CMOS Microflow Cytometer for Magnetic Label Detection and Classification

Murali, Pramod; Niknejad, Ali M.; Boser, Bernhard E.

doi:10.1109/jssc.2016.2621036

Cited by 28 publications

(15 citation statements)

References 24 publications

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“…Fig. 9 overlays two previously measured data sets of the spectral properties of different beads [10], [15] on top of the expected SRF of our coupled sensor, for a different number of turns, N, and different diameters of the core inductors. The desired frequency of operation dictates the sensor size; for example, in order to measure the real part (or magnitude) of χ of iron-oxide nanoparticles up to 1 GHz, we require SRF > 5 GHz.…”

Section: A Choosing the Frequency Of Operationmentioning

confidence: 88%

“…In reality, f Z ,in and f out slightly differ due to the distributed nature of the parasitic elements, but the approximation is very Complex frequency response of two types of magnetic beads [10] (top). Change in magnitude of χ versus frequency [15] for three beads types (bottom).…”

Section: Parasitic Effectsmentioning

confidence: 99%

“…Their simulated gains are 24 and 19 dB, respectively, to buffer and sufficiently amplify the bridge output. The receiver's simulated input-referred noise is lower than 10 nV/ √ Hz, theoretically allowing a measurement of 500 nV at the sensor output with an SNR = 10 dB at a 250-Hz bandwidth or, equivalently, with a detection time of ∼3 ms [28], fast enough for cell-sorting applications [10]. Additional peripheral circuitry includes an RF-to-dc amplitude detector for driver swing estimation and four thermometers for temperature gradient monitoring.…”

Section: Excitation and Receivermentioning

confidence: 99%

“…Frequency shift oscillators [6] are compact and have the highest sensitivity, but suffer from oscillator long-term drift [7], [8]. Integrated transformers, on the other hand [9], [10], are more suitable for cell sorting applications but use additional tuning inductors to achieve their required single-bead sensitivity. In addition, the physical implementations of these systems rely on an intuitive approach, often with only qualitative prediction of performance metrics.…”

Section: Introductionmentioning

confidence: 99%

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Analysis and Design of Coupled Inductive Bridges for Magnetic Sensing Applications

Gal-Katziri

Hajimiri

2019

IEEE J. Solid-State Circuits

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This paper presents the analysis and design of a novel magnetic sensor. We study the underlying physics of inductance shift sensors as a special case of the broader family of magnetic energy deviation sensors. The result is a quantitative definition of performance metrics with all assumptions and approximations explicitly stated. This analysis is then used to design a modified ac Wheatstone bridge that uses two inductorpairs in a cross-coupled configuration, to half its size and double its transducer gain while maintaining a fully differential structure with a matched frequency response. A proof-of-concept sensor was fabricated with peripheral circuitry in a 65-nm bulk CMOS process to operate between 770 and 1450 MHz with an effective sensing area of 200 μm × 200 μm. The new bridge sensor is fully characterized at a frequency of 770 MHz and demonstrates a reliable and continuous detection of 4.5-μm iron-oxide magnetic beads over time periods longer than 30 min, appreciably longer than previously reported works.

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Section: A Choosing the Frequency Of Operationmentioning

confidence: 88%

Section: Parasitic Effectsmentioning

confidence: 99%

Section: Excitation and Receivermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Analysis and Design of Coupled Inductive Bridges for Magnetic Sensing Applications

Gal-Katziri

Hajimiri

2019

IEEE J. Solid-State Circuits

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“…Several methods of magnetic detection have been proposed based on magnetic resonance effect, susceptibility measurements, giant magnetoimpedance (GMI), Hall Effect, Tunnel Magneto Resistance effect (TMR) or Giant Magneto Resistance effect (GMR) [24,39,40,41,42,43,44]. As biological objects are not magnetic and cannot be detected alone using magnetic sensors, the target must first be bound to magnetic particles (MPs or beads).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of In-Flow Magnetoresistive Chip Cell—Counter as a Diagnostic Tool

et al. 2019

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Inexpensive simple medical devices allowing fast and reliable counting of whole cells are of interest for diagnosis and treatment monitoring. Magnetic-based labs on a chip are one of the possibilities currently studied to address this issue. Giant magnetoresistance (GMR) sensors offer both great sensitivity and device integrability with microfluidics and electronics. When used on a dynamic system, GMR-based biochips are able to detect magnetically labeled individual cells. In this article, a rigorous evaluation of the main characteristics of this magnetic medical device (specificity, sensitivity, time of use and variability) are presented and compared to those of both an ELISA test and a conventional flow cytometer, using an eukaryotic malignant cell line model in physiological conditions (NS1 murine cells in phosphate buffer saline). We describe a proof of specificity of a GMR sensor detection of magnetically labeled cells. The limit of detection of the actual system was shown to be similar to the ELISA one and 10 times higher than the cytometer one.

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Electroformed Inverse‐Opal Nanostructures for Surface‐Marker‐Specific Isolation of Extracellular Vesicles Directly from Complex Media

Lin

Jiang

Yee

et al. 2023

Adv Materials Technologies

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be reflective of their cells of origin. For a wide range of clinical questions across diseases including cancer, infectious diseases, and traumatic brain injury, EVs have demonstrated unique clinical potential as a blood-based source of biomarkers that can be used as an adjunct or alternative to standard-of-care tissue biopsy. [1][2][3][4][5][6][7] Unlike liquid biopsy analytes such as circulating tumor cells (CTCs), EVs are abundant in circulation (1-10 CTCs mL −1 in cancer patients [8] vs up to 10 12 EVs mL −1 in serum [9] ); however, precise numbers for the concentration of most disease-associated EVs in patient blood have not been established. Moreover, single EVs contain multiple proteins and nucleic acid cargoes from their cells of origin, [10] yielding a more comprehensive view of the complex, heterogeneous, and often dynamically changing disease states, especially when compared to single-analyte readouts such as circulating serum-based antigens (e.g., carcinoembryonic antigen, CEA). [11] Also, EVs are a growing area of biological inquiry, in particular for their role in intercellular interactions, including interactions with immune cells [12] and metastatic sites in cancer. [13] Despite their widely appreciated potential as biomarkers, EVs have yet to be translated to widespread clinical use beyond proofof-concept studies. One fundamental hurdle to the translation of EV biomarkers to address clinical questions is the lack of an adequately specific, robust, and reproducible isolation technology for relatively sparse disease-associated EVs from the large background of EVs present in the blood. [2,6,10] To solve this problem, we were inspired by the field of CTC isolation, where rare cells (as rare as 1 in 10 9 hematologic cells in patient blood) tagged with antibodyfunctionalized magnetic nanoparticles (MNPs) have been precisely isolated from or quantified in whole blood by matching the feature size of the sorting or detection element on microfluidic chips to the given target analyte (e.g., 9-19 µm for a CTC). [14][15][16] The nanoscale size (30-200 nm for exosomes, [17] 50 nm − 1 µm for microvesicles [5] ) of EVs, however, has made it challenging to develop technology analogous to what has been successful in CTCs due to the difficulty and expense of fabricating nanoscale devices and their susceptibility to clogging. As a result, many Extracellular vesicles (EVs) -nanoscale membranous particles that carry multiple proteins and nucleic acid cargoes from their mother cells of origin into circulation -have enormous potential as biomarkers. However, devices appropriately scaled to the nanoscale to match the size of EVs (30-200 nm) have orders of magnitude too low throughput to process clinical samples (10 12 EVs mL −1 in serum). To address this challenge, we develop a novel approach that incorporates billions of nanomagnetic sorters that act in parallel to precisely isolate sparse EVs based on immunomagnetic labeling directly from clinical samples at flow rates billions of times greater than that of a single na...

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CMOS Microflow Cytometer for Magnetic Label Detection and Classification

Cited by 28 publications

References 24 publications

Analysis and Design of Coupled Inductive Bridges for Magnetic Sensing Applications

Analysis and Design of Coupled Inductive Bridges for Magnetic Sensing Applications

Evaluation of In-Flow Magnetoresistive Chip Cell—Counter as a Diagnostic Tool

Electroformed Inverse‐Opal Nanostructures for Surface‐Marker‐Specific Isolation of Extracellular Vesicles Directly from Complex Media

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