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Medical Instrumentation

Guest Editors-in-Chief 
Wang, Weiqi, Fudan University, China
He, Bin, University of Minnesota, USA

Executive Associate Editors
Xu, Lisa X., Shanghai Jiao Tong University, China
Fowlkes, J. Brian, University of Michigan, USA

Brown, Emery, Massachusetts Institute of Technology, USA 
Cheng, Jing, Tsinghua University, China
Gambhir, Sanjiv Sam, Stanford University, USA 
Glover, Gary H., Stanford University, USA 
Laugier, Pascal, University Pierre and Marie CURIE , France
Lee, Raphael, University of Chicago, USA 
O’Donnell, Matthew, University of Washington, USA 
Tian, Jie, Chinese Academy of Science, China 
Tong, Shanbao, Shanghai Jiao Tong University, China 
Wheeler, Bruce, University of Florida, USA 
Yang, Guang-Zhong, Imperial College of London, UK

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Systems Neuroengineering: Understanding and Interacting with the Brain
Bradley J. Edelman, Nessa Johnson, Abbas Sohrabpour, Shanbao Tong, Nitish Thakor, Bin He
Engineering    2015, 1 (3): 292-308.   DOI: 10.15302/J-ENG-2015078
Abstract   HTML   PDF (9823KB)

In this paper, we review the current state-of-the-art techniques used for understanding the inner workings of the brain at a systems level. The neural activity that governs our everyday lives involves an intricate coordination of many processes that can be attributed to a variety of brain regions. On the surface, many of these functions can appear to be controlled by specific anatomical structures; however, in reality, numerous dynamic networks within the brain contribute to its function through an interconnected web of neuronal and synaptic pathways. The brain, in its healthy or pathological state, can therefore be best understood by taking a systems-level approach. While numerous neuroengineering technologies exist, we focus here on three major thrusts in the field of systems neuroengineering: neuroimaging, neural interfacing, and neuromodulation. Neuroimaging enables us to delineate the structural and functional organization of the brain, which is key in understanding how the neural system functions in both normal and disease states. Based on such knowledge, devices can be used either to communicate with the neural system, as in neural interface systems, or to modulate brain activity, as in neuromodulation systems. The consideration of these three fields is key to the development and application of neuro-devices. Feedback-based neuro-devices require the ability to sense neural activity (via a neuroimaging modality) through a neural interface (invasive or noninvasive) and ultimately to select a set of stimulation parameters in order to alter neural function via a neuromodulation modality. Systems neuroengineering refers to the use of engineering tools and technologies to image, decode, and modulate the brain in order to comprehend its functions and to repair its dysfunction. Interactions between these fields will help to shape the future of systems neuroengineering—to develop neurotechniques for enhancing the understanding of whole-brain function and dysfunction, and the management of neurological and mental disorders.

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Smartphone-Imaged HIV-1 Reverse-Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) on a Chip from Whole Blood
Gregory L. Damhorst, Carlos Duarte-Guevara, Weili Chen, Tanmay Ghonge, Brian T. Cunningham, Rashid Bashir
Engineering    2015, 1 (3): 324-335.   DOI: 10.15302/J-ENG-2015072
Abstract   HTML   PDF (12306KB)

Viral load measurements are an essential tool for the long-term clinical care of human immunodeficiency virus (HIV)-positive individuals. The gold standards in viral load instrumentation, however, are still too limited by their size, cost, and sophisticated operation for these measurements to be ubiquitous in remote settings with poor healthcare infrastructure, including parts of the world that are disproportionately affected by HIV infection. The challenge of developing a point-of-care platform capable of making viral load more accessible has been frequently approached but no solution has yet emerged that meets the practical requirements of low cost, portability, and ease-of-use. In this paper, we perform reverse-transcription loop-mediated isothermal amplification (RT-LAMP) on minimally processed HIV-spiked whole blood samples with a microfluidic and silicon microchip platform, and perform fluorescence measurements with a consumer smartphone. Our integrated assay shows amplification from as few as three viruses in a ~ 60 nL RT-LAMP droplet, corresponding to a whole blood concentration of 670 viruses per μL of whole blood. The technology contains greater power in a digital RT-LAMP approach that could be scaled up for the determination of viral load from a finger prick of blood in the clinical care of HIV-positive individuals. We demonstrate that all aspects of this viral load approach, from a drop of blood to imaging the RT-LAMP reaction, are compatible with lab-on-a-chip components and mobile instrumentation.

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Characterizing Thermal Augmentation of Convection-Enhanced Drug Delivery with the Fiberoptic Microneedle Device
R. Lyle Hood, Rudy T. Andriani, Tobias E. Ecker, John L. Robertson, Christopher G. Rylander
Engineering    2015, 1 (3): 344-350.   DOI: 10.15302/J-ENG-2015077
Abstract   HTML   PDF (9041KB)

Convection-enhanced delivery (CED) is a promising technique leveraging pressure-driven flow to increase penetration of infused drugs into interstitial spaces. We have developed a fiberoptic microneedle device for inducing local sub-lethal hyperthermia to further improve CED drug distribution volumes, and this study seeks to quantitatively characterize this approach in agarose tissue phantoms. Infusions of dye were conducted in 0.6% (w/w) agarose tissue phantoms with isothermal conditions at 15 °C, 20 °C, 25 °C, and 30 °C. Infusion metrics were quantified using a custom shadowgraphy setup and image-processing algorithm. These data were used to build an empirical predictive temporal model of distribution volume as a function of phantom temperature. A second set of proof-of-concept experiments was conducted to evaluate a novel fiberoptic device capable of generating local photothermal heating during fluid infusion. The isothermal infusions showed a positive correlation between temperature and distribution volume, with the volume at 30 °C showing a 7-fold increase at 100 min over the 15 °C isothermal case. Infusions during photothermal heating (1064 nm at 500 mW) showed a similar effect with a 3.5-fold increase at 4 h over the control (0 mW). These results and analyses serve to provide insight into and characterization of heat-mediated enhancement of volumetric dispersal.

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Visual Prostheses: Technological and Socioeconomic Challenges
John B. Troy
Engineering    2015, 1 (3): 288-291.   DOI: 10.15302/J-ENG-2015080
Abstract   HTML   PDF (176KB)

Visual prostheses are now entering the clinical marketplace. Such prostheses were originally targeted for patients suffering from blindness through retinitis pigmentosa (RP). However, in late July of this year, for the first time a patient was given a retinal implant in order to treat dry age-related macular degeneration. Retinal implants are suitable solutions for diseases that attack photoreceptors but spare most of the remaining retinal neurons. For eye diseases that result in loss of retinal output, implants that interface with more central structures in the visual system are needed. The standard site for central visual prostheses under development is the visual cortex. This perspective discusses the technical and socioeconomic challenges faced by visual prostheses.

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Optical Molecular Imaging Frontiers in Oncology: The Pursuit of Accuracy and Sensitivity
Kun Wang,Chongwei Chi,Zhenhua Hu,Muhan Liu,Hui Hui,Wenting Shang,Dong Peng,Shuang Zhang,Jinzuo Ye,Haixiao Liu,Jie Tian
Engineering    2015, 1 (3): 309-323.   DOI: 10.15302/J-ENG-2015082
Abstract   HTML   PDF (15201KB)

Cutting-edge technologies in optical molecular imaging have ushered in new frontiers in cancer research, clinical translation, and medical practice, as evidenced by recent advances in optical multimodality imaging, Cerenkov luminescence imaging (CLI), and optical image-guided surgeries. New abilities allow in vivo cancer imaging with sensitivity and accuracy that are unprecedented in conventional imaging approaches. The visualization of cellular and molecular behaviors and events within tumors in living subjects is improving our deeper understanding of tumors at a systems level. These advances are being rapidly used to acquire tumor-to-tumor molecular heterogeneity, both dynamically and quantitatively, as well as to achieve more effective therapeutic interventions with the assistance of real-time imaging. In the era of molecular imaging, optical technologies hold great promise to facilitate the development of highly sensitive cancer diagnoses as well as personalized patient treatment—one of the ultimate goals of precision medicine.

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A Confocal Endoscope for Cellular Imaging
Jiafu Wang, Min Yang, Li Yang, Yun Zhang, Jing Yuan, Qian Liu, Xiaohua Hou, Ling Fu
Engineering    2015, 1 (3): 351-360.   DOI: 10.15302/J-ENG-2015081
Abstract   HTML   PDF (9477KB)

Since its inception, endoscopy has aimed to establish an immediate diagnosis that is virtually consistent with a histologic diagnosis. In the past decade, confocal laser scanning microscopy has been brought into endoscopy, thus enabling in vivo microscopic tissue visualization with a magnification and resolution comparable to that obtained with the ex vivo microscopy of histological specimens. The major challenge in the development of instrumentation lies in the miniaturization of a fiber-optic probe for microscopic imaging with micron-scale resolution. Here, we present the design and construction of a confocal endoscope based on a fiber bundle with 1.4-μm lateral resolution and 8-frames per second (fps) imaging speed. The fiber-optic probe has a diameter of 2.6 mm that is compatible with the biopsy channel of a conventional endoscope. The prototype of a confocal endoscope has been used to observe epithelial cells of the gastrointestinal tracts of mice and will be further demonstrated in clinical trials. In addition, the confocal endoscope can be used for translational studies of epithelial function in order to monitor how molecules work and how cells interact in their natural environment.

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An Ultrasonic Backscatter Instrument for Cancellous Bone Evaluation in Neonates
Chengcheng Liu, Rong Zhang, Ying Li, Feng Xu, Dean Ta, Weiqi Wang
Engineering    2015, 1 (3): 336-343.   DOI: 10.15302/J-ENG-2015079
Abstract   HTML   PDF (5181KB)

Ultrasonic backscatter technique has shown promise as a noninvasive cancellous bone assessment tool. A novel ultrasonic backscatter bone diagnostic (UBBD) instrument and an in vivo application for neonatal bone evaluation are introduced in this study. The UBBD provides several advantages, including noninvasiveness, non-ionizing radiation, portability, and simplicity. In this study, the backscatter signal could be measured within 5 s using the UBBD. Ultrasonic backscatter measurements were performed on 467 neonates (268 males and 199 females) at the left calcaneus. The backscatter signal was measured at a central frequency of 3.5 MHz. The delay (T1) and duration (T2) of the backscatter signal of interest (SOI) were varied, and the apparent integrated backscatter (AIB), frequency slope of apparent backscatter (FSAB), zero frequency intercept of apparent backscatter (FIAB), and spectral centroid shift (SCS) were calculated. The results showed that the SOI selection had a direct influence on cancellous bone evaluation. The AIB and FIAB were positively correlated with the gestational age (|R| up to 0.45, P<0.001) when T1 was short (<8 µs), while negative correlations (|R| up to 0.56, P<0.001) were commonly observed for T1>10 µs. Moderate positive correlations (|R| up to 0.45, P<0.001) were observed for FSAB and SCS with gestational age when T1 was long (>10 µs). The T2 mainly introduced fluctuations in the observed correlation coefficients. The moderate correlations observed with UBBD demonstrate the feasibility of using the backscatter signal to evaluate neonatal bone status. This study also proposes an explicit standard for in vivo SOI selection and neonatal cancellous bone assessment.

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