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EP-4737004-A1 - A FLUID PROCESSING DEVICE FOR PROCESSING DROPLETS

EP4737004A1EP 4737004 A1EP4737004 A1EP 4737004A1EP-4737004-A1

Abstract

The present invention relates to a fluid processing device for processing droplets. The device comprises a plate-like structure comprising a plurality of functional pixels. Each functional pixel is adapted to perform multiple operations on a droplet located on the pixel. Specifically, each pixel can selectively carry out at least two of the following processing operations: manipulating the droplet (e.g., its position), applying heat to the droplet, and subjecting the droplet to a magnetic field. These different operations can be selectively performed at different times on the same pixel, allowing for complex, multi-step protocols to be executed in a single, compact device. This solution enables the integration of various microfluidic functions, typically requiring separate instruments, into one unified platform. The invention can be applied to biochemical analysis, molecular diagnostics, and drug discovery, where precise control over small volumes of fluids is crucial.

Inventors

  • YURT, Abdulkadir
  • SET, Ying Ting
  • Moloudi, Reza
  • VANDEVELDE, BART

Assignees

  • Imec VZW

Dates

Publication Date
20260506
Application Date
20241031

Claims (20)

  1. A fluid processing device comprising: a plate-like structure (10) for processing one or more droplets located on the plate-like structure (10), wherein the plate-like structure (10) comprises a plurality of functional pixels (11a, 11b, 11c), wherein each functional pixel (11a, 11b, 11c) as a whole is adapted to selectively perform at least two of the following processing operations at different times on a droplet located on the functional pixel: manipulating the droplet; applying heat to the droplet; and applying a magnetic field to the droplet.
  2. The fluid processing device according to claim 1, wherein the plurality of functional pixels (11a, 11b, 11c) are arranged adjacently across a continuous part of the plate-like structure (10).
  3. The fluid processing device according to claim 1 or 2, wherein each functional pixel (11a, 11b, 11c) comprises a conductive element configured to perform each of the at least two processing operations.
  4. The fluid processing device according to any one of claims 1 to 3, further comprising a plurality of metal coils embedded in the plate-like structure (10), wherein each functional pixel (11a, 11b, 11c) is associated with one or more metal coils, and each functional pixel (11a, 11b, 11c) as a whole is adapted to perform the at least two processing operations on the droplet located on the functional pixel (11a, 11b, 11c) by respectively applying different signals to the one or more metal coils.
  5. The fluid processing device according to claim 4, wherein the one or more metal coils associated with a functional pixel (11a, 11b, 11c) are adapted to: manipulate the droplet located on the functional pixel (11a, 11b, 11c) in response to receiving a voltage with no current flow; apply heat to droplet located on the functional pixel (11a, 11b, 11c) in response to receiving an alternating current; or apply the magnetic field to the droplet located on the functional pixel (11a, 11b, 11c) in response to receiving a direct current.
  6. The fluid processing device according to any one of claims 1 to 3, wherein each functional pixel (11a, 11b, 11c) comprises a plurality of stacked layers (221, 222; 231, 232, 233), wherein each layer (221, 222, 231, 232, 233) is adapted to perform one or more of the at least two processing operations.
  7. The fluid processing device according to claim 6, wherein each functional pixel (11a, 11b, 11c) comprises a first layer (221) adapted to manipulate the droplet located on the functional pixel, and a second layer (222) adapted to apply heat and the magnetic field to the droplet located on the functional pixel.
  8. The fluid processing device according to claim 7, wherein each functional pixel (11a, 11b, 11c) comprises an electrowetting element in the first layer (221) for manipulating the droplet, and an electrode in the second layer (222) for applying heating and the magnetic field to the droplet.
  9. The fluid processing device according to claim 6, wherein each functional pixel (11a, 11b, 11c) comprises a first layer (231) adapted to manipulate the droplet located on the functional pixel, a second layer (232) adapted to apply the magnetic field to the droplet located on the functional pixel, and a third layer (233) adapted to apply heat to the droplet located on the functional pixel.
  10. The fluid processing device according to claim 9, wherein each functional pixel (11a, 11b, 11c) comprises an electrowetting element in the first layer (231) for manipulating the droplet, a thermal element in the second layer (232) for applying heating to the droplet, and a magnetic element in the third layer (233) for applying the magnetic field to the droplet.
  11. The fluid processing device according to any one of claims 1 to 10, wherein one or more of the plurality of functional pixels (11a, 11b, 11c) are configured to provide light onto and/or detect light emitted by one or more droplets located on the one or more functional pixels (11a, 11b, 11c).
  12. The fluid processing device according to claim 11, further comprising one or more light emitting devices (54) configured to emit the light of at least one predetermined wavelength, and/or one or more photodetectors (55) configured to detect the light emitted by the one or more droplets located on the one or more functional pixels (11a, 11b, 11c), wherein the one or more light emitting devices (54) and the one or more photodetectors (55) are arranged on or besides an outer surface of the one or more functional pixels (11a, 11b, 11c).
  13. The fluid processing device according to any one of claims 1 to 12, further comprising: one or more input ports, each input port being configured to receive the one or more droplets and to provide the one or more droplets onto the plate-like structure; and/or one or more output ports, each output port being configured to eject the one or more droplets from the fluid processing device.
  14. The fluid processing device according to any one of claims 1 to 13, wherein each functional pixel (11a, 11b, 11c) is adapted to receive at least two different control signals at different times for respectively controlling each functional pixel (11a, 11b, 11c) to perform the at least two different processing operations.
  15. The fluid processing device according to claim 14, wherein each functional pixel (11a, 11b, 11c) is connected with a circuitry (95), the circuitry comprising at least one electronic switching element configured to selectively provide the at least two different control signals to each functional pixel (11a, 11b, 11c) at different times.
  16. The fluid processing device according to claim 15, wherein the at least one electronic switching element is connectable to a common circuit line (101a, 101b), wherein the common circuit line (101a, 101b) is adapted to produce the at least two different signals at different times.
  17. The fluid processing device according to claim 15, wherein the at least one electronic switching element is configured to switch among a current waveform circuit line (111), a potential circuit line (112), and a ground circuit line (113) at different times, so as to selectively provide the at least two different signals to each functional pixel (11a, 11b, 11c) at different times.
  18. The fluid processing device according to any one of claims 14 to 17, wherein the at least two different signals for performing the at least two different processing operations differ in terms of their amplitude and/or frequency and/or waveform and/or duty cycle.
  19. The fluid processing device according to any one of claims 1 to 18, further comprising a controller (91) configured to address the plurality of functional pixels (11a, 11b, 11c).
  20. A fluid processing array (1410) comprising a plurality of fluid processing devices (1401) according to one of the claims 1 to 19.

Description

TECHNICAL FIELD The present disclosure relates to a device for processing one or more droplets of a fluid or liquid. The disclosure provides such a device, which is adapted to selectively perform different processing operations to one or more droplets located on a same area at different times. The droplet processing device may be used for implementing a workflow, for instance, library preparation for next-gen gene sequencing, nucleic acid synthesis. BACKGROUND Synthetic DNA manufacturing and next-generation sequencing (NGS) are cuttingedge fields that have revolutionized genetic research, biotechnology, and medicine. These technologies have enabled rapid advancements in our understanding of genetic variation, disease mechanisms, and biological systems, with wide-ranging applications in clinical research, diagnostics, reproductive health, and environmental studies. Synthetic DNA manufacturing involves creating artificial DNA sequences in the laboratory. The process begins with oligonucleotide synthesis, where short DNA fragments are chemically synthesized. These fragments are then assembled into longer sequences, known as genes, through automated processes. Techniques like Gibson Assembly and Golden Gate Assembly are employed to join multiple DNA fragments seamlessly, enabling the construction of complex genetic circuits and synthetic genomes. Synthetic DNA has numerous applications, including the development of mRNA vaccines, gene therapies, and precision medicines, as well as the creation of new biological systems and organisms in synthetic biology. Next-generation sequencing, on the other hand, allows for the rapid and costeffective sequencing of DNA and RNA. Unlike traditional Sanger sequencing, which sequences one DNA fragment at a time, NGS enables the simultaneous sequencing of millions of fragments, providing ultra-high throughput, scalability, and speed. The NGS process begins with the preparation of a sequencing library, where DNA or RNA samples are fragmented into shorter pieces and tagged with unique molecular barcodes. These fragments are then amplified and sequenced in parallel, generating massive amounts of data in a single run. Both synthetic DNA manufacturing and NGS rely heavily on the preparation of DNA libraries. Library preparation is an indispensable step that entails the adaptation of samples to make them compatible with downstream processes. This step typically involves multiple processing stages, including DNA fragmentation, end repair, adapter ligation, and amplification. These processes require precise manipulation of small volumes of fluids, careful temperature control, and often the use of magnetic beads for purification steps. SUMMARY As the demand for synthetic nucleic acid synthesis and sequencing services continues to rise, several challenges have become increasingly prominent, including: Complexity of workflows: Protocols often consist of many steps, each requiring precise control over various parameters such as temperature, reaction time, and reagent concentrations. In an example of nucleic acid synthesis, the reagent of monomers or nucleic acid fragments are delivered in precise volumes with minimized dead volume requirements. Multiple chemistry reagents, buffers and other liquid elements are involved with varying physical properties. Accuracy and selectivity of reactions play critical roles to prevent errors and impact on follow-up steps in the protocols. In many cases, quality control steps are required to prevent low yields and to ensure repeatability of the protocols.Sample quantity and quality: Many applications require processing of numerous samples, often with limited quantity and variable quality, necessitating highly efficient and flexible preparation methods.Accuracy and purity: Achieving the necessary length, accuracy, and purity of the DNA produced remains a primary challenge, particularly in synthetic DNA manufacturing.Time and cost: Current methods can be time-consuming and expensive, with library preparation accounting for a significant portion of the total time and cost in many genomic studies.Scalability: As demand increases, there is a growing need for systems that can handle higher throughput without compromising on quality or flexibility.Automation: While some steps have been automated, many workflows still require significant manual intervention, leading to potential errors and inconsistencies. Current laboratory workflow implementations, particularly in the fields of synthetic DNA manufacturing and next-generation sequencing, face several significant challenges. Existing lab workflow implementations are cumbersome, error-prone, and expensive. They typically require multiple dedicated instruments and a large number of consumables, as well as substantial manual labor to execute complex workflows. This approach necessitates the use of numerous types of consumables such as pipette tips, well-plates, and tubes, leading to increased costs and potential for