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EP-4497505-B1 - BIOPARTICLE ENRICHMENT APPARATUS

EP4497505B1EP 4497505 B1EP4497505 B1EP 4497505B1EP-4497505-B1

Inventors

  • HUANG, CHUNG-ER
  • HO, HSIN-CHENG

Dates

Publication Date
20260506
Application Date
20231121

Claims (8)

  1. A bioparticle enrichment apparatus (1000) provided for selecting at least one target bioparticle (B1) from a liquid specimen (L) having the bioparticles (B), the bioparticle enrichment apparatus (1000) comprising: a pico-droplet generator (100) including: a light sensing structure (1) including: a first substrate (11); a first electrode layer (12) and a photoelectric layer (13) respectively formed on two opposite sides of the first substrate (11); and an insulating layer (14) covering the photoelectric layer (13); a mating structure (2) spaced apart from the light sensing structure (1), wherein at least one of the mating structure (2) and the light sensing structure (1) is transparent, and the mating structure (2) includes a second substrate (21) and a second electrode layer (22) that is formed on the second substrate (21), and wherein the second electrode layer (22) faces toward the insulating layer (14); a bonding layer (3) that is connected in-between the light sensing structure (1) and the mating structure (2) along a thickness direction (D1) so as to jointly define a selection channel (5) along a flowing direction (D2) perpendicular to the thickness direction (D1), wherein at least one of the mating structure (2) and the bonding layer (3) has an inlet (31) that is located at an upstream of the selection channel (5) and an outlet (32) that is located at a downstream of the selection channel (5), and wherein the bonding layer (3) has a selection hole (33) that is in spatial communication with the selection channel (5) along a dripping direction (D3) perpendicular to the thickness direction (D1) and the flowing direction (D2); and a piezoelectric member (4) disposed on the bonding layer (3), wherein the piezoelectric member (4) and the selection hole (33) are respectively located at two opposite sides of the bonding layer (3) along the dripping direction (D3), and wherein the pico-droplet generator (100) has a pico-droplet emission region (R) defined as extending from the selection hole (33) toward the piezoelectric member (4); a power device (200) electrically coupled to the first electrode layer (12) and the second electrode layer (22); a pressure balance device (300) including a first valve (301) that is assembled to the inlet (31) and a second valve (302) that is assembled to the outlet (32), wherein the pressure balance device (300) is configured to control a velocity and a pressure of the liquid specimen (L) in the selection channel (5) through the first valve (301) and the second valve (302); a camera device (400) corresponding in position to a viewable segment (51) of the selection channel (5), wherein the pico-droplet emission region (R) is arranged in the viewable segment (51), and the camera device (400) is configured to take a real-time image of the liquid specimen (L) in the viewable segment (51); a control device (500) electrically coupled to the piezoelectric member (4), wherein, when the real-time image obtained by the camera device (400) shows that at least one target bioparticle (B1) is located in the pico-droplet emission region (R), the control device (500) allows the piezoelectric member (4) to output a pico-droplet (L1) by driving the liquid specimen (L) in the pico-droplet emission region (R) to pass through the selection hole (33), and wherein the pico-droplet (L1) covers the at least one target bioparticle (B1); and a light source mechanism (600) being in cooperation with the pico-droplet generator (100); wherein the photoelectric layer (13) includes: a collector layer (131) formed on the first substrate (11), wherein the collector layer (131) includes a plurality of collector regions (1312) spaced apart from each other, and an end of each of the collector regions (1312) away from the first electrode layer (12) has a first slot-like portion (1313); a plurality of base regions (1321) respectively formed in the first slot-like portions (1313) of the collector regions (1312), wherein an end of each of the base regions (1321) away from the first electrode layer (12) has a plurality of second slot-like portions (1322) spaced apart from each other; and a plurality of emitter regions (1331) respectively formed in the base regions (1321), wherein each of the emitter regions (1331) includes a plurality of emitter pads (1332) respectively formed in the second slot-like portions (1322) of a corresponding one of the base regions (1321), wherein each of the base regions (1321), a corresponding one of the collector regions (1312), and a corresponding one of the emitter regions (1331) are jointly formed as a vertical transistor (130), and wherein the insulating layer (14) covers the vertical transistors (130) and separates the vertical transistors (130) from each other, and an end of each of the emitter pads (1332) away from the first electrode layer (12) is exposed from the insulating layer (14); wherein any one of the vertical transistors (130) is configured to be irradiated by the light source mechanism (600) so as to enable a plurality of DEP forces to be applied to move the at least one target bioparticle (B1) through a distribution of the emitter pads (1332) and an electric field difference that is generated from non-uniform electric fields of the emitter pads (1332).
  2. The bioparticle enrichment apparatus (1000) according to claim 1, wherein, in each of the vertical transistors (130), the emitter pads (1332) include a first pad (1332a) arranged along an inner ring-shaped path (P1) and a second pad (1332b) that is arranged along an outer ring-shaped path (P2) surrounding the inner ring-shaped path (P1), and a width of the first pad (1332a) is different from a width of the second pad (1332b).
  3. The bioparticle enrichment apparatus (1000) according to claim 2, wherein, in each of the vertical transistors (130), the emitter pads (1332) include a third pad (1332c) arranged along an additional ring-shaped path (P3) located between the inner ring-shaped path (P1) and the outer ring-shaped path (P2), and a width of the third pad (1332c) is within a range from the width of the first pad (1332a) and the width of the second pad (1332b).
  4. The bioparticle enrichment apparatus (1000) according to claim 1, wherein the pico-droplet generator (100) has a hydrophobic surface (34) surrounding the selection hole (33), and the pressure balance device (300) enables the liquid specimen (L) to form a liquid level (L2) in the selection hole (33) that is coplanar with an outer surface of the bonding layer (3).
  5. The bioparticle enrichment apparatus (1000) according to claim 4, further comprising a first container (700) for receiving the pico-droplet (L1), wherein the pressure balance device (300) includes: an air pump (303); a switch (304) connected to the air pump (303); a pressure balance bottle (305) being in fluid communication with the air pump (303) and the switch (304); a liquid injection bottle (306) being in fluid communication with the switch (304) and the first valve (301), wherein the liquid injection bottle (306) enables the liquid specimen (L) received therein to be injected into the selection channel (5) through the first valve (301) and the inlet (31); and a second container (307) being in fluid communication with the second valve (302).
  6. The bioparticle enrichment apparatus (1000) according to claim 1, wherein a width (W33) of the selection hole (33) along the flowing direction (D2) is within a range from 40 µm to 300 µm, and a boundary of the viewable segment (51) is spaced apart from a center of the selection hole (33) along the flowing direction (D2) by a distance within a range from 100 µm to 300 µm.
  7. The bioparticle enrichment apparatus (1000) according to claim 1, wherein the pico-droplet emission region (R) is arranged in a projection area defined by orthogonally projecting the selection hole (33) onto the piezoelectric member (4) along the dripping direction (D3).
  8. The bioparticle enrichment apparatus (1000) according to claim 7, wherein a boundary of the pico-droplet emission region (R) is spaced apart from a center of the selection hole (33) along the dripping direction (D3) by a distance within a range from 50 µm to 200 µm.

Description

FIELD OF THE INVENTION The present invention relates to a droplet generator, and more particularly to a bioparticle enrichment apparatus. BACKGROUND OF THE INVENTION An enrichment process is the first step in conventional research for biological particles, but the conventional enrichment process still requires a significant amount of manpower. Accordingly, how apparatuses or devices can be incorporated in the process to quickly and accurately implement the enrichment process has been one of the important areas of research and development in the relevant field. US 2013/319861A discloses a micro-fluidic device, which can include a processing mechanism for processing micro-objects in a liquid medium and an outputting mechanism for expressing from the device a droplet of the medium containing one or more of the micro-objects. The outputting mechanism can include an expressing mechanism having a reservoir for holding a quantity of the liquid medium and a striking mechanism for striking and compressing the expressing mechanism to express a droplet of the medium from the expressing mechanism. US 2008/286751A discloses a dispensing device for droplets comprising a first channel (8, 10), known as main channel, for circulation of a first fluid flow, a second channel (12, 13) for circulation of fluid, which forms with the first channel an intersection zone (27) and terminates in an ejection orifice (20), means (4) for measuring a physical property particles or cells in the first channel (18), and means for engendering a pressure wave in the second channel (12, 13). SUMMARY OF THE INVENTION In response to the above-referenced technical inadequacies, the present invention provides a bioparticle enrichment apparatus for effectively improving on the issues associated with conventional enrichment processes according to independent claim 1. The dependent claims show further embodiments of claim 1. In order to solve the above-mentioned problems, one of the technical aspects adopted by the present invention is to provide a bioparticle enrichment apparatus provided for selecting at least one target bioparticle from a liquid specimen having the bioparticles. The bioparticle enrichment apparatus includes a pico-droplet generator, a power device, a pressure balance device, a camera device, a control device, and a light source mechanism. The pico-droplet generator includes a light sensing structure, a mating structure, a bonding layer, and a piezoelectric member. The light sensing structure includes a first substrate, a first electrode layer and a photoelectric layer respectively formed on two opposite sides of the first substrate, and an insulating layer covering the photoelectric layer. The mating structure is spaced apart from the light sensing structure. At least one of the mating structure and the light sensing structure is transparent, and the mating structure includes a second substrate and a second electrode layer that is formed on the second substrate. The second electrode layer faces toward the insulating layer. The bonding layer is connected in-between the light sensing structure and the mating structure along a thickness direction so as to jointly define a selection channel along a flowing direction perpendicular to the thickness direction. At least one of the mating structure and the bonding layer has an inlet that is located at an upstream of the selection channel and an outlet that is located at a downstream of the selection channel. The bonding layer has a selection hole that is in spatial communication with the selection channel along a dripping direction perpendicular to the thickness direction and the flowing direction. The piezoelectric member is disposed on the bonding layer. The piezoelectric member and the selection hole are respectively located at two opposite sides of the bonding layer along the dripping direction. The pico-droplet generator has a pico-droplet emission region defined as extending from the selection hole toward the piezoelectric member. The power device is electrically coupled to the first electrode layer and the second electrode layer. The pressure balance device includes a first valve that is assembled to the inlet and a second valve that is assembled to the outlet. The pressure balance device is configured to control a velocity and a pressure of the liquid specimen in the selection channel through the first valve and the second valve. The camera device corresponds in position to a viewable segment of the selection channel. The pico-droplet emission region is arranged in the viewable segment, and the camera device is configured to take a real-time image of the liquid specimen in the viewable segment. The control device is electrically coupled to the piezoelectric member. When the real-time image obtained by the camera device shows that at least one target bioparticle is located in the pico-droplet emission region, the control device allows the piezoelectric member to output a pico-droplet