Table 1.
Summary of Screening Platforms Reviewed.
| Authors, Year | Reference | Purpose | Advantage(s) | Disadvantage(s) |
|---|---|---|---|---|
| Platforms for Size-Based Sorting | ||||
| Solvas et al. (2011) | [33] | Size-Based Sorting | Can separate larvae from adults with high accuracy and efficiency | Does not separate between differing larval stages |
| Ai et al. (2014) | [34] | Size-Based Sorting | Sequential separation of all larval stages at >85% efficiency | Multiple devices needed for separating all stages, leading to increased chance of operational error |
| Dong et al. (2016) | [35] | Size-Based Sorting | One device can separate any developmental stage based on pressure input | Throughput is 3.5 worms per second, lower than other platforms |
| Han et al. (2012) | [36] | Size-Based Sorting | Worms of all developmental stages can be sorted, first use of electrotaxis for size-based separation in C. elegans | Imperfect separation for L2–L4 stages, only 80% of worms undergo directed movement due to electrotaxis |
| Rezai et al. (2012) | [37] | Size-Based Sorting | Selectivity for a given developmental stage is at least 90% | Uncertain structural and molecular effects due to paralysis |
| Wang et al. (2015) | [38] | Size-Based Sorting | Separates all worm stages simultaneously in one device, can also isolate male worms and size mutants | Purity for certain separations as low as 82% |
| Zhu et al. (2018) | [39] | Size Measurement | Quantitatively measures worm size using impedance cytometry, individual worms can be sorted for forward genetic screening | Accuracy for identifying L3 worms is only 81% |
| Dong et al. (2019) | [40] | Size Measurement | Worm size determined using automated image analysis, individual worms can be sorted for forward genetic screens | Throughput limited to 10.4 worms per minute, clogging of channel can completely disrupt sorting |
| Neurobiological Studies | ||||
| Rohde et al. (2007) | [31] | High-Resolution Imaging and Sorting | Worms immobilized for high-resolution imaging and sorted, worms not imaged can be recycled, sorted worms can be fed to well plate | Multiple active steps required to load one worm for imaging |
| Chung et al. (2008) | [26] | High-Resolution Imaging and Sorting | Simplified loading step allows for fast sequential imaging | Additional microfluidic control layer must be interfaced with flow layer |
| Cacéres et al. (2012) | [27] | High-Resolution Imaging and Sorting | Modified channel orients worms in the lateral orientation for nerve cord imaging | Additional microfluidic control layer must be interfaced with flow layer |
| Lee et al. (2013) | [28] | High-Resolution Imaging and Sorting | Similar function to [26] but only consists of one microfluidic layer | Device clogging can lead to disruption in sorting |
| Ma et al. (2009) | [41] | Long-Term High-Resolution Imaging | Individual worms can be imaged at multiple time points throughout most of their lifespan | No straightforward method for recovery of individual worms after imaging |
| Larsch et al. (2013) | [42] | Calcium Transient Imaging | Calcium transients can be imaged in multiple worms | Limited to lower resolution phenotypes |
| Lockery et al. (2012) | [43] | Electrophysiological Measurements of Neurons | Electropharyngeograms of multiple worms can be measured simultaneously | Worms cannot be recovered after data acquisition |
| Hu et al. (2013) | [44] | Electrophysiological Sorting | Worms can be sorted sequentially based on electrophysiological data, three times faster than manual methods | Data acquisition on chip not fully automated |
| Larval and Embryonic Development Studies | ||||
| Uppaluri et al. (2015) | [45] | Environmental Effects on Larval Growth | Software quantitatively tracks size growth of individual worms | Only eight larvae can be tracked simultaneously on a chip |
| Keil et al. (2017) | [30] | High-Resolution Imaging of Larvae | Individual larvae can be imaged at high resolution | No worm outlet |
| Cornaglia et al. (2015) | [46] | High-Resolution Imaging of Embryos | Individual embryos maintained in incubation chambers for high-resolution imaging, operation is passive | Screening multiple chemicals would require operation of multiple platforms in parallel |
| Letizia et al. (2018) | [47] | High-Resolution Imaging of Embryos and Worms | Operates using same mechanisms as [46], but can image worms after each embryo hatches | Screening multiple chemicals would require operation of multiple platforms in parallel |
| Atakan et al. (2019) | [48] | Imaging and Behavioral Analysis of Embryonic Development | Can acquire both imaging data and locomotion rate for groups of worms | Immobilization not complete, so high-resolution imaging is not possible, only three worms can fit in each chamber for unrestricted motion |
| Lifespan and Aging Studies | ||||
| Xian et al. (2013) | [49] | Lifespan Analysis of Worm Populations with Age | Worm populations can be studied for their whole lifespan by automated analysis | Multiple chambers must be arranged in parallel for screening multiple chemicals |
| Doh et al. (2016) | [20] | Lifelong Behavioral Analysis Using Axenic Media | Can feed worms and determine worm size at defined intervals | Effects of axenic media on some aspects of worm biology are still unknown |
| Wen et al. (2012) | [50] | Lifelong Stress Studies | Worms can be imaged and stored in individual chambers over time | Multiple device layers make fabrication more challenging |
| Li et al. (2015) | [51] | Lifelong Reproductive Measurement | Chambers in device converge in parallel for real-time counting of progeny from each worm | Device contains many narrow regions which may increase the chance of clogging |
| Banse et al. (2019) | [52] | Measurement of Survival Under Stress | Large data sets (~600 worms per device) can be acquired, individual worms can be tracked over time | Chip cannot perform on-chip immobilization for high-resolution imaging |
| Toxicology and Pathogenesis Studies | ||||
| Zhang et al. (2014) | [53] | Toxic Effects on Neurons | Device inlets are mixed to create a gradient of concentrations across the device, counting mechanism loads the desired number of worms | Device must me interfaced with an electrode layer, making fabrication more complicated |
| Kim et al. (2017) | [54] | Toxic Effects of Nanoparticles | Tapered channels are used for immobilization, and the distance traveled along the channel is correlated with worm size | Small features could lead to device clogging |
| Yang et al. (2013) | [55] | Effect of Pathogens and Antimicrobials | Device inlets are mixed to create a gradient of concentrations across the device, counting mechanism loads the desired number of worms | Only four gradient mechanisms are present on each chip, limiting the number of drugs that can be screened at a time |
| Hu et al. (2018) | [56] | Effect of Pathogens and Antimicrobials | Worm survival can be studied for several days, device can perform high-resolution imaging | Multiple layers are required for fabrication and device assembly |
| Behavioral Studies | ||||
| Stirman et al. (2010) | [57] | Optogenetic Response | Data acquisition rate orders of magnitude higher than for data acquired on plate | Individual worms cannot be recovered |
| Albrecht et al. (2011) | [58] | Chemotaxis Response | Channels in device can create a variety of spatiotemporal odorant patterns | Different devices must be used for different types of spatial patterns |
| Chung et al. (2011) | [32] | Chemical Effects on Behavior | Worms are simultaneously loaded into chambers, making the loading process quick | Small features can lead to clogging |
| Salam et al. (2013) | [59] | Electrotaxis Response | Response to electrotaxis can be quantified | Needs to be scaled up to perform a large-scale screen |
| Liu et al. (2016) | [60] | Electrotaxis Response | Worms can be sorted based on electrotaxis response | Only 20 worms can be screened per hour |
| Johari et al. (2011) | [61] | Mechanical Strength Measurements | Mechanical strength can be detected by measuring the deflection of PDMS | More chambers with a separate inlet for each chamber could increase the chambers size for chemical screens |
| Drug Screening Platforms | ||||
| Carr et al. (2011) | [62] | Drug Behavioral Response | Device can be used to many behavioral parameters, individual worms are assessed for the entire period of drug application | Does not incorporate a feature for high-resolution imaging |
| Mondal et al. (2016) | [63] | High Resolution Imaging Drug Screens | High-resolution phenotypes can be acquired, ~4000 worms can be screened in 16 min | Imaging may be challenging with young adults or larvae |
| Ding et al. (2017) | [64] | Anthelmintic Drug Screens | Feedback control system automatically optimizes concentration of drugs fed to device based on previous data | Only three chambers and three drug inlets per device |
| Dong et al. (2018) | [65] | Embryonic Drug Screens | Worms are compressed to extract embryos for drug screening | Larvae cannot be studied after embryos hatch |
| Migliozzi et al. (2018) | [66] | Multimodal Imaging for Drug Screening | Large data quantities extracted from both brightfield and fluorescent images | Only three drug inlets per device |
| Cellular Ablation Studies | ||||
| Allen et al. (2008) | [67] | Neuronal Laser Ablation | Worms are immobilized on-chip in parallel for laser ablation | Worms must leave device through inlet, requires more time than for devices with inlet and outlet |
| Guo et al. (2008) | [14] | Neuronal Laser Ablation | Complete immobilization is achieved for precise ablation | Sorting requires more steps than other platforms |
| Chung et al. (2009) | [68] | Neuronal Laser Ablation | Laser ablation is more high-throughput than for previous platforms | Multiple layers are required for device assembly |
| Samara et al. (2010) | [69] | Laser Ablation Chemical Screen | Worms transferred from multi-well plate to channel for ablation | Operation is not fully automated |
| Gokce et al. (2014) | [70] | Neuronal Laser Ablation | Device operation is fully automated | Multiple layers are required for device assembly |
| Lee et al. (2014) | [71] | Optogenetic KillerRed Ablation | Ablation can occur in many worms simultaneously | Separate strains must be generated to ablate different cells |
| Miscellaneous Applications | ||||
| Ghorashian et al. (2013) | [72] | Well-Plate Retrieval | Recover worms from a well plate within seconds for use in a microfluidic device | Only 16 wells are interfaced with the device |
| Aubry et al. (2015) | [73] | High Resolution L1 Larval Imaging | Hydrogel immobilization does not require tiny features that clog easily, worms can be recovered after imaging | Hydrogel and spacing fluid are new elements that are not commonly present in microfluidic labs |
| Robotics for Microfluidic Screening | ||||
| Desta et al. (2017) | [74] | Transfer worms from device to well plate | Robotic arm automatically transfers worms from a screening platform to a well plate | Robot setup may be challenging to replicate in a different lab environment |
| Lagoy et al. (2018) | [75] | Deliver chemicals from well-plate to device | Robotic arm transfers specified chemicals to device for screening | More time-consuming than delivery to devices with one inlet per well |
| Non-Microfluidic Screening Platforms | ||||
| Pulak (2006) and others | [76] | COPAS Flow Cytometry Sorting | Can sort ~100 worms per second | Platform is expensive, only large-scale phenotypes can be assessed |
| Gomez-Amaro et al. (2015) | [77] | Measuring Food Absorption | Techniques can either measure food consumed or protein accumulation in an organism | Assessing protein accumulation requires mass-spectrometry equipment |
| Churgin et al. (2017) | [78] | Behavioral Decline with Age | Worms can be maintained within individual chambers on solid media, without requiring regular bacterial perfusion | Worms must be manually placed in each chamber |