening grippers361tighten the caps912to the corresponding containing bodies911to seal the residual specimens in the specimen containers91, and then the rotating table32rotates 90 degrees again and the specimen transfer module80moves the specimen containers91back to the specimen-organizing plate93.

Then, the specimen transfer module80, the cap mechanism30, and the dispensing mechanism40continue to process rest of the specimen containers91such that rest of the specimens in said specimen containers91are injected into rest of the extraction recesses921on the extraction plate92.

Finally, the extraction plate transfer mechanism50moves the extraction plate92with the specimens inside the extraction recesses921to the nucleic acid extraction module60where nucleic acid extraction process is performed.

After finishing nucleic acid extraction, the extraction plate transfer mechanism50removes the extraction plate92from the nucleic acid extraction module60and moves the extraction plate92to an extraction plate output mechanism94(as shown inFIG.2). The extraction plate92on the extraction plate output mechanism94is then clamped by another device not belonging to the present invention to perform subsequent molecular testing processes.

In summary, the film-flipping mechanism20automatically separates the sealing film922from the extraction plate92; the cap mechanism30automatically opens up the specimen container91; the dispensing mechanism40automatically transfers the specimens from the specimen containers91to the extraction plates92; the extraction plate transfer mechanism50automatically moves the extraction plate92to the nucleic acid extraction module60to perform nucleic acid extraction process. As a result, nucleic acid extraction is highly automated to greatly reduce labor and improve processing quality.