The advent of microfluidics in the 1990s promised a revolution in multiple industries, from healthcare to chemical processing. Deterministic Lateral Displacement (DLD) is a continuous-flow microfluidic particle separation method discovered in 2004 that has been applied successfully and widely to the separation of blood cells, yeast, spores, bacteria, viruses, DNA, droplets, and more. DLD is conceptually simple and can deliver consistent performance over a wide range of flow rates and particle concentrations.Despite wide use and in-depth study, DLD has not yet been fully understood or fully optimised, with different approaches to the same problem yielding varying results. We endeavour here to provide an up-to-date expert opinion on the state-of-art and current fundamental, practical, and commercial challenges as well as experimental and modelling opportunities. Since these challenges and opportunities arise from constraints on hydrodynamics, fabrication and operation at the micro-and nano-scale, we expect this article to serve as a guide for the broader micro-and nanofluidic community to identify and address open questions in the field.

BACKGROUND: Only a few clinical trials have been conducted in patients with advanced pancreatic cancer after failure of first-line gemcitabine-based chemotherapy. Therefore, there is no current consensus on the treatment of these patients. We conducted a randomised phase II study of the modified FOLFIRI.3 (mFOLFIRI.3; a regimen combining 5-fluorouracil (5-FU), folinic acid, and irinotecan) and modified FOLFOX (mFOLFOX; a regimen combining folinic acid, 5-FU, and oxaliplatin) regimens as second-line treatments in patients with gemcitabine-refractory pancreatic cancer. METHODS: The primary end point was the 6-month overall survival rate. The mFOlFIRI.3 regimen consisted of irinotecan (70 mg m À2 ; days 1 and 3), leucovorin (400 mg m À2 ; day 1), and 5-FU (2000 mg m À2 ; days 1 and 2) every 2 weeks. The mFOLFOX regimen was composed of oxaliplatin (85 mg m À2 ; day 1), leucovorin (400 mg m À2 ; day 1), and 5-FU (2000 mg m À2 ; days 1 and 2) every 2 weeks. RESULTS: Sixty-one patients were randomised to mFOLFIRI.3 (n ¼ 31) or mFOLFOX (n ¼ 30) regimen. The six-month survival rates were 27% (95% confidence interval (CI) ¼ 13 -46%) and 30% (95% CI ¼ 15 -49%), respectively. The median overall survival periods were 16.6 and 14.9 weeks, respectively. Disease control was achieved in 23% (95% CI ¼ 10 -42%) and 17% patients (95% CI ¼ 6 -35%), respectively. The number of patients with at least one grade 3/4 toxicity was identical (11 patients, 38%) in both groups: neutropenia (7 patients under mFOLFIRI.3 regimen vs 6 patients under mFOLFOX regimen), asthaenia (1 vs 4), vomiting (3 in both), diarrhoea (2 vs 0), and mucositis (1 vs 2). CONCLUSION: Both mFOLFIRI.3 and mFOLFOX regimens were tolerated with manageable toxicity, offering modest activities as second-line treatments for patients with advanced pancreatic cancer, previously treated with gemcitabine.

Deterministic lateral displacement (DLD) is a technique for size fractionation of particles in continuous flow that has shown great potential for biological applications. Several theoretical models have been proposed, but experimental evidence has demonstrated that a rich class of intermediate migration behavior exists, which is not predicted. We present a unified theoretical framework to infer the path of particles in the whole array on the basis of trajectories in a unit cell. This framework explains many of the unexpected particle trajectories reported and can be used to design arrays for even nanoscale particle fractionation. We performed experiments that verify these predictions and used our model to develop a condenser array that achieves full particle separation with a single fluidic input.nanofluidics | deterministic ratchet | particle tracking D eterministic lateral displacement (DLD) is an efficient technology used to sort and purify small particles (1). Since their introduction (2), DLD pillar arrays have been used in applications from cell sorting (3) to biosensors (4) and can efficiently sort, separate, and enrich a broad range of particles, including parasites (5), bacteria (6), blood cells (7-9), circulating tumor cells (10), and exosomes (11). The original theory (12) predicts that particle trajectories fall into one of two modes, bumping or zigzag, as determined by the critical diameter Dc defined by the array geometry (2, 12). However, experimental evidence is clear that a rich class of intermediate migration behavior exists between these modes (13,14). Although a few theoretical models (15-17) have been proposed to explain this behavior, a general framework to study how geometric symmetry caused by pillar array influences particle trajectories is still missing.The symmetry of the pillar array can be explained in a specifically chosen unit cell. A typical DLD pillar array and associated unit cell are schematically represented in Fig. 1 A and B. Rows of pillars with diameter D0 are located along the y direction, with the pillars separated by a distance Dy , leaving a gap G = Dy −D0 in between pillars in the y direction. Adjacent rows of pillars are separated by a distance Dx in the x direction and shifted a distance in the y direction. The shift between one row and the N -th nearest row is then N . If this shift is chosen to coincide with Dy , then the array is periodic, and invariant to a translation of NDx in the x direction. Therefore, the array geometry has a built-in angle θp (smallest angle in the red triangle in Fig. 1B), such that tan(θp) = 1/N when Dx = Dy . Note that two types of array designs have been studied in the literature: the row-shifted parallelogram array (or stretched array) and the rotated square lattice (18,19). Here, we only studied the stretched DLD array design as shown in Fig. 1A. Our results do not extend to the rotated square array layout.Because of the invariance of NDx translational transformation, the fluid streamlines are assumed to have the same symmetry. When a...