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Dialysis like therapeutic (DLT) device

A microfluidic device and channel technology, applied in dialysis systems, injection devices, measurement devices, etc., can solve the problems of narrow ligand range and limited system capacity.

Inactive Publication Date: 2014-07-02
PRESIDENT & FELLOWS OF HARVARD COLLEGE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Additionally, the capabilities of these systems are limited by the exposed surface area
Another major limitation is the narrow and specific binding of ligands that typically only recognize one type or class of pathogens

Method used

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  • Dialysis like therapeutic (DLT) device
  • Dialysis like therapeutic (DLT) device
  • Dialysis like therapeutic (DLT) device

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0399] Example 1: High flow microfluidic device

[0400] The microfluidic device is made of polysulfone, an FDA-approved blood-compatible material. The device is laminated from an optically clear film covered with adhesive on one side. The inventors have previously tested the capability of the device at high flow rates up to 360 mL / h; however, the blood perfusion time was short. Therefore, the present inventors circulated heparinized human whole blood collected from healthy human donors at flow rates of 100 mL / h and 200 mL / h for 2 hours ( FIG. 14 ). After circulating the blood through the device, the blood remaining in the channel was washed with PBS buffer. There are no blood clots formed by shear stress in the device. However, when circulating non-heparinized human whole blood through the device for 2 hours, the inventors found several large blood clots adhering to the channel surface. Applying an anticoagulant surface such as SLIPS to the device would address this issue...

Embodiment 2

[0403] Embodiment 2: sepsis animal model

[0404] The inventors modified the previous microfluidic device design to enhance the separation efficiency of pathogens bound to 1 μm MBL-conjugated magnetic beads. To take advantage of the high magnetic flux density gradient across the device to pull the bead-bound pathogens out, the inventors replaced the top and bottom polysulfone layers with a thin polymer membrane coated with an adhesive on one side, which Reduce the distance between the stationary magnet and the bottom blood channel through which bead-bound pathogens flow. Since the magnetic flux density gradient greatly decreases with increasing distance from the magnet, this improved preparation enables the exploitation of extremely strong magnetic forces near the magnet surface. In addition, computational modeling studies that provide more accurate estimates of magnetic field strength near magnets reveal that magnetic force can be improved by modifying the magnet's geometry....

Embodiment 3

[0410] Embodiment 3: Rat sepsis model

[0411] The inventors modified the microfluidic device and tubing setup to tune the microfluidic system to a rat sepsis model. The small blood volume in rats allows for a reduced volume of devices and tubing to prime with crystalloid solutions, thereby minimizing the dilution effect on the rat blood. A modified design of the device has a 1.2 mL blood channel network and 1 mL tubing, whereas the previous device enabled the blood channel network to perfuse 2.5 mL. Furthermore, in order to completely eliminate the air bubbles in the microfluidic system, the inventors added a bubble trapping device (#25014, www.restek.com) Integration with the DLT system ( Figure 18 ). Air bubbles that occur accidentally in the pipeline can be completely removed. If excess air bubbles get into the line, those bubbles can be removed through the three-way valve before the bubble trap.

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Abstract

A dialysis like therapeutic (DLT) device is provided. The DLT device includes at least one source channel connected at least one collection channels by one or more transfer channels. Fluid contacting surface of the channels can be an anti-fouling surface such as slippery liquid-infused porous surface (SLIPS). Fluids can be flown at high flow rates through the channels. The target components of the source fluid can be magnetic or bound to magnetic particles using an affinity molecule. A source fluid containing magnetically bound target components can be pumped through the source channel of the microfluidic device. A magnetic field gradient can be applied to the source fluid in the source channel causing the magnetically bound target components to migrate through the transfer channel into the collection channel. The collection channel can include a collection fluid to flush the target components out of the collection channel. The target components can be subsequently analyzed for detection and diagnosis. The source channel and the collection channels of the microfluidic device are analogous to the splenic arterioles and venules, respectively; the transfer channels mimic the vascular sinusoids of the spleen where opsonized particles are retained. Thus, the device acts as a dialysis like therapeutic device by combining fluidics and magnetics.

Description

[0001] Cross References to Related Applications [0002] This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application No. 61 / 470,987, filed April 1, 2011, the contents of which are hereby incorporated by reference in their entirety. [0003] governmental support [0004] This invention was made with U.S. Government support under Grant No. N66001-11-1-4180 awarded by the Defense Advanced Research Projects Agency (DARPA) and Grant No. W81XWH-07-2-0011 awarded by the U.S. Department of Defense completed. The US Government has certain rights in this invention. technical field [0005] The present disclosure generally relates to microfluidic devices having microchannels and methods of use and manufacture thereof. Background technique [0006] Sepsis is a major killer of infected soldiers in the field as well as of patients in the intensive care units (ICUs) of top hospitals, as blood-borne microbes often overcome even the strongest available antibio...

Claims

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Application Information

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IPC IPC(8): G01N33/569G01N35/10G01N35/08B81B1/00
CPCB01L2400/043B01L2400/0487A61M1/3618B01L3/50273B01L2300/0864B01L3/56B03C1/01B01L3/502761B03C1/0332B03C1/288B03C1/0335A61M1/36B01L2300/0867B01L2200/0652B03C1/002B03C2201/26B01L3/502715B01L7/525B01L2300/0887C12Q1/04G01N33/54326A61M1/3603Y02A50/30A61M1/14G01N35/08B81B1/00
Inventor 瑞安·M·库珀唐纳德·E·英格贝尔米歇尔·舒普尔康洙勋亚历克萨·舒克尔特戴维德·卡里希理查德·特里卡雷尔·多曼斯凯容庄永
Owner PRESIDENT & FELLOWS OF HARVARD COLLEGE
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