Name: robotic mirror therapy system for functional recovery of hemiplegic arms
Uploaded: 2016-08-15T15:00:00
Description: Watch this Scientific Journal Video about Robotic Mirror Therapy System for Functional Recovery of Hemiplegic Arms at JoVE.com

This work was supported by the Brain Fusion Program of Seoul National University (800-20120444) and the Interdisciplinary Research Initiatives Program from College of Engineering and College of Medicine, Seoul National University (800-20150090).

&#160;All of the procedures were reviewed and approved by the Institutional Review Board of Seoul National University Hospital.
1. Mirror Therapy Tasks
<ol>
	<li>Examples of 2-dimensional mirror therapy tasks (Figure 3)
	<ol>
		<li>Freely move the healthy arm while looking in the mirror about 5 min for warm-up exercise. 
		NOTE: One may utilize a metronome so that the patient can exercise the motion of the healthy arm in a rhythmic manner.</li>
		<li>On healthy side, dribble and place a sma...

<ol>
	<li>Hamzei, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+plasticity+induced+by+mirror+training:+the+mirror+as+the+element+connecting+both+hands+to+one+hemisphere.">Functional plasticity induced by mirror training: the mirror as the element connecting both hands to one hemisphere.</a> Neurorehabil Neural Repair. 26 (5), 484-496 (2012).</li><li>Thieme, H., Mehrholz, J., Pohl, M., Behrens, J., Dohle, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mirror+therapy+for+improving+motor+function+after+stroke.">Mirror therapy for improving motor function after stroke.</a> Cochrane Database Syst Rev. 3, CD008449 (2012).</li><li>Dohle, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mirror+therapy+promotes+recovery+from+severe+hemiparesis:+a+randomized+controlled+trial.">Mirror therapy promotes recovery from severe hemiparesis: a randomized controlled trial.</a> Neurorehabil Neural Repair. 23 (3), 209-217 (2009).</li><li>Pervane Vural, S., Nakipoglu Yuzer, G. F., Sezgin Ozcan, D., Demir Ozbudak, S., Ozgirgin, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+Mirror+Therapy+in+Stroke+Patients+With+Complex+Regional+Pain+Syndrome+Type+1:+A+Randomized+Controlled+Study.">Effects of Mirror Therapy in Stroke Patients With Complex Regional Pain Syndrome Type 1: A Randomized Controlled Study.</a> Arch Phys Med Rehabil. 97 (4), 575-581 (2016).</li><li>De Santis, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Robot-assisted+training+of+the+kinesthetic+sense:+enhancing+proprioception+after+stroke.">Robot-assisted training of the kinesthetic sense: enhancing proprioception after stroke.</a> Front Hum Neurosci. 8, 1037 (2015).</li><li>Smorenburg, A. R., Ledebt, A., Deconinck, F. J., Savelsbergh, G. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Practicing+a+matching+movement+with+a+mirror+in+individuals+with+spastic+hemiplegia.">Practicing a matching movement with a mirror in individuals with spastic hemiplegia.</a> Res Dev Disabil. 34 (9), 2507-2513 (2013).</li><li>Semrau, J. A., Herter, T. M., Scott, S. H., Dukelow, S. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Robotic+identification+of+kinesthetic+deficits+after+stroke.">Robotic identification of kinesthetic deficits after stroke.</a> Stroke. 44 (12), 3414-3421 (2013).</li><li>Niku, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chapter+4,+Dynamic+Analysis+and+Forces.">Chapter 4, Dynamic Analysis and Forces.</a> Introduction to Robotics: Analysis, Systems, Applications. , (2001).</li><li>Sanford, J., Moreland, J., Swanson, L. R., Stratford, P. W., Gowland, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reliability+of+the+Fugl-Meyer+assessment+for+testing+motor+performance+in+patients+following+stroke.">Reliability of the Fugl-Meyer assessment for testing motor performance in patients following stroke.</a> Phys Ther. 73 (7), 447-454 (1993).</li><li>Bohannon, R. W., Smith, M. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interrater+reliability+of+a+modified+Ashworth+scale+of+muscle+spasticity.">Interrater reliability of a modified Ashworth scale of muscle spasticity.</a> Phys Ther. 67 (2), 206-207 (1987).</li><li>Shah, S., Vanclay, F., Cooper, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improving+the+sensitivity+of+the+Barthel+Index+for+stroke+rehabilitation.">Improving the sensitivity of the Barthel Index for stroke rehabilitation.</a> J Clin Epidemiol. 42 (8), 703-709 (1989).</li><li>Lo, A. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Robot-assisted+therapy+for+long-term+upper-limb+impairment+after+stroke.">Robot-assisted therapy for long-term upper-limb impairment after stroke.</a> N Engl J Med. 362 (19), 1772-1783 (2010).</li><li>Ho, N. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+EMG-driven+exoskeleton+hand+robotic+training+device+on+chronic+stroke+subjects:+task+training+system+for+stroke+rehabilitation.">An EMG-driven exoskeleton hand robotic training device on chronic stroke subjects: task training system for stroke rehabilitation.</a> IEEE Int Conf Rehabil Robot. , 5975340 (2011).</li><li>Hesse, S., Schulte-Tigges, G., Konrad, M., Bardeleben, A., Werner, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Robot-assisted+arm+trainer+for+the+passive+and+active+practice+of+bilateral+forearm+and+wrist+movements+in+hemiparetic+subjects.">Robot-assisted arm trainer for the passive and active practice of bilateral forearm and wrist movements in hemiparetic subjects.</a> Arch Phys Med Rehabil. 84 (6), 915-920 (2003).</li><li>Lum, P. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MIME+robotic+device+for+upper-limb+neurorehabilitation+in+subacute+stroke+subjects:+A+follow-up+study.">MIME robotic device for upper-limb neurorehabilitation in subacute stroke subjects: A follow-up study.</a> J Rehabil Res Dev. 43 (5), 631-642 (2006).</li><li>Yang, C. L., Lin, K. C., Chen, H. C., Wu, C. Y., Chen, C. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pilot+comparative+study+of+unilateral+and+bilateral+robot-assisted+training+on+upper-extremity+performance+in+patients+with+stroke.">Pilot comparative study of unilateral and bilateral robot-assisted training on upper-extremity performance in patients with stroke.</a> Am J Occup Ther. 66 (2), 198-206 (2012).</li><li>Nef, T., Mihelj, M., Riener, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=ARMin:+a+robot+for+patient-cooperative+arm+therapy.">ARMin: a robot for patient-cooperative arm therapy.</a> Med Biol Eng Comput. 45 (9), 887-900 (2007).</li><li>Ozkul, F., Barkana, D. E., Demirbas, S. B., Inal, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+proprioceptive+sense+of+the+elbow+joint+with+RehabRoby.">Evaluation of proprioceptive sense of the elbow joint with RehabRoby.</a> IEEE Int Conf Rehabil Robot. , 5975466 (2011).</li><li>Pehlivan, A. U., Celik, O., O'Malley, M. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanical+design+of+a+distal+arm+exoskeleton+for+stroke+and+spinal+cord+injury+rehabilitation.">Mechanical design of a distal arm exoskeleton for stroke and spinal cord injury rehabilitation.</a> IEEE Int Conf Rehabil Robot. , 5975428 (2011).</li><li>Zhang, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Feasibility+studies+of+robot-assisted+stroke+rehabilitation+at+clinic+and+home+settings+using+RUPERT.">Feasibility studies of robot-assisted stroke rehabilitation at clinic and home settings using RUPERT.</a> IEEE Int Conf Rehabil Robot. , 5975440 (2011).</li></ol>

The primary purpose of this study was to develop a real-time mirror robot system for functional recovery of a hemiplegic arm using an automatic control algorithm. The effect of robot-assisted therapy on long-term recovery of upper-limb impairment after stroke was proven beneficial in previous studies12, and various kinds of arm robots have been introduced13-20. However, previous studies of upper extremity robots that realized bilateral arm movement applied mechanical connections without using a mirr...

For patients with stroke, dysfunction of a hemiplegic arm has debilitating effect. The ability to perform bimanual activities is essential for daily life, but functional deficit of a hemiplegic arm often remains even a few years after stroke onset. Among various training programs in the hospital, an exercise to increase the range of motion or passive repetition of simple tasks have little effect on functional recovery of a hemiplegic arm. For this reason, training of meaningful tasks related to activities of daily living (ADLs) has been applied to occupational therapy in hospitals.
The effects of mirror therapy were proven by previous studies in neurorehabilitation1-4. Mirror therapy is conducted by eliciting an illusion through use of a mirror as if the hemiplegic arm is moving in real-time while moving the healthy arm. It can facilitate brain neuroplasticity by activation of the sensorimotor cortex1. Thus, motor power and function of the hemiplegic arm can be improved. However, conventional mirror therapy has a critical limitation in that the hemiplegic arm is not actually moving.
Therefore, we developed a real-time 2-axis mirror robot system as a simple add-on module to conventional mirror therapy, using closed feedback mechanism. This may convey proprioceptive input to the sensory cortex, which is considered important in neuroplasticity and functional recovery of a hemiplegic arm (Figures 1 and 2)5-7.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>LabVIEW</td>
			<td>National Instruments</td>
			<td></td>
			<td>System design software</td>
		</tr>
		<tr>
			<td>24V power supply</td>
			<td>XP Power</td>
			<td>MHP1000PS24 24V</td>
			<td>Any 24V power supply should do</td>
		</tr>
		<tr>
			<td>AHRS sensor receiver</td>
			<td>E2box</td>
			<td>EBRF24GRCV</td>
			<td></td>
		</tr>
		<tr>
			<td>AHRS sensors</td>
			<td>E2box</td>
			<td>EBIMU-9DOFV2</td>
			<td>You will need total 3 sensors. Any AHRS sensors will do</td>
		</tr>
		<tr>
			<td>EC90 flat motor module</td>
			<td>Maxon</td>
			<td>323772 + 223094 + 453231</td>
			<td>Any geared motor with higher than 30Nm should do. (For our custom machined parts, you will need these particular flat motor and gear module, but the gear ratio and encoder may vary)&#160;</td>
		</tr>
		<tr>
			<td>EC45 flat motor module</td>
			<td>Maxon</td>
			<td>397172</td>
			<td>Any geared motor with higher than 10Nm should do (For our custom machined parts, you should use the same gear module but the gear ratio, motor, and encoder may vary)</td>
		</tr>
		<tr>
			<td>EPOS2 70/10 controller</td>
			<td>Maxon</td>
			<td>375711</td>
			<td>This can be replaced with EPOS 24/5 controller</td>
		</tr>
		<tr>
			<td>EPOS2 24/5 controller</td>
			<td>Maxon</td>
			<td>367676</td>
			<td></td>
		</tr>
		<tr>
			<td>Connector and cable set</td>
			<td>Maxon</td>
			<td>381405 + 384915 + 275934 + 354045</td>
			<td>You can also make these cables. Connectors and corresponding wire info can be found in &#34;300583-Hardware-Reference-En.pdf&#34; and &#34;300583-Cable-Starting-Set-En.pdf&#34;</td>
		</tr>
		<tr>
			<td>Coupling- Oldham, Set Screw Type</td>
			<td>Misumi</td>
			<td>MCORK30-10-12</td>
			<td>Type may vary</td>
		</tr>
		<tr>
			<td>Coupling- High Rigidity, Oldham, 
			Set Screw Type</td>
			<td>Misumi</td>
			<td>MCOGRK34-12-12</td>
			<td>Type may vary</td>
		</tr>
		<tr>
			<td>Shaft Collars</td>
			<td>Misumi</td>
			<td>SCWDM10-B &#160;</td>
			<td>You will need 4 sets</td>
		</tr>
		<tr>
			<td>Shaft Collars</td>
			<td>Misumi</td>
			<td>SDBJ10-8</td>
			<td>You will need 2 sets</td>
		</tr>
		<tr>
			<td>Precision Linear Shaft</td>
			<td>Misumi</td>
			<td>&#160;PSSFG10-200</td>
			<td>Any straight 10mm diameter shaft with at least 200mm length should do&#160;</td>
		</tr>
		<tr>
			<td>Bearings with housings</td>
			<td>Misumi</td>
			<td>BGRAB6801ZZ</td>
			<td></td>
		</tr>
		<tr>
			<td>Elbow motor force dispersion shaft&#160;</td>
			<td>custom machined</td>
			<td>3D CAD&#160;</td>
			<td></td>
		</tr>
		<tr>
			<td>Lower elbow support</td>
			<td>custom machined</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>Elbow rooftop frame</td>
			<td>custom machined</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>Support wall</td>
			<td>custom machined</td>
			<td>Part Drawings</td>
			<td>You will need 2 frames.</td>
		</tr>
		<tr>
			<td>Elbow coupling hollow cylinder cover&#160;</td>
			<td>custom machined</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>Wrist motor force dispersion shaft</td>
			<td>custom machined</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>Wrist rooftop frame</td>
			<td>custom machined</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>Upper wrist coupling hollow cylinder cover</td>
			<td>custom machined</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>Lower wrist coupling hollow cylinder cover</td>
			<td>custom machined</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>Joint movement limiter</td>
			<td>custom machined</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>Handle</td>
			<td>3D printed</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>Upper elbow support</td>
			<td>3D printed</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>Friction reduction ring</td>
			<td>3D printed</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>Acrylic mirror</td>
			<td>custom laser cutting</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>Task table</td>
			<td>custom machined</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>Silicone sponge</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>DOF limiter</td>
			<td>3D printed</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>DOF limiter lid</td>
			<td>3D printed</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>Healthyarm handle</td>
			<td>3D printed</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>Ball rollers - Press fit</td>
			<td>Misumi</td>
			<td>BCHA18</td>
			<td></td>
		</tr>
		<tr>
			<td>Goalpost</td>
			<td>3D printed</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>Circle trace</td>
			<td>3D printed</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
		<tr>
			<td>Angled assist</td>
			<td>3D printed</td>
			<td>Part Drawings</td>
			<td>Optional</td>
		</tr>
		<tr>
			<td>Curved assist</td>
			<td>3D printed</td>
			<td>Part Drawings</td>
			<td>Optional</td>
		</tr>
		<tr>
			<td>Plain assist</td>
			<td>3D printed</td>
			<td>Part Drawings</td>
			<td>Optional</td>
		</tr>
		<tr>
			<td>Task board</td>
			<td>custom laser cutting</td>
			<td>Part Drawings</td>
			<td></td>
		</tr>
	</tbody>
</table>

robotic mirror therapy system for functional recovery of hemiplegic arms

Mirror therapy has been performed as effective occupational therapy in a clinical setting for functional recovery of a hemiplegic arm after stroke. It is conducted by eliciting an illusion through use of a mirror as if the hemiplegic arm is moving in real-time while moving the healthy arm. It can facilitate brain neuroplasticity through activation of the sensorimotor cortex. However, conventional mirror therapy has a critical limitation in that the hemiplegic arm is not actually moving. Thus, we developed a real-time 2-axis mirror robot system as a simple add-on module for conventional mirror therapy using a closed feedback mechanism, which enables real-time movement of the hemiplegic arm. We used 3 Attitude and Heading Reference System sensors, 2 brushless DC motors for elbow and wrist joints, and exoskeletal frames. In a feasibility study on 6 healthy subjects, robotic mirror therapy was safe and feasible. We further selected tasks useful for activities of daily living training through feedback from rehabilitation doctors. A chronic stroke patient showed improvement in the Fugl-Meyer assessment scale and elbow flexor spasticity after a 2-week application of the mirror robot system. Robotic mirror therapy may enhance proprioceptive input to the sensory cortex, which is considered to be important in neuroplasticity and functional recovery of hemiplegic arms. The mirror robot system presented herein can be easily developed and utilized effectively to advance occupational therapy.

Six healthy subjects conducted a &#39;pen marking task&#39; (touching the two small boards alternately with a pen attached on the healthy hand as shown in Figure 17) 10 times which took on average 106 sec per subject. No adverse event was observed, and robotic mirror therapy was proven to be feasible.
In addition, a clinical study on rehabilitation doctors was conducted. We requested expert opinions to determine...

Watch this Scientific Journal Video about Robotic Mirror Therapy System for Functional Recovery of Hemiplegic Arms at JoVE.com

Robotic Mirror Therapy System for Functional Recovery of Hemiplegic Arms

We developed a real-time mirror robot system for functional recovery of hemiplegic arms using automatic control technology, conducted a clinical study on healthy subjects, and determined tasks through feedback from rehabilitation doctors. This simple mirror robot can be applied effectively to occupational therapy in stroke patients with a hemiplegic arm.

Mirror therapy has been performed as effective occupational therapy in a clinical setting for functional recovery of a hemiplegic arm after stroke. It is ...

The overall goal of this procedure is to introduce a real-time robotic mirror therapy system for functional recovery of hemiplegic arms. This method can help answer key questions in translationary neurorehab biomedical engineering research by showing that functional recovery of hemiplegic arms with advanced occupational therapy is achievable. The main advantage of this robotic mirror therapy is that it can enhance proprioceptive input to the sensory cortex, which is very important in brain neuroplasticity for stroke patients.Individuals new to this method may struggle, as it was complicated to develop the software protocol, and assemble frames and motors. We first had the idea for this method when we observed conventional neurotherapy, which was limited in that the hemiplegic arm was not actually moving. Visual demonstration of this method is critical, as the sensor settings, assembly, and setup for robotic mirror therapy are difficult to learn.Begin by obtaining a three attitude and heading reference system, or AHRS sensors, and connect them to a computer, one at a time, with a USB connector. Use communications software to configure the general sensor settings on the computer. Set each sensor to RS 232.And select the COM port. Then, set the baud rate to 115, 200 bits per second. Data bits to eight.Parity to none. Stop bits to one. And the flow control to none.To check the COM port, click the home button on the bottom-left corner. Right-click on the computer, select properties, device manager, and click on the port tab to expand it. Once the communication has been established, the hyperterminal will display sensor readings.Then, set the channels and assign different IDs for each sensor. Repeat the configuration, COM port check, and channel and ID assignment for each sensor. Finally, set the output format as quaternions.And set the sensors to display the battery reserve. Begin assembling the elbow-joint motor by putting one of the coupling bodies with a keyway on the motor shaft. And securing it using an M5 hex-socket screw.Secure the elbow coupling hollow cylinder cover to the elbow motor by using four 10 millimeter M5 socket-head screws. And place a second buffer coupling body on top of the first coupling body. Then, plug the ball bearing into the elbow rooftop frame, and secure it with four eight millimeter M4 socket-head screws.Next, plug the elbow motor force dispersion shaft into the lower elbow support, and secure it with four six millimeter M3 socket-head screws. Then, place the upper elbow support on top of the lower elbow support and secure it using eight 12 millimeter M3 socket-head screws. Place part C on top, part B in the middle, and another coupling body at the bottom.Join them together and secure the coupling body with one 10 millimeter M5 hex-socket screw. Then, attach part A to the bottom of this assembly with four 15 millimeter M5 socket-head screws. Next, secure a lower-wrist coupling hollow cylinder cover with the wrist motor, using four 10 millimeter M4 socket-head screws.Then, place a coupling body on the motor shaft. Secure it with one M4 hex-socket screw, and follow that with a buffer coupling body on top. Attach a friction-reduction ring on top of the wrist rooftop frame with double-sided tape.Then, plug the wrist motor force dispersion shaft into the handle, and secure it using four M2.5 socket-head screws. Join part F on top, part E in the middle, and a coupling body on the bottom. Fix the coupling body with a 10 millimeter M4 hex-socket screw.Add an upper-wrist coupling hollow cylinder cover to the bottom of this assembly, using four 10 millimeter M3 socket-head screws. Then, secure part D to the bottom of the upper-wrist coupling hollow cylinder cover using four 15 millimeter socket-head screws. Next, secure two join-movement limiters, wrapped with sponges for safety reasons, and two shaft collars with levers, using four 15 millimeter M4 socket-head screws.Then, slide the shaft collars in part G into the shafts, and use two normal shaft collars to secure the shafts and the wrist rooftop frame together, using eight eight millimeter M3 socket-head screws. Secure additional shaft collars with the lower-elbow support using four 15 millimeter M4 socket-head screws. Then, join the two parts and secure with a lever.Finally, attach a support wall to the assembly using six 15 millimeter M4 socket-head screws, and secure a table stand using six 15 millimeter M6 socket-head screws. Begin by placing the AHRS sensors on the handle, the wrist frame, and the edge of the platform on the participant's healthy side, making sure to align them in parallel with the robot's orientation. Then, start the therapy software on the computer.Choose the hemiplegic side by clicking the patient side switch button. Set the following joint angle limits:Elbow flexion at less than 50 degrees, elbow extension at more than minus 70 degrees, wrist flexion at less than 80 degrees, and wrist extension at more than minus 60 degrees. Then, set the velocity value between zero and 22.5 RPM for the elbow motor.Use a velocity value between zero and 33 RPM for the wrist motor, and set the maximum acceleration and deceleration values as well. Next, turn on all the AHRS sensors. Then, run the program by clicking the arrow button in the upper-left corner of the program.When the Save As"prompt pops up, write the file name for the results data and press OK.Finally, while the robot and healthy arm are at the initial position, where both hands are away from the body and parallel to each other, press the calibration button to initiate sensor values to zero. Begin by informing the participant that they will use their healthy arm to complete a set of mirror therapy tasks. The ball in holes, soccer game, dots tracing, and moving a cup task.For the ball in holes task, place a small ball into the chosen hole, similar to the game of billiards. Likewise, for the soccer game, dribble and place a small ball into a goal, much like in a real game of soccer. Next, for the dots tracing task, use numbered stickers placed on a table as a guide to repeatedly move a handle in numerical order.And then return it in the reverse direction. Finally, for the moving a cup task, take a cup with the handle and push it to a chosen location. Repeat until five minutes have elapsed.Here, results are shown from a patient who suffered a right basal ganglia hemorrhage 19 months ago and received robotic mirror therapy for two weeks. The Fugl-Meyer assessment of the hemiplegic arm improved from 12 to 17 after ten sessions. Furthermore, the modified Ashworth scale of elbow flexors, measuring spasticity, was reduced from grade two, to one plus.And the left-lateral pinch power was increased from zero to three pounds. Once mastered, the robotic mirror therapy can be completed in 40 minutes, if it is performed properly. While performing this procedure, it's important to know that the illusion of sychronicity between both arms is essential for the mirror therapy.After its development, this procedure will pave the way for the research in the field of neuro-rehabilitation to explore the effects of advanced occupational therapy to enhance proprioception in patients with brain legions, such as stroke. After watching this video, you should have a good understanding of how to make and conduct a real-time robotic mirror therapy system for functional recovery of hemiplegic arms.

robotic-mirror-therapy-system-for-functional-recovery-hemiplegic

Research

JoVE Journal

Bioengineering

Robotic Production of Cancer Cell Spheroids with an Aqueous Two-phase System for Drug Testing

Cancer cell spheroids present a relevant in vitro model of avascular tumors for anti-cancer drug testing applications. A detailed protocol for producing both mono-culture and co-culture spheroids in a high throughput 96-well plate format is described in this work. This approach utilizes an aqueous two-phase system to confine cells into a drop of the denser aqueous phase immersed within the second aqueous phase. The drop rests on the well surface and keeps cells in close proximity to form a single spheroid. This technology has been adapted to a robotic liquid handler to produce size-controlled spheroids and expedite the process of spheroid production for compound screening applications. Spheroids treated with a clinically-used drug show reduced cell viability with increase in the drug dose. The use of a standard micro-well plate for spheroid generation makes it straightforward to analyze viability of cancer cells of drug-treated spheroids with a micro-plate reader. This technology is straightforward to implement both robotically and with other liquid handling tools such as manual pipettes.

A protocol for robotic printing of cancer cell spheroids in a high throughput 96-well plate format using an aqueous two-phase system is presented.

Cancer cell spheroids present a relevant in vitro model of avascular tumors for anti-cancer drug testing applications. A detailed protocol for producing ...

Rod-based Fabrication of Customizable Soft Robotic Pneumatic Gripper Devices for Delicate Tissue Manipulation

Soft compliant gripping is essential in delicate surgical manipulation for minimizing the risk of tissue grip damage caused by high stress concentrations at the point of contact. It can be achieved by complementing traditional rigid grippers with soft robotic pneumatic gripper devices. This manuscript describes a rod-based approach that combined both 3D-printing and a modified soft lithography technique to fabricate the soft pneumatic gripper. In brief, the pneumatic featureless mold with chamber component is 3D-printed and the rods were used to create the pneumatic channels that connect to the chamber. This protocol eliminates the risk of channels occluding during the sealing process and the need for external air source or related control circuit. The soft gripper consists of a chamber filled with air, and one or more gripper arms with a pneumatic channel in each arm connected to the chamber. The pneumatic channel is positioned close to the outer wall to create different stiffness in the gripper arm. Upon compression of the chamber which generates pressure on the pneumatic channel, the gripper arm will bend inward to form a close grip posture because the outer wall area is more compliant. The soft gripper can be inserted into a 3D-printed handling tool with two different control modes for chamber compression: manual gripper mode with a movable piston, and robotic gripper mode with a linear actuator. The double-arm gripper with two actuatable arms was able to pick up objects of sizes up to 2 mm and yet generate lower compressive forces as compared to elastomer-coated and non-coated rigid grippers. The feasibility of having other designs, such as single-arm or hook gripper, was also demonstrated, which further highlighted the customizability of the soft gripper device, and it's potential to be used in delicate surgical manipulation to reduce the risk of tissue grip damage.

This protocol describes a rod-based approach, combining 3D-printing and soft lithography techniques for fabricating the soft gripper devices. This approach eliminates the need for an external air source by incorporating a chamber component and reduces the chance of occlusion during the sealing process, particularly for miniaturized pneumatic channels.

Soft compliant gripping is essential in delicate surgical manipulation for minimizing the risk of tissue grip damage caused by high stress concentrations ...

Automated Robotic Dispensing Technique for Surface Guidance and Bioprinting of Cells

This manuscript describes the introduction of cell guidance features followed by the direct delivery of cells to these features in a hydrogel bioink using an automated robotic dispensing system. The particular bioink was selected as it allows cells to sediment towards and sense the features. The dispensing system bioprints viable cells in hydrogel bioinks using a backpressure assisted print head. However, by replacing the print head with a sharpened stylus or scalpel, the dispensing system can also be employed to create topographical cues through surface etching. The stylus movement can be programmed in steps of 10 &#181;m in the X, Y and Z directions. The patterned grooves were able to orientate mesenchymal stem cells, influencing them to adopt an elongated morphology in alignment with the grooves&#39; direction. The patterning could be designed using plotting software in straight lines, concentric circles, and sinusoidal waves. In a subsequent procedure, fibroblasts and mesenchymal stem cells were suspended in a 2% gelatin bioink, for bioprinting in a backpressure driven extrusion printhead. The cell bearing bioink was then printed using the same programmed coordinates used for the etching. The bioprinted cells were able to sense and react to the etched features as demonstrated by their elongated orientation along the direction of the etched grooves.

This protocol describes a bioprinting methodology using an automated robotic depositing system that incorporates etched topographical guidance cues with the precision deposition of a cell bearing hydrogel bioink. The printed cells are directly delivered to the etched features and are able to sense and orientate with them.

This manuscript describes the introduction of cell guidance features followed by the direct delivery of cells to these features in a hydrogel bioink using ...

Automated Robotic Liquid Handling Assembly of Modular DNA Devices

Recent advances in modular DNA assembly techniques have enabled synthetic biologists to test significantly more of the available &#34;design space&#34; represented by &#34;devices&#34; created as combinations of individual genetic components. However, manual assembly of such large numbers of devices is time-intensive, error-prone, and costly. The increasing sophistication and scale of synthetic biology research necessitates an efficient, reproducible way to accommodate large-scale, complex, and high throughput device construction.
Here, a DNA assembly protocol using the Type-IIS restriction endonuclease based Modular Cloning (MoClo) technique is automated on two liquid-handling robotic platforms. Automated liquid-handling robots require careful, often times tedious optimization of pipetting parameters for liquids of different viscosities (e.g. enzymes, DNA, water, buffers), as well as explicit programming to ensure correct aspiration and dispensing of DNA parts and reagents. This makes manual script writing for complex assemblies just as problematic as manual DNA assembly, and necessitates a software tool that can automate script generation. To this end, we have developed a web-based software tool, http://mocloassembly.com, for generating combinatorial DNA device libraries from basic DNA parts uploaded as Genbank files. We provide access to the tool, and an export file from our liquid handler software which includes optimized liquid classes, labware parameters, and deck layout. All DNA parts used are available through Addgene, and their digital maps can be accessed via the Boston University BDC ICE Registry. Together, these elements provide a foundation for other organizations to automate modular cloning experiments and similar protocols.
The automated DNA assembly workflow presented here enables the repeatable, automated, high-throughput production of DNA devices, and reduces the risk of human error arising from repetitive manual pipetting. Sequencing data show the automated DNA assembly reactions generated from this workflow are ~95% correct and require as little as 4% as much hands-on time, compared to manual reaction preparation.

Here, an automated workflow to perform modular DNA &#34;device&#34; assembly using a modular cloning DNA assembly method on liquid-handling robots is presented. The protocol uses an intuitive software tool for generating liquid handler picklists for combinatorial DNA device library generation, which we demonstrate using two liquid handling platforms.

Recent advances in modular DNA assembly techniques have enabled synthetic biologists to test significantly more of the available &#34;design space&#34; ...

Synthesis of Cationized Magnetoferritin for Ultra-fast Magnetization of Cells

Many important biomedical applications, such as cell imaging and remote manipulation, can be achieved by labeling cells with superparamagnetic iron oxide nanoparticles (SPIONs). Achieving sufficient cellular uptake of SPIONs is a challenge that has traditionally been met by exposing cells to elevated concentrations of SPIONs or by prolonging exposure times (up to 72 hr). However, these strategies are likely to mediate toxicity. Here, we present the synthesis of the protein-based SPION magnetoferritin as well as a facile surface functionalization protocol that enables rapid cell magnetization using low exposure concentrations. The SPION core of magnetoferritin consists of cobalt-doped iron oxide with an average particle diameter of 8.2 nm mineralized inside the cavity of horse spleen apo-ferritin. Chemical cationization of magnetoferritin produced a novel, highly membrane-active SPION that magnetized human mesenchymal stem cells (hMSCs) using incubation times as short as one minute and iron concentrations as lows as 0.2 mM.

A protocol for the synthesis and cationization of cobalt-doped magnetoferritin is presented, as well as a method to rapidly magnetize stem cells with cationized magnetoferritin.

Many important biomedical applications, such as cell imaging and remote manipulation, can be achieved by labeling cells with superparamagnetic iron oxide ...

3D Microtissues for Injectable Regenerative Therapy and High-throughput Drug Screening

To upgrade traditional 2D cell culture to 3D cell culture, we have integrated microfabrication with cryogelation technology to produce macroporous microscale cryogels (microcryogels), which can be loaded with a variety of cell types to form 3D microtissues. Herein, we present the protocol to fabricate versatile 3D microtissues and their applications in regenerative therapy and drug screening. Size and shape-controllable microcryogels can be fabricated on an array chip, which can be harvested off-chip as individual cell-loaded carriers for injectable regenerative therapy or be further assembled on-chip into 3D microtissue arrays for high-throughput drug screening. Due to the high elastic nature of these microscale cryogels, the 3D microtissues exhibit great injectability for minimally invasive cell therapy by protecting cells from mechanical shear force during injection. This ensures enhanced cell survival and therapeutic effect in the mouse limb ischemia model. Meanwhile, assembly of 3D microtissue arrays in a standard 384-multi-well format facilitates the use of common laboratory facilities and equipment, enabling high-throughput drug screening on this versatile 3D cell culture platform.

This protocol describes the fabrication of elastic 3D macroporous microcryogels by integrating microfabrication with cryogelation technology. Upon loading with cells, 3D microtissues are generated, which can be readily injected in vivo to facilitate regenerative therapy or assembled into arrays for in vitro high-throughput drug screening.

To upgrade traditional 2D cell culture to 3D cell culture, we have integrated microfabrication with cryogelation technology to produce macroporous ...

A Spine Robotic-Assisted Navigation System for Pedicle Screw Placement

Pedicle screw implantation has excellent treatment effects and is often used by surgeons in spinal fusion surgery. However, due to the complexity of human body anatomy, this surgical procedure is difficult and challenging, especially in minimally invasive surgery or patients with congenital anomalies and kyphoscoliosis deformity. In addition to the abovementioned factors, the surgical experience and technique of the surgeon also affect the recovery rates and complications of the patients after the surgical operation. Therefore, accurately performing pedicle screw implantation has is a constant topic of common concern for surgeons and patients. In recent years, with the technological development, robot-assisted navigation systems have gradually become adopted. These robot-assisted navigation systems provide surgeons with complete preoperative planning before surgery. The system provides 3D reconstructed images of each vertebra, allowing surgeons to understand the patient&#39;s physiological characteristics more quickly. It also provides 2D images of sagittal, coronal, axial and oblique planes so that surgeons can accurately perform pedicle screw placement plan.
Previous studies have demonstrated the effectiveness of robot-assisted navigation systems for pedicle screw implantation procedures, including accuracy and safety assessments. This step-by-step protocol aims to outline a standardized surgical technique note for robotic-assisted pedicle screw placement.

This article presents a standardized surgical technique for robotic-assisted pedicle screw placement by using robotic-assisted navigational systems. We present a step-by-step protocol and describe the workflow and precautions of this procedure.

Pedicle screw implantation has excellent treatment effects and is often used by surgeons in spinal fusion surgery. However, due to the complexity of human ...

Magnetic-, Acoustic-, and Optical-Triple-Responsive Microbubbles for Magnetic Hyperthermia and Pothotothermal Combination Cancer Therapy

The precision delivery of anti-cancer agents which aim for targeted and deep-penetrated delivery as well as a controlled release at the tumor site has been challenged. Here, we fabricate iron oxide nanoparticle shelled microbubbles (NSMs) through self-assembly, synergizing magnetic, acoustic, and optical responsiveness in one nanotherapeutic platform. Iron oxide nanoparticles serve as both magnetic and photothermal agents. Once intravenously injected, NSMs can be magnetically guided to the tumor site. Ultrasound triggers the release of iron oxide nanoparticles, facilitating the penetration of nanoparticles deep into the tumor due to the cavitation effect of microbubbles. Thereafter, magnetic hyperthermia and photothermal therapy can be performed on the tumor for combinational cancer therapy, a solution for cancer resistance due to the tumor heterogeneity. In this protocol, the synthesis and characterization of NSMs including structural, chemical, magnetic and acoustic properties were performed. In addition, the anti-cancer efficacy by thermal therapy was investigated using in vitro cell cultures. The proposed delivery strategy and combination therapy holds great promise in cancer treatment to improve both delivery and anticancer efficacies.

Presented here is a protocol for the fabrication of iron oxide nanoparticle-shelled microbubbles (NSMs) through self-assembly, synergizing magnetic, acoustic, and optical responsiveness in one nanotherapeutic platform for magnetic hyperthermia and photothermal combination cancer therapy.

The precision delivery of anti-cancer agents which aim for targeted and deep-penetrated delivery as well as a controlled release at the tumor site has ...

Manipulation of Single Neural Stem Cells and Neurons in Brain Slices using Robotic Microinjection

A central question in developmental neurobiology is how neural stem and progenitor cells form the brain. To answer this question, one needs to label, manipulate, and follow single cells in the brain tissue with high resolution over time. This task is extremely challenging due to the complexity of tissues in the brain. We have recently developed a robot, that guide a microinjection needle into brain tissue upon utilizing images acquired from a microscope to deliver femtoliter volumes of solution into single cells. The robotic operation increases resulting an overall yield that is an order of magnitude greater than manual microinjection and allows for precise labeling and flexible manipulation of single cells in living tissue. With this, one can microinject hundreds of cells within a single organotypic slice. This article demonstrates the use of the microinjection robot for automated microinjection of neural progenitor cells and neurons in the brain tissue slices. More broadly, it can be used on any epithelial tissue featuring a surface that can be reached by the pipette. Once set up, the microinjection robot can execute 15 or more microinjections per minute. The microinjection robot because of its throughput and versality will make microinjection a broadly straightforward high-performance cell manipulation technique to be used in bioengineering, biotechnology, and biophysics for performing single-cell analyses in organotypic brain slices.

This protocol demonstrates the use of a robotic platform for microinjection into single neural stem cells and neurons in brain slices. This technique is versatile and offers a method of tracking cells in tissue with high spatial resolution.

A central question in developmental neurobiology is how neural stem and progenitor cells form the brain. To answer this question, one needs to label, ...

Functional Transcranial Doppler Ultrasound for Monitoring Cerebral Blood Flow

Functional transcranial Doppler ultrasound (fTCD) is the use of transcranial Doppler ultrasound (TCD) to study neural activation occurring during stimuli such as physical movement, activation of tactile sensors in the skin, and viewing images. Neural activation is inferred from an increase in the cerebral blood flow velocity (CBFV) supplying the region of the brain involved in processing sensory input. For example, viewing bright light causes increased neural activity in the occipital lobe of the cerebral cortex, leading to increased blood flow in the posterior cerebral artery, which supplies the occipital lobe. In fTCD, changes in CBFV are used to estimate changes in cerebral blood flow (CBF).
With its high temporal resolution measurement of blood flow velocities in the major cerebral arteries, fTCD complements other established functional imaging techniques. The goal of this Methods paper is to give step-by-step instructions for using fTCD to perform a functional imaging experiment. First, the basic steps for identifying the middle cerebral artery (MCA) and optimizing the signal will be described. Next, placement of a fixation device for holding the TCD probe in place during the experiment will be described. Finally, the breath-holding experiment, which is a specific example of a functional imaging experiment using fTCD, will be demonstrated.

Functional transcranial Doppler ultrasound complements other functional imaging modalities, with its high temporal resolution measurement of stimulus-induced changes in cerebral blood flow within the basal cerebral arteries. This Methods paper gives step-by-step instructions for using functional transcranial Doppler ultrasound to perform a functional imaging experiment.&#160;

Functional transcranial Doppler ultrasound (fTCD) is the use of transcranial Doppler ultrasound (TCD) to study neural activation occurring during stimuli ...