02922nas a2200757   4500000000100000000000100001008004100002260001500043653002200058653001100080653001800091653001400109653002300123653002600146653002400172653002200196653002600218653002000244653001600264653002300280653002300303653002300326653001600349100001700365700001600382700001700398700002100415700002000436700001900456700002000475700002100495700001900516700001500535700001900550700002200569700001700591700001500608700002000623700001100643700002000654700002000674700001900694700002100713700001900734700001300753700002400766700001700790700001700807700001400824700001900838700001700857700001900874700001600893700002300909700002500932700001800957700002600975700001701001700001401018700001601032245007501048300001501123490000701138520100501145022001402150       2022                            d  c2022-06-0210aColonic Neoplasms10aHumans10aImmunotherapy10aorganoids10aPrecision Medicine10aadoptive cell therapy10abispecific antibody10acolorectal cancer10adroplet microfluidics10aimmune-oncology10alung cancer10amicro-organosphere10aPrecision Medicine10aprecision oncology10atumorsphere1 aShengli Ding1 aCarolyn Hsu1 aZhaohui Wang1 aNaveen R. Natesh1 aRosemary Millen1 aMarcos Negrete1 aNicholas Giroux1 aGrecia O. Rivera1 aAnders Dohlman1 aShree Bose1 aTomer Rotstein1 aKassandra Spiller1 aAthena Yeung1 aZhiguo Sun1 aChongming Jiang1 aRui Xi1 aBenjamin Wilkin1 aPeggy M. Randon1 aIan Williamson1 aDaniel A. Nelson1 aDaniel Delubac1 aSehwa Oh1 aGabrielle Rupprecht1 aJames Isaacs1 aJingquan Jia1 aChao Chen1 aJohn Paul Shen1 aScott Kopetz1 aShannon McCall1 aAmber Smith1 aNikolche Gjorevski1 aAntje-Christine Walz1 aScott Antonia1 aEstelle Marrer-Berger1 aHans Clevers1 aDavid Hsu1 aXiling Shen00aPatient-derived micro-organospheres enable clinical precision oncology  a905-917.e60 v293 aPatient-derived xenografts (PDXs) and patient-derived organoids (PDOs) have been shown to model clinical response to cancer therapy. However, it remains challenging to use these models to guide timely clinical decisions for cancer patients. Here, we used droplet emulsion microfluidics with temperature control and dead-volume minimization to rapidly generate thousands of micro-organospheres (MOSs) from low-volume patient tissues, which serve as an ideal patient-derived model for clinical precision oncology. A clinical study of recently diagnosed metastatic colorectal cancer (CRC) patients using an MOS-based precision oncology pipeline reliably assessed tumor drug response within 14 days, a timeline suitable for guiding treatment decisions in the clinic. Furthermore, MOSs capture original stromal cells and allow T cell penetration, providing a clinical assay for testing immuno-oncology (IO) therapies such as PD-1 blockade, bispecific antibodies, and T cell therapies on patient tumors.  a1875-9777