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WO2020030090A1 - Systèmes de manipulation automatisée d'échantillons de fluide afin de former des gouttelettes microfluidiques pour un diagnostic in vitro - Google Patents

Systèmes de manipulation automatisée d'échantillons de fluide afin de former des gouttelettes microfluidiques pour un diagnostic in vitro Download PDF

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Publication number
WO2020030090A1
WO2020030090A1 PCT/CN2019/099942 CN2019099942W WO2020030090A1 WO 2020030090 A1 WO2020030090 A1 WO 2020030090A1 CN 2019099942 W CN2019099942 W CN 2019099942W WO 2020030090 A1 WO2020030090 A1 WO 2020030090A1
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WO
WIPO (PCT)
Prior art keywords
assembly
wells
droplets
fluid
cartridge
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2019/099942
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English (en)
Inventor
Ho Cheung Shum
Yuk Heng TANG
Man Ho WONG
Hui Sheng ZHANG
Tong Yuan WU
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shenzhen University
Versitech Ltd
Original Assignee
Shenzhen University
Versitech Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Shenzhen University, Versitech Ltd filed Critical Shenzhen University
Priority to CN201980052964.1A priority Critical patent/CN113841053B/zh
Publication of WO2020030090A1 publication Critical patent/WO2020030090A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid

Definitions

  • the number of clinical samples which need to be processed is tremendous in clinics and hospitals.
  • the clinical samples are usually present in containers such as test tubes, centrifuge tubes, and multi-well plates.
  • containers such as test tubes, centrifuge tubes, and multi-well plates.
  • To transfer the clinical samples to microfluidic device the process is mainly manually done and is not an effective approach that consumes laboring costs.
  • the users may also require having sufficient skill and knowledge to operate the microfluidic device. Without an assembly for these containers and microfluidic devices, it may fail to persuade doctors or inspectors to comfortably use new technology to handle a large number of different samples.
  • a new sampling assembly which seamlessly bridges current sampling method with microfluidic technology is provided.
  • the subject invention provides an assembly, including hardware and software, for handling fluid samples to form emulsions.
  • the assembly can include a robotic liquid handler to manipulate fluid from sample tubes to a cartridge, and to collect emulsions from the cartridge to vials.
  • the assemble can apply pressure for the manipulation of fluid and emulsions within the body of the assembly.
  • the assembly can stop applying pressure to the fluid when a predefined condition is arrived. The change can indicate the endpoint of fluid manipulation is achieved.
  • Figure 1 depicts schematics for the assembly design.
  • the machine control unit serves as the core unit to perform different function, such as the pressure control and motion control for droplet generation and transfer.
  • the user can control the assembly through the computer, which will be connected to the assembly by USB/RS232 to the universal asynchronous receiver/transmitter (UART) on the assembly.
  • USB/RS232 to the universal asynchronous receiver/transmitter (UART) on the assembly.
  • UART universal asynchronous receiver/transmitter
  • Figure 2 depicts the workflow of the assembly for droplet generation (enclosed by yellow dotted line) , liquid transfer and cleaning procedures (enclosed by green and blue dotted line) .
  • Figure 3 depicts a schematic for waste disposal schematics.
  • Figure 4 shows a front side of the assembly, where the user interacts with. After the user places the sample tube, the assembly automates the process of sample transfer, droplet preparation, and droplet transfer. The user collects the droplets on the PCR tubes after the automated processing. Thus, the user does not need to concern about the whole process.
  • Figure 5 depicts a microfluidic adaptor is fixed by 2 clamps on the side. 2 screws are used to tighten the adaptor on the place holder.
  • Figure 6 depicts a transparent view of the clamp after fixing the microfluidic adaptor.
  • Figure 7 shows a rear side of the assembly, where the valves, sensors, and pumps rest in.
  • the pressure module which we developed in previous progress updates, is composed of rotary pump 1, solenoid valve 1 & 2, pressure chamber, and pressure sensor.
  • the piston pump with valve controls the infuse-and-withdraw function of the liquid handler.
  • the rotary pump 2 & 3, and solenoid valve 3 & 4 are involved in the washing process for the liquid handler to prevent cross-contaminations.
  • Figure 8 depicts a pressure detection module.
  • the pressure sensor is embedded in between the diaphragm pump and the microfluidic outlet chamber. The sensor then collects the pressure value and send the data back to the pressure control module. With a comparison between the user defined pressure value and the value from the sensor, the control module then controls the rotary speed of the diaphragm pump thus to increase/decrease the control pressure. This feedback mechanism allows a precise control on the size of the droplet being generated.
  • Figure 9 depicts a pressure control module.
  • the large electronic board supplies power and receive pressure data to and from the small electronic board, which is the pressure acquisition module.
  • Figure 10 shows a CAD drawing of the standard adaptor. Top view of the adaptor. The tapered corner is for correct orientation on the assembly place holder.
  • Figure 11 depicts an overview of the adaptor, with the blue arrow indicating the row of outlets.
  • Figure 12 depicts a bottom view of the adaptor, with the orange arrow indicating one of the pin structures.
  • Figure 13 depicts a CAD drawing of the microfluidic channels.
  • the white parts indicate the microfluidic channels.
  • the oil flows into the oil inlets (red) and the samples flow into the sample inlets (green) when a negative pressure is applied at the outlets (blue) .
  • the samples meet with the oil at the cross-junction and become emulsified into droplets.
  • Figure 14 depicts a 3D-printed adaptor consists of 3 rows of pins corresponding to the oil inlets, samples inlets, and outlets.
  • the pins are inserted into the ports on the PDMS chip, indicated by the direction of the yellow arrow, to finish the final assembly.
  • the pin structure is enlarged in the dotted white square for clear representation.
  • Figure 15 shows that after the assembly, the oil inlets are pre-filled with oil, and the sample inlets are pre-filled with the sample before the suction starts.
  • the white 3D-printed part seals the outlet to prevent air leak. Negative pressure is applied to the outlets to initiate the droplet generation processes. Note that in the final assembly, the white 3D-printed part belongs to the pressure sealer on the assembly.
  • Figure 16 graphically illustrates the polydispersity of the droplets generated from different microchannels.
  • the droplets polydispersity are within 9%, suggesting the droplets are stable after the droplet generation using the custom-design adaptors.
  • Figure 17 graphically illustrates variations of the droplet generation rate of individual microfluidic channels.
  • a negative pressure 4 psi
  • High speed camera is used to monitor the droplet generation.
  • Figure 18 graphically illustrates pressure value against the size of the droplet generated with different oil system, silicone oil and FC40.
  • Figure 19 depicts droplet stability after the droplet generation process, with different oil and surfactant as the outer phase: Silicon oil and DC749, FC40 and commercial surfactant, FC40 and self-synthesized surfactant. Under the same pressure setting, the FC40 groups show better stability performance than the silicone oil group, suggesting FC40 is the suitable choice for the emulsion system.
  • Figure 20 graphically illustrates droplets generated with the improved pressure modules, under the pressure value of -4 psi, -5 psi, -6 psi, -7 psi, -8 psi, and -10 psi.
  • the droplets are of similar sizes under the pressure values of -5 psi, -6 psi, and -7 psi, regardless of the surfactant used.
  • Scale bar 200 ⁇ m.
  • Figure 21 graphically illustrates quantitative analysis of the droplet size uniformity based on the cross-sectional area of droplets generated using the commercial surfactant. Box plot showing the size distribution of droplets against pressure values of -4 psi, -5 psi, -6 psi, -7 psi, -8 psi, and -10 psi.
  • Figure 22 graphically illustrates the polydispersity of the droplets are within 10%under the pressure value of -5 psi, -6 psi, which provides a narrower operating pressure range than that generated using the custom-synthesized surfactant.
  • Figure 23 graphically illustrates beads with different diameter and concentrations investigated in the experiments.
  • Figure 24 depicts selected bright field images of the droplets with beads. Three sizes of beads, 1 ⁇ m, 9.51 ⁇ m, and 20 ⁇ m were encapsulated in the droplets. The beads are indicated by the yellow arrows, suggesting that the beads can be encapsulated inside the droplets with the current setup. With a high concentration of beads, most of the droplets encapsulated the beads. By further diluting the bead concentration, the number of beads in the droplet decreased, and the probability of the encapsulation followed Poisson statistics. Scale bar: 200 ⁇ m.
  • Figure 25 depicts bright field and fluorescence images of the droplets with 50nm blue fluorescent polystyrene beads.
  • Figure 26 depicts fluorescence images of the droplets with 1 ⁇ m green fluorescent polystyrene beads.
  • the droplets were observed under a fluorescence microscope at the outlet of the microfluidic chip.
  • a 1,000 times higher concentration of fluorescence beads gives a brighter fluorescence than at a low bead concentration in the droplets (right) .
  • Scale bar 200 ⁇ m.
  • Figure 27 depicts the CAD drawing of the microfluidic channels for mixing.
  • the white parts indicate the microfluidic channels.
  • the oil flows into the oil inlets (red) and the samples flow into the sample inlets (green) when a negative pressure is applied at the outlets (blue) .
  • the samples meet with the oil at the cross-junction and become emulsified into droplets.
  • the droplets flow downstream to a serpentine channel, which create vortices within droplet to enhance mixing.
  • Figure 28 graphically illustrates calibration of droplet fluorescence.
  • the droplets are collected after generation, and their fluorescence are monitored under a fluorescence microscope.
  • the fluorescence intensities are analyzed using ImageJ. More than 30 droplets are analyzed in each data point.
  • Figure 29 graphically illustrates calibration curve of the droplet fluorescence intensities.
  • Fluorescence dye solution of 46.875 nM, 93.75 nM, 187.5 nM, 375 nM, and 750 nM are monitored with a custom-built platform.
  • the droplets are scanned by a laser line and the corresponding fluorescence intensities are recorded. More than 1,000 droplets are analyzed in each data point.
  • Figure 30 graphically illustrates characterization of the fluorescence of mixture after 0, 1, 3, 5, and 10 pipette up-and-down motions. After different degree of mixing, the samples are dispersed into droplets. The droplet fluorescence are monitored by a laser line scan. The solution is homogenous when its fluorescence intensities fall in the + and –10%range of the expected mean signal. More than 1,000 droplets are analyzed in each data point.
  • Figure 31 graphically illustrates characterization of the mixing efficiency after 0, 1, 3, 5, and 10 pipette up-and-down motions. After different degree of mixing, the samples are dispersed into droplets. The droplet fluorescence is monitored by a laser line scan. From the experimental result, at least 5 pipette up-and-down motions is required to obtain a >95%homogenous solution.
  • Figure 32 depicts a physical model of the assembly.
  • Figure 33 charts droplet sizes and standard deviations.
  • Figure 34 graphically illustrates the variation of pressures inside the chamber during a 32-second interval experiment. The percentage of pressure variations is within 2%.
  • Figure 35 depicts an exemplary user interface.
  • the present disclosure provides a micro-fluidic platform to generate droplets for analysis by application of robotic arm.
  • a physical model was developed to describe the model.
  • the system was applied to generation of droplets.
  • the system was tested with different parameters.
  • the adaptor was designed to standardise the dimension of microfluidic chips.
  • a pressure sealer will be pressed onto the outlets of the adaptor along the Z-axis. Therefore, there will be a bending moment on the adaptor, leading to potential air leakage of the sealer.
  • the microfluidic adaptor is fixed by 2 clamps on the side. After inserting the microfluidic adaptor, the microfluidic adaptor is tightened by the clamps with 2 screws on the place holder, as shown in Figure 5. After the microfluidic adaptor is fixed, the adaptor slides along the X-axis inside the assembly.
  • the assembly runs and the process is automated.
  • the liquid handler will first go to the sample tube to withdraw the sample. The samples are then transferred into the 8 sample wells on the microfluidic adaptor.
  • the fluid transfer function of the liquid handler is achieved by the piston pump with valve module at the back of the assembly.
  • the pressure sealer covers all outlets on the microfluidic adaptor and the assembly starts the negative pressure.
  • the negative pressure is applied by the pressure module, which have been developed previously.
  • Figure 34 shows the pressure variation of pressure module during 32 seconds interval.
  • the module is placed at the back side of the assembly, and is composed of rotary pump1, solenoid valve 1 & 2, pressure chamber, and pressure sensor ( Figure 7) .
  • the pressure sealer is released from the microfluidic adaptor.
  • the liquid handler moves to the outlets of the adaptor, and transfers the droplets into PCR tubes. PCR tubes filled with droplets can now be collected.
  • the nozzle of the liquid handler is washed between each operation.
  • the nozzle of the liquid handler will dip into the reservoirs for washing.
  • This washing step is done with the washing modules, which are composed of rotary 2 & 3, and solenoid valve 3 & 4.
  • the components and modules are protected from the back side of the assembly, as shown in Figure 7.
  • the solenoid values, pumps, and motors the sample preparation steps are then automated.
  • the physical model of the assembly is shown in Figure 32.
  • the microfluidic adapter there are 8 sets of inlets for the oil, 8 sets of inlets for the sample, and 8 sets of outlets for the negative pressure. Since the smallest dimension of the channel is ⁇ 35 ⁇ m, any dust in the environment can clog the channels, leading to operation failure. This problem was tackled by designing passive filter structures at the inlets.
  • the passive filters consist of patterns with gaps of only ⁇ 15 ⁇ m. Thus, dust or any objects that is larger than 15 ⁇ m are filtered and the flow downstream is preserved.
  • Flow resistor is also designed at the droplet generation junction to stabilize the flow against fluctuations introduced during the droplet generation process.
  • 6 ‘+’ signs on the pattern are included to aid our fabrication process. After the PDMS is cured on the mould, the edge was trimmed closely of the 6 ‘+’ signs to minimize the size variation of the PDMS replica from batch to batch.
  • the pattern of the microfluidic channel is shown in Figure 13.
  • the PDMS replica and the glass slide were treated under air plasma; subsequently, the PDMS replica and the glass slide are bonded together to form an irreversible seal.
  • Aquapel was infused into the channel. This can enhance the wettability of the fluorocarbon oil on the PDMS channel wall. Excess Aquapel are flushed out carefully with pressurized air, and the PDMS chip is heated at 90°C to evaporate the residual Aquapel.
  • the PDMS chip is connected with the 3D-print adaptor. The pins on the adaptor are aligned on top of the PDMS chip and compressed to form one piece. This “pin to hole, and go” design facilitates a quick preparation of the final device, as shown in Figure 14.
  • the robustness of the adaptor was examined during the droplet generation process. An important parameter was the droplet generation rate. If there is any air leakage between the pin and the ports on the PDMS chip, the fluid flow will be affected and stop the droplet generation. The droplet generation process was therefore monitored with a high speed camera. Video of the droplet generation was recorded, and the number of droplets generated per second was counted. The droplet generation rate of the channels shows a variation of 5%to 20%from mean, as shown in Figure 17. The experimental result is better than the reported result in literature, which shows a 4-25%variations [1] . The remaining variations may originate from error in measuring the droplet generation rate in the video, and the fabrication defects on the adaptor. Other means, such as injection molding, can enhance the quality of the adaptor.
  • the droplet size was investigated under an inverted microscope.
  • the size of the droplets was analyzed using ImageJ (NIH) .
  • the size of the droplets and their standard deviations are shown in Figure 33.
  • the polydispersity was plotted against each outlet of the adaptors, as shown in Figure 16.
  • the droplets polydispersity are within 9%, suggesting the droplets are stable after the droplet generation using the custom-design adaptors.
  • the mixing steps are done by liquid handler in the assembly.
  • water was first pipetted into the wells on the adaptor.
  • Another water sample was then transferred with fluorescence dye to the adaptor.
  • the sample was mixed with the pipette-up-and-down motion.
  • a calibration curve was set up with different concentration of fluorescence dye in the water.
  • Dye solution was prepared with concentrations of 46.875 nM, 93.75 nM, 187.5 nM, 375 nM, and 750 nM and their corresponding fluorescence intensities was monitored. The result is plotted in figure 33. More than 1,000 droplets were analyzed in each data point.
  • the minimal rounds of pipetting motion required was further investigated to achieve a thorough mixture.
  • the mixture was pipetted with 0, 1, 3, 5, and 10 up-and-down motions, and the sample was dispersed into droplets.
  • the fluorescence intensities of the droplets was monitored with laser line scan on a custom-built platform. When the droplets flow across the laser line, the fluorescence signal is acquired by a photomultiplier tube, and recorded in the computer. If the mixing is complete, the mixture is homogenous and the fluorescence signal should fit the values predicted in the calibration curve. 10 ⁇ L of water was mixed with 10 ⁇ L of 750 nM fluorescence dye solution, and the fluorescence of the droplets was monitored. A fluorescence intensity of around 2 a.u. was expected. The observed droplet fluorescence is indeed around 2 a. u. after 5 pipette up-and-down motions, as shown in Figure 34. Based on the assumption that the droplets are monodisperse, the mixing efficiency is defined as:
  • the techniques described herein can be applied to any device and/or network including a multiprocessor system. It is to be understood, therefore, that handheld, portable and other computing devices and computing objects of all kinds are contemplated for use in connection with the various non-limiting embodiments, i.e., anywhere that a device may wish to implement automated handling systems. Accordingly, a computer for implementing the automated handling systems is but one example, and the disclosed subject matter can be implemented with any client having network/bus interoperability and interaction. Thus, the disclosed subject matter can be implemented in an environment of networked hosted services in which very little or minimal client resources are implicated, e.g., a networked environment in which the client device serves merely as an interface to the network/bus, such as an object placed in an appliance.
  • aspects of the disclosed subject matter can partly be implemented via an operating system, for use by a developer of services for a device or object, and/or included within application software that operates in connection with the component (s) of the disclosed subject matter.
  • Software may be described in the general context of computer executable instructions, such as program modules or components, being executed by one or more computer (s) , such as projection display devices, viewing devices, or other devices.
  • computer such as projection display devices, viewing devices, or other devices.
  • a figure or a parameter from one range may be combined with another figure or a parameter from a different range for the same characteristic to generate a numerical range.

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  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

L'invention concerne un ensemble, comprenant du matériel et un logiciel, pour manipuler des échantillons de fluide afin de former des émulsions. L'ensemble peut comprendre un manipulateur robotique de liquide qui manipule un fluide provenant de tubes d'échantillon vers une cartouche, et collecte des émulsions provenant de la cartouche vers des flacons. L'ensemble peut appliquer une pression pour la manipulation du fluide et d'émulsions au sein du corps de l'ensemble. Dans certains modes de réalisation, l'ensemble peut arrêter d'appliquer une pression sur le fluide lorsqu'une condition prédéfinie est remplie. Ce changement peut indiquer le point final de la manipulation du fluide.
PCT/CN2019/099942 2018-08-09 2019-08-09 Systèmes de manipulation automatisée d'échantillons de fluide afin de former des gouttelettes microfluidiques pour un diagnostic in vitro Ceased WO2020030090A1 (fr)

Priority Applications (1)

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CN201980052964.1A CN113841053B (zh) 2018-08-09 2019-08-09 用于将流体样本自动化处理成微流体液滴以用于体外诊断的系统

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US201862716409P 2018-08-09 2018-08-09
US62/716,409 2018-08-09

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101128262A (zh) * 2005-02-08 2008-02-20 Lab901有限公司 用于处理微流体装置的分析仪器
CN101512018A (zh) * 2006-09-06 2009-08-19 佳能美国生命科学公司 用于进行微流体化验的化验片和化验盒的结构设计
CN101715552A (zh) * 2006-11-24 2010-05-26 新加坡科技研究局 用于处理液滴中样品的仪器及其使用方法
CN101957383A (zh) * 2010-08-10 2011-01-26 浙江大学 基于液滴顺序组装技术的微流控液滴生成系统及使用方法
CN102405402A (zh) * 2008-09-23 2012-04-04 阔达生命有限公司 基于液滴的测定系统
CN105452839A (zh) * 2013-06-21 2016-03-30 伯乐生命医学产品有限公司 具有流体收集管的微流体系统
US20160136646A1 (en) * 2013-06-26 2016-05-19 President And Fellows Of Harvard College Interconnect Adaptor

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005072353A2 (fr) * 2004-01-25 2005-08-11 Fluidigm Corporation Dispositifs de formation de cristaux et systemes et procedes de fabrication et d'utilisation de ceux-ci
US9089844B2 (en) * 2010-11-01 2015-07-28 Bio-Rad Laboratories, Inc. System for forming emulsions
US9975121B2 (en) * 2014-06-12 2018-05-22 University Of Notre Dame Microfluidic devices, systems, and methods for evaluating tissue samples
CN105567560A (zh) * 2015-12-30 2016-05-11 西安交通大学 一种集成式液滴微流控芯片

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101128262A (zh) * 2005-02-08 2008-02-20 Lab901有限公司 用于处理微流体装置的分析仪器
CN101512018A (zh) * 2006-09-06 2009-08-19 佳能美国生命科学公司 用于进行微流体化验的化验片和化验盒的结构设计
CN101715552A (zh) * 2006-11-24 2010-05-26 新加坡科技研究局 用于处理液滴中样品的仪器及其使用方法
CN102405402A (zh) * 2008-09-23 2012-04-04 阔达生命有限公司 基于液滴的测定系统
CN101957383A (zh) * 2010-08-10 2011-01-26 浙江大学 基于液滴顺序组装技术的微流控液滴生成系统及使用方法
CN105452839A (zh) * 2013-06-21 2016-03-30 伯乐生命医学产品有限公司 具有流体收集管的微流体系统
US20160136646A1 (en) * 2013-06-26 2016-05-19 President And Fellows Of Harvard College Interconnect Adaptor

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