A handheld microspheroid generator and dispenser

The handheld microspheroid generator and dispenser addresses the need for precise microspheroid generation and dispensing by integrating microfluidics, optical imaging, and microcontroller-based control, enabling rapid and automated production of heterogeneous tissue models for personalized drug screening and cancer therapy planning.

WO2026159754A1PCT designated stage Publication Date: 2026-07-30ISMO BIO-PHOTONICS PVT LTD +1
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Patent Information

Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
ISMO BIO-PHOTONICS PVT LTD
Filing Date
2026-01-26
Publication Date
2026-07-30

AI Technical Summary

Technical Problem

Current technologies lack a user-friendly, compact, and automated device for precise generation, enumeration, and dispensing of microspheroids for personalized drug screening and tissue engineering, particularly for cancer therapy planning and preclinical research.

Method used

A handheld microspheroid generator and dispenser integrating microfluidics, optical imaging, and microcontroller-based control to generate, visualize, enumerate, and precisely dispense microspheroids from 3D spheroid cultures, enabling simultaneous production of heterogeneous tissue models and drug screening.

Benefits of technology

Facilitates rapid, precise, and automated microspheroid generation and dispensing, supporting personalized drug testing and tissue engineering applications, including cancer therapy planning and preclinical research.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention relates to a compact, automated handheld device (10) for accurate generation, enumeration, and high-speed dispensing of microspheroids with homogeneous size control The device features a microfluidic architecture comprising multiple on-chip vials (19) or cascaded chip configured for simultaneous, sequential, or on-demand generation of heterogeneous microspheroids form different cell types. An integrated optical sensor-based imaging system comprising a CMOS camera (8) and imaging lens (7) enables real-time visualization and quantification of the generated microspheroids prior to dispensing. A microcontroller-based control system (9) regulates fluid flow parameters to ensure precise size control, accurate counting, and automated dispensing. The microfluidic system delivers spheroid culture suspensions with controlled dimensions onto different target membranes or materials for applications including drug screening. The device is further adaptable for generation and dispensing of induced pluripotent stem cell (iPSC)-derived organoids or induced organoids for heterogeneous tissue modeling and research purposes.
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Description

A HANDHELD MICROSPHEROID GENERATOR AND DISPENSER FIELD OF INVENTION

[0001] The present invention relates to interdisciplinary fields such as Biotechnology, Mechanical Engineering, Electrical and Electronic engineering, Software engineering, and Biomedical sciences. Collaboratively, they contribute to developing a compact device with accurate generation, high-speed dispensing, enumerating, and homogeneous size of microspheroids for a 3D spheroid culture with precision microspheroid size control, also accurate counting and dispensing of microspheroids.BACKGROUND OF THE INVENTION

[0002] Microspheres are polymeric micron range particles with sizes from 1 to 1000 pm used for drug delivery, wherein the drug can be encapsulated or entrapped form. Based on the polymeric nature, microspheres can be classified into two types: natural and synthetic. Microspheres can be made from biodegradable polymers such as starch, gelatin, albumin, polypropylene, and dextran.

[0003] Microspheres can be produced by different methods which have been enumerated below:1. Emulsion evaporation: This method involves dissolving lipophilic raw materials in an organic solvent, emulsifier in water, and then injecting the oil phase into the water phase under high shear and is used most commonly.2. Phase separation or coacervation: This method involves adding a third component, usually an organic non-solvent, to a polymer-drug-solvent system and stirring.3. Spray drying: This method involves atomizing a solvent containing dissolved polymer using high pressure to create a fine spray that dries quickly and forms spherical particles.4. Other methods: These include forming an emulsion of water in oil (w / o) and adding a crosslinking agent to coagulate the microbeads, or dissolving microsphere materials in a volatile organic solvent and dispersing them in another solvent

[0004] Microfluidic chips have been widely applied in biology and medical research for stably generating uniform droplets that can be solidified into hydrogel microspheres.

[0005] A microfluidic chip is a pattern of microchannels, molded or engraved. This network of microchannels incorporated into the microfluidic chip is linked to the macroenvironment by several holes of different dimensions hollowed out through the chip. It is through these pathways that fluids are injected into and evacuated from the microfluidic chip. Fluids are directed, mixed, separated or manipulated to attain multiplexing, automation, and high-throughput systems. The microchannels network design must be precisely elaborated to achieve the desired features (lab-on-a-chip, detection of pathogens, electrophoresis, DNA analysis , etc).

[0006] Lab-on-a-chip technologies involve the use of micro engineered devices to enable sample preparation, analyte separation, and detection, performed in miniaturized formats providing testing away from the laboratory with examples including medical, veterinary (penside), and environmental analysis.

[0007] A few of the patent and non-patent literature pertaining to our present invention have been discussed below:

[0008] In the patent, “Apparatus for a mass production of monodisperse biodegradable polymer-based microspheres and a multi-channel forming device incorporatable therein” (KR101902471B1) which relates to a mass-production apparatus which includes a multichannel manufacturing section, a first raw material reservoir containing the first raw material and in fluid communication with the plurality of first microchannels, and a second raw material reservoir containing the second raw material and being in fluid communication with the plurality of second microchannels A flow control unit configured to supply a first gas to a first raw material flow rate to the first raw material storage tank and a second gas to a second raw material storage tank at a second raw material flow rate; And a product reservoir for receiving the microspheres formed from the multi-channel manufacturing portion.

[0009] The patent “Organic microspheres used in personalized medicine and drug development” (JP2023553838A) relates to a system which may include an organic microsphere generator configured to form a set of organic microspheres from a mixture of biological sample and fluid. A controller may be coupled to the imaging device. The controller is configured to receive imaging data corresponding to one or more of the mixture or the set of organic microspheres and to estimate one or more properties of the set of organic microspheres based at least on the imaging data.

[0010] In the non-patent literature “An integrated microfluidic platform for on-demand single droplet dispenser with high accuracy by electrohydrodynamic (EHD) printing technique,” an integrated microfluidic droplet dispenser based on the electrohydrodynamic (EHD) principle, capable of on-demand single droplet dispensing with high accuracy has been studied. This system uses optical signal activation and EHD actuation to isolate and dispense droplets. The microfluidic droplet auto dispenser consists of four main modules: a pump-drive chip module, an optical automatic signal recognition module, a high voltage control module, and an automated X-Y translation stage module.

[0011] In the non-patent literature “In silico design and fabrication of an SFI chip-based microspheroid culture system”, a CFD application in an in silico-designed and spheroid-based flow integration 3D cell culture chip (SFI chip) to illustrate cell culture, drug screening, cytokine delivery, and differentiation of cells in a platform that partially recapitulates the natural environment has been developed and studied.

[0012] At present, there are microfluidic droplet dispensers on the microarray chip or well plates but there is a need for a device designed to deliver microspheroids with precise size on chips or well plates for personalized drug screening assays at the cellular level and to evaluate the spheroids response to the drug's activity in vitro. Thus, based on the cellular response the treatment plan or type of cancer therapy can be suggested or diseases can be identified.

[0013] Currently, in biomedical inventions, there are no products that are user-friendly, similar to our present invention in the current market. While most of the models are still in thebrainstorming and lab testing phases as well as being larger in size, our present invention provides compaction and operation; thus our present invention will make the diagnosis procedure simpler and rapid for screening the various drug combinations in a single platform.

[0014] Our present invention will generate, enumerate, and dispense micro spheroids with size control for the spheroid culture designed to deliver a personalized drug testing platform for different diseases models as well as facilitate the study of various tissue or cellular functionalities in an in vitro microenvironment similar to the in vivo conditions.OBJECTIVE OF THE INVENTION

[0015] The primary objective of this invention is to provide a user-friendly, absolutely automated handheld device that delivers microspheroids generated in vitro for personalized drug testing on different cancer models as well as to study cells of different tissue origin, cocultured cells study etc.

[0016] Another objective of our present invention is to generate and deliver the microspheroids with greater precision, and rapid dispensing, compatible on various diagnostics targets or laboratory testing materials.

[0017] Also, the device is set up with an optical sensor based imaging system to visualize the generated micropsheroids and to quantify. One of the major advantages of our device is the microcontroller system for precision dispensing of the micropsheroids. Another objective of our present invention is to be used in diagnostics and Centres for Cancer Research where treatment plans or suitable therapy for the patients can be done, as the generated and dispensed micro spheroids are compatible for personalized drug screening assays, also it is a boon to tissue engineering and preclinical research.

[0018] Another objective of our present invention is to produce microspheres for study, research, and testing platform to figure out the appropriate treatment for the patient alongwith the assessment of side effects, prescribing the dosage and the course of therapy required based on the cancer type and its phase.

[0019] Another objective of our present invention is that, also the induced pluripotent stem cell (iPSC) based organoids or induced organoids can also be generated and dispensed precisely to create heterogeneous tissue models for research purposes or multiple disease studies.SUMMARY OF THE INVENTION

[0020] The following summary is provided to facilitate a clear understanding of the new features in the disclosed embodiment and it is not intended to be a full, detailed description. A detailed description of all the aspects of the disclosed invention can be understood by reviewing the full specification, the drawing and the claims and the abstract, as a whole.

[0021] The present invention is completely automated handheld micro spheroid generator and dispenser that is capable of precision generation, high speed dispensing of micro spheroids from a 3D spheroid culture with accuracy in spheroid size and enumeration of the dispensed spheroids. These spheroids will be a closely related model of study to plan the treatment regimen for the patient’s disease cure or can also be employed in research for the study of different tissues or cell characteristics.

[0022] The monolithic design of the microspheroid generator chip facilitates the cascading of multiple units within a single device or the integration of multiple vials on a single chip. This architecture enables the simultaneous or on-demand generation of different cell types and heterogeneous co-cultured microspheroids. The multichannel microspheroid dispensing system delivers these varied microspheroids onto the targeted platform simultaneously, with precise dimension control and rapid dispensing facilitated by the integrated microfluidic and microcontroller system.BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 illustrates an external perspective view of a handheld microspheroid generator and dispenser according to the present invention.

[0024] Figure 2 illustrates an internal arrangement of microfluidic, optical imaging, control, and dispensing components housed within the enclosure of the device.

[0025] Figure 3 illustrates a microfluidic chip layout showing droplet generation, UV curing, on-chip phase exchange, imaging region, and dispensing outlet.

[0026] Figure 4 illustrates a cascaded microfluidic chip architecture featuring multiple on- chip vials and independent pressure control lines for the simultaneous generation of different microspheroid types.REFERENCE NUMERALS1 Microfluidic chip2 Output tip3 Rubber sealing gasket4 Microfluidic chip docking holder5 UV curing LED for hydrogel curing6 UV LED glass window7 Imaging lens8 CMOS camera9 Microcontroller board10 EnclosureIllumination with diffuser LED for11microscope12 Magnet13 Touch display for monitoring and control14 UV curing area15 UV blocker for T-junctionOil and spheroid separator with culture media16mixer17 Culture media inlet18 Continuous phase inlet (oil) for microfluidicsOn-chip vial to load UV-curable hydrogel +19cell mixture20 T-junction to generate spheroids21 Imaging windowPressure inlet to control hydrogel mixture22flow23 Used oil collector24 Oils with surfactants25 Oil particle separation point viewing windowDETAILED DESCRIPTION OF THE INVENTION

[0027] The principles of operation, design configurations and evaluation values in these non-limiting examples can be varied and are merely cited to illustrate at least one embodiment of the invention, without limiting the scope thereof.

[0028] The embodiments disclosed herein can be expressed in different forms and should not be considered as limited to the listed embodiments in the disclosed invention. The various embodiments outlined in the subsequent sections are constructed such that it provides a complete and thorough understanding of the disclosed invention, by clearly describing the scope of the invention, for those skilled in the art.

[0029] Throughout this specification, various indications have been given as to preferred and alternative embodiments of the invention. It should be understood that it is the appended claims, including all equivalents, which are intended to define the spirit and scope of this invention.Our present invention, the Handheld Microspheroid Generator and Dispenser is equipped with the following components:1. Pump,2. microfluidic chips,3. multichannel microspheroid dispensers,4. digital display,5. valves,6. sheath fluid chamber,7. cartridges for loading cell suspension and scaffold material8. generating and curing chambers to separate Sheath fluid and microspheroid,9. Optical sensor based imaging system10. light source.

[0030] The cell suspension is combined with the scaffold material (eg. hydrogel) loaded in the cartridge of our handheld microspheroid generator and dispenser.

[0031] The size control, flow rate parameters are adjusted in the digital display on our device.

[0032] The cell suspension with scaffold material is pumped into the microfluidic chip or multiple microfluidics chips are used to generate different microspheroids simultaneously in a sheath fluid medium.

[0033] The multiple microfluidics system facilitates the microspheroid generation from different cell sources and dispenses simultaneously on the single platform through the multichannel microspheroid dispenser tips.

[0034] In the generation chamber, the light source solidifies the scaffold material with the microspheroid entrapped within.

[0035] The valves are used to control the flow rate, pressure and smooth dispensing of the generated micro spheroids on the target platform.

[0036] The pump creates a pressure to push the microspheroid generated into the curing chamber on the microfluidic chip, where the sheath fluid is separated and the generated microspheroid is released into the appropriate culture medium or buffers.

[0037] A separate channel on the microfluidic chip pumps the culture medium which confirms the quality of generated microspheroids and selectively allows the movement of the ideal microspheroid into the dispensing tip. The count of microspheroids dispensed is viewed in the digital display.

[0038] The generated microspheroids are visualized as individual single microspheroids and enumerated by the optical sensor based imaging system and real time count is displayed on the digital display in one embodiment of our present invention.

[0039] Then the generated microspheroid in the curing chamber is dispensed precisely in the target platform through the multichannel microspheroid dispenser. The generated single type of microspheroid or multiple types of microspheroids can be dispensed simultaneously on the target platform.The working of the preferred embodiment of our present invention has been given below:Step 1 : The source of spheroid culture can be stem cells (such as adult stem cells, pluripotent stem cells, induced PSC, etc), biopsy derived cells, cells from different tissue origin also cocultured cells, etc. The cells are maintained in appropriate culture medium without contamination.Step 2: The desired cell type is combined with the Scaffold material (hydrogel) and loaded into the cartridge of our device.Step 3: The size parameters, and flow rate are adjusted in the digital display. The spheroid suspension with scaffold material is pumped into the microfluidic chips. The microspheroids aregenerated in the sheath fluid medium by the solidification of scaffold material with the light source.Step 4: The multiple microfluidics chips in our device facilitate the microspheroid generation from different cell sources and dispense simultaneously on the single platform through the multichannel microspheroid dispenser tips.Step 4: At the generation and curing chamber the generated microspheroid is separated from sheath fluid and replaced with a culture medium or appropriate buffer to maintain the viability. Step 5: The sensor based imaging system enables the visualization and enumeration of microspheroids to be dispensed. Confirming the quality of microspheroid, a separate microfluidic channel on the chip pump culture medium to selectively allow the movement of the generated microspheroid to the dispensing tip. The count of microspheroids dispensed is viewed on the digital display.Step 7: Thus our device generates, enumerates, and dispenses the accurate size of microspheroids as on different target membranes or materials for drug screening and analysis.

[0040] The present invention relates to a completely automated, handheld microspheroid generation and dispensing device configured to generate, solidify, visualize, enumerate, and precisely dispense microspheroids derived from three-dimensional (3D) spheroid cultures. The invention integrates microfluidics, optical imaging, and microcontroller-based control within a compact enclosure to enable controlled microspheroid formation and delivery suitable for applications such as drug screening, cell-based assays, and tissue engineering.

[0041] In an advanced embodiment of the present invention, the device is configured to facilitate the production of heterogeneous tissue models through a multi-channel microfluidic architecture. The microfluidic chip (1) is designed with multiple on-chip vials (19) or, alternatively, multiple microfluidic chips (1) are cascaded in series or parallel within the docking holder (4). This configuration allows the system to generate different types of microspheroids comprising various cell types, co-cultures, or differentiated organoids simultaneously, sequentially, or on-demand. Each vial is coupled to independent pressure inlets (22) controlled by the microcontroller (9), enabling precise, programmable coordinationof flow. By integrating these multiple generation streams, the device can dispense a diverse population of spheroids through the multichannel output tip (2), providing a high-throughput platform for simulating complex biological environments in a single dispensing cycle.

[0042] Referring to the embodiment illustrated herein, the handheld microspheroid generator and dispenser comprises an enclosure (10) forming the external body of the device, within which multiple functional subsystems are integrated. The enclosure (10) houses a microfluidic chip (1) mounted on a microfluidic chip docking holder (4) and sealed using a rubber sealing gasket (3) to prevent leakage and ensure pressure stability during operation.

[0043] The microfluidic chip (1) includes an on-chip vial (19) configured to receive a mixture comprising a cell suspension and a scaffold material, such as a hydrogel. The hydrogel may include, but is not limited to, alginate, gelatin methacrylate, polyethylene glycol-based hydrogels, collagen, fibrin, or combinations thereof. Cells loaded into the on-chip vial (19) may include stem cells, primary cells, biopsy-derived cells, immortalized cell lines, or cocultured cell populations.

[0044] A culture media inlet (17) is fluidly connected to the microfluidic chip (1 ) to supply biologically compatible aqueous media, while a continuous phase inlet (18) is configured to introduce a carrier oil containing surfactants (24). A pressure inlet (22) is provided to regulate fluid flow rates within the chip using controlled pneumatic or pump-based actuation. The flow parameters are governed by a microcontroller board (9) operatively connected to the pressure inlet (22).

[0045] Within the microfluidic chip (1), a T-junction (20) is formed, wherein the cellhydrogel mixture introduced from the on-chip vial (19) intersects with the continuous oil phase introduced via the inlet (18). At the T-junction (20), discrete droplets of the cellhydrogel mixture are generated due to controlled shear forces and flow-focusing dynamics. The dimensions of the droplets, and thereby the resulting microspheroids, are controlled by adjusting flow rates, pressure differentials, channel geometry, and fluid viscosities, all of which are set via a touch display (13) connected to the microcontroller board (9).

[0046] Downstream of the T-junction (20), the microfluidic chip (1) includes a curing area (14) positioned adjacent to a UV curing LED (5). The curing LED (5) emits ultraviolet radiation through a UV LED glass window (6) to initiate crosslinking or polymerization of the scaffold material, thereby solidifying the droplets into structurally stable microspheroids. A UV blocker (15) is positioned between the curing area (14) and the T-junction (20) to prevent ultraviolet exposure at the droplet formation zone, thereby avoiding premature curing and potential channel clogging.

[0047] Following curing, the microspheroids enter an oil / spheroid separator and media mixer (16). This region utilizes a widened channel geometry to significantly reduce horizontal flow velocity. Due to the differential density between the hydrogel microspheroids and the carrier oil, the spheroids undergo gravitational sedimentation, transitioning across the biphasic interface into the lower culture media (17) phase. The lighter, spheroid-free oil phase is then skimmed off into the used oil collector (23) while the 'washed' spheroids in the aqueous media proceed to the output tip (2).

[0048] The separated oil phase is directed toward a used oil collector (23), while the microspheroids suspended in culture media proceed downstream toward the output tip (2). An oil particle separation viewing window (25) is provided adjacent to the separator (16) to enable visual confirmation of effective phase separation during operation.

[0049] The device further includes an optical sensor based imaging system integrated within the enclosure (10). The imaging system comprises an illumination source with diffuser LED (11), an imaging lens (7), and a CMOS camera (8) aligned with an imaging window (21) formed in the microfluidic chip (1). The imaging window (21) permits optical access to the flow path containing the microspheroids prior to dispensing. The CMOS camera (8) captures real-time images or video of the generated microspheroids, enabling visualization, size assessment, and enumeration.

[0050] Image data captured by the CMOS camera (8) is processed by the microcontroller board (9), which may execute embedded image analysis algorithms to count microspheroidsand optionally assess dimensional parameters such as diameter or circularity. The quantified data is displayed on the touch display (13), allowing an operator to monitor microspheroid generation and dispensing in real time.

[0051] The output tip (2) is configured to dispense microspheroids suspended in culture media onto a target platform, membrane, substrate, or receptacle with controlled positioning and flow rate. The precision dispensing is governed by the microcontroller-based control system, which synchronizes pressure regulation, imaging feedback, and flow actuation to ensure accurate delivery and repeatability.

[0052] In certain embodiments, the device may incorporate multiple microfluidic chips (1) arranged in parallel, enabling simultaneous generation and dispensing of microspheroids derived from different cell types, different scaffold compositions, or co-cultured systems. The multichannel configuration facilitates high-throughput microspheroid production and delivery within a single handheld unit.

[0053] A magnet (12) may be incorporated within the enclosure (10) to stabilize chip positioning or assist in handling magnetically responsive components where applicable. The handheld configuration of the enclosure (10), combined with integrated electronics, optics, and fluidics, enables portable and automated operation without reliance on external laboratory infrastructure.

[0054] Figure 1 illustrates an external perspective view of the handheld microspheroid generator and dispenser according to the present invention. The device comprises an enclosure (10) forming a compact handheld body configured to house all functional subsystems of the invention. The enclosure (10) supports portability and single-hand operation while protecting internal microfluidic, optical, and electronic components.

[0055] A touch display (13) is provided on the outer surface of the enclosure (10) to enable user interaction, parameter input, and real-time visualization of operational data including flow settings and microspheroid enumeration. The enclosure (10) further accommodatesinternal illumination components, imaging components, and a dispensing outlet, while maintaining alignment and mechanical stability of the internal assemblies.

[0056] Figure 2 illustrates the internal arrangement of components housed within the enclosure (10). A microfluidic chip (1) is positioned within the enclosure (10) and mounted on a microfluidic chip docking holder (4). A rubber sealing gasket (3) is provided between the microfluidic chip (1) and the docking holder (4) to ensure leak-proof sealing and pressure integrity during fluid flow.

[0057] A microcontroller board (9) is disposed within the enclosure (10) and is electrically connected to the touch display (13), an illumination source with diffuser LED (11), a CMOS camera (8), and a pressure inlet (22). The microcontroller board (9) is configured to regulate flow parameters, control imaging operations, and synchronize dispensing functions.

[0058] An imaging lens (7) is aligned with the CMOS camera (8) and positioned to capture images through an imaging window (21) provided in the microfluidic chip (1). The illumination source with diffuser LED (11) is arranged to uniformly illuminate the imaging window (21) for accurate visualization of microspheroids.

[0059] The enclosure (10) further houses a UV curing LED (5) positioned adjacent to the microfluidic chip (1) such that ultraviolet radiation is transmitted through a UV LED glass window (6) formed in the chip. A magnet (12) may be incorporated within the enclosure (10) to assist in chip positioning or stabilization. A used oil collector (23) is provided within the enclosure (10) to receive separated oil during phase exchange.

[0060] Figure 3 illustrates the structural layout and functional regions of the microfluidic chip (1). The microfluidic chip (1) comprises an on-chip vial (19) configured to receive a mixture of cells and scaffold material such as a hydrogel. The on-chip vial (19) is fluidly connected to a T-junction (20).

[0061] A continuous phase inlet (18) is provided for introducing oils with surfactants (24), while a culture media inlet (17) is configured to supply aqueous culture media. A pressure inlet (22) is operatively connected to the microfluidic pathways to control flow rates within the chip.

[0062] At the T-junction (20), the cell-scaffold mixture intersects with the continuous oil phase, resulting in the formation of discrete droplets. Downstream of the T-junction (20), a curing area (14) is formed, wherein the droplets are exposed to ultraviolet radiation emitted by the UV curing LED (5) through the UV LED glass window (6), thereby solidifying the droplets into microspheroids. A UV blocker (15) is positioned between the T-junction (20) and the curing area (14) to prevent ultraviolet exposure at the droplet generation site.

[0063] The monolithic design of the microspheroid generator chip make it possible cascading multiple copies in single chip making it possible to achieve simultaneous or on-demand generation of different cell types with multiwell on single chip as shown in Figure 4. Multichannel microspheroid generator and dispensing systems that deliver microspheroids of different cell types or co-cultured microspheroids on the targeted platform. The microfluidics system designed in our device is to deliver precise dimension control of spheroid culture suspension and rapid dispensing on different target membranes or materials for drug screening.

[0064] Following curing, the microspheroids enter an oil / spheroid separator and media mixer (16), which is characterized by a widened microchannel configured to reduce flow velocity; this enables density-driven sedimentation of solidified microspheroids from the oil phase into the culture media phase supplied via the culture media inlet (17), effectively performing an on-chip phase exchange. An oil particle separation viewing window (25) is provided adjacent to the separator (16) to visually monitor phase separation.

[0065] The lighter oil phase is directed toward the used oil collector (23), while the microspheroids suspended in culture media proceed toward the imaging window (21). Theimaging window (21) permits optical access for visualization and enumeration by the imaging lens (7) and CMOS camera (8).

[0066] The microspheroids are finally delivered through an output tip (2), which is configured to dispense the microspheroids in a controlled and precise manner under regulation of the microcontroller board (9).

[0067] Thus, the present invention provides a compact, integrated system capable of controlled microspheroid generation, on-chip curing, phase exchange, real-time visualization, enumeration, and precision dispensing within a single handheld device.

Claims

/ We Claim:

1. A handheld microspheroid generator and dispenser device, comprisingan enclosure (10) housing at least one microfluidic chip (1), the microfluidic chip comprising a T-junction (20) and an output tip (2) for dispensing microspheroids, characterized in that the microfluidic chip (1) includes on-chip vials (19) or is operably coupled in a cascaded microfluidic chip configuration, the arrangement being configured to selectively generate heterogeneous microspheroids from different cell types in a simultaneous, sequential, or on-demand manner, the microfluidic chip (1) comprises:a UV curing area (14) positioned downstream of the T-junction (20) and operatively coupled to a UV curing LED (5) through a UV LED glass window (6) for solidifying droplets into microspheroids,a UV blocker (15) disposed between the T-junction (20) and the UV curing area (14) to prevent premature curing, andan integrated oil / spheroid separator and media mixer (16) formed as a widened microchannel configured to enable density-driven sedimentation of cured microspheroids from a continuous oil phase into a culture media phase supplied via a culture media inlet (17), and wherein the enclosure (10) houses:an optical sensor-based imaging system comprising an imaging lens (7), a CMOS camera (8), and an imaging window (21) configured to visualize and enumerate microspheroids prior to dispensing, anda microcontroller board (9) operatively coupled to a pressure inlet (22) and a touch display (13) to control flow parameters and enable precision dispensing of microspheroids through the output tip (2).

2. The handheld microspheroid generator and dispenser device as claimed in claim 1 , wherein the oil / spheroid separator and media mixer (16) is configured to reduce flow velocity to facilitate gravitational sedimentation based on density differences between the microspheroids and the oil phase.

3. The handheld microspheroid generator and dispenser device as claimed in claim 1 , wherein the microfluidic chip (1) comprises a continuous phase inlet (18) configured to introduce oils with surfactants (24) for controlled droplet formation at the T-junction (20).

4. The handheld microspheroid generator and dispenser device as claimed in claim 1 , wherein the microcontroller board (9) regulates droplet size and dispensing accuracy by controlling pressure supplied through the pressure inlet (22).

5. The handheld microspheroid generator and dispenser device as claimed in claim 1 , wherein the imaging system is configured to generate real-time microspheroid count data displayed on the touch display (13).

6. The handheld microspheroid generator and dispenser device as claimed in claim 1 , wherein the microfluidic chip (1) is mounted within the enclosure (10) using a microfluidic chip docking holder (4) and sealed by a rubber sealing gasket (3).

7. The handheld microspheroid generator and dispenser device as claimed in claim 1 , wherein the device comprises an illumination source with diffuser LED (11) configured to provide uniform illumination of the imaging window (21).

8. The handheld microspheroid generator and dispenser device as claimed in claim 1 , wherein the separated oil phase is directed to a used oil collector (23) housed within the enclosure (10).

9. The handheld microspheroid generator and dispenser device as claimed in claim 1 , wherein the microfluidic chip (1) is configured as one of a plurality of microfluidic chips arranged in parallel within the enclosure (10).

10. The handheld microspheroid generator and dispenser device as claimed in claim 1, wherein the imaging and dispensing operations are synchronized by the microcontroller board (9) to enable controlled enumeration-based dispensing of microspheroids.